February 2024
Comparison of videolaryngoscopy (Glidescope®) and direct laryngoscopy for tracheal intubation for cesarean section
Nevin Aydın 1, Osman Esen 2
1 Department of Anesthesiology and Reanimation, Faculty of Medicine, University of Health Sciences, Kanuni Sultan Suleyman Hospital, 2 Department of Anesthesiology and Reanimation, Istinye University, Istanbul, Turkey
DOI: 10.4328/ACAM.21310 Received: 2022-07-12 Accepted: 2023-02-07 Published Online: 2023-12-07 Printed: 2024-02-01 Ann Clin Anal Med 2024;15(2):71-75
Corresponding Author: Nevin Aydın, Department of Anesthesiology and Reanimation, Faculty of Medicine, University of Health Sciences, Kanuni Sultan Suleyman Hospital, Küçükçekmece, Istanbul, Turkey. E-mail: nevinaydin4334@gmail.com P: +90 212 404 15 00 F: +90 212 571 47 90 Corresponding Author ORCID ID: https://orcid.org/0000-0003-0189-5865
Aim: The aim of this study was to retrospectively investigate the perioperative features and clinical outcomes in cesarean section (C/S) patients who underwent endotracheal intubation using direct laryngoscopy and Glidescope® videolaryngoscopy (GSVL).
Material and Methods: This retrospective study was performed using data gathered from the medical files of 179 C/S patients who underwent C/S under general anesthesia. After the induction of anesthesia with intravenous injection of propofol 2 mg/kg, and vecuronium 0.1 mg/kg, orotracheal intubation was performed using either direct laryngoscopy or GSVL. The patients underwent C/S after endotracheal intubation using either direct laryngoscopy or GSVL. Group I (n=47) was intubated via direct laryngoscopy, while Glidescope® was used in Group II (n=132).
Results: Baseline descriptives, craniofacial morphological measurements, duration of intubation and number of attempts for intubation, Cormack Lehane and Mallampati scores, as well as hemodynamic and respiratory parameters including blood pressure, heart rate, oxygen, and carbon dioxide levels were compared between two groups. The interincisal mouth opening (p=0.003) and CO2 levels (p=0.023) were increased in Group II. In Group I, the number of patients with protruding front teeth was higher than that in Group II (p=0.043).
Discussion: Our results demonstrated that the GSVL could be a safe, effective, and practical device for endotracheal intubation in patients scheduled for C/S. Our data imply that GSVL can be incorporated into routine clinical practice in obstetric anesthetic practice for C/S since it allows improved visualization of the larynx in pregnants without bringing any significant burden.
Keywords: Intubation, Intratracheal Intubation, Cesarean Section
Introduction
Challenges encountered in the management of the airway and its associated risks of aspiration, maternal, and fetal hypoxia are the significant causes of morbidity and mortality associated with general anesthesia [1]. Pregnant women are known to have a failure rate for endotracheal intubation that is 5 to 7 times higher than that of non-pregnant women [2].
When a pregnancy is planned for a cesarean section (C/S), access to the airway can be challenging, especially when the typical anatomy is distorted and prevents the upper airway from being properly directly visualized with a laryngogram. In order to improve intubation, fiberoptic and videoscopic techniques can make it easier to image the laryngeal inlet. For patients who need tracheal intubation, videolaryngoscopy has the potential to boost the success rate of the procedure. The first videolaryngoscope to be sold commercially was the Glidescope®. The camera on the hyperangulated blade is linked to a video screen, which enhances larynx visibility. The utility of Glidescope® videolaryngoscopy (GSVL) must be considered in case of failure of direct laryngoscopy and blind intubation [3].
When compared to direct laryngoscopy, tracheal intubation performed by doctors with little intubation experience (10 intubations per year) using the Glidescope® videolaryngoscope has a greater first-pass success rate and takes less time to complete [3]. Video technology has recently been introduced to facilitate the management of the upper airway since it provides a better vision for identification of the upper airway. Videoscopic intubation is contraindicated in high-grade upper airway obstructions and excessive secretions, which hinder the visualization of the upper airway. Therefore, anesthesiologists must be aware of the advantages and restrictions of GSVL for orotracheal intubation in pregnants scheduled for C/S [3,4].
The purpose of the present study was to compare the clinical features and perioperative findings in C/S patients who underwent orotracheal intubation utilizing either direct laryngoscopy and GSVL in our academic center.
Material and Methods
This retrospective study was performed by the Anesthesiology & Reanimation and Obstetrics & Gynecology Departments of our tertiary care center after the approval of the local institutional review board (10.03.2021/86). Data were extracted from medical files of 179 patients who underwent C/S under general anesthesia following orotracheal intubation with either GSVL (Group I, n=47) or direct laryngoscopy (Group II, n=132). Information regarding the age, height, weight, body mass index (BMI), pre-existenting or pregnancy-related diseases, American Society of Anesthesiologists (ASA) physical status, Mallampati, and Cormack Lehane laryngoscopic scores, number of attempts for intubation, duration of intubation and complications encountered during surgery were gathered from the hospital database. Intubation procedures were performed by two senior anesthesiologists with ≥ 5 years of anesthetic experience.
Exclusion criteria were known airway pathology, cervical spine injury or other contraindication to neck extension, small mouth opening, ASA score of III or higher, ischemic heart disease, cerebrovascular disease, respiratory disease, and body mass index (BMI) > 35 kg/m2. Patients planned for C/S with ASA scores of I or II were considered eligible for this study. According to routine practice, all patients were pre-oxygenated for 5 minutes before the induction of anesthesia. Anesthesia was induced with fentanyl 2 µg/kg, vecuronium 0.1 mg/kg, and propofol 2 mg/kg injected through intravenous route [6].
The vast majority of patients (161, 89.9%) had a fasting period of 4 to 6 hours prior to C/S. The remaining 18 patients (10.1%) were anesthetized and operated without waiting for the fasting period due to the need for emergent C/S. Emergency C/S was performed due to fetal indications such as non-reassuring fetal status, fetal bradycardia, and prolapse of the umbilical cord or fetal limbs or maternal causes like placenta previa, ablatio placenta, eclampsia, previous uterine surgery, trauma, and uterine rupture. Failed tracheal intubation is described as unsuccessful attempts for placement of a tracheal tube using either direct laryngoscopy or alternative intubating equipment, the need to proceed with surgery with a non-elective unsecured airway or the need to abort intubation or surgery and awaken the patient before the surgery [7,8].
The Glidescope® GSVL was prepared according to the manufacturer’s instructions. The surface of the GSVL blade was adequately lubricated with a silicone-based lubricant. We have used the Glidescope® (Saturn Biomedical, Burnaby, BC, Canada), which has been commercially available after 2002. It is used both in adult and pediatric orotracheal intubation practice. It is comprised of a MacIntosh type laryngoscope blade and a curved laryngoscope blade with a fixed micro-video camera. The video image is transmitted to a high-quality LCD monitor with a cable. Currently, GSVL is often used in intensive care units and emergency departments where unique airway challenges may often occur. It can be rapidly performed and it is resistant to fogging and does not necessitate force for lifting. The Glidescope® allows a visualized control of insertion and advancement of an endotracheal tube. It facilitates the insertion of nasogastric tubes and transesophageal echocardiographic probes. The technique for GSVL is similar to direct laryngoscopy, it can be readily performed by the experienced anesthesiologist and it is excellent for teaching purposes. The disadvantages of Glidescope® involve high cost compared to direct laryngoscopic devices, the need for training, the difficulty to overcome barriers for visualization of the laryngeal opening and need for adequate mouth opening [3]. After successful intubation, the teeth, and oral cavity were examined for any signs of trauma. In case any bloodstains were detected on GSVL blade, direct laryngoscopy was performed to determine its source. GSVL intubation was omitted if patients were in Cormack Lehane grades III and IV and spO2 decreased to < 95% due to prolonged intubation procedure. After recognition of the failure of intubation procedure with GSVL, 100% oxygen was supplied using a facemask.
All patients were followed up for 24 hours postoperatively. During follow-up, the mouth, pharynx, and larynx were examined using indirect laryngoscopy and a tongue blade. Complications were recorded. Baseline descriptives (age, body-mass index, history of smoking and previous surgery), craniofacial morphologic features (tooth morphology, inter incisor distance, thyromental distance, mandibulohyoid distance, neck range of motion), American Society of Anesthesiologists (ASA) scores as well as Mallampati and Cormack Lehane classes, postoperative dysphagia and sore throat, blood pressure, pulse rate, peripheral oxygen (O2) saturation and carbon dioxide (CO2) levels were recorded and compared between two groups.
Anthropometric criteria used to predict difficult airway involved thyromental distance, mandibulohyoid distance, and interincisor distances. Thyromental distance was described as the distance from the mentum to the thyroid notch, while mandibulohyoid distance was measured from the chin to hyoid. The interincisor distance was defined as the distance between the upper and lower incisors [9].
Statistical analysis
Our data were analyzed using the Statistical Package for Social sciences program version 21.0 (SPSS Inc., Chicago, IL, USA). Descriptive data have been expressed as mean, standard deviation, median, minimum and maximum for qualitative variables, while categorical variables have been given as numbers and percentages. Normality was assessed using the Kolmogorov-Smirnov test. The significance of the difference between the 2 groups was tested with either the T-test or the Mann-Whitney U test. The Chi-square test was employed to analyze the relationship between categorical variables. Analysis of variance (ANOVA) was performed to compare repeated measurements between groups and various time intervals. A p-value <0.05 was considered statistically significant.
Results
Our series consisted of 179 women (average age: 31.54±5.67 years). The body mass index was 32.04 ± 5.06. ASA status was I in 122 (68.2%) patients, while 57 patients (31.8%) had ASA status II. Comorbidities (hypertension, diabetes mellitus, etc.) were evident in 37 (20.7%) patients. C/S was primary in 54 (30.2%) cases, while 125 patients had repeat C/S (69.8%). An overview of baseline descriptive data and clinical features is presented in Table 1. Patients were allocated into 2 groups according to the method used for orotracheal intubation. Group I (n=47) involved patients intubated using direct laryngoscopy, while Group II (n=132) included patients who underwent GSVL for intubation.
In 4 patients who were planned for GSVL, 6 attempts for intubation failed. In one of these patients, tonsil laceration was detected. In one patient, the initial attempt for intubation with direct laryngoscopy resulted in failure, and intubation was successfully performed using GSVL.
All patients who underwent emergent C/S were successfully extubated after surgery, and no patients exhibited signs of aspiration of gastric contents. The establishment of a surgical airway was not needed and no maternal mortality was detected due to general anesthesia for C/S in this series.
Table 2 displays a comparative presentation of baseline descriptives and clinical features in Groups I and II. Mouth opening was found to be significantly higher in Group II (p=0.003). Overbite deformity was more common in Group I (p=0.043). The other variables under investigation did not exhibit any remarkable differences between patients intubated via direct laryngoscopy and GSVL. Hemodynamic and respiratory parameters including blood pressure, pulse rate, peripheral oxygen saturation, and carbon dioxide levels before and after intubation are demonstrated in Table 3. Blood pressure and pulse rate values before and after intubation did not exhibit any noteworthy differences between the 2 groups. Peripheral oxygen saturation after intubation was found to be increased compared to that before intubation for the whole study population (n=179). Carbon dioxide levels in Group II were significantly higher than that in Group I (p=0.023).
Discussion
The treatment of anesthesia for various types of surgery has changed as a result of recent advancements in general anesthesia. The prioritization of avoiding general anesthesia in C/S led to insufficient efforts being made to optimize and improve emerging procedures in this subgroup [10].
Inability to breathe or oxygenate after general anesthesia was produced and problems with the airways associated with intubation failure are the leading causes of anesthesia-related mortality in pregnant women. Due to the anatomical and physiological changes that take place during pregnancy, pregnant women are more prone to desaturation, difficult mask breathing, and failed intubation. Currently, videolaryngoscope is the preferred method in the event of a failed intubation. Videolaryngoscopes increase the success rate of unexpectedly difficult intubation in patients who have failed traditional direct laryngoscopy by giving appropriate glottis and vocal cord visualization [1].
In the operating theatre, the incidence of difficult tracheal intubations ranges from 1.2% to 3.8% in routine clinical practice, and increases to 5.3% in emergency situations. Up to 600 people are thought to have died from tracheal intubation-related problems. Particularly in patients with anatomical traits that can make tracheal intubation challenging, direct laryngoscopy does not always permit optimal viewing of the glottis [5,6]. The Glidescope can be used for routine intubations and difficult or failed intubations both in children and adults. It can be suitable for the high anteriorly positioned larynx where direct laryngoscopy has failed and in conditions where cervical immobilization is necessary or mouth opening is limited or in case of airway trauma with blood or secretions in the airway [6].
The anesthesiologists’ ability to manage the airway in pregnant patients planned for C/S is hampered by conditions such as shorter apnea times without desaturation, a higher risk of aspiration, tissue edema, mucosal hyperemia, and large breasts. Additionally, in a peripartum environment, the effects of intubation failure are more severe [11,12].
Complications of videoscopic intubation involve palatal perforation and hemorrhage. GSVL must be remembered as an option in cases of failure of ventilation and oxygenation. Mouth opening is an important parameter to be remembered during the selection of the method for intubation. Orotracheal intubation using a GlideScope® offers advantages of an easy and simple operation, and satisfactory laryngeal view in patients with a difficult laryngoscopy [13]. Trauma-related to intubation using the GlideScope is rare [13]. Our results support that GSVL is a favorable and safe way to establish an airway in selected C/S patients.
We observed that mouth opening was significantly increased in patients who underwent intubation via GSVL. This difference may be attributed to the fact that GSVL cannot be performed in patients with a mouth opening < 18 mm. Similarly, overbite deformity may be a factor that restricts mouth opening, and its incidence may be in patients who underwent intubation with direct laryngoscopy. An increase in carbon dioxide levels in patients intubated with GSVL may be linked with the delay due to the failed initial attempt via direct laryngoscopy.
Hoshijima et al. reported that the hemodynamic response following tracheal intubation was not diminished by the GlideScope in comparison to the Macintosh laryngoscope [14]. Our results yielded that there was no difference between the two groups concerning neither the blood pressure nor pulse rates. This may be due to effective suppression of the pressure response to orotracheal intubation by general anesthesia. Practice and familiarity with the equipment are critical points for the successful use of GSVL in case of failure of direct laryngoscopic intubation. The key to successful use is proper training and anticipation of situations when their use may be necessary for C/S patients.
Our limitations include retrospective design, information confined to the experience of a single center, and possible variations in the grading of Mallampati and Cormack Lehane scores, and ASA status. Since our institution is tertiary care with teaching facilities, an anesthesia resident may initially try the first attempt intubation and senior residents or attending anesthesiologists may take charge of the intubation procedure. The personal preferences for GSVL as the initial method of intubation may have led to an underestimation of the incidence of intubation failures.
Conclusion
Increased awareness of possible risks, anticipation with challenging situations, familiarity with the new devices and improvement of skills with effective training programs are key points to optimize outcomes with general anesthesia and intubation procedures performed in C/S patients. The results of the present study yielded that orotracheal intubation via GSVL provides a safe, secure and practical method in C/S patients which may have additional risks and difficulties for the management of the upper airway.
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 comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Nevin Aydın, Osman Esen. Comparison of videolaryngoscopy (Glidescope®) and direct laryngoscopy for tracheal intubation for cesarean section. Ann Clin Anal Med 2024;15(2):71-75
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Comparison of postoperative analgesic efficacy of bupivacaine and levobupivacaine for dorsal penile block
Hayrünisa Kahraman Esen 1, Osman Esen 2, Turan Yıldız 3, Zekeriya İlçe 4
1 Department of Pediatric Surgery, University of Health Sciences, Fatih Sultan Mehmet Training and Research Hospital, İstanbul, 2 Department of Anesthesiology and Reanimation, İstinye University, İstanbul, 3 Department of Pediatric Surgery, Faculty Of Medicine, İnönü University, Malatya, 4 Department of Pediatric Surgery, University of Health Sciences, Ümraniye Training and Research Hospital, İstanbul, Turkey
DOI: 10.4328/ACAM.21453 Received: 2022-10-16 Accepted: 2023-01-25 Published Online: 2023-12-25 Printed: 2024-02-01 Ann Clin Anal Med 2024;15(2):76-80
Corresponding Author: Hayrünisa Kahraman Esen, Department of Pediatric Surgery, University of Health Sciences, Fatih Sultan Mehmet Training and Research Hospital, Maltepe, İstanbul, Turkey. E-mail: nisakahraman@hotmail.com P: +90 505 713 68 23 F: +90 216 575 04 06 Corresponding Author ORCID ID: https://orcid.org/0000-0002-3541-6546
This study was approved by the Ethics Committee of Kocaeli University Clinical Research (Date: 2013-04-24, No: 2013/120)
Aim: In this study, we aimed to evaluate the postoperative analgesic efficacy and side effects of bupivacaine and levobupivacaine for dorsal penile blockage in circumcised patients.
Material and Methods: A total of 84 circumcised patients (age range: 7-11 years) were enrolled in this study. The patients were divided into two groups according to the dorsal penile block method: bupivacaine utilized Group B, levobupivacaine utilized Group L. Blocks were administered preoperatively with 1mL kg-1 of 0.25% bupivacaine and levobupivacaine. Postoperative pain scores and sedation were evaluated. Pain assessment was performed using the Wong-Baker faces Pain Scale (WBPS). The number of patients without pain within the first 6 hours, analgesia duration, time of first analgesia, and total paracetamol consumption were recorded.
Results: Mean scores of WBPS were found statistically higher at the first, second and third hours in group B than in group L (p<0,05). The results showed no statistically significant differences between groups according to the WBAS assessment at 4, 5 and 6 hours, rates of rescue analgesic requirement and also rescue paracetamol dose between the groups.
Discussion: Administration of levobupivacaine for dorsal penile blockage was found to be more efficient to provide postoperative analgesia and also to reduce postoperative analgesia utilization than bupivacaine in circumcised children under general anesthesia.
Keywords: Bupivacaine, Levobupivacaine, Blocks
Introduction
The number of outpatient minor surgeries due to various indications is increasing. Optimal analgesia in outpatient surgery enhances patient satisfaction, reduces the length of hospitalization, and prevents unnecessary hospital admissions [1].
Postoperative pain control is essential for medical, ethical and social reasons. The operation type, pain location and severity, as well as children’s socio-cultural state, pain recognition level, emotional and behavioral development should be carefully taken into consideration when planning the optimal pain therapy. Perioperative pediatric analgesia should be provided optimally [2-6].
Severe pain occurs mostly within the first 2 hours after circumcision surgery. Conventional pain control management has been commonly provided by systemic non-steroidal anti-inflammatory drugs or opioids. Recently, various pain control techniques are available such as caudal epidural block, dorsal penile block, subpubic penile block, subcutaneous ring block and pudendal nerve block, which provide perioperative pain control by adding local analgesics into the systemic analgesic drugs [4,7-11]. Although it is crucial to provide adequate analgesia for a painless period after operation by long-acting local analgesics with a single dose, it has not been achieved yet in circumcision procedures [12]. Levobupivacaine is the racemic enantiomer of bupivacaine, additionally, both levobupivacaine and bupivacaine have similar anesthetic and analgesic effects at the same doses [13].
In the present study, we aimed to compare the postoperative analgesic effects of %0.25 bupivacaine and %0.25 levobupivacaine for dorsal penile blockage under general anesthesia in circumcised patients.
Material and Methods
This study was performed with the Institutional Review Board protocol approval number 2013/120 at Kocaeli Derince Research and Education Hospital, Department of Burn Treatment Center. According to the American Society of Anesthesiologists (ASA) criteria, 84 ASA I and II group male children (aged 7 to 11 years) were included in this study with planning for a future circumcision procedure. This is a prospective, single-center, randomized, double-blind and controlled study. Exclusion criteria were: history of allergy to amid-type local anasthetics, history of seizures, the existence of chronic pain and history of analgesic drug utilization, presence of bleeding diathesis and an systemic disease (cardiac, renal, hepatic or respiratory).
All patients received the same anesthetic after a 6-hour fasting. To prevent anesthesia induction and surgical stress, premedication with 0.5 mg/kg oral midazolam was performed 60 minutes before the operation. Patients were monitored, and anesthesia induction was provided by intravenous bolus application of propofol 2-3 mg/kg. A laryngeal mask suitable for the age and weight of the children was placed after the induction. The anesthesia depth required for surgical intervention was provided by 50% N2O+50% O2 and 1-4% sevoflurane. Opioids, benzodiazepines and other medicines that affect central pain were not used.
The patients were divided into two groups using a sealed envelope technique, which is based on computer-generated random numbers. Bupivacaine 0.25% was prepared for Group B and 0.25% levobupivacaine was prepared for Group L preoperatively with a total volume of 1mL kg-1 by a physician who was not a participant of the present study. All the blocks and the surgical procedure were performed by a physician who even did not know what medicine was given to the patients. The blocks were performed through the dorsal penile blockage and ventral preputium infiltration via 25-gauge needles in the supine position under sterile conditions.
Before the surgical incision, the depth of analgesia was assessed by sending a mechanical stimulus with a surgical clamp to the foreskin. The adequacy of analgesia was determined as the absence of gross body movements (extension or flexion of the arms and legs, chest extension, flexion of the head, abdominal contraction) or absence of significant (±15%) change in MBP and HR.
The awakened patients were taken to the recovery room at the end of the operation. The Modified Aldrete Recovery Scores (MARS) was used to assess recovery level, scores of 9 and higher indicated the complete recovery state.
Demographic data (age, weight, duration of surgery), existence of pain and pain level throughout 1-6 hours, time of first analgesia administration, and consumption of rescue analgesic (paracetamol) within the first 6 hours were documented and recorded. Postoperatively, pain and sedation scores were also assessed. The Wong-Baker faces Pain Scale (WBPS) was used to assess as a pain rating scale.
The administration of rescue analgesic (paracetamol 10mg.kg-1IV) was only applied to the children with higher WBPS 4 scores postoperatively. The time of the first analgesic order was measured. Children were observed for pain, postoperative anesthesia, and surgical complications for six hours. Follow-up patients who were comfortable, mobile, able to conceive oral fluids and able to urinate were discharged on the same day.
Statistical analysis
All data were analyzed with SPSS (Statistical Package for the Social Sciences) software for Windows (v21.0; IBM, Armonk, NY, USA). Individual and aggregate data were summarized using descriptive statistics, including mean, standard deviations, medians (min-max), frequency distributions and percentages. Analysis of intermittent data (requirement for rescue analgesia, nausea and vomiting etc.) was compared using Pearson’s Chi-Square test. Continuous variables such as age, weight and operation duration were compared using the Student t-test. Evaluation of continuous variables obtained from measures (first analgesic time, etc.) performed using the Mann-Whitney U test. P-Values <0.05 were considered statistically significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Eighty-four patients who underwent circumcision operation were enrolled in this study. The patients were divided into two groups: bupivacaine was utilized in Group B (n=42), levobupivacaine was utilized in Group L (n=42). There was no statistically significant difference between the groups according to age, body weight, ASA state and operation duration.
According to results of WBAS evaluation at 1, 2, 3, 4, 5 and 6 hours between the groups, mean scores of WBPS were statistically higher at 1, 2 and 3 hours in Group B than in Group L (respectively, p:0,015, p:0,009, p:0,034). Meanwhile, the results showed no statistically significant differences at 4, 5 and 6 hours between the groups (Table 1).
In addition, no statistically significant differences were found according to the rates of additional analgesic requirement at 1, 2, 3, 4, 5 and 6 hours between the groups (p<0.05). There was also no significant difference (p=0.21) between the groups according to the rate of total rescue analgesic requirement between the groups (Table 2). Similarly, there was no significant difference between the groups according to the postoperative administration of the total paracetamol dose (Figure 1).
There were no postoperative surgical complications, nausea, vomiting, headache, dizziness or itchiness observed in any of our patients. Additionally, there was no statistically significant difference found between the groups according to the rates of postoperative surgical complications (p>0,05).
Discussion
As with all invasive procedures, pain management is also important in minor surgery. Numerous studies documented that the effect of analgesia varies according to the type of surgery, the age of the patient, and also the type and amount of local anesthetic drug [14,15].
Different methods are used to assess pain in children. Children older than three years can give information about the localization, severity and quality of the pain, depending on their own developmental status. In the face scale system, which is the most frequently used method of pain measurement based on personal expression, the child has an opportunity to express his pain through the scales with different expression drawings.
Although methods such as pain thermometers, color analog scales, etc. are used in children aged 5 years and older, the face scale system is considered the most reliable one [16]. In this study, the children were between the ages of 7 to 11 and were able to express their pain, therefore we used the Wong-Baker Faces Pain Scale.
However, there are a considerable number of studies comparing caudal block and penile block, and comparing bupivacaine and levobupivacaine in caudal block for postoperative analgesia in circumcision operation, to our knowledge no published data are available such as a comparison of bupivacaine and levobupivacaine for dorsal penile blockage in circumcision operation. In the present study, we compared the postoperative analgesic efficiency of %0.25 bupivacaine and %0.25 levobupivacaine for dorsal penile blockage under general anesthesia in circumcised patients.
Levobupivacaine is a racemic S-(-) enantiomer of bupivacaine, which shows no definitive physicochemical differences compared to racemic bupivacaine. It has less toxic effect on the central nervous and the cardiovascular systems. Randomized double-blind studies have shown that bupivacaine and levobupivacaine both have similar anesthetic and analgesic effects when used in equal dosages. However, compared to bupivacaine levobupivacaine has a tendency to exhibit less motor blockade and a more elongated sensory block, thus creating a longer postoperative duration of analgesic impact [13, 17].
In a prospective randomized double-blind study Locatelli et al. have compared caudally administered 0.25% levobupivacaine, 0.25% bupivacaine and 0.25% ropivacaine with a total dosage of 1 ml/kg in an undescended testis or inguinal hernia repair, additionally with a total dosage of 0.5 ml/kg in phimosis and incisions below L3. They have reported a elongated analgesic effects of bupivacaine compared to levobupivacaine and ropivacaine [14]. Kaya et al. also have used a 0.5 ml/kg total dosage of 0.25% levobupivacaine and 0.25% bupivacaine in comparison with one another for caudal administration in circumcision surgery; they reported longer periods of analgesic effects of bupivacaine than levobupivacaine, thus stating that it has provided better analgesia [18]. In our study, for the first second and third hours of postoperative duration, average WBAS scores of Group B were higher than that of Group L in a statistically significant percentage (respectively, p=0.015, p=0.009, p=0,034). However, in a second evaluation of WBAS scores after four hours, no statistically significant differences have been detected between the two groups (respectively, p=0.43, p=0.7, p=0,32). We consider that in a dorsal penile blockage, administration of % 0.25 levobupivacaine is more effective for maintaining analgesia than % 0.25 bupivacaine in the first postoperative three hours. When comparing the need for rescue analgesics in the 1st, 2nd and 3rd hours consecutively for the two groups, no statistically significant differences were observed (respectively, p=0.079, p=0.24, p=0.32). The total requirement of rescue analgesic ratios was not significantly different either (p=0,21). After the fourth hour of postoperative duration, patients in both groups did not require any additional analgesia. As a result, we think that for the children undergoing circumcision operations under general anesthesia, administration of dorsal penile block with the use of 0.25% levobupivacaine and 0.25% bupivacaine provide the needed analgesia after the 4th hour of the postoperative process.
Bengisun et al. have compared caudal and penile levobupivacaine for circumcision operation in terms of postoperative pain management, and researchers have found that caudal block was superior to the penile levobupivacaine block, even though there was a motor block risk and a significantly prolonged time of first walk [19]. Cochrane noted that penile block is an appropriate method for children with gait disturbance in his study. Although there is no motor block in the dorsal penile nerve block, it is well known that current local anesthetics have narrow therapeutic index [20]. In our study, there was dorsal penile nerve block but no motor block was reported in both groups.
Matsota et al. compared levobupivacaine, intravenous fentanyl (1µg/kg) and paracetamol (30 mg/kg) for penile block in circumcised patients under general anesthesia. The better cardiovascular stability obtained intraoperatively in the group, which was administered penile block additionally provided a longer duration of analgesia postoperatively and provided better recovery levels [21]. Moreover, in case of accidental intravenous injection of high doses, levobupivacaine was found to be safer than bupivacaine because patients can tolerate higher doses [22]. In our study, none of our patients experienced accidental intravenous injections or postoperative nausea, vomiting, headache, dizziness and itchiness.
The administration of %0.25 levobupivacaine for dorsal penile blockage was found to be more efficient in providing postoperative analgesia and also in reducing postoperative analgesia utilization compared to %0.25 bupivacaine in circumcised children under general anesthesia.
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 comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
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2. Richman DC. Ambulatory surgery: how much testing do we need? Anesthesiol Clin. 2010;28(2):185-97.
3. Bastos Netto JM, de Araújo JG Jr, de Almeida Noronha MF, Passos BR, de Bessa J Jr, Avarese Figueiredo A. Prospective randomized trial comparing dissection with Plastibell® circumcision. J Pediatr Urol. 2010;6(6):572-7.
4. Sayed JA, Fathy MA. Postoperative analgesia for circumcision in children: A comparative study of caudal block versus high dose rectal acetaminophen or EMLA cream. J Am Science. 2012;8:512-6.
5. Görgel SN, Erten Tol B. The application of a penile block before circumcision: effects on the postoperative FLACC score and analgesic requirement. Turk J Urol. 2013;39(1):39-42
6. Ozen V, Yigit D. A comparison of the postoperative analgesic effectiveness of low dose caudal epidural block and US-guided dorsal penile nerve block with in-plane technique in circumcision. J Pediatr Urol. 2020;16(1):99-106.
7. Aksu C, Akay MA, Şen MC, Gürkan Y. Ultrasound-guided dorsal penile nerve block vs neurostimulator-guided pudendal nerve block in children undergoing hypospadias surgery: A prospective, randomized, double-blinded trial. Pediatr Anesth. 2019;29(10):1046-52.
8. Dalia E, Gahan AE. Levobupivacaine versus hyperbaric bupivacaine in spinal anesthesia for hypospadias surgery in children. The Medical Journal of Cairo University. 2021;89:373-9.
9. Karatas A, Eti EZ, Umuroglu T, Zengin SU, Gogus FY. Topical and systemic analgesia versus caudal epidural and dorsal penile nerve block in relieving pain after pediatric circumcision. Marmara Medical Journal. 2021;34(3):292-7.
10. Naja Z, Al-Tannir MA, Faysal W, Daoud N, Ziade F, El-Rajab M. Comparison of pudendal block vs. dorsal penile nerve block for circumcision in children: A randomized controlled study. Anesthesia. 2011;66(9):802-7.
11. Joshi GP, Rawal N, Kehlet H, PROSPECT collaboration; Bonnet F, Camu F, et al. Evidence-based management of postoperative pain in adults undergoing open inguinal hernia surgery. Br J Surg. 2012;99(2):168-85.
12. Atan A, Tuncel A. Pain mechanisms after male genitourinary tract surgeries and treatment approaches. The New Journal of Urology. 2013;8(1):72-6
13. Kingsnorth AN, Cummings CG, Bennett DH. Local anesthesia in elective inguinal hernia repair: A randomized, double-blind study comparing the efficacy of levobupivacaine with racemic bupivacaine. Eur J Surg. 2002;168(7):391-6.
14. Locatelli B, Ingelmo P, Sonzogni V, Zanella A, Gatti V, Spotti A, et al. Randomized, double-blind, phase III, controlled trial comparing levobupivacaine 0.25%, ropivacaine 0.25% and bupivacaine 0.25% by the caudal route in children. Br J Anaesth. 2005;94(3):366-71.
15. Boretsky KR. A review of regional anesthesia in infants. Pediatric Drugs. 2019;21(6):439-49.
16. Hadjistavropoulos HD, Craig KD, Grunau RV, Grunau RV, Johnston CC. Judging pain in newborns: facial and cry determinants. J Pediatr Psychol. 1994;19(4):485-91.
17. Foster RH, Markham A. Levobupivacaine: A review of its pharmacology and use as a local anaesthetic. Drugs. 2000;59(3):551-79.
18. Kaya Z, Süren M, Arıcı S, Karaman S, Tapar H, Erdemir F. Prospective, randomized, double-blinded comparison of the effects of caudally administered levobupivacaine 0.25% and bupivacaine 0.25% on pain and motor block in children undergoing circumcision surgery. Eur Rev Med Pharmacol Sci. 2012;16(14):2014-20.
19. Kazak Bengisun Z, Ekmekci P, Haliloğlu AH. Levobupivacaine for postoperative pain management in circumcision: caudal blocks or dorsal penile nerve block. Ağrı. 2012;24(4):180-6
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21. Matsota P, Papageorgiou-Brousta M. Intraoperative and postoperative analgesia with subcutaneous ring block of the penis with levobupivacaine for circumcision in children. Eur J Pediatr Surg. 2004;14(3):198-202.
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Infectious agents and antibiotic resistance in the burn unit
Bülent Kaya 1, Sibel Doğan Kaya 2, Öznur Ak 3
1 Department of Infectious Diseases and Clinical Microbiology, University of Health Sciences, Kartal Dr Lütfü Kırdar City Hospital, Istanbul, 2 Department of Infectious Diseases and Clinical Microbiology, University of Health Sciences, Kartal Koşuyolu Research and Training Hospital, Istanbul, 3 Department of Infectious Diseases and Clinical Microbiology, University of Health Sciences, Kutahya, Turkey
DOI: 10.4328/ACAM.21678 Received: 2023-03-03 Accepted: 2023-07-31 Published Online:2023-11-24 Printed: 2024-02-01 Ann Clin Anal Med 2024;15(2):81-84
Corresponding Author: Bülent Kaya, Department of Infectious Diseases and Clinical Microbiology, University of Health Sciences, Kartal Dr Lütfü Kırdar City Hospital, Istanbul, Turkey. E-mail: badeatakaya@hotmail.com P: +90 505 552 01 70 Corresponding Author ORCID ID: https://orcid.org/0000-0003-3027-5868
Aim: In terms of hospital infections, patients in the burn unit have a special importance. In these patients, the physical, cellular and humoral defense systems are impaired, and the potential of microorganisms to cause infection increases. In our study, it was aimed to determine the types of microorganisms isolated from all cultures taken from patients hospitalized in the burn unit of our hospital, the types of infections they cause, and antibiotic resistance and antibiotic resistance rates.
Material and Methods: In our study, microorganisms and antibiotic resistance profiles isolated from patients hospitalized in the Burn Unit of Dr. Lutfi Kirdar Kartal Training and Research Hospital between January 1 and December 31, 2009 were evaluated retrospectively.
Results: During this period, 458 patients hospitalized in the burn unit were followed up and 327 microorganisms were isolated from 116 (25.3%) patients.Of these microorganisms, 72.2% were Gram-negative bacteria, 20.2% were Gram-positive bacteria, and 7.6% were fungi. The most frequently isolated microorganisms were Pseudomonas aeruginosa (31.2%) and Acinetobacter baumannii (29.4%), followed by Staphylococcus aureus (9.2%) and Candida spp. (7.0%). The antibiotics to which Pseudomonas aeruginosa was most sensitive were amikacin, ciprofloxacin, gentamicin, meropenem and imipenem, respectively, while the most antibiotic resistance was found to cefoperazone-sulbactam and piperacillin-tazobactam. Acinetobacter baumannii was most sensitive are colistin and tigecycline; while no resistance to colistin was detected, resistance to tigecycline was found to be 14.3%. There was more than 90% resistance to other antibiotics. Methicillin resistance was found in 83.3% of the isolated Staphylococcus aureus strains, and no resistance was found to vancomycin, teicoplanin and linezolid in any of the Gram-positive bacteria.
Discussion: Gram-negative bacteria, mainly Pseudomonas aeruginosa and Acinetobacter baumannii, constitute the dominant flora in the burn unit, and in these microorganisms, high resistance to antibiotics was noted. For the empirical antibiotic approach, each unit should follow its own infection surveillance and antibiotic resistance rates, and in order to prevent infections, infection control measures should be followed and the appearance of infection should be prevented.
Keywords: Burn Unit, Antibiotic Resistance, Infectious Agents
Introduction
The burn is caused by contact with the skin of hot, cold or chemicals, most often it occurs as a result of thermal damage caused by hot water or flame. The depth of the resulting burn depends on the intensity of the heat, the contact time and the thickness of the skin [1]. If the burn is limited by the epidermis, it is defined as a first-degree burn; second-degree burns affect both the epidermis and the dermis; third-degree burns affect muscles and the bone under the dermis; if all layers of the skin are affected, this is defined as carbonization [2].
The type of burn, the depth and width of the burn area are determining factors for the number of colonizing microorganisms [2,3]. In the early period (within the first 48 hours), the burn area is colonized by staphylococci present in the sweat glands, hair follicles or intact skin flora outside the burn area, colonization of Gram-negative bacteria occurs after 48 hours and fungi after about a month [2,4,5]. Gram-negative bacteria play an important role in colonization and invasion because they are motile, develop resistance to antibiotics, and secrete enzymes such as elastase, collagenase, lipase, and protease [2,6].
Infections are important causes of morbidity and mortality in burn patients. The treatment of burn patients requires multidisciplinary approaches such as early debridement of necrotic tissue, closure of the wound, adequate nutrition, providing fluid-electrolyte support, as well as appropriate antibiotic treatment and infection control measures.
The agent distribution and antibiotic sensitivity in each unit are different. For this reason, in the burn unit, where the risk of infection is very high, it is important to know the most common pathogens and their sensitivity to antibiotics, to take infection control measures for these agents and direct empirical treatments.
In our study, it was aimed to determine the types of microorganisms isolated from all cultures taken from patients hospitalized in the burn unit of our hospital, the types of infections they cause, and antibiotic resistance and antibiotic resistance rates.
Material and Methods
In our study, microorganisms and antibiotic resistance profiles isolated from patients hospitalized in the Burn Unit of Dr. Lutfi Kirdar Kartal Training and Research Hospital between January 1 and December 31, 2009 were evaluated retrospectively. During this period, 458 patients hospitalized in the burn unit were followed up and 327 microorganisms were isolated from 116 (25.3%) patients.
Deep tissue culture and blood culture (Bact/Alert 3D) were taken from patients with suspected burn wound infection. Microorganisms growing in both cultures were identified. Classical microbiological methods were used for this purpose. Additionally, API 20E (BIOMERIEUX) and API 20N (BIOMERIEUX) systems were used to identify Gram-negative bacteria.
The evaluation was carried out according to NCCLS (National Committee of Clinical Laboratory Standards) / CLSI (Clinical Laboratory Standards Institute) criteria.
Results
Out of 458 patients followed in the burn unit of our hospital between January 1 and December 31, 2009, 31.9% (n=146) were females, 68.1% (n=312) were males, and the female/male ratio was approximately ½. Infection developed in 116 of 458 patients. Of these 116 patients, 30 (25.9%) were female and 86 (74.1%) were male, with an age range of 1-66 and a median age of 29.2 years. Burns due to flame and hot water were observed most frequently in these patients.
The percentages of burns in which infection developed the most were 20-29%, 40-49% and 10-19%, respectively.
Of 116 patients, 29.3% (n=34) were classified as second-degree burns and the remaining 70.7% (n=82) as third-degree burns. Partial charring occurred in three patients with third-degree burns.
A total of 327 microorganisms were isolated from 116 patients included in the study, of which 217 (66.4%) were in deep tissue culture taken from the burn area, 52 (15.9%) in blood culture, 32 (9.8 %) in urine culture, 16 (4.9%) catheter tip culture, 9 (2.9%) deep tracheal aspirate culture, 1 (0.3%) eye swab culture.
Of the 327 isolated microorganisms, 236 (72.2) were Gram-negative bacteria, 66 (20.2%) were Gram-positive bacteria and 25 (7.6%) were fungi (Table-1).
The first three were P.aeruginosa, A.baumannii and S.aureus. These three were the causative agents in 69.8% of all burn infections. P.aeruginosa and A.baumannii constituted 83.9% of Gram-negative bacteria, and the remaining 16.1% were other Enterobacteriaceae family members such as E.coli, Klebsiella spp., Proteus spp., Citrobacter spp. and Enterobacter spp. When the distribution of the agents according to the materials was examined, in deep tissue culture, P.aeruginosa, A.baumannii and S.aureus took the first three places, while in blood and urine cultures, the first three places were taken by A.baumannii, Candida spp. and P.aeruginosa (Table 2).
When studying the sensitivity of the most frequently distinguished microorganism P.aeruginosa to antibiotics, it was found that P.aeruginosa is most sensitive to amikacin (86.3%) ciprofloxacin (75.8%), meropenem (71.8%), gentamicin (69.4%) and imipenem (69.1%), respectively. The antibiotics to which it was most resistant were cefoperazone-sulbactam (53.8%) and piperacillin-tazobactam (44.7%) (Table 3).
The antibiotic to which A.baumannii is most sensitive is tigecycline with 85.7%. The rate of resistance to tigecycline was 14.3%. Colistin susceptibility of 19 A.baumannii isolates isolated from blood was measured with the E test and all were found susceptible (Table 3).
Apart from these two Gram-negative microorganisms, Enterobacteriaceae family members E.coli, Proteus spp., Citrobacter spp., Klebsiella spp. and Enterobacter spp. were isolated.
Although the number of isolates is not high, it is noteworthy that antimicrobial resistance patterns were high. While the antibiotics to which they were most sensitive were imipenem,
meropenem, amikacin and gentamicin, an average of 50% resistance was found to other antibiotics. Extended-spectrum beta-lactamase (ESBL) production rate was determined as 29% in these isolates.
Among Gram-positive bacteria, S.aureus, Diphtheroids spp. and Coagulase-negative Staphylococci are the most common cause of burn infections. 83.3 % methicillin resistance in S.aureus strains and 86.7 % resistance in Coagulase-negative Staphylococci were detected. While all staphylococci were resistant to penicillin, no Gram -positive bacteria were resistant to vancomycin, teicoplanin and linezolid.
Discussion
In our study, the most common infections in our burn unit were burn wound infections at 66.4%, bloodstream infections at 15.9% and urinary tract infections at 4.9%. Similar to our study, Ekrami et al. reported the most common infections in 182 burn patients in a one-year period such as burn wound infections in 72.5%, bloodstream infections in 18.6%, and urinary tract infections in 8.9% [7].
72.2% were Gram-negative bacteria, 20.2% were Gram-positive bacteria and 7.6% were fungi. According to the agent distribution, P.aeruginosa with 31.2% (n=102), A.baumannii with 29.4% (n=96) and S.aureus with 9.2% (n=30) were in the top three. In the nine-year study by Al-Akayleh AT, the distribution was as follows: Pseudomonas spp. 50.7%, Klebsiella spp. 42.6%, S.aureus 36.4%, Proteus spp. 29.9%, E.coli 21.5%, Candida spp. Reported as 11.3% [8].
In our study, P.aeruginosa was the most common causative agent, whereas in other studies it accounted for 18%-59%, in our study, it was isolated at a rate of 31.2%. An important problem in the burn unit is antibiotic resistance. The least resistance was to amikacin (13.7%). Resistance to ciprofloxacin was 28.2%, to meropenem 30.6%, to gentamicin 30.9%, to cefepime 37.9%, to ceftazidime 39.8%, to piperacillin-tazobactam 44.7%, and to cefaperazone-sulbactam 53.8%.
The second most common agent was A.baunannii. While all strains were sensitive to colistin, there was 14.3% resistance to tigecycline. This rate was found to be high compared to other studies. Ludvik et al. found high sensitivity to colistin in their study in 2009 (9).
The third agent was S.aureus (n=30) at 9.2%, and MRSA-resistance was 83.3% (10). Reig A et al. found the average hospital stay of infected patients to be 30 days (11).
Candida spp. (7%) and Aspergillus spp. (0.6%) were isolated as fungal agents in 25 (7.6%) of the 327 isolates included in the study. Lorente L et al. detected Candida spp., Aspergillus spp. and Fusarium spp. in burn infections [12].
Conclusion
Each burn unit should carry out its own infection surveillance and determine the infecting microorganisms and antibiotic resistance pattern. Infection control strategy should be made more effective in burn units, staff training and hand hygiene should be emphasized.
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 comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
The authors declare no conflict of interest.
References
1. Mayhall CG. Nosocomial burn wound infection. In: Mayhall CG Hospital Epidemiology and Infection Control. Baltimore: Williams and Wilkins; 1996. p.225-36.
2. Elald N, Bakir M. Yanık enfeksiyonları: Son durum (Burn infections: The latest situation). Cumhuriyet Üniversitesi Tıp Fakültesi Dergisi/ Journal of Cumhuriyet University Faculty of Medicine. 2003;25(2):79-88.
3. Wysocki AB. Evaluating and managing open skin wounds: Colonization versus infection. AACN Clin Issues. 2002; 13(3):382-97.
4. Altoparlak U, Erol S, Akçay MN, Celebi F, Kadanali A. The time-related changes of antimicrobial resistance patterns and predominant bacterial profiles of burn wounds and body flora of burned patients. Burns 2004;30(7):660-4.
5. Wurtz R, Karajovic M, Dacumos E, Jovanovic B, Hanumadass M. Nosocomial Infections in a Burn Intensive Care Unit. Burns. 1995;21(3):181-4.
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7. Ekrami A, Kalantar E. Bacterial infections in burn patients at a burn hospital in Iran. Indian J Med Res. 2007;126(6):541-4.
8. Al-Akayleh AT. Invasive Burn Wound Infection. Annals of Burns and Fire Disasters. 1999;12(4):204-6.
9. Ludvik BK, Al-Mousawi A, Rivero H, Jeschke MG, Sanford AP et al. Emerging Infections in Burns. Surgical Infections. 2009; 10(5):389-97.
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Serum adropin levels in patients with migraine
Fatma Ebru Algul 1, Hatice Tosun 2
1 Department of Neurology, Faculty of Medicine, Inonu University, Malatya, 2 Department of Neurology, Eskisehir City Hospital, Eskisehir, Turkey
DOI: 10.4328/ACAM.21706 Received: 2023-03-29 Accepted: 2023-09-12 Published Online: 2023-12-14 Printed: 2024-02-01 Ann Clin Anal Med 2024;15(2):85-88
Corresponding Author: Fatma Ebru Algul, Department of Neurology, Faculty of Medicine, Inonu University, Malatya, Turkey. E-mail: ebruycl86@yahoo.com P: +90 530 864 78 48 Corresponding Author ORCID ID: https://orcid.org/0000-0003-0318-7571
This study was approved by the Ethics Committee of Istanbul Medipol University (Date: 2020-09-04, No: 10840098-772.02-E.43591)
Aim: In this study, we aimed to investigate the relationship between migraine and serum adropin levels.
Material and Methods: This is a randomized control study. The study was conducted for 6 months starting from January 2021. Fifty-four migraine patients were selected for the study as a case group and matched with 35 healthy participants for the control group. We compared serum adropin, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), total cholesterol (TC) and triglyceride (TG) concentration and body-mass index (BMI) between the case and control groups. In addition, the relationship between migraine disease duration, monthly pain frequency and pain duration, and serum adropin level in the patient group was analyzed.
Results: There was no significant difference between the two groups regarding age, gender, triglyceride, LDL-C, HDL-C, BMI levels and serum adropin levels (p<0.05). Also, there was no significant difference in migraine disease duration, frequency of headache (within a month) and headache duration depending on serum adropin levels. A negative correlation was determined between adropin levels and age and BMI (p<0.05).
Discussion: Serum adropin concentrations are not associated with migraine in our population. Besides, serum adropin levels decrease with increasing BMI and with age. With this knowledge, however, it is difficult to make a definitive conclusion. Further studies with larger populations are needed.
Keywords: Migraine, Adropin, Body Mass Index, Nitric Oxide
Introduction
Migraine is a common neurovascular disorder characterized by attacks of severe headache, and autonomic and neurological symptoms. The molecular mechanism of migraine has not been fully clarified yet. The pathophysiology of migraine is correspondingly complex and includes neurogenic inflammation, endothelial dysfunction and oxidative stress [1].
During migraine attacks as a consequence of trigeminovascular activation, nitric oxide (NO) and CGRP, which although transitory, can occur. NO has been implicated in pain processing and is most commonly associated with migraine headache [2]. It was suggested that hemodynamic changes during migraine attacks may be related to alterations in the activity of NO [3]. NO can precipitate the attacks by causing vasodilatation, increased local blood flow, and decreased vascular resistance in cerebral circulation [4].
Adropin is a 4.9 kDa peptide encoded by the Energy Homeostasis Associated gene (Enho) located on chromosome 9 [5]. A variety of organs, including the central nervous system (neurons, neuroglial cells, pia mater, vascular area, Purkinje cells, and granular layer), heart, kidney, liver, pancreas, and human umbilical vein synthesize adropin [6].
Adropin activates vascular endothelial growth factor receptor 2 (VEGFR2) and modulates the expression of endothelial nitric oxide synthase (eNOS) by posttranscriptional stimulation of eNOS protein. Also, adropin increases the endothelial cells proliferation, migration and potential to form capillary-like structures. Recently, it has been found that adropin reduces endothelial permeability [7-9].
As a result of these reports, we aimed to investigate the relationship between migraine, which is well-known to nitric oxide and endotelial dysfunction plays a role in the pathogenesis and serum adropin levels.
Material and Methods
This cross-sectional study was conducted with 89 participants with migraine and a control group of healthy individuals at Elazig Fethi Sekin City Hospital in Turkey January 2021- June 2021.Participants were selected among 18-60 year-old patients with clinical features of migraine and no history of another disease. Patients with no diagnosis of migraine or with peripheral artery disease, active inflammatory disease, autoimmune disease, malignancy, diabetes mellitus, coronary artery disease, severe kidney or liver disease were excluded from the study.
Fifty-four migraine patients were selected as the case group and were matched with 35 healthy participants. We compared serum adropin, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), total cholesterol (TC) and triglyceride (TG) concentration and body-mass index (BMI) between the case and control groups. In addition, the relationship between migraine disease duration, monthly pain frequency and pain duration, and serum adropin level in the patient group was analyzed.
Measurement of adropin levels in plasma
Venous blood samples were obtained from participants after overnight fasting for at least 10 hours, centrifugated and stored at -80℃ until analysis. Serum adropin concentrations were measured using an enzyme-linked immunosorbent assay kit and adropin detection limit range was 0.011-100 ng/ml.
Anthropometric and biochemical measurements
BMI, an assessment of general obesity, was calculated as body weight in kilograms/height in square metres (kg/m2). Serum TC, HDL-C, LDL-C and TG were measured by enzymatic methods using an autoanalyzer.
Details of the present study were explained to the eligible subjects and written informed consent was obtained.
Statistical analysis
Data analysis was tested using the IBM SPSS Statistics 26.0 (Statistical Package for Social Science) package program. Probability was assessed using a two-tailed P-value of <0.05 to indicate statistical significance. Continuous variables were checked for normality by using the Kolmogorov-Smirnov Normality test. Differences between migraine patients and healthy controls were evaluated with the Mann-Whitney U test for independent non-normally distributed variables, while the independent T-test was used for normally distributed variables. The correlations between parameters to determine test-retest reliability and validity analysis were defined by the Spearman correlation.
Ethical Approval
Ethical approval for the study was obtained from Non-Interventional Clinical Research Ethics Committee of Istanbul Medipol University (Date: 2020-09-04, No: 10840098-772.02-E.43591).
Results
The baseline characteristics of the two groups are shown in Table 1. Compared with the controls, the migraine patients had no significant difference regarding age, TC, LDL-C, HDL-C, TG, BMI and serum adropin levels (p>0.05) as shown in Table 2. We performed the Spearman correlation test to assess the correlations between adropin and clinical characteristics in migraine patients and the control group. As demonstrated in Table 3, serum adropin levels were negatively correlated with age for both groups and the total population (migraine; r = -0,29 (p=0.005), control; r = -0,35 (p=0.037), total population; r = -0,31 (p=0.021)), and BMI only for total population (r = -0,23 (p=0.029)). There was no correlation between serum adropin levels with other variables.
Discussion
To the best of our knowledge, this was the first study to determine the association between serum adropin levels and migraine, migraine attack frequency and migraine attack duration. We could not find any significant results with serum adropin levels between the control group and migraine patients, and there was no association with serum adropin level and migraine attack frequency and migraine attack duration.
Migraine affects more than 10% of the world’s population, causes substantially more individual morbidity, and creates a significant socioeconomic burden on the individual and society. Despite considerable research into the pathogenesis of idiopathic headaches, such as migraine, the pathophysiological mechanisms underlying them remain poorly understood [10]. A few of the underlying mechanisms are endothelial dysfunction, oxidative stress, vascular inflammation, and hypercoagulability [11]. It is suggested that NO could be an important mediator in the initiation or propagation of a neurogenic cranial vessel inflammatory response that might eventually result in a migraine attack [12]. Nitric oxide is one of the indicators of oxidative stress and causes vasodilation and endothelial dilatation and increases vascular endothelial growth factor (VEGF) [13].
Adropin is a newly discovered regulatory protein encoded by the Enho gene [6]. Adropin appears to have a significant role in energy homeostasis, and may be involved in the metabolic adaptation to fasting and dietary macronutrients [14]. It also might play a role in endothelium by increasing NO secretion and activating eNOS to repair endothelial damage and increasing eNOS expression through the VEGFR2-PI3K-Akt and VEGFR2-ERK1/2 (extracellular signal-regulated kinases 1/2) pathways and inhibition of the Rho/ROCK pathway [6-8]. Although many studies have been conducted in the literature on diseases that are known to play a role in the etiology of endothelial dysfunction such as coronary syndrome, atherosclerosis, diabetes mellitus, obstructive apnea syndrome, erectile dysfunction in coronary artery disease patients [14-19] and low serum adropin levels, there is not any study in the literature with migraine and adropin levels whose pathophysiology is caused by endothelial dysfunction.
In the present study, we have reported a negative correlation between serum concentrations of adropin and BMI and age (p<0.05). Zang et al. [20] and Lian et al. [21] found a significant association between BMI and serum adropin levels. In another study by Hu et al., it was shown that BMI was negatively correlated with the serum concentration of adropin in diabetic nephropathy patients. In the same study, no significant correlation of serum adropin with dislipidemia was found [22]. Our study findings are consistent with their study. Furthermore, in Beigi et al.’s study on gestational diabetes mellitus patients showed that there was no significant correlation between serum adropin levels and serum lipid profile, including LDL, HDL, cholesterol and triglyceride concentration, and our study confirmed those results. Although, Beigi et al. found no significant correlation between serum adropin levels and BMI [23].
In many studies in the literature, the association of BMI and serum adropin levels has been established in patients with metabolic diseases such as diabetes, coroner aterosclerosis [14-17]. In our study we found these results without a history of metabolic disease in both the patient and the control group. This can provide a different perspective.
Previous studies have shown a negative correlation between serum adropin levels and age, and this finding was repeated in our study [23,24]. Additionally, Yang et al. found significantly reduced plasma adropin levels in old rats compared to young rats [9]. Also, Celik et al. found a significant correlation between maternal age in gestational diabetes mellitus and cord blood adropin levels [25].
This present study has several limitations. First, the sample size was not sufficiently large to achieve definitive conclusions. Further studies with larger populations are needed. Second, the present study was designed as cross-sectional. Future longitudinal studies are required to determine the causal relationship.
In summary, serum adropin concentrations are not associated with migraine in our population. Besides, serum adropin levels decrease with increasing BMI and with age.
Conclusion
This is the first study to explore the serum adropin levels of migraine patients and the frequency of migraine attacks or the contribution of adropin to the development of migraine, which is a relatively new protein. It is still unclear whether adropin plays a role in the pathophysiology of migraine. Studies with a larger population would be instructive. We think that this study is beneficial for public health as migraine is the most common headache in the world.
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 comparable ethical standards.
Funding: None
Conflict of interest
The authors declare no conflict of interest.
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3. Schmidtko A, Tegeder I, Geisslinger G. NO, no pain? The role of nitric oxide and cGMP in spinal pain processing. Trends Neurosci. 2009;32(6):339-46.
4. Olesen J. Nitric oxide-related drug targets in headache. Neurotherapeutics. 2010;7(2):183-90.
5. Ashina M, Hansen JM, Bara AD, Olesen J. Human models of migraine – short-term pain for long-term gain. Nat Rev Neurol. 2017;13(12):713-24.
6. Toda N, Ayajiki K, Okamura T. Cerebral blood flow regulatıon by nitric oxide in neurological disorders. Can J Physiol Pharmacol. 2009;87(8):581-94.
7. Aydin S. Three new players in energy regulation: preptin, adropin and irisin. Peptides. 2014;56:94-110. DOI:10.1016/j.peptides.2014.03.021.
8. Lovren F, Pan,Y, Quan A, Singh K, Shukla PC, Gupta M, et al. Adropin is a novel regulator of endothelial function. Circulation. 2010;122(Suppl. 11):S185-92.
9. Yang C , DeMars KM, Hawkins K.E, Candelario-Jalil E. Adropin reduces paracellular permeability of rat brain endothelial cells exposed to ischemia-like conditions. Peptides. 2016;81:29-37.
10. Robbins MS, Lipton RB. The epidemiology of primary headache disorders. Semin Neurol. 2010;30(2):107-19.
11. Martinez MD, Goadsby PJ. Pathophysiology and Therapy of Associated Features of Migraine. Cells. 2022;11(17):2767. DOI:10.3390/cells11172767.
12. Tietjen G, Herial N, White L, Utley C, Kosymna J, Khuder S. Migraine and biomarkers of endothelial activation in young women. Stroke. 2009;40(9):2977-82.
13. Barbanti P, Egeo G, Aurilia C, Fofi L, Della-Morte D. Drugs targeting nitric oxide synthase for migraine treatment. Expert Opin Investig Drugs. 2014;23(8):1141-8.
14. Erman, H. Ozdemir A, Sitar ME, Cetin SI, Boyuk B. Role of serum adropin measurement in the assessment of insulin resistance in obesity. J Investig Med. 2021;69(7):1318-23.
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16. Topuz M, Celik A, Aslantas T, Demir AK, Aydin S, Aydin S. Plasma adropin levels predict endothelial dysfunction like flow-mediated dilatation in patients with type 2 diabetes mellitus. J Investig Med. 2013;61(8):1161-4.
17. Gozal D, Kheirandish-Gozal L, Bhattacharjee R, Molero-Ramirez H, Tan HL, Bandla HP. Circulating adropin concentrations in pediatric obstructive sleep apnea: potential relevance to endothelial function. J Pediatr. 2013;163(4):1122-6.
18. Celik A, Balin M, Kobat MA, Erdem K, Baydas A, Bulut M. Deficiency of a new protein associated with cardiac syndrome X; called adropin. Cardiovasc Ther. 2013;31(3):174-8.
19. Wu L, Fang J, Chen L, Zhao Z, Luo Y, Lin C, et al. Low serum adropin is associated with coronary atherosclerosis in type 2 diabetic and non-diabetic patients. Clin Chem Lab Med. 2014;52(5):751-8.
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Current practice of the adult patient population in a new bronchology and interventional pulmonology unit: A three-year experience
Ozlem Sogukpinar 1, Ulku Aka Akturk 1, Levent Alpay 2, Dilek Ernam 1
1 Department of Chest Diseases, 2 Department of Thoracic Surgery, University of Health Sciences, Süreyyapasa Chest Diseases and Thoracic Surgery Training and Research Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.21781 Received: 2023-06-09 Accepted: 2023-08-07 Published Online: 2023-12-10 Printed: 2024-02-01 Ann Clin Anal Med 2024;15(2):89-93
Corresponding Author: Ozlem Sogukpinar, Department of Chest Diseases, University of Health Sciences, Süreyyapasa Chest Diseases and Thoracic Surgery Training and Research Hospital, 34854, Maltepe, Istanbul, Turkey. E-mail: ozlemsogukpinar@yahoo.com P: +90 532 774 70 99 Corresponding Author ORCID ID: https://orcid.org/0000-0001-8483-8510
This study was approved by the Ethics Committee of Süreyyapasa Chest Diseases and Thoracic Surgery Training and Research Hospital (Date: 2023-03-16, No: 116.2017.R-279)
Aim: Interventional pulmonology involves both diagnostic and therapeutic procedures that primarily use a rigid bronchoscope. There is still a lack of consensus on case management, the choice of treatment method and treatment procedures. It is important to share the procedures adopted and the individual cases in interventional pulmonology, as this is still a developing field. Accordingly, we share here our first experiences in our newly founded interventional pulmonology unit.
Material and Methods: This study is a retrospective cohort study based on a review of interventional procedures performed for diagnostic and therapeutic purposes between January 1, 2016, and June 30, 2018.
Results: One hundred twenty-four interventional procedures were performed on 107 cases in our interventional pulmonology unit. The mean age of the patients was 54.3±17.5 years, and 71% were male, 29% were female. The reasons for the procedures were diagnostic in 16.9%, therapeutic in 35.4%, and both diagnostic and therapeutic in 47.7%. Of the procedures performed, 42.0% were for tumor excision due to malignant obstruction, 15.3% for diagnostic biopsy, 12.9% for total lung lavage, 16.1% to determine the etiology of hemoptysis, 9.7% for tracheal dilatation and stent applications, and 4% foreign body removal.
Discussion: We believe that sharing interventional bronchology procedures will help more patients benefit from such treatments and contribute to the standardization of practices.
Keywords: Bronchoscopy, Airway Management, Argon Plasma Coagulation, Cryotherapy
Introduction
Interventional pulmonology involves both diagnostic and therapeutic procedures that primarily use a rigid bronchoscope under general anesthesia in the operating room. There are many indications for rigid bronchoscopy, including hemorrhage, foreign body extraction, the need for a deeper biopsy specimen when a fiberoptic specimen is inadequate, the dilation of tracheal or bronchial strictures, the relief of airway obstructions, the insertion of stents [1]. The methods used during rigid bronchoscopy procedures include mechanical methods such as mechanical tumor ablation, rigid dilatation, and stents; heat-based methods such as electrocautery, argon plasma coagulation and laser; and cold-based methods such as cryotherapy.
Patients with newly diagnosed lung cancer have been reported to develop complications related to partial or complete airway obstruction during follow-up at a rate of 20–30% [2]. In tumor cases with airway obstruction, advanced endoscopic therapies enable palliation by maintaining airway patency, while also allowing for adjuvant therapy in cases with morbidities that preclude surgical therapy or chemoradiotherapy.
Endobronchial therapies have gained increased importance in the management of central airway pathologies [3]. The method to be applied is determined considering the patient’s overall status, lesion form, urgency of the clinical condition and complaints, disease stage, available resources, and the experience of the clinician [4].
Patients with airway obstruction secondary to benign tumors are candidates for surgery [5,6]. Surgeries on large airways are challenging, and bronchoscopic therapy plays a key role in removing the obstruction and improving ventilation [7]. The bronchoscopic techniques most commonly used for the treatment of benign tracheobronchial tumors include electrocautery, argon-plasma coagulation and neodymium-doped yttrium aluminum garnet (Nd: YAG) laser and cryotherapy [8].
Despite the available information, there is still a lack of consensus on case management, the choice of treatment method and treatment procedures in terms of interventional pulmonology. It is important to share the procedures adopted and the individual cases in interventional pulmonology, as it is still a developing field. Accordingly, we share here our first experiences in our newly founded interventional pulmonology unit.
Material and Methods
The study involved a retrospective analysis of the files of cases that underwent diagnostic and therapeutic interventional procedures between January 1, 2016, and June 30, 2018, in the newly founded Department of Interventional Pulmonology at our hospital. The data recorded about each case included demographic, clinical, and radiological details, indications, the interventional procedures applied, complications, and diagnoses.
Argon plasma coagulation (40 Watt, blended mode-continuous flow) was performed using a device manufactured by ERBE Elektromedizine GBMH (Tubingen, Germany). Standardized protocols for appropriate power selections were used in accordance with the manufacturer’s recommendations. Cryotherapy was performed using the ERBOKRYO system (Elektromedizine GBMH,Tübingen,Germany). Electrocautery applications were performed using the electrosurgical unit, ERBE Medizintechnik, GmbH, Tübingen, Germany). All the patients were intubated by a rigid bronchoscope (Efer Endoscopy, LaCiotat, France) under general anesthesia using Standard techniques, and mechanical debridement was performed when necessary.
All procedures were performed in the operating room. Prior to the procedure, informed consent forms were obtained from all cases and an anesthesia assessment was made. Cases for which no consent forms could be obtained, or those who declined anesthesia, were excluded from the study. The treatment to be applied was determined by two interventional pulmonologists based on the type and localization of the lesions and the clinical condition of each case. Ethics committee approval was received for our study (Süreyyapasa Chest Diseases and Thoracic Surgery Training and Research Hospital Ethics Committee; 116.2017.R-279/16.03.2023). The study was conducted following the principles and guidelines of the Declaration of Helsinki for medical research involving human subjects.
Statistical Analysis
The Statistical Package for the Social Science for Windows 15.0 package program (SPSS Inc., Chicago, IL, USA) was used in our study. The median with interquartile range was employed for nonparametric continuous variables, and mean±standard deviation was used for parametric continuous variables. P<0.05 values were considered statistically significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Between January 1, 2016, and June 30, 2018, 124 interventional procedures were performed on 107 cases in our interventional pulmonology unit. The mean age of the patients was 54.3±17.5 years, and 71% were male. The reason for the procedures was diagnostic in 16.9%, therapeutic in 35.4%, and both diagnostic and therapeutic in 47.7%.
The distribution of the applied processes is shown in Table1. Twenty-five of the tumors were located in the right bronchial system, 19 in the left bronchial system and 8 in the trachea.
Of the malignant tumor cases, 33 (49.2%) were squamous cell carcinoma, 14 (20.9%) were adenocarcinoma, 11(16.4%) were small-cell carcinoma, five (7.5%) were carcinoid tumor, two (3.0%) were verrucous carcinoma and one (1.5%) was a mixed tumor with a neuroendocrine tumor component. Obstruction-related post-obstructive pneumonia or dyspnea was identified in three and hemoptysis in two of the five carcinoid cases.
The benign lesions undergoing procedures in the interventional pulmonology unit were diagnosed with anthracosis, glandular papilloma, mucosal polyp, aortobronchial fistula, endobronchial tuberculosis and hamartoma. The method applied for the endobronchial therapy of malignant and benign lesions was cryotherapy in 43%, tumor debulking in 51%, APC in 38%, electrocautery in 24% and tracheal dilatation in 11%. These endobronchial therapies were used alone or in combination, depending on the patient and lesion.
A foreign body was extracted using a rigid bronchoscope in five cases other than the malignant and benign cases. Rigid bronchoscopy was performed to detect the focus of bleeding due to massive and sub-massive hemoptysis in 20 of the cases. Additionally, three cases diagnosed with Pulmonary Alveolar Proteinosis (PAP) underwent a total of 16 whole lung lavage procedures.
Among the 12 cases in which tracheal stenosis was detected, 10 were post-intubation stenosis, one was caused by a post-intubation tracheal fungal infection, and one was caused by tracheobronchopathia osteochondroplastica. Patients with post-intubation stenosis were dilated with a rigid bronchoscope, and for cases requiring operations, consultation with the Thoracic Surgery Department was carried out. A tracheal stent was placed in three of these cases: with a stenotic silicon stent fitted in two cases and straight silicone in one case.
Considering the complications, no procedure-related deaths occurred among our cases, although two cases developed massive hemoptysis during the procedure and were placed in intensive care. One case was intubated with a double-lumen endotracheal tube due to massive hemoptysis and placed in intensive care after becoming stable. For the other case, a tracheostomy was required because ventilation could not be provided through intubation during the procedure. The patients were followed up in intensive care, and then discharged.
Discussion
In this study, which was conducted to share the three years of experience gained in our new Interventional Pulmonology unit, we convey the characteristics and diagnoses of the cases to date, along with the endobronchial therapy methods used.
The treatment modalities recommended for the reduction of cough, hemoptysis, and dyspnea in patients with symptomatic airway stenosis in lung cancer are mechanical or thermal ablation, brachytherapy, or stent placement [9].
Recently, heat-based methods (laser, electrocautery, APC) have been used in combination with mechanical methods to maintain airway patency in interventional pulmonology. Such combinations have increased the success rates of clearing intraluminal obstructions, while minimizing hemorrhagic complications. Previous studies have agreed that mechanical resection combined with heat-based methods is the optimum approach to maintaining airway patency [8].
Among primary lung cancers, squamous cell carcinoma affects the major airways more often than adenocarcinoma, although both non-small cell carcinomas may lead to malignant airway obstructions [10]. In our study, the cases undergoing procedures due to malignant airway obstructions underwent argon plasma coagulation (APC), electrocautery and cryotherapy in addition to mechanical procedures.
In the study by Cosano et al., sharing their 5 years of experience, the authors detailed the interventional bronchoscopic therapy methods performed on 136 cases with central airway stenosis, which included laser therapy, balloon or mechanical dilatation, electrocauterization and stent applications [11]. Airway patency was provided with success rates of 92% and 96% in tumor-related and nontumor-related airway stenoses. The authors reported a mortality rate of 1.4%, with the most common complication being stent migration and granuloma formation. Interventional bronchoscopy is an effective method for the resolution of life-threatening obstructions of the central airways. Dyspnea improves immediately and there is no significant morbidity or mortality.
In this study, similar endoscopic therapies were used in the presence of airway obstructions in around half of the cases. We opted to use APC rather than a laser, and our rate of airway clearance was 92.3%, which is consistent with the literature. In the cases in our study, the number of stent applications was limited, and so there was a low rate of stent-related complications. There were no procedure-related deaths in the present study. As a major complication, two of the cases developed massive hemoptysis and were admitted to the intensive care after the procedure for follow-up and treatment.
Most carcinoid tumors emerge in the proximal airways and patients typically present with obstruction-related symptoms or hypervascularity-related bleeding [12]. There were obstruction-related post-obstructive pneumonia and dyspnea in three and hemoptysis in two of the five carcinoid cases in our study. Although surgical resection of the entire tumor is recommended for the treatment of carcinoid tumors, there have been studies supporting endobronchial therapy [13]. Distant organ metastasis, lymph node metastasis, and bronchial wall invasion are important when choosing the treatment for carcinoid tumors. In this study, cryotherapy was applied to the bronchial wall penetrated by the tumor after the tumor resection. The study by Brokx et al. reported that no surgical treatment was required in 42% of 112 cases with a centrally located pulmonary carcinoid who initially received bronchoscopic therapy after a minimum five-year follow-up [13]. Endobronchial therapy methods were applied to two cases in our study and no signs of recurrence were observed during a two-year follow-up. Two of our cases were treated surgically, and due to distant organ metastasis, one was administered systemic chemotherapy.
Tracheal tumors are rare but are mostly malignant. Squamous cell carcinomas and adenoid cystic carcinomas are the most common primary tracheal tumors [14]. In this study, in seven of the 10 cases undergoing procedures for tracheal tumors, the tumors were found to be malignant, while two patients were diagnosed with verrucous carcinoma, which caused airway obstruction as a result of tracheal invasion of the laryngeal tumor. Of the cases undergoing procedures for primary tracheal tumors, two were diagnosed with squamous cell carcinoma. Although rare in literature, one of our cases was diagnosed with adenocarcinoma. There were no signs of recurrence throughout the oncological treatment administered after the endotracheal therapy and in almost three years of follow-up. In one case, airway patency was maintained through endobronchial therapy methods as a result of tracheal invasion and the luminal extension of the thyroid papillary carcinoma.
Benign tracheal lesions include hemangiomas, hamartomas, neurogenic tumors, granular cell tumors and squamous papillomas [15]. In our study, one case was diagnosed with a hamartoma causing airway obliteration. Although hamartoma is the most common benign tumor of the lung, there are only a limited number of reports of endotracheally located hamartomas in the literature [16,17]. In line with the two cases presented by Hon et al., the lesion in the case in the present study was a pedunculated polypoid in the tracheal lumen [18]. Among the limited cases in the literature, surgical therapy was preferred for the case localized on the tracheal lumen with a wide base [17], while mechanical excision [18] or electrocautery combined with a mechanical method [16] was used in the thin-stalk polypoid cases, similar to the present study.
In the past, benign tumors were managed conventionally by surgical resection to maintain airway patency and to minimize symptoms. More recently, however, the development of endobronchial bronchoscopic methods has increased the use of laser, argon plasma coagulation, and cryotherapy for the management of benign tumors. The study of Dalar et al. identified endobronchial therapy to be as effective as invasive surgical methods in symptomatic benign tumors [19]. In the present study, endobronchial therapy was applied to benign lesions such as anthracosis, glandular papillomas, mucosal polyps, aortobronchial fistulas, endobronchial tuberculosis and hamartomas. APC, electrocautery, and cryotherapy were used in addition to mechanical methods during the procedures.
The conditions associated with non-malignant airway obstruction are defined in the literature as foreign body aspiration, tracheoabronchomalacia and tracheal stenosis due to endotracheal tube or anastomosis. In the present study, tracheal stenosis was detected in five cases, with three being post-intubation stenosis, one caused by tracheobronchopathia osteochondroplastica and the last being attributed to a post-intubation fungal infection in the granulation tissue.
Tracheobronchopathia osteochondroplastica is a rare disease that has been observed in 0.4% of bronchoscopies [20]. It is characterized by submucosal, bony, and cartilaginous nodules with a membranous tracheal wall preserved histologically. Despite the distinctive radiographical changes, severe airway obstruction is unusual [21]. Besides symptom-relieving treatment, no specific treatment is recommended. Laser ablation, surgical resection, and cryotherapy can be performed in cases complicated by severe airway stenosis or recurrent infection [22]. In the case in our study, dilatation was attempted due to severe airway stenosis, however airway patency could not be maintained and so a flat silicone stent was inserted into the stenotic area. For the two cases in the present study with post-intubation tracheal stenosis, a stenotic silicone stent was used following dilatation via a rigid bronchoscopy. Our two cases were operated on.
Foreign body aspiration is mostly seen in childhood, although it may also cause serious problems in adults. Risk factors for adults include trauma, drug or alcohol intoxication, or loss of consciousness due to anesthesia. In the present study, none of the risk factors were noted in cases identified with foreign body aspiration. Greater experience in bronchoscopy results in increased foreign body extraction via fiberoptic bronchoscopy, although rigid bronchoscopy is recommended for foreign bodies that cannot be extracted with a flexible bronchoscope [23]. The extracted foreign bodies were bone fragments and organic objects such as almonds and chickpeas.
Pulmonary alveolar proteinosis, known also as pulmonary alveolar phospholipoproteinosis is a rare disease of the lung that is characterized by the deposition of amorphous PAS (periodic acid-Schiff)-positive lipoprotein materials in distal air spaces [24]. Whole lung lavage is a therapeutic procedure used for the treatment of pulmonary alveolar proteinosis. In the present study, a total of 16 whole lung lavage procedures were performed on three cases diagnosed with PAP for therapeutic purposes. Consistent with the application methods noted in the literature, the whole lung lavage procedure was carried out through double lumen intubation under general anesthesia, followed using physiological saline solution at body temperature in two separate sessions, one week apart [25].
Conclusion
We believe that sharing the experience of bronchoscopists about developments in interventional bronchology procedures will contribute to the standardization of applications, and such treatments of more patients will improve achievements in this regard. Endobronchial therapies performed in interventional bronchoscopy are effective treatments for eligible patients and are highly effective in the presence of life-threatening central airway stenosis. Furthermore, such therapies are of great importance for patients who are illegible for surgery due to their clinical condition during the process of making them eligible for palliative and/or curative treatment. We believe that interventional procedures can be performed by bronchoscopists at experienced centers with low rates of mortality and morbidity.
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 comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
The authors declare no conflict of interest.
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Effects of the genetic variants and serum levels of TIMP-1 and TIMP-2 on type 2 diabetes mellitus in the Turkish population
Faruk Celik 1, Umit Yilmaz 2, Nesibe Yilmaz 3, Kerem Ozyavuz 4, Cem Basaran 5, Osman Fazliogullari 6, Arzu Ergen 1, Umit Zeybek 1
1 Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, 2 Department of Physiology, Faculty of Medicine, Karabuk University, Karabuk, 3 Department of Anatomy, Faculty of Medicine, Karabuk University, Karabuk, 4 Department of Internal Medicine, Haydarpasa Numune Training and Research Hospital, Istanbul, 5 Department of Cardiovascular Surgery, Medicana Bahcelievler Hospital, Istanbul, 6 Department of Cardiovascular Surgery, Avicenna Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.21788 Received: 2023-06-12 Accepted: 2023-11-27 Published Online: 2023-12-06 Printed: 2024-02-01 Ann Clin Anal Med 2024;15(2):94-98
Corresponding Author: Umit Zeybek, Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Vakıf Gureba Caddesi, Istanbul, Turkey. E-mail: umz67@yahoo.com P: +90 212 414 20 00 Corresponding Author ORCID ID: https://orcid.org/0000-0001-8403-2939
This study was approved by the Ethics Committee of the Faculty of Medicine, Istanbul University (Date: 2010-07-08, No: 233-41)
Aim: Genetic and environmental factors are very important in the formation of type 2 diabetes mellitus (T2DM). Tissue inhibitors of matrix metalloproteinases (TIMPs) play central roles in inhibition of the extent of extracellular matrix degradation. The aim of this study is to investigate serum levels and gene polymorphisms of TIMP-1 and TIMP-2, and their effects on T2DM in the Turkish population.
Material and Methods: One hundred seventeen patients with T2DM and 127 healthy controls were included in this study. TIMP-1 372 T>C, TIMP-2 303C>T, and TIMP-2 418 G>C polymorphisms were determined by PCR-RFLP method and serum TIMPs levels were measured by ELISA.
Results: The frequencies of the TT genotype and T allele of the TIMP-2 303 C>T polymorphism were significantly higher in the patient group than in the control group. The frequency of the C allele for TIMP-2 418 G>C polymorphism was significantly higher in the control group than in patients. TIMP-1 372 T>C polymorphism was not statistically significant between patients and controls. Additionally, TIMP-1 serum levels were statistically higher in T2DM patients than in controls.
Discussion: This study provides the first evidence that the TT genotype and T allele of the TIMP-2 303 C>T polymorphism significantly contribute to the risk of T2DM in the Turkish population. Also, carrying the C allele of the TIMP-2 418 G>C polymorphism had a protective effect against the development of T2DM. In addition, our results suggest that the C allele of the TIMP-1 372 T>C polymorphism may have protective effects against the development of T2DM.
Keywords: Type 2 Diabetes Mellitus (T2DM), Polymorphism, TIMP-1, TIMP-2, ELISA
Introduction
Diabetes mellitus (DM) is one of the most common complex diseases in the world and is characterized by the ability to produce enough insulin. DM develops due to an increase in fasting glucose levels, accompanied by disturbances in lipid and protein metabolism [1]. Type 2 diabetes mellitus (T2DM) constitutes about 85–90% of diabetes cases and typically occurs in older age, but recently, it has also been seen in young adults and children [2]. The T2DM pathogenesis is controversial, its inheritance is polygenic, developing due to several abnormal genes or polymorphisms. For the presence of T2DM, a complex interaction between multiple genes and environmental factors is necessary [3].
Tissue inhibitors of metalloproteinases (TIMPs), first discovered in 1975, are natural inhibitors of the matrix metalloproteinase (MMP) and inhibit the proteolytic activity of MMPs. The TIMPs have four members (TIMP-1, 2, 3, and 4), and there are structural and biochemical differences between these genes [4]. An imbalance between TIMPs and MMPs causes pathological processes such as arthritis, aneurysm formation, plaque disruption, atherosclerosis and diabetic nephropathy [5]. It has been shown that plasma TIMP-1 and TIMP-2 levels are increased in type 1 and type 2 diabetic patients. TIMP-1 prevents the activation and enzyme activity of MMP-9, while TIMP-2 prevents the activation and enzymatic function of MMP-2. TIMP-1 and TIMP-2 are defectively synthesized, while MMP-9 and MMP-2 are excessively produced in chronic diabetic wounds of because TIMP-1 and TIMP-2 can bind non-covalently to MMP-9 and MMP-2 [6].
It has been established that TIMP-1 and TIMP-2 play various roles in the pathogenesis of diabetes [7]. However, until now, there have been no reports on the effects of TIMP-1 372 T>C, TIMP-2 303 C>T, and TIMP-2 418 G>C polymorphisms in the development of T2DM. Therefore, we investigated the association between TIMP-1 372 T>C, TIMP-2 303 C>T, and TIMP-2 418 G>C polymorphisms and T2DM in the Turkish population.
Material and Methods
Study group
One hundred seventeen T2DM patients and 127 healthy individuals were included in this study. The patients were followed up at the Department of Internal Medicine, Istanbul Training and Research Hospital, and Istanbul Medicana Hospital, Istanbul, Turkey. Healthy control subjects did not have any sign of a family history of diabetes mellitus. Serum and whole blood samples were taken from all individuals.
DNA isolation
The peripheral blood was taken from the volunteers (patients and healthy individuals) who agreed to participate in the study into tubes containing EDTA for DNA to be used in the study. The genomic DNA was obtained from these blood samples according to the salting-out method as described in our previous studies [8, 9]. All collected DNA samples were stored in Tris-EDTA buffer (Sigma-Aldrich, USA) at +4 °C until analysis.
SNP detection
The TIMP-1 372 T>C, TIMP-2 303 C>T, TIMP-2 418 G>C polymorphisms were analyzed from the isolated genomic DNA samples by PCR-RFLP as described in our previous studies [10, 11]. For detection of related polymorphisms, the reaction was performed in 25 µl volume containing genomic DNA, reaction buffer (Invitrogen, USA), dNTP (Invitrogen, USA), specific primer (Invitrogen, USA) for each, and Taq polymerase (Invitrogen, USA). The annealing temperature for TIMP-1 372 T>C, TIMP-2 303 C>T, and TIMP-2 418 G>C polymorphisms is 56 °C. The PCR products were restricted with convenient restriction enzymes (Invitrogen, USA), and then separated in a 3% agarose gel electrophoresis, visualized under ultraviolet light. All primers, restriction enzymes and genotyping used to identify these polymorphisms are presented in Table 1.
TIMPs assay
Fresh blood samples taken from all participants for ELISA analyzes were centrifuged at 3000 rpm for 5 minutes on the same day to ensure serum separation. Afterwards, serum samples were frozen and stored at -20 °C until ELISA analysis. Serum TIMP-1 and TIMP-2 levels were analyzed with ELISA using TIMP-1 and TIMP-2 human ELISA kits (Quantikine R&D System, USA).
Statistical analysis
Statistical analyzes were performed with the IBM SPSS 24.0 program (IBM, USA). The conformity of the data to the normality was determined with the Kolmogorov-Smirnov test. The normally distributed data were detected with the independent sample t-test. The data of the groups did not show normal distribution, the difference between the groups was evaluated with the Mann-Whitney test. Demographic parameters were stated as mean±standard deviation for data showing normal distribution, as median (min.-max.) for data showing abnormal distribution. Pearson’s Chi-square test was evaluated to compare genotype and allele frequencies between groups. p<0.05 was considered significant.
Ethical Approval
The study was performed with the approval of the Ethics Committee of the Faculty of Medicine, Istanbul University, (Date: 2010-07-08, No: 233-41). Informed consent was obtained from each case included in the study.
Results
A total of 117 patients with T2DM and 127 controls were included in this study. The mean age of the patients with T2DM and healthy controls was 64.36 ± 8.82 and 59.78 ± 8.8 years, respectively. There was no significant difference in age between the patient and control groups. LDL-Cholesterol (p:0.009) level was significantly higher in the patient group compared with the controls. It was also found that HDL-Cholesterol (P:0.037, 95% Cl:0.40-12.45) level was higher in the control group than in patients. The demographic parameters of the subjects and clinical characteristics of patients with T2DM are shown in Table 2.
The allele and genotype distribution of the study groups for TIMP-1 372 T>C, TIMP-2 303 C>T, and TIMP-2 418 G>C polymorphisms is presented in Table 3. Firstly, we evaluated the association of the TIMP-1 372 T>C polymorphism between type 2 diabetes patients and the control group. There was no statistical difference between the patients and the control group in terms of TIMP-1 372 T>C polymorphism.
T2DM patients and the control group were compared in terms of serum levels of TIMP-1 and TIMP-2. The TIMP-1 serum levels (p:0.001, 95% Cl:1.11-2.84) were statistically higher in type 2 diabetes patients (5.82 ± 2.37 ng/ml) than in the control group (3.84 ± 1.4 ng/ml). TIMP-2 serum level was 3.01 ± 0.97 ng/ml in the T2DM patient group and 2.92 ± 0.51 ng/ml in the control group, and there was no statistically significant difference between the two groups. In the patient group, serum levels of TIMP-1 and TIMP-2 were analyzed according to the genotype distributions in each of the three polymorphisms. There was no significant relationship between serum TIMP-1 and TIMP-2 levels and all three polymorphisms. In the control group, TIMP-1 levels were observed to be increased in individuals with CT genotype (p:0.015, 95% Cl:0.22 – 1.94).
Discussion
TIMPs are proteins that belong to a family of specific inhibitors and regulate the proteolytic activity of all MMPs. They also play a role in several biological activities such as cell differentiation, apoptosis, cell growth, invasion and angiogenesis [12]. The association between levels of TIMP-1 and TIMP-2 was previously evaluated in cardiovascular diseases [13, 14], sepsis [15], many cancers [7], obesity [16], and diabetes mellitus [17]. Lee et al. showed that plasma TIMP-1 concentration is significantly increased in patients with T2DM than in control subjects [18]. According to another study, the TIMP-1 and TIMP-2 levels were found higher in type 1 diabetic patients than in controls. Also, it is suggested that TIMP-1 plays a central role in the development of metabolic disorders in type 1 diabetes [19]. In diabetic nephropathy, circulating TIMP-1 and TIMP-2 were found to decrease in patients compared to either chronic renal failure or diabetes [20]. Moreover, Kanauchi et al. have suggested that TIMP-1 has a role in diabetic neuropathy and nephropathy [21]. In this study, TIMP-1 serum levels were statistically higher in T2DM patients than in the control group. No significant relationship was found between serum TIMP-1 and TIMP-2 levels and all three polymorphisms in the patients. In the control group, TIMP-1 levels were observed to be increased in individuals with the CT genotype.
The TIMP-1 372 T>C, TIMP-2 303 C>T, and TIMP-2 418 G>C polymorphisms have not been studied in diabetes mellitus; this study provides the first evidence. Lorente et al. have investigated the TIMP-1 serum levels and TIMP-1 372 T>C polymorphism in sepsis patients. They reported that septic patients carrying the T allele for the 372 T>C polymorphism of TIMP-1 had increased serum TIMP-1 levels and decreased survival rates [15]. The TIMP-1 372 C>T and TIMP-2 418 G>C polymorphisms were investigated in patients with endometrial cancer. Patients with the TIMP-1 372 CC genotype were found to be at higher risk for endometrial cancer. However, no significant differences were found in the TIMP-2 418 G>C polymorphism between endometrial carcinoma individuals and healthy subjects [22]. Ikebuchi et al. have investigated the association between the TIMP-1 372 C>T and TIMP-2 418 G>C polymorphisms with the progression of chronic liver disease related to the hepatitis C virus. According to their results, it has been determined that the pathology of liver fibrosis was more advanced in individuals carrying the TIMP-2 418 GG genotype [23]. In a current study, the C allele frequency for the TIMP-2 418 G>C polymorphism was found significantly higher in abdominal aortic aneurysm patients than in healthy controls [24]. According to our results, there was no statistical difference in terms of the TIMP-1 372 T>C polymorphism between patients with T2DM and the healthy controls. C allele incidence of the TIMP-2 418 G>C polymorphism was not statistically significant between T2DM patients and the control group. When we compared the TIMP-2 303 C>T polymorphism between the study groups, the mutant TT genotype and T allele frequencies were found statistically higher in patients.
The small number of individuals included in the study is one of the factors limiting our results. It can be said that to exactly elucidate the role of TIMP-1 372 T>C, TIMP-2 303 C>T, and TIMP-2 418 G>C gene polymorphisms in T2DM, the number of individuals participating in the study should be increased and more studies should be conducted on this subject. However, even if only a small number of individuals were included in the study, the results may contribute to the understanding of the molecular mechanisms of TIMP genes in T2DM.
In conclusion, our findings provide new evidence for the association between TIMP-1 372 T>C, TIMP-2 303 C>T, and TIMP-2 418 G>C gene polymorphisms and the T2DM risk in the Turkish population. Our results suggest that the TT genotype and T allele of the TIMP-2 303 C>T polymorphism significantly contribute to the risk of T2DM in the Turkish population. Also, carrying the C allele for the TIMP-2 418 G>C polymorphism had a protective effect against the development of T2DM. In addition, our results suggest that the C allele for the TIMP-1 372 T>C polymorphism may have protective effects against the development of T2DM.
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 study was supported by the Research Support Unit of Istanbul University, project no: 9865.
Conflict of Interest
The authors declare that there is no conflict of interest.
References
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14. Panayiotou AG, Kamilari E, Griffin M, Tyllis T, Georgiou N, Bond D, et al. Association between serum levels of pro-metalloproteinase 1, tissue inhibitor of metalloproteinases 1 and 2 and prevalent cardiovascular disease in a population-based study. Int Angiol. 2013;32(6):599-604.
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Faruk Celik, Umit Yilmaz, Nesibe Yilmaz, Kerem Ozyavuz, Cem Basaran, Osman Fazliogullari, Arzu Ergen, Umit Zeybek. Effects of the genetic variants and serum levels of TIMP-1 and TIMP-2 on type 2 diabetes mellitus in the turkish population.Ann Clin Anal Med 2024;15(2):94-98
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A novel marker for esophageal cancer: Senescence marker protein-30
Remzi Kiziltan 1, Mehmet Akif Aydin 2, Sermin Algul 3, Ozgur Kemik 1
1 Department of General Surgery, Van Yuzuncu Yil University, Van, 2 Department of General Surgery, Altinbas University, Istanbul, 3 Department of Physiology, Faculty of Medical, Van Yuzuncu Yil University, Van, Turkey
DOI: 10.4328/ACAM.21810 Received: 2023-07-06 Accepted: 2023-08-07 Published Online: 2024-01-03 Printed: 2024-02-01 Ann Clin Anal Med 2024;15(2):99-102
Corresponding Author: Remzi Kiziltan, Department of General Surgery, Faculty of Medical, Van Yuzuncu Yil University, 65080, Van, Turkey. E-mail: mdremzikiziltan@gmail.com P: +90 532 385 71 17 F: +90 432 216 83 52 Corresponding Author ORCID ID: https://orcid.org/0000-0001-7235-3794
This study was approved by the Ethics Committee of Yüzüncü Yıl University Hospital (Date: 2021-06-18, No: 2021/07-07)
Aim: Esophageal cancer is one of the most common malignancies causing the majority of cancer-related deaths worldwide. The aim of this study was to examine the importance of preoperative Senescence marker protein-30 (SMP30) levels in patients with esophageal cancer.
Material and Methods: Medical records of 85 patients who were diagnosed with esophageal cancer were reviewed and compared with those of the control subjects. The tumor marker was measured with Enzyme-linked immunosorbent assay (ELISA).
Results: No statistically significant difference was found between the patient and study groups in terms of age and gender. In our study, we found that serum SMP30 levels were significantly lower in esophageal cancer patients than in healthy controls.
Discussion: We found that the adhesion of esophageal cancer cells was significantly reflected by preoperative serum levels of the studied marker, indicating the adhesive strength of cancer cells. SMP30 may be a novel strategy for clinical diagnosis of the disease.
Keywords: Senescence Marker Protein-30, SMP30, Esophageal Cancer
Introduction
Esophageal cancer is a serious and deadly cancer and is the seventh leading cause of cancer related deaths worldwide [1]. Esophageal cancer remains an important cause of cancer related death and with a 6-fold increase in incidence worldwide [2]. Male gender, smoking, alcohol consumption, gastroesophageal reflux disease, diet, obesity, body composition and genetics are among the risk factors. The incidence of esophageal cancer varies widely according to location from 30 to 800 cases per 100000 persons. Esophageal cancer is aggressive in nature, spreading by a various routes such as direct expansion, lymphatic spread and hematogenous metastasis [3]. Five-year overall survival ranges between 15% and 25% [4, 5]. Although improvements have been seen in its early-stage detection, many tumors are at an advanced stage at the time of primary diagnosis [6].
Conventional pathological staging of endoscopic biopsies has been regarded as the major standard for diagnosing esophageal cancer. Early diagnosis and treatment are the mainstay of the management of esophageal cancer. However, so far no novel specific molecular marker that is effective for the early diagnosis of this aggressive malignancy has been introduced. There is an urgent need for defining the molecular alterations associated with the early stages of esophageal cancer development to allow early detection, appropriate management, and prolongation of survival in this disease.
Senescence marker protein-30 (SMP30), also known as regucalcin, was discovered in 1988 [7] as a calcium-binding protein. SMP30 is a cell factor involved in vitamin C synthesis and antiapoptosis. SMP30 performs an important role in the protection against apoptsosis and oxidative stress [8]. It has been demonstrated that overexpression of SMP30 suppressed cell proliferation by decreasing DNA synthesis [9].
In some reports, it has been shown that SMP30 is related to hepatocellular carcinoma [10, 11]. Different expression levels of SMP30 have been reported in various stages of breast cancer [12]. SMP30 is downregulated in human breast and prostate cancers via control of cell proliferation [13]. It has been reported that SMP30 inhibits tumor growth in non-small cell lung cancer by reducing HDAC4 expression [14].
The present study was performed to test the hypothesis that preoperative serum levels of SMP30 may be of clinical importance in understanding the development and progression of esophageal cancer patients.
Material and Methods
Patients
Before the beginning, the study protocol was approved by the local Ethics Committee of Yüzüncü Yıl University Hospital (date: 18/06/2021 and decision number: 2021/07-07). This study did not require any intervention for the treatment of patients. The selected patients and their families were informed about the purpose, methods, and possible risks of the study, and all of them signed an informed consent form.
Eighty-five esophageal cancer patients were included in our study from May 2018 to May 2020, including 45 males and 40 females aged 55 to 69 years, with a mean age of 62.67±3.90 years. The control group consisted of 31 males and 19 females aged 54 to 69 years, with a mean age of 61.944.07 years.
Assays
Samples were collected from the patients and the control group for the detection of SMP30. After centrifugation at 4 °C for 10 minutes, the samples were stored at -80 °C until the analysis. We used enzyme-linked immunosorbent assay (ELISA) method for sample analysis (Catalog No: MBS9428874, MyBioSource) (Detection range: 0.312 ng/mL-20 ng/mL; sensitivity: less than 0.1 ng/mL).
Statistical Analysis
The normality of study data was checked using the Shapiro-Wilk test and the single-sample Kolmogorov-Smirnov test, histograms, Q-Q plot, and box plot graphs. Since the variables were non-normally distributed, the continuous variables were presented as median, minimum, maximum, values and categorical variables as frequency, and percentage. The variables were compared between the two groups with the Mann-Whitney U test. Nominal variables were compared using the Chi-square test with Yates correction. The level of two-sided significance was taken as p<0.05. Data analyses were performed using the NCSS 10 (2015. Kaysville, Utah, USA) software program.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Demographic variables are shown in Table 1 and Figure 1. Accordingly, no statistically significant difference was found between the patient and control groups in terms of age and gender (p>0.05). Serum SMP30 was measured in 50 healthy individuals and 85 patients with ESCC. Serum SMP30 level was significantly higher in the healthy controls than the ESCC patients, (16.28 ng/mL vs 3.09 ng/mL, respectively) (Table 2 and Figure 2).
Discussion
Esophageal cancer is an invasive cancer with a comparatively late stage at diagnosis, rapid clinical progression, and very poor survival [15]. Survival rate can be as low as 10% in high-risk population, where medical facilities are less developed [16]. Esophagectomy is generally the most widely accepted standard treatment for localized disease; however, the results of the procedure are disappointing due to the high recurrence rate [17, 18]. In a study by Lou et al. with 1147 esophageal cancer patients, the recurrence rate was 38% [19]. This has prompted researchers to seek novel preoperative biomarkers for better and more efficient management of patients with esophageal cancer, improvements in survival and reduction of recurrence.
SMP30 has been shown to modulate the balance of protein tyrosine kinase phosphates, and to regulate NF-ĸB-related inflammatory activity [20]. On the other hand, in human cells, SMP30 might regulate cell survival by regulating the redox state of the cell. Oxidative stress is manifested by an imbalance between the formation of pro-oxidants such as reactive oxygen species (ROS) and/or reactive nitrogen species, and the production of antioxidant defenses [21]. Downregulation of SMP30 is caused by an increased generation of the oxygen-reactive entity of ROS [22].
To explain the specific role of SMP30 in apoptotic crypt cells, various issues have to be investigated. There is a probability that SMP30 can protect crypt cells directly from irradiation-induced apoptosis. A decrease in the SMP30 level results in the promotion of apoptosis when epithelial cells are subjected to irradiation.
SMP30 has been studied in various publications as a marker of various cancers. Mo et al. investigated SMP30 expression in hepatocellular carcinoma (HCC). They reported that low SMP30 expression was strongly correlated with an overall survival rate of HCC patients, and that SMP30 may be useful in developing a reliable prognostic marker and HCC therapeutic target [23]. Baek et al. studied the expression patterns of SMP30 in mammary tumors and concluded that SMP30 may help to establish diagnosis in human breast cancer [12]. Shao et al. investigated the patterns of SMP30 in non small cell lung cancer (NSCLC). They stated that SMP30 inhibited proliferation of NSCLC by reducing HDAC4 expression and that SMP30 and HDAC4 may serve as novel prognostic markers and potential targets in NSCLC [14].
For the first time in the literature, the present study suggested that SMP30 is responsible for tumor angiogenesis and tumor growth in esophageal cancer cells. The clinical significance of these results warrants further investigation. Serum SMP30 levels were significantly reduced in ESCC patients. Based on our study, SMP30 may be used as an eventual therapeutic target in the treatment of esophageal cancer. Serum SMP30 levels may be impressed by surgical treatment. Finally, numerous markers have been studied using ELISA as a testing method in previous studies. The combination of different biomarkers and detection methods can be used to monitor the therapeutic outcome of different subsets of patients.
Study Limitations
The main limitations of this study include its relatively small sample size and being conducted in a single center. However, given that it is the first study to investigate the role of SMP30 in esophageal cancer, we believe that our findings will be guiding for further comprehensive studies.
Conclusion
The results of this study indicate that the adhesion of esophageal cancer cells was significantly reflected by preoperative serum levels of the studied marker, indicating the adhesive strength of cancer cells. SMP30 may be a novel strategy for diagnosing esophageal cancer clinically. However, further prospective observational studies are needed to draw more definitive conclusions.
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 comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
The authors declare no conflict of interest.
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Remzi Kiziltan, Mehmet Akif Aydin, Sermin Algul, Ozgur Kemik. A novel marker for esophageal cancer: Senescence marker protein-30. Ann Clin Anal Med 2024;15(2):99-102
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Retrospective evaluation of children and adolescents admitted to the pediatric intensive care unit due to suicide attempts
Aslı Akın 1, Mustafa Törehan Aslan 2, Nedim Samancı 3
1 Department of Pediatrics, 2 Department of Pediatrics, Division of Neonatology, 3 Department of Pediatrics and Pediatric Intensive Care, Faculty of Medicine, Tekirdağ Namık Kemal University, Tekirdağ, Turkey
DOI: 10.4328/ACAM.21981 Received: 2023-09-20 Accepted: 2023-10-31 Published Online: 2023-12-29 Printed: 2024-02-01 Ann Clin Anal Med 2024;15(2):103-107
Corresponding Author: Nedim Samancı, Department of Pediatrics Intensive Care, Faculty of Medicine, Tekirdağ Namık Kemal University, Tekirdağ, Turkey. E-mail: samancitr@yahoo.com P: +90 532 295 71 98 Corresponding Author ORCID ID: https://orcid.org/0000-0002-3947-3492
This study was approved by the Ethics Committee of Tekirdağ Namık Kemal University, Faculty of Medicine Non-Interventional Clinical Research Ethics Committee (Date: 2022-07-26, No: 2022.150.07.17)
Aim: Suicide is a public health problem that, although not common in childhood, becomes increasingly common in adolescence. Pediatricians primarily investigate and recognize these risk factors and prevent and treat suicidal behavior by communicating with other specialties. This study aimed to determine the sociodemographic characteristics, factors leading to suicide, and suicide methods of patients who were followed up in the Pediatric Intensive Care Unit due to suicide attempts and to be able to take preventive approaches.
Material and Methods: The study included 45 patients between the ages of 10 and 18 who attempted suicide between January 2019 and January 2022 and were admitted to the Pediatric Intensive Care Unit. In the study, the patients were retrospectively evaluated based on sociodemographic characteristics, nature of the suicide attempt, their psychopathology status chronic disease status.
Results: The average age of 45 cases included in the study was 15.31±1.61 years. A statistically significant relationship was found between previous suicide attempts, psychiatric illness history, and psychiatry referrals. A statistically significant association was found between non-suicidal self-harm behavior and psychiatric disease history, psychopathology status, earlier referral to psychiatry, and psychiatric check-ups after a suicide attempt.
Discussion: Suicide remains a serious cause of death worldwide. Not all suicides are preventable, but a systematic approach to suicide risk assessment can enable healthcare providers to identify and manage patients at risk for suicide. Considering the increasing incidence of suicide, especially in adolescence, comprehensive suicide risk assessment should be one of the pediatricians’ primary and critical duties.
Keywords: Suicide, Suicide Attempt, Self-Harm Behavior, Child, Adolescent
Introduction
Although suicide is not common in childhood, it appears to be an entity whose frequency increases towards adolescence. The pediatrician is involved in identifying and managing youth with suicidal behavior. The pediatrician must be able to detect the presence of warning signs for suicide/suicide attempts in children and adolescents because warning signs indicate that a suicide attempt may occur within a few hours or days and that immediate intervention is required. Risk factors that lead to suicide include psychiatric illness, previous suicide attempts, family factors, substance use, sexual and physical abuse, gender identity disorders, and bullying. Pediatricians primarily investigate and recognize these risk factors and prevent and treat suicidal behavior by communicating with other specialties. In particular, the American Academy of Pediatrics (AAP) recommends annual suicide screening in adolescents during visits for acute diseases and routine check-ups [1,2]. Suicide attempts can be considered a symptom of an emotional and communication problem. Suicide prevention is a highly challenging issue for healthcare professionals. It is reported that suicide victims, especially in adulthood, frequently visit their doctors before attempting suicide [3,4]. Suicide attempts in adolescents have become one of the most common reasons for emergency room admission among psychiatric admissions. The study aimed to determine the sociodemographic characteristics, factors leading to suicide, and suicide methods of patients who attempted suicide in the child and adolescent age group and were followed up in the Pediatric Intensive Care Unit of our hospital to be able to take preventive approaches.
Material and Methods
The study included 45 patients aged 10-18 years who attempted suicide between January 2019 and January 2022 and were admitted to the Pediatric Intensive Care Unit (PICU) of our hospital. The study did not include pediatric patients admitted to the PICU due to accidental medication intake. Patient files were retrospectively examined according to gender, age, educational status/continuation, season in which the suicide attempt was made, and suicide. Attempt method, characteristics of the suicide attempt, parental relationship status/loss of a parent, number of siblings, whether there is a history of psychiatric disease in themselves or their family before, psychopathology conditions detected by the Child Mental Health and Diseases department after the attempt, chronic disease conditions, previous attempts were examined. They were examined in terms of whether they had been present, the number of prior attempts, whether there was non-suicidal self-harming behavior, the presence of stressor factors that led to suicide, psychosocial risk factors, whether they were followed up by the Department of Child Mental Health and Diseases before or after the attempt, and the relationships between these factors.
Statistical analyses
NCSS (Number Cruncher Statistical System) 2007 (Kaysville, Utah, USA) program was used for statistical analysis. Descriptive statistical methods (mean, standard deviation, median, frequency, percentage, minimum, maximum) were used when evaluating the study data. The suitability of quantitative data for normal distribution was tested with the Shapiro-Wilk test and graphical analysis. The Mann-Whitney U test was used to compare two groups of quantitative variables that did not show normal distribution. The Kruskal-Wallis test was used to compare three or more groups of quantitative variables that did not show a normal distribution. Fisher’s Exact test and Fisher-Freeman-Halton test were used to compare qualitative data. Statistical significance was accepted as p<0.05
Ethical Approval
Ethical approval for the study was received from Tekirdağ Namık Kemal University Faculty of Medicine Non-Interventional Clinical Research Ethics Committee (Date: 2022-07-26, No: 2022.150.07.17).
Results
Of the cases, 13.3% (n=6) were male and 86.7% (n=39) were female. Their ages ranged from 10 to 18 years, averaging 15.31±1.61 years. Most cases had at least one sibling (85.7%). The status of parents being together was higher than that of being apart. The suicide attempt method was found to be 95.6% (n=43) taking medication, 2.2% (n=1) hanging, and 2.2% (n=1) taking corrosive substances. It was observed to be more common in the summer months (44.5%). It was observed that most of them (95.6%) did not have an initiative plan.
The rate of cases with a psychiatric history was 24.4% (n=11). The detection rate of psychopathological findings was 86.7% (n=39), 61.5% (n=24) of these cases had depressive disorder, 15.4% (n=6) had behavioral disorder, 7.7% had borderline personality disorder (n=3), anxiety disorder in 5.1% (n=2), prolonged grief disorder in 5.1% (n=2), 2.6% (n=1) post-traumatic stress disorder and 2.6% (n=1) were diagnosed with bipolar disorder. It was determined that 93.3% (n=42) of the cases had a source of stress in their lives. When considering stress factors, 45.2% (n=19) were family problems, 28.6% (n=12) were romantic relationship problems, 11.9% (n=5) were childhood troubles, 9.5% (n= 4) were imminent death and 4.8% (n=2) were found to have a history of abuse (Table 1).
A statistically significant relationship was found between a history of psychiatric illness and previous suicide attempts (p=0.002; p<0.01). The intervention rate in the group with a history of psychiatric disease was higher than in the group without. A statistically significant relationship was also detected between previous admission to psychiatry and previous suicide attempts (p=0.001; p<0.01). The intervention rate in the group that applied was higher than in the group that did not (Table 2). A statistically significant relationship was found between a history of psychiatric illness and non-suicidal self-harm behavior (p=0.033; p<0.05). The rate of self-harm in the group with a history of psychiatric illness was higher than in the group without a history of disease. A statistically significant relationship was found between psychopathology status and non-suicidal self-harm behavior (p=0.032; p<0.05). The rate of self-harm in the group with psychopathological findings was higher than in the group without symptoms. A statistically significant relationship was found between previous admission to psychiatry and non-suicidal self-harm behavior (p=0.001; p<0.01). The rate of self-harm in the group that applied was higher than in the group that did not use (Table 3).
Discussion
Suicide attempts are more common in adolescent girls than boys. A study by Randall et al. found that the one-year prevalence of suicide attempts was twice as high in girls than in boys [5]. In our study, 86.7% (n=39) of the cases were determined to be female, and 13.3% (n=6) were male. However, the rate of suicide is higher in adolescent boys than in girls. Public health data from the United States indicate that the suicide death rate for boys ages 10 to 19 is 7 per 100,000, and for girls is 2 per 100,000 [6]. Differences in suicide completion rates are associated with the method chosen. Girls choose less lethal means, such as high doses of drugs or incisions, while boys choose firearms and hanging [7]. In our study, the most common method of suicide attempt was found to be taking medication, with a rate of 95.6% (n = 43). The fact that the most frequently used method is taking medication suggests that this may be due to the easy accessibility of drugs. In our study, the ages of the cases ranged between 10-18 years, and the average was determined as 15.31±1.61 years. In the study by Özdemir et al., the average age was similarly stated as 14.8±1.4 years [8]. Therefore, given the increasing incidence of suicide in adolescence, the pediatrician can play a critical role in assessing the suicide risk level and identifying protective factors. When the sibling status of the cases in our study was examined, it was found that 13.3% (n = 6) did not have a sibling, while 86.7% (n = 39) had at least one sibling. The study by Eraslan et al. detected at least one sibling condition in 89.5% of the cases [9]. There are also publications stating that the increase in the number of children in the family may be associated with suicide [3,10].
Most adolescents who attempt or commit suicide have a psychiatric disorder, the most common being a depressive disorder. Literature data show that approximately 90% of adolescents who commit suicide suffer from a psychiatric disorder (especially mood disorder), and more than 60% of youth are depressed at the time of death [1,11]. 24.4% (n=11) of the cases in our study had a history of psychiatric disease. The rate of detecting psychopathology in the patients was 86.7% (n=39). 61.5% (n=24) of these cases had depressive disorder, 15.4% (n=6) had behavioral disorder, and 7.7% (n=3) had behavioral disorder. 5.1% (n=2) had anxiety disorder, 5.1% (n=2) had prolonged grief disorder, and 2.6% (n=1) had borderline personality disorder. Post-traumatic stress disorder 2.6% (n=1) and also bipolar disorder 2.6% (n=1) were diagnosed. In the study by Atesci et al., 53.3% of the cases had a history of psychiatric illness, and 48% had a history of psychopharmacological treatment. In comparison, most of those who attempted suicide (46.7%) were diagnosed with depressive disorder in their psychiatric evaluation [12]. Eraslan et al. found a diagnosis of depressive disorder in 42.1% of the cases in their study [10] .
Our study determined that 93.3% (n=42) of the cases had a source of stress in their lives. When stress factors are examined, 45.2% (n=19) had family problems, 28.6% (n=12) had romantic relationship problems, 11.9% (n=5) had childhood troubles, 9.5% (n=4) were recent death, and 4.8% (n=2) were found to have a history of abuse. Different studies have found that the most common cause of suicide is familial stressors [3,8]. Considering that most individuals in adolescence live with their families and the importance of the family in terms of social support, the relationship between familial factors and suicide can be understood.
Suicide attempts in adolescents significantly increase the risk of suicide over many years. In our study, the rate of cases who had previously attempted suicide was 24.4% (n=11). In total, 75.6% (n=34) of the patients had attempted suicide once, 13.3% (n=6) had attempted suicide twice, and 11.1% (n=5) had attempted suicide three times. Finkelstein et al. in an extensive series cohort study, identified patients who survived their first self-poisoning episode (n>20,000) and controls without such a history (n>1 million), and follow-up data for up to 12 years were obtained. Among adolescents who experienced their first self-poisoning episode, the risk of suicide within one year was 30 times higher than in the control group. In addition, the risk of suicide after ten years of follow-up was ten times higher. The average suicide time for adolescents experiencing their first self-poisoning attack was found to be three years. Risk factors for suicide in the study included recurrent self-poisoning and male gender, as well as a history of previous psychiatric treatment. Contact with a psychiatrist the year before self-poisoning has been associated with an increased risk of suicide [13]. Our study found a statistically significant relationship between a history of psychiatric disease and previous suicide attempts (p=0.002; p<0.01). The intervention rate was higher in the group with a history of psychiatric disorder than in the group without a history of disease. Our study found a statistically significant relationship between previous admission to psychiatry and the last suicide attempt (p=0.001; p<0.01). A study by Eraslan et al. showed that 52.6% of the cases had a previous psychiatric admission [9]. Similarly, in our study, 53.3% (n=24) of the patients had previously applied to the child psychiatry outpatient clinic.
A meta-analysis of 119 community studies from Asia, Australia, Europe, and North America evaluated individuals (n>230,000) and found the estimated lifetime prevalence of non-suicidal self-harm to be 17% in adolescents (10-17 years) and 17% in young adults (18-24 years) was found to be 13% and 6% in adults (≥25 years old) (14). In our study, the non-suicidal self-harm rate of the cases was 42.2% (n=19), and the average age of these cases was 15.32±1.53. Fox et al. in their study investigating non-suicidal self-injury (NSSI) risk factors stated that NSSI history and hopelessness, the most substantial risk factors, were also significant risk factors for suicidal thoughts and behaviors [15]. A meta-analysis found that the previous history of NSSI was one of the most vital risk factors identified for future suicide attempts, and hopelessness was one of the strongest predictors of suicidal ideation and suicide death [16]. Our study found a statistically significant relationship between psychopathology status and non-suicidal self-harm behavior (p=0.032; p<0.05). The rate of self-harm in the group with psychopathological findings was higher than in the group without symptoms. Similarly, a statistically significant relationship was found between a history of psychiatric illness, previous admission to psychiatry, and non-suicidal self-harm behavior (p=0.033; p<0.05). The rate of self-harm in the group with a history of psychiatric illness was higher than in the group without a history of disease. The results of the study by Kerr et al. also confirm our study [17].
Conclusion
As a result, suicide remains a serious cause of death worldwide. Not all suicides are preventable, but a systematic approach to suicide risk assessment can enable healthcare providers to identify and manage patients at risk for suicide. Considering the increasing incidence of suicide, especially in adolescence, a comprehensive suicide risk assessment should be one of the pediatricians’ primary and critical duties.
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.21981
Aslı Akın, Mustafa Törehan Aslan, Nedim Samancı. Retrospective evaluation of children and adolescents admitted to the pediatric intensive care unit due to suicide attempts. Ann Clin Anal Med 2024;15(2):103-107
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Skin analysis findings and disease severity in fibromyalgia patients
Semra Aktürk 1, Raikan Büyükavcı 1, Nihal Altunışık 2, Dursun Türkmen 2, Burcu Kayhan Tetik 3
1 Department of Physical Medicine and Rehabilitation, 2 Department of Dermatology, 3 Department of Family Medicine, Faculty of Medicine, Inönü University, Malatya, Turkey
DOI: 10.4328/ACAM.22011 Received: 2023-10-17 Accepted: 2023-11-20 Published Online: 2023-11-30 Printed: 2024-02-01 Ann Clin Anal Med 2024;15(2):108-111
Corresponding Author: Semra Aktürk, Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Inönü University, Malatya, Turkey. E-mail: drsemra44@gmail.com P: +90 422 341 06 60 F: +90 422 341 27 08 Corresponding Author ORCID ID: https://orcid.org/0000-0001-9960-6851
This study was approved by the Ethics Committee of Malatya Clinical Trials (Date: 2022-03-02, No: 2022/10)
Aim: Fibromyalgia syndrome is a non-inflammatory disease characterized by widespread pain and various musculoskeletal symptoms. It can cause signs and symptoms in different systems of the body. Dermatological manifestations have not been fully clarified.
Material and Methods: Participants were divided into two groups as patients and healthy controls . 25 people were included in each group. The disease severity of the patients and its impact on daily activities were evaluated with the Fibromyalgia Impact Questionnaire (FIQ) and Visual Analogue Scale (VAS). Skin analysis of both groups was performed with the API-100 Skin Analyzer. Erythema was assessed with the Clinician’s Erythema Severity Index.
Results: In this study %94 of the participants were women and %6 were men. The average age was 41.06±6.55. When the groups were compared, it was observed that the parameters determining skin quality were statistically significant in the control group than in the patient group. It was observed that fibromyalgia patients with skin erythema and sensitivity had higher VAS and FIQ scores than controls (p<0.05).
Discussion: As a multisystemic disease, fibromyalgia is also likely to cause dermatologic symptoms. A multidisciplinary approach may be recommended in the treatment and follow-up of these patients.
Keywords: Fibromyalgia, Skin Findings, Pain, Quality of Life
Introduction
Fibromyalgia syndrome (FMS) is a non-inflammatory rheumatic disorder characterized by chronic and widespread musculoskeletal pain. The prevalence of FMS is between 1-4% in the normal population and is approximately three times more common in women than in men [1]. Abnormalities in central pain mechanisms are thought to play a critical role in etiopathogenesis, although it is not clear . Fibromyalgia patients are thought to have pain regulation disorder. The pain is usually accompanied by other systemic symptoms. Fatigue, stiffness, sleep quality disturbance, numbness in the extremities, migraine, intestinal irregularities, pelvic pain, Raynaud-like symptoms, depression and anxiety disorder are among these symptoms [2, 3].
Recently, the role of peripheral nerves and neurogenic inflammation have been implicated in the pathophysiology of fibromyalgia. As one of the results of this process, skin findings can also be observed in FMS. Skin-related symptoms such as burning, tenderness, itching, as well as diseases such as seborrheic dermatitis, eczema, rosacea, lichen simplex chronicus, and dermographism have been reported in fibromyalgia patients. It has been observed that the frequency of rosacea and seborrheic dermatitis especially increases in these patients. It is thought that central mechanisms play a role in hyperthermia and erythema in rosacea patients [4]. However, it cannot be said that there are sufficient studies on skin involvement in fibromyalgia patients. Therefore, as a result of our study, we aimed to evaluate the skin findings of these patients and measure their the relationship between these findings with and disease severity.
Material and Methods
Patients between the ages of 25-55, diagnosed with fibromyalgia according to the 2010 American College of Rheumatology criteria, and healthy controls were included in the study. Patients having a history of systemic or inflammatory diseases or receiving active treatment for any skin disease were excluded from the study. This study was approved by the ethics committee (ID 2022/10), and it was performed in accordance with the Helsinki Declaration. Informed. and written consent was obtained from all participants.
A Turkish validation of Fibromyalgia Impact Questionnaire (FIQ) and Visual Analogue Scale (VAS) were used to determine the clinical severity and functional disability of the FMS patients. FIQ consists of 10 self-administered scales related to physical functioning, work status, sleep, stiffness, depression, anxiety, pain, fatigue and wellbeing [5]. The visual analoganalogue scale is scored from 0 to 10 and is used to determine pain severity [6].
Skin analyses were performed with the API-100 skin analyser. During the analysis, skin hydration, elasticity, sebum, sensitivity, melanin accumulation, acne, moisture, pores and wrinkles were evaluated. Analysis results were recorded. Skin erythema was assessed by the same dermatologist using the Clinician’s Erythema Severity Index which is a 5-point scale for measuring erythema severity [7].
Healthy volunteers consisted of people who applied to the Family Medicine outpatient clinic for periodic health examination and agreed to participate in the study. Skin analysis was performed and erythema scale was applied to all healthy controls.
Statistical Analysis
All statistical analyses were performed using Statistical Package of Social Sciences (SPSS) software (version 22.0 for Windows). The results were expressed as mean ± standard deviation (SD). The clinical profile of the patients was analysed by chi-square test for qualitative variables. Mann-Whitney U test was performed to compare quantitative variables. Spearman correlation test was used to evaluate the correlation of within-group variables with each other. Statistical significance was defined as p< 0.05.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
A total of 50 people (25 FMS patients, 25 healthy controls) were included in the study. The mean age for the patient and control groups was 39,8±6,51 and 42,3±6,47 years, respectively. No significant difference was observed between the two groups in terms of age and gender, marital status, occupational distribution and education level (Table 1) (p<0.05).
When the skin analysis findings were evaluated, it was seen that 36% of fibromyalgia patients had skin sensitivity, while it was present in 22% of the control group (Figure 1). While skin elasticity was observed it was significantly higher in the control group, and dry skin findings were present in FMS patients (p<0.05) (Table 2).
When the relationship between VAS and FIQ scores and skin analysis findings in fibromyalgia patients was evaluated, a positive correlation was found between disease activity and erythema level, sensitivity and pain in the patient group (Table 3).
Discussion
In this study, skin findings in fibromyalgia patients were analysed and compared with healthy controls, and their the relationship between these findings with and disease activity was also evaluated. In our study, it was observed that some dermatological findings, especially erythema and sensitivity, were observed more frequently in FMS patients than in healthy controls. Recent studies have revealed the role of peripheral nerves and neurogenic inflammation in FMS [8]. Fibromyalgia is not considered a disease classically associated with skin findings, but pathological examinations of the skin of FMS patients have detected changes such as oxidative stress, elevated cytokines and mast cells. The reason why erythema and sensitivity findings are observed in FMS patients can be explained by the role of substance P, mast cells, interleukin-1β and tumor necrosis factor-alpha, which contribute to neurogenic inflammation. In a study comparing skin biopsy samples, fibromyalgia patients not only had greater mean mast cell counts but also had increased mast cell degranulation and intradermal immunoglobulin G deposition, supporting the possibility of neurogenic inflammation in fibromyalgia patients [8, 9]. Researchers thought that structural differences in the skin may underlie the pathogenesis of fibromyalgia. They noted that due to a difference in collagen metabolism, the accumulation of collagen deposits around peripheral nerves may also have reduced pain tolerance in these patients (10). Additionally, there are studies showing that the incidence of fibromyalgia increases in skin patients with skin diseases such as psoriasis, acne vulgaris, rosacea, seborrheic dermatitis, SLE and urticaria, as well as skin findings detected in FMS [11-16].
In our study, it was observed that the participants in the FMS group had less skin elasticity and moisture content. Living conditions such as intense stress, hormonal factors, environmental pollution, nutrition, smoking and alcohol are among the factors that affect the skin structure. When the skin is exposed to these living conditions for a long time, dryness of the skin, wrinkle formation, loss of elasticity and thinning of the dermis may occur over time [17]. Considering the role of stress and living conditions in the FMS mechanism, it is possible that the skin collagen structure is disrupted in the early stages in these patients. Similarly, in a study conducted in patients with papulopustular rosacea, it was reported that transepidermal water loss increased, thus moisture levels decreased and pH levels increased [14]. It has been observed that the physiological response of the central nervous system to hyperthermia is impaired in rosacea patients, and it is thought that this system may play a role in the pathogenesis. This disorder has also been held responsible for rash attacks [4]. All of these findings may suggest the possibility that the role of the central nervous system is similar in the pathogenesis of FMS and skin diseases.
In this study, sebum level and acne tendency in FMS patients were similar to the control group. When the literature was reviewed, no study showing a relationship between FMS and acne tendency was found. Many factors such as genetic predisposition, bacterial infections, hormonal disorders, smoking and diet may cause acne [18]. We did not observe any significant difference between the groups in terms of melanin deposition and wrinkle formation, which are other parameters of skin analysis.
When we evaluated VAS and FIQ scores in our study, we observed higher values in the FMS group compared to healthy controls in accordance with previous studies [19]. In addition, when we looked at the relationship of skin findings with VAS and FIQ scores in FMS patients, we found that sensitivity and erythema were positively correlated with disease severity. This may indicate that common pathophysiological mechanisms, such as neuroinflammation, may have developed in both conditions. FMS patients with skin involvement may be expected to have more pain and less participation in activities of daily living.
Conclusion
In our study, findings that we objectively measured and evaluated by skin analysis such as erythema, sensitivity and loss of elasticity were observed at a higher rate in FMS patients compared to healthy controls. Considering the complex pathogenesis of FMS, clinicians may need to take a more multidisciplinary approach in the treatment and follow-up of these patients. It may be recommended to evaluate this disease, which may have systemic involvement, in terms of skin findings and to seek the opinion of a dermatologist when necessary.
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 comparable ethical standards.
Funding: This study was supported by a research grant from the İnönü University Scientific Research Project Unit (İnubap) with the code TSA-2022-2961.
Conflict of Interest
The authors declare that there is no conflict of interest.
References
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2. Abeles AM, Pillinger MH, Solitar BM, Abeles M. Narrative review: the pathophysiology of fibromyalgia. Ann Intern Med. 2007;146(10):726-34.
3. Bellato E, Marini E, Castoldi F, Barbasetti N, Mattei L, Bonasia DE, et al. Fibromyalgia syndrome: Etiology, pathogenesis, diagnosis, and treatment. review article. Hindawi Publishing Corporation. Pain Res Treat. 2012;2012(6):1-17.
4. Bakar Ö, Demirçay Z. The Etiopathogenesis and the new classification system of rosacea. J Turkderm. 2007;41(3):77-80.
5. Bennett R. The Fibromyalgia Impact Questionnaire (FIQ): a review of its development, current version, operating characteristics and uses. J Clinical and experimental rheumatology. 2005;23(5):154-62.
6. Crichton N. Visual analogue scale (VAS). J Clin Nurs. 2001;10(5):697-706.
7. Coutinho JC, Westphal, DC, Lobato LC, Schettini AP, Santos M. Rosacea fulminans: unusual clinical presentation of rosacea. An Bras Dermatol. 2016;91(5):151-3.
8. Blanco I, Béritze N, Argüelles M, Cárcaba V, Fernández F, Janciauskiene S, et al. Abnormal overexpression of mastocytes in skin biopsies of fibromyalgia patients. Clin Rheumatol. 2010;29(12):1403-12.
9. Salemi S, Rethage J, Wollina U, Michel BA, Gay RE, Gay S, et al. Detection of interleukin 1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha in skin of patients with fibromyalgia. J Rheumatol. 2003;30(1):146–50.
10. Kim, Seong-Ho. Skin biopsy findings: implications for the pathophysiology of fibromyalgia. J Medical hypotheses. 2007;69(1):141-4.
11. Thune, Per O. The prevalence of fibromyalgia among patients with psoriasis. J Acta dermato-venereologica. 2005;85(1):33-7.
12. Yazmalar L, Çelepkolu T, Batmaz İ, Sariyildiz MA, Sula B, Alpayci M, et al. High frequency of fibromyalgia in patients with acne vulgaris. Archives of Rheumatology. 2016;31(2):170-5.
13. Torresani C, Salvatore B, and Giuseppe P. Chronic urticaria is usually associated with fibromyalgia syndrome. Acta dermato-venereologica. 2009;89(4):389-92.
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Semra Aktürk, Nihal Altunışık, Raikan Büyükavcı, Dursun Türkmen, Burcu Kayhan Tetik. Skin analysis findings and disease severity in fibromyalgia patients. Ann Clin Anal Med 2024;15(2):108-111
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Evaluation of the incidence of anomaly in fetus and neonates of prenatal aneuploidy screening
Salih Demir 1, Mustafa Törehan Aslan 2, İlke Özer Aslan 1
1 Department of Obstetrics and Gynecology, 2 Department of Pediatrics, Division of Neonatology, Faculty of Medicine, Tekirdağ Namık Kemal University, Tekirdağ, Turkey
DOI: 10.4328/ACAM.22012 Received: 2023-10-13 Accepted: 2023-11-20 Published Online: 2023-11-29 Printed: 2024-02-01 Ann Clin Anal Med 2024;15(2):112-116
Corresponding Author: İlke Özer Aslan, Department of Obstetrics and Gynecology, Faculty of Medicine, Tekirdağ Namık Kemal University, Tekirdağ, Turkey. E-mail: ilkeozeraslan@nku.edu.tr P: +90 505 389 48 00 Corresponding Author ORCID ID: https://orcid.org/0000-0002-3175-8354
This study was approved by the Ethics Committee of Tekirdağ Namık Kemal University (Date: 2022-07-26, No: 2022.145.07.12)
Aim: Our study aimed to investigate the frequency of anomalies and related maternal and neonatal outcomes in pregnant women who were admitted in our clinic in the last five years and underwent prenatal aneuploidy screening.
Materials and Methods: The prenatal fetal aneuploidy screening results of the pregnant women who participated in the study, the pregnant and maternal outcomes of the pregnant women who underwent amniocentesis according to these results, and the detection rates of chromosomal aneuploidy in infants were retrospectively analyzed.
Results: According to the first-trimester screening test, 22.4% of the cases (n=121); According to the second-trimester screening test, 11.8% (n=6) of the patients were found to be at high risk for chromosomal aneuploidy. Amniocentesis was recommended to 199 participating in the study, and 17.6% (n=35) of these cases were accepted. Chromosomal aneuploidy was found in 1.8% (n=3) of those who underwent amniocentesis. Two pregnancies with aneuploidy were terminated at the request of the families. The anxiety levels of the pregnant women who had prenatal screening tests were higher in the studies.
Discussion: Fetal aneuploidy screening tests may give false positive results at high rates, adversely affecting maternal anxiety and, thus, pregnancy outcomes. To increase the prenatal diagnosis rates cost-effectively, it is helpful to perform combined tests to increase the sensitivity or more sensitive tests are needed.
Keywords: Amniocentesis, Aneuploidy, First Trimester Screening, Second Trimester Screening, Prenatal Screening.
Introduction
Considering that newborns with congenital anomalies cause problems for families and society, screening tests for chromosomal abnormalities are recommended for pregnant women in our country, as in many countries. The purpose of prenatal screening tests is to identify pregnant women with a high risk for chromosomal aneuploidy in the early weeks of pregnancy and to inform each pregnant woman by considering their current troubles and preferences.
Prenatal diagnosis can be made through invasive and non-invasive testing (NIPT). The American Society of Obstetricians and Gynecologists (ACOG) and the Maternal-Fetal Medicine Association (SMFM) recommend that prenatal genetic screening tests be offered to all pregnant women, regardless of age or risk for chromosomal abnormality [1].
Screening tests from maternal blood, free human chorionic gonadotropin (free β-hCG) and pregnancy-associated protein A (PAPP-A) in the first trimester, a triple screening test (alpha-fetoprotein (AFP), free β-hCG and unconjugated protein A (PAPP-A) in the second trimester) estriol (uE3). The detection rate for Trisomy 21 with the first-trimester screening test varies between 82-87%, using a 5% positive screening rate depending on the laboratory [2]. The advantage of this test is that the test can be performed in the early stages of pregnancy (10-13 weeks of pregnancy) [3,4]. Patients who agree to have a diagnostic test at 10-13. Chorionic villus sampling (CVS) may be recommended during gestational weeks or amniocentesis from the 15th gestational week (26). 16-18. It is known that the triple screening test (AFP, β-hCG, E3) performed during gestational weeks has an accuracy rate of 60% with a false positive rate of 5% [5,6]. The most important expectation from screening tests is a high congenital anomaly detection rate and low false positivity. However, screening at an early gestational week allows for earlier prenatal diagnosis by calculating the possible increased risk earlier. With the detection of chromosomal anomalies by diagnostic tests, a termination option can be offered in the early weeks.
When the results of the screening tests are received, negative or positive results should be communicated to the family promptly. Even if the screening test result is negative or low-risk, the patient should be advised that an abnormality may still exist. In case of a high-risk outcome, the family should be informed about additional diagnostic testing options, if desired [1,7].
It is aimed to investigate whether diagnostic tests are performed and what their results are and to examine the contribution of prenatal screening tests to patients and physicians in a versatile way.
Material and Methods
Among the pregnant women who applied to the Tekirdağ Namık Kemal University, Faculty of Medicine Health Practice and Research Hospital Gynecology and Obstetrics Polyclinic between 01.07.2017 and 01.07.2022, the pregnant women who were screened for fetal aneuploidy in a different clinic gave birth in a different clinic under the age of 18. This is a retrospective cross-sectional study in which a total of 542 pregnant women and their newborns were examined, excluding those with twin pregnancies, those whose screening results were not reported, and those whose screening results were not reported. Patient data and examination results were obtained through the hospital automation system, outpatient follow-up forms and phone calls. This data includes patients’ name, surname, age, comorbidities, smoking, weight, gravida, parity, abortion, number of living children, number of curettages, and family history were questioned. PAPP-A, β-hCG, NT, uE3, AFP test results, Trisomy 21 (T21) risk score, Trisomy 13 and Trisomy 18 (T13-18) risk score, NTD risk score, according to results of double screening and triple screening. The pregnant women who underwent amniocentesis and their genetic influences, the week of the birth of the pregnant women who were born in our hospital, the birth weight of the newborn, the mode of delivery, the Apgar score of the newborn at birth, whether there was a need for neonatal intensive care after delivery, and the results of the neonates whose postpartum chromosomal analysis was performed from peripheral blood were recorded. In any of the prenatal screening tests, those with a cut-off value greater than 1/250 were considered high-risk, and those that were small were considered low-risk. Those with NT greater than 2.5 mm were considered high-risk, and those with undersized NT were deemed low-risk.
Statistical analysis
The NCSS (Number Cruncher Statistical System) 2007 (Kaysville, Utah, USA) program was used for statistical analysis. Descriptive statistical methods (mean, standard deviation, median, frequency, percentage, minimum, maximum) were used while evaluating the study data. The conformity of the quantitative data to the normal distribution was tested with the Shapiro-Wilk test and graphical examinations. Independent groups t-test was used to compare two groups of normally distributed quantitative variables. Fisher’s exact test was used to compare qualitative data. Spearman correlation analysis was used to evaluate the relationships between quantitative variables. Statistical significance was accepted at p <0.05.
Ethical Approval
The current study was approved by the ethics committee of Tekirdağ Namık Kemal University (Date: 26.07.2022 / No: 2022.145.07.12). The study was conducted in accordance with the Helsinki Declaration rules.
Results
Our study was conducted with 542 cases, all women, who were admitted to our hospital between 01.07.2017 and 01.07.2022. The age of the study’s subjects ranged from 18 to 45, and the mean age was 28.91±5.37.
It was observed that 1.3% (n=7) of the cases participating in the study had a family history. The chromosomal anomaly was found in 0.54% (n=3) of the genetic results of the neonates.
When the dual screening test results of the subjects participating in the study were examined, 19.8% (n=107) had an age-related risk, 4.1% (n=22) had a T21 risk, and 0.6% (n=3). T13-18 risk was observed in 0.6% (n=3) of NT-related risk. It was determined that there was a risk in first-trimester screening test results in 22.4% (n=121) of the cases.
The second-trimester screening test was performed in 9.4% (n=51) of the cases in the study. In the test results of the cases, it was determined that 8.3% (n=3) had an age-related risk, 3.1% (n=1) had an NTD risk, and 4.2% (n=2) had a T21 risk. T13-18 risk was not detected in any of the cases. It was determined that there was a risk in 11.8% (n=6) of the issues due to the triple screening test. While chromosomal aneuploidy was detected in one of the neonates of three pregnant women who were found to be risky for fetal aneuploidy, according to NT, chromosomal aneuploidy was not detected in two neonates. Amniocentesis was recommended for 199 cases participating in the study. It was determined that 17.6% (n=35) of the cases who were recommended to perform amniocentesis accepted the amniocentesis procedure, and 1.8% (n=3) had positive test results. Two pregnancies with positive test results were terminated at the family’s request.
According to the double screening test results, no statistically significant difference was found between the chromosomal anomaly results of the cases (p>0.05). Since only one of the three cases with chromosomal abnormality had a risk in the double screening test, the test’s sensitivity was 33.3%, and the specificity was 77.6%. Its positive predictive value was 82.6%, and its negative predictive value was 99.5%.
There was a very weak statistically significant correlation between the ß-hCG measurement values of the subjects and the 1st minute Apgar scores (r=0.160; p=0.022; p<0.05) in the negative direction (As ß-hCG increases, Apgar score decreases). There was a very weak statistically significant correlation between the PAPP-A measurement values of the cases and the 1st minute Apgar scores (r=0.160; p=0.030; p<0.05).
In addition, the weights of cases with high risk in the first-trimester screening test were statistically significantly higher than those without risk (p=0.001; p<0.01). The consequences of patients with increased risk in the first or second-trimester screening test were statistically significantly higher than those without risk (p=0.001; p<0.01). The risk rate in smokers’ first or second-trimester screening test was statistically significantly higher than that of non-smokers (p=0.049; p<0.05).
Discussion
Prenatal screening tests have been developed to detect fetal aneuploidies. These tests and their combinations applied in the first and second trimesters have different detection rates for chromosomal aneuploidies. Screening tests for chromosomal aneuploidies do not definitively tell whether the fetus is abnormal; instead, they can tell whether the fetus has a low or high probability of having the condition [8].
According to Kaya et al., a risk group of 5.75% was determined according to the results of the second-trimester screening test in a study conducted on 1841 pregnant women [9]. In their study, Atak et al. found a high risk of Down syndrome in 1.5% (n=78) of those who underwent the first-trimester screening test and in 5.9% (n=353) of those who experienced the second-trimester screening test [10]. Similarly, in our study, the risk of Down syndrome was high in 4.1% (n=22) of those who underwent the first-trimester screening test and 4.2% (n=2) of those who experienced the second-trimester screening test. In addiition, the high-risk rate for the anomaly in the first-trimester screening test was 22.4% (n=121), and the high-risk rate in the second-trimester screening test was 11.8% (n=6). In our study, only 51 cases also had the second-trimester screening test. Since the first-trimester screening test showed a risk in only one of the three cases with the chromosomal anomaly, the test’s sensitivity was 33.3%, and the specificity was 77.6%. Its positive predictive value was 82.6%, and its negative predictive value was 99.5%. It is known that there are differences in the sensitivity of screening tests. When the studies in the literature are examined, we see that prenatal screening tests recommend using contingency screening and fully integrated screening strategies that combine first and second-trimester screening tests to increase the rate of catching chromosomal aneuploidy [11,12].
Screening tests require a blood sample from the mother and a fetal ultrasonographic evaluation, so there is no increased risk of losing the pregnancy. Diagnostic testing for chromosomal abnormalities requires sampling fetal or placental fluid or tissue. There is a slight increase in the risk of losing the pregnancy (about 1/200 for chorionic villus sampling (CVS) and 1/300-1/600 for amniocentesis) [13]. Chromosomal aneuploidy was detected in three of the patients who underwent amniocentesis. In two of them, the family terminated the pregnancy, and the fate of the third woman’s pregnancy is unknown since she continued her follow-up in an external center. The benefits of screening programs should be more pronounced than the adverse physical and psychological effects that may occur from participating in the screening program. It is essential to inform society adequately about the screening test, considering the anxiety that the screening tests may cause to pregnant women in our study, in which the rates of patients found to be at high risk as a result of screening tests are also examined. This is one of our study’s most critical clinical results.
When the literature is examined in detail, it has been shown in studies that although screening tests have benefits, the obtained risk estimation significantly increases the anxiety level of pregnant women [14]. If an increased risk is detected in terms of chromosomal anomaly in the screening test, performing these screening tests in cases that will not go to the diagnostic test or terminate the pregnancy does not mean anything other than unnecessary cost and an increase in the anxiety rate in patients. Similar to our study, in the study of Kömül et al. concluded that it is essential that prenatal screening tests can be used more effectively by informing families about Down syndrome in detail. Thus, the expenditures made for screening tests for cases that do not want termination are used to solve the health problems of live-born Down syndrome cases, increase the quality of life, and reintegrate them into society. Kömül et al. stated that it will be more effective [15]. Therefore, some studies stated that these high-risk cases should be followed carefully throughout pregnancy [16,17]. The idea that maternal serum PAPP-A and ß-hCG values may also be significant in predicting complications in the advancing gestational weeks, apart from determining the risk of chromosomal anomaly prompted researchers to conduct numerous studies on this subject [18,19]. In other studies, significant correlations were found between pregnancy complications such as gestational diabetes, low birth weight, high birth weight, intrauterine growth restriction and preterm labor, and maternal serum PAPP-A and ß-hCG values [20,21]. On the other hand, Morssink et al. also stated that first-trimester PAPP-A and ß-hCG values were not significantly associated with preterm labor [22]. While examining the results of the cases in our study, we also investigated whether there is a relationship between PAPP-A and ß-hCG values of pregnant women who need admission to the neonatal intensive care unit (NICU) for their babies. However, it did not detect a statistically significant association. In addition, there is no statistically significant relationship between the birth weight of newborns and PAPP-A measurement values and ß-hCG values in pregnant women (p>0.05).
The body weights of the cases with risk in the first-trimester screening test were statistically significantly higher than those without risk (p=0.001; p<0.01). In addition, the risk rate in the double or triple screening test of smokers was statistically significantly higher than that of non-smokers (p=0.049; p<0.05). Our findings, in line with the literature, support that maternal body weight and smoking effectively increase the risk of chromosomal anomalies [23]. We think the relationship of some pregnancy-related biochemical markers with pregnancy complications and possible complications in the newborn in the postnatal period will be revealed in different studies, including more extensive case series.
In conclusion, the aim of prenatal diagnosis applications is not only to detect anomalies in fetal life but to terminate such pregnancies. To provide necessary counseling on many issues, such as ensuring the preparation of the required conditions for postnatal care and enabling prenatal treatment of the affected fetus. Screening tests for chromosomal aneuploidies do not definitively say whether the fetus is abnormal. It can only tell whether the fetus has a low or high probability of having this condition.
Conversely, a diagnostic test can definitively tell if the fetus is abnormal. In this regard, it can be said that counseling for pregnant women is not sufficient. Accurate and effective prenatal screening tests are vital for adequate prenatal diagnosis. We emphasize the importance of these prenatal tests and reporting the patients correctly.
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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Association between gastric abnormalities and cholelithiasis: A cross-sectional study
Medeni Sermet
Department of General Surgery, Faculty of Medicine, Medeniyet University, Goztepe Prof. Dr. Suleyman Yalcin City Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.22017 Received: 2023-10-18 Accepted: 2023-11-20 Published Online: 2024-01-03 Printed: 2024-02-01 Ann Clin Anal Med 2024;15(2):117-121
Corresponding Author: Medeni Sermet, Department of General Surgery, Faculty of Medicine, Medeniyet University, Goztepe Prof. Dr. Suleyman Yalcin City Hospital, Istanbul, Turkey. E-mail: sermetmedeni@gmail.com P: +90 507 236 70 20 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6119-0037
This study was approved by the Ethics Committee of Istanbul Medeniyet Univesity (Date: 2022-07-22, No: 254)
Aim: The study aims to reveal the relationship between the most common abnormalities of the upper digestive tract and cholelithiasis.
Materials and Methods: This cross-sectional study included 7651 patients, of whom 14318 tested positive for Helicobacter pylori (H. Pylori). Patients who underwent abdominal ultrasonography (USG) and esophagogastroduodenoscopy (between January 2014 and June 2022) were included. The following gastroesophageal conditions were examined to determine whether they affect the risk of cholelithiasis: atrophic gastritis (AG), gastric polyps, esophagitis, bile reflux, gastric ulcers, gastric mucosal erosion, superficial gastritis, and gastric H. Pylori infection. Logistic regression was used to calculate the unadjusted and adjusted odds ratios (OR) of H. Pylori infection for cholelithiasis occurrence. In addition, we examined whether AG influences the association between cholelithiasis and H. Pylori infection.
Results: A total of 8753 patients (61.1%) were diagnosed with cholelithiasis. Multivariate logistic regression analysis showed that H. Pylori infection (OR 1.28; 95% CI 1.10-1.42) and atrophic gastritis (OR 1.38; 95% CI 1.21-1.41) were significantly associated with cholelithiasis, as were age, female gender (OR 1.82; 95% CI 1.56-2.01), gastric polyps (OR 1.45; 95% CI 1.06-1.82). No additional interaction was observed between H. Pylori infection and AG; however, the overall effect on the risk of cholelithiasis was only slightly greater than the sum of the individual effects.
Discussion: Gastric disorders, such as gastric polyps, H. Pylori infection, and AG, increase the risk of cholelithiasis. However, there was no association between the development of cholelithiasis and esophagitis, bile reflux, erosive gastritis, gastric ulcers, or superficial gastritis.
Keywords: Cholelithiasis, Helicobacter Pylori, Gastritis, Atrophy, Gastric Polyp
Introduction
Cholelithiasis is a common digestive disease with a high incidence and relatively low mortality [1]. Cholelithiasis is one of the most common diseases and its prevalence is increasing worldwide [2].
Although cholelithiasis is the result of a complex interaction of genetic, environmental, metabolic, and related conditions, factors such as advanced age and sex cannot be modified. Diet and physical activity may be modifiable risk factors [3].
Although there are numerous studies on the risk factors of cholelithiasis, there is a lack of data on its association with benign diseases of the stomach.
One-third of detected cholelithiasis cases are symptomatic. Similar symptoms were observed in gastric pathologies. Although several studies have examined the relationship between H. Pylori infection and the risk of cholelithiasis, the results are still controversial [4, 5]. On the other hand, the relationship between gastric pathologies such as AG, superficial gastritis, gastric polyps, bile reflux, esophagitis with gallstone formation is unknown.
Today, the easy accessibility of esophagogastroduodenoscopy (EGD) and ultrasonography (USG) procedures facilitates the diagnosis and treatment of gastric and gallbladder diseases.
Large population-based cohort studies are rare in the research literature on factors associated with gallstones [5, 6]. Therefore, we performed a retrospective analysis of a database of 65451 patients who underwent EGD to identify possible associations between cholelithiasis and various upper gastrointestinal diseases. We also examined the effect of the association between AG and H. Pylori infection in cholelithiasis.
Material and Methods
Study Participants
We conducted a cross-sectional study of patients who underwent EGD and USG at our facility between January 2014 and June 2022. During this period, 65451 patients underwent gastroscopy and 107218 patients underwent USG. We included 15840 patients with a maximum interval of six months between EGD and USG. For repeated endoscopies, only the initial data were considered.
We excluded 1522 patients for the following reasons.
1) If the time between EGD and USG was more than 6 months
2) Technically inadequate or incomplete endoscopy
3) Gastrointestinal surgery.
4) Diagnosis revealed gastrointestinal tumors.
5) Continuous PPI and anti-ulcer drug use
6) Diagnosis of acute cholecystitis, choledocholithiasis, and cholangitis.
Finally, 14318 participants were included in the analysis. (Figure 1).
A patient flowchart is shown in Figure 1.
Gastrointestinal (GI) tract endoscopic examinations were performed by specialized gastroscopists. The endoscopy center database contains descriptive endoscopic findings. The presence or absence of gastric mucosal atrophy, gastric polyps, esophagitis, bile reflux, gastric ulcers, gastric mucosal erosion, and superficial gastritis were considered significant gastric disorders. The diagnostic criteria for the listed disorders were based on endoscopic and pathological findings.
Analytical Statistics
Categorical data are summarized as frequency (%) and continuous variables as mean standard deviation (SD). The chi-square test and Mann-Whitney U-test were used for group comparisons. Collinearity between the gastric variables was examined using variance inflation factors, and no correlation was found.
Univariate logistic regression analysis was used to determine the association between gastric outcomes and cholelithiasis. Variables with P < 0.1 were then added to a multivariate analysis. OR and 95% CI were used to determine results. Statistical significance was set at P < 0.05. Data analysis was performed using R 4.1.2 and SPSS statistics version 23.
The effects we also examined whether the combined effect of H. Pylori infection or AG on cholelithiasis were greater than the sum of the individual effects of each factor. Individuals were divided into four groups according to their H. Pylori and AG status: H. Pylori (-) and AG (-), H. Pylori (−), AG (+), H. Pylori (+), AG (−), H. Pylori (+) and AG (+). Using the H. Pylori (-) and AG (-) groups as the reference analysis, we calculated the ORs of the other three categories. We assessed the occurrence of additional interactions by calculating the synergy index (SI), attributable rate (AP) due to interaction, and relative excess risk (RR) due to interaction. The 95% CI of RR and AP were > 0 and the 95% CI of SI was > 1, indicating a positive interaction; the 95% CI of RR and AP included 0 [7].
Ethical Approval
This study was approved by the Ethics Commitee of Istanbul Medeniyet Univesity (Date: 2022-07-22, No: 254).
Results
Common features of the topics
Of the 14318 registered cases, 8753 (61,1%) had cholelithiasis. Of the study population, 60.5% were female, and the mean age was 52,3 years.
Table 1 lists the clinical characteristics of the participants with cholelithiasis and the controls without cholelithiasis. Age is expressed as mean (SD), and all other data are expressed as number (proportion).
Compared with the group without cholelithiasis, patients with cholelithiasis were older and had a female-to-male sex ratio of 1.52. They also had higher rates of atrophic gastritis, esophagitis, alkaline bile reflux, gastric polyps, gastric ulcers, erosive gastritis, superficial gastritis, and Helicobacter pylori infection.
The findings of logistic regressions of the two study populations are shown in Table 2.
One included all 14318 study participants, while the other included 7651 cases with H. Pylori (+) data. Univariate analyses of the two populations were performed. All studies showed that the risk of cholelithiasis was significantly influenced by age, sex, gastric polyps, esophagitis, gastric ulcer, erosive gastritis, superficial gastritis, AG, and H. Pylori.
Multivariate analysis included all indicators of the univariate analysis (Table 2) (P <0.1). The findings showed that age, sex, gastric polyps, H. Pylori infection, and AG were independent risk factors for cholelithiasis. We also performed a trend test and stratified age into four quartiles with 10-year intervals. An OR of 3.27 (95% CI, 2.82-3.96) (P for trend 0.001) was observed in those in the highest age quartile (> 60) (Table3).
The incidence of cholelithiasis was 27.5% in AG (-) and H. Pylori (-) patients, 34,9% in H. Pylori (+) and AG (-) patients, 44,9% in AG (+) and H. Pylori (-) patients, and 55.6% in AG (+) and H. Pylori (+) patients. People with AG (OR: 1.78, 95% CI: 1.56-2.05) had a higher incidence of cholelithiasis than people without atrophy and without H. Pylori infection, while people with H. Pylori infection (OR: 1.13, 95% CI: 0.99-1.30) had a lower incidence of cholelithiasis.
However, the relative excess risk attributed to the interaction was not statistically significant (RR: 0.14 (-0.31-0.55), AP: 0.07 (-0.14-0.26), SI: 1.14 (0.72-1.71). In addition, H. Pylori infection and AG were associated with a high risk of developing cholelithiasis.
Discussion
In this study, the USG and typical EGD findings of 14318 individuals were compared. These findings suggest that individuals with sex, age, gastric polyps, AG, and H. Pylori infection have an increased risk of developing cholelithiasis. In addition, individuals with concurrent AG and H. Pylori infections may have an even higher chance of developing cholelithiasis.
Recently, the link between H. Pylori infection and cholelithiasis has attracted the attention of several researchers [8, 9, 10]. However, these results have not yet been conclusive. Although a number of studies have found a link between H. Pylori and cholelithiasis, other studies have found no link between the two [11, 12]. We hypothesized that these inconsistent findings may be partly related to the various H. Pylori detection techniques, geographic regions, racial groups, and small sample sizes. Based on 477293 individuals in a nationwide database, a very large prospective analysis was performed to evaluate the association between cholelithiasis and the effect of gastric acid-suppressive drugs on gallbladder histology. The results showed an association with increased gallstone formation [13], whereas a retrospective cohort of 27881 individuals preliminarily evaluated the presence of H. Pylori and concluded that it may not be associated with the development of gallstones [14].
According to a previous study, the risk of developing cholelithiasis was higher in people with intestinal metaplasia, gastric polyps, and H. Pylori infection, and findings showed that AG is an important parameter for cholelithiasis [15].
Recently, it has been hypothesized that H. Pylori infection is associated with a higher risk of developing cholelithiasis when coexisting with chronic AG [16]. In our study, we found that the combined effects of H. Pylori infection and AG on cholelithiasis were only slightly greater than those of each factor individually. Therefore, we hypothesized that H. Pylori and AG may interact together and conducted additional research to support this hypothesis. Therefore, we performed additional tests for erosive and superficial gastritis. Although our data showed a positive additive interaction between these two factors and the likelihood of cholelithiasis, this was not statistically significant. However, we still recommend, especially in patients with AG, that H. Pylori eradication may reduce the prevalence of cholelithiasis; however, this needs to be confirmed in the future [17]. In addition, cholelithiasis was independently linked to AG without H. Pylori infection but not solely to H. Pylori infection alone.
As most AGs are typically caused by H. Pylori infection, prolonged H. Pylori infection may be more important for the development of cholelithiasis.
Other theories have been proposed to explain the mechanisms underlying the association between H. Pylori infection and cholelithiasis. First, H. Pylori infection and AG cause hypergastrinemia, which may help in the development of cholelithiasis by promoting gallbladder mucosal damage [18]. Some studies have found a link between gastrin and cholelithiasis, while others have found the opposite [19, 20]. Second, persistent H. Pylori infection causes chronic AG by reducing acid secretions. Low gastric acid levels can alter the gastrointestinal microbiota and cause bacterial overgrowth, which may contribute to the development of cholelithiasis [20, 21].
Several studies have revealed that the detection rate of H. Pylori in cholecystectomy is higher than in normal mucosa [21, 22]. Consequently, H. Pylori may locally trigger cholelithiasis by contacting the mucosa.
In a cohort study, the prevalence of cholelithiasis was higher in individuals with gastric polyps [22]. However, the mechanisms involved remain unclear. The majority of gastric fundic gland polyps, which constitute the majority of gastric polyps, are symptoms associated with long-term proton pump inhibitor therapy [23]. Polyps may develop as a result of a decrease in the gastric acid barrier. Gastric polyps are closely associated with H. Pylori infection and atrophic gastritis; however, the physiopathologic explanation for this association is still unclear [24]. Another hypothesis is that lifestyle, environmental and hereditary factors may significantly influence the mechanism underlying this association [24]. In our study, the presence of gastric polyps was more common in patients with H. Pylori, and a significant association with cholelithiasis was found in parallel.
We understand that the risk of cholelithiasis is higher in females and older participants. Similarly, our study found that women were more likely to develop cholelithiasis than men were. In addition, the prevalence of cholelithiasis increases over time with age, with the highest OR 3.27; 95% CI: 2.82-3.96) seen in the older age group.
Therefore, it is necessary to discuss possible flaws in this study. First, because the present analysis is based on histological diagnoses and endoscopic findings, there may be subjectivity and diagnostic variability among observers. Although the lesions were described on endoscopy, the endoscopists did not biopsy every lesion. However, our endoscopists applied a standardized algorithm that enabled them to report similar interpretations on similar images.
Second, because the study was retrospective, we were unable to collect data on dietary patterns, lifestyle choices, medical history, substance use, and other confounding variables, but in other studies these confounding variables have had little or no effect on these associations [25]. Third, we used data from only one data center; therefore, different groups should establish the generalizability of our findings. Despite these drawbacks, our study is the first to examine the link between cholelithiasis and endoscopically detected gastric abnormalities using a large sample size.
Independent risk factors for cholelithiasis include gastrointestinal diseases such as gastric polyps, H. Pylori infection, and AG. In addition, the combination of AG and H. Pylori infections may cause a marginal increase in the risk of developing cholelithiasis. However, it is likely that the presence of cholelithiasis is not associated with conditions such as esophagitis, bile reflux, gastric mucosal erosion, gastric ulcers, and superficial gastritis. Therefore, screening ultrasonography should be considered when individuals are found to have gastric polyps, AG, or H. Pylori infection after EGD.
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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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Our experience with ERCP (endoscopic retrograde cholangio pancreatography) as the first line treatment for simple bile duct leakage
Yunushan Furkan Aydoğdu 1, Tamer Akay 2, Alpaslan Fedayi Çalta 3, Ali Duran 4, Serhat Oğuz 3
1 Department of General Surgery, Faculty of Medicine, Bandırma Training and Research Hospital, 2 Department of General Surgery, Faculty of Medicine, Bandırma Royal Hospital, 3 Department of General Surgery, Faculty of Medicine, Bandırma Onyedi Eylül University, 4 Department of General Surgery, Faculty of Medicine, Balıkesir University, Balıkesir, Turkey
DOI: 10.4328/ACAM.22019 Received: 2023-10-20 Accepted: 2023-11-20 Published Online: 2023-11-27 Printed: 2024-02-01 Ann Clin Anal Med 2024;15(2):122-125
Corresponding Author: Yunushan Furkan Aydoğdu, Department of General Surgery, Bandırma Training and Research Hospital, Balıkesir, Turkey. E-mail: yfaydogdu92@gmail.com P: +90 537 561 66 81 Corresponding Author ORCID ID: https://orcid.org/0000-0002-2418-2393
This study was approved by the Ethics Committee of Bandırma Onyedi Eylül University (Date: 2022-11-16, No: 2022-173)
Aim: Endoscopic retrograde cholangio-pancreatography (ERCP) should be performed as the first-line treatment after appropriate imaging and drainage in non-complete biliary tract injuries. Our aim is to present our treatment strategy in such injuries in a tertiary center with the aim of contributing to the literature.
Material and Methods: Between January 2016 and January 2022, 39 patients who underwent ERCP for iatrogenic simple biliary tract injury were included in our study. Magnetic resonance cholangiopancreatography was performed in all patients before the procedure. Sphincterotomy, balloon, basket catheter or balloon dilatation and plastic stent were performed under sedo-analgesia. Complication rates of the procedures were recorded.
Results: 39 patients were included in the study. The mean age was 61.94±15.60 years. When the procedure characteristics of the patients who underwent ERCP were evaluated, 33 patients underwent selective cannulation and 6 patients underwent pre-cut. Primary cannulation was performed in 27 patients and secondary cannulation was performed in 12 patients. When we looked at the complications after ERCP, bleeding was not seen in any patient, while pancreatitis developed in 6 (15.40%) patients. After sphincterotomy and stenting, the procedure was successful in 35 (89.70%) patients and bile leakage disappeared in the follow-up.
Discussion: Endoscopic interventional procedures should be considered as the first choice for idiopathic simple biliary tract leaks after laparoscopic cholecystectomy because they are minimally invasive, have a high success rate and eliminate the need for reoperation. Our early results are similar to the literature.
Keywords: Common Bile Duct, Iatrogenic Injury, Endoscopic Retrograde Cholangiopancreatography (ERCP), Cannulation, Pancreatitis.
Introduction
The most common causes of biliary tract injuries are cholecystectomy surgeries and liver hydatid cyst surgeries [1]. Currently, laparoscopic cholecystectomy (LC) is the first-line treatment for symptomatic cholelithiasis. The incidence of biliary tract injury in LC is reported to be 0.2%-0.9% in the current literature [2].
Timing of treatment is recognized as the most important parameter in the success of treatment of iatrogenic biliary tract injuries [3]. For example, there is a time frame for surgical repair after injury that should be optimally avoided between two and six weeks [4].
Endoscopic Retrograde Cholangio Pancreatography (ERCP ) is indicated as the first choice method in the treatment of bile duct leaks after appropriate imaging and drainage [5]. ERCP is an effective method in both diagnosis and treatment. Studies have shown that ERCP has a very high success rate in cases without a full-thickness injury to the choledochus [1,6].
In addition, the clinical guideline of the European Society of Gastrointestinal Endoscopy recommends sphincterotomy followed by temporary stent placement instead of sphincterotomy alone during ERCP performed for diagnosis and treatment after biliary tract injuries [7].
Our study was planned to reveal the ERCP applications we performed as the first treatment method in simple biliary tract leaks and to reveal the power of endoscopic methods in the management of biliary tract leaks and to contribute to the literature on endoscopic management by creating a preliminary idea in patient follow-up .
Material and Methods
This study was conducted retrospectively as a single-center study.
The interventional endoscopy unit affiliated to the general surgery clinic of our hospital, which is a tertiary health center, is accepted as a reference endoscopy center in our region.
Therefore, the included patient population consists of patients referred to our center and primary patients of our own clinic. Between January 2016 and January 2022, 74 patients who
underwent ERCP procedure classified as Amsterdam type A due to biliary tract leakage were evaluated. 2 patients under 18 years of age were excluded from the study. We excluded other 8
patients whose postoperative follow-up was not performed by us and 25 patients who underwent surgical procedures other than laparoscopic cholecystectomy (Figure 1).
Our study aims to reveal the ERCP applications we performed as the first treatment method in simple biliary tract leaks and to reveal the power of endoscopic methods in the management
of biliary tract leaks. The study also aims and to contribute to the literature on endoscopic management by creating a preliminary idea in patient follow-up.
Magnetic resonance cholangiopancreatography (MRCP) was performed before the endoscopic procedure. Patients were also evaluated by an anesthesiologist before the procedure. Sphincterotomy, balloon, basket catheter or balloon dilatation and plastic stent application were performed after ERCP imaging with a side view duodenoscope under sedo-analgesia under anesthesiologist guidance.
Demographic data (age, gender), preoperative comorbid conditions, location of bile leakage during endoscopic procedure, sphincteromy and stent application, precut rates during the procedure, selective cannulation rates, duration of hospitalization after the procedure, necessity of surgical procedure for bile leakage, biluribin, amylase and leukocyte values before and after endoscopic procedure, duration of the procedure, development of complications during the procedure were evaluated.
Statistical Analysis
Statistical analysis were performed using Statistical Package for the Social Sciences (SPSS) (version 26.0, SPSS Inc, Chicago, IL, USA) program. Besides descriptive statistical methods (mean, median, frequency, rate), the Kruskal-Wallis test was used to compare quantitative data, and the Mann-Whitney U test was used for two-group comparisons. The Pearson’s chi-squared test and Fisher’s exact test were used to compare qualitative data. p<0.05 was considered as statistically significant.
Ethical Approval
Study approval was obtained from the Bandırma Onyedi Eylül University Ethics Committee with the decision (Date: 16.11.2022, No: 2022-173). The study protocol is in accordance with the Declaration of Helsinki.
Results
A total of 39 patients were included in our study regarding the endoscopic interventional procedures we performed in our clinic in for the intervention of idiopathic bile leaks in the Type
A group according to the Amsterdam classification, which occurred after laparoscopic cholecystectomies. Of the included patients, 22 were female and 17 were male. The mean age of the included patients was 61.94±15.60 years. When we evaluated the comorbid diseases of the patients included in the study, 19 (48.70%) patients had congestive heart failure, 5 (12.80%) patients had chronic kidney disease, 7 (17.90%) patients had chronic lung disease, and 1 (2.60%) patient had a history of malignancy. The most common presenting symptom of patients with idiopathic bile leakage after laparoscopic cholecystectomy was bile from the drain (48.70%). Other presenting complaints included abdominal pain, nausea and vomiting, and fever. The median total bilirubin value of the included patients at presentation was 1.20 mg/dL. The median direct bilirubin value was 0.90 mg/dL, and the diameter of the common bile duct measured on MRCP for evaluation at admission was 14.00 mm (Table 1).
When the procedural characteristics of patients who underwent ERCP for postoperative bile leakage were evaluated, it was seen that selective cannulation was performed in 33 (84.60%)
patients and precut procedure was performed in 6 (15.40%) patients. When the cannulation procedure was detailed, primary cannulation was performed in 27 patients and secondary cannulation was performed in 12 patients. When we looked at the complications after ERCP, bleeding was never seen, while pancreatitis developed in 6 (15.40%) patients. The median procedure time was 20.0 (10.0-60.0) minutes. The median post-procedure biochemical control amylase value was 57.0 (19.0-1956.0). After sphincterotomy+stent application during ERCP procedure for bile leakage, the procedure was successful in 35 (89.70%) patients and the bile leakage disappeared in the follow-up. However, in 4 patients, the intervention was not successful and surgery was required. When we evaluated the duration of hospitalization in the clinic after the procedure, a median hospitalization period of 1.0 (0.0-15.0) days was observed (Table 2).
Discussion
Laparoscopic cholecystectomy surgery is one of the most frequently performed surgeries worldwide [8].
Iatrogenic biliary tract injuries after gallbladder surgeries are seen with a probability of 0.3%-0.7% and can have important consequences [1,9]. Endoscopic interventional procedures are at the forefront of treatment modalities after biliary tract injuries
[1]. Sphincterotomy and biliary stent placement constitute the golden standard treatment [10,11]. With sphincterotomy, sphincter pressure decreases and following stent placement, bile flow to the duodenum is facilitated and healing is achieved [12].
In our study, we aimed to reveal the ERCP applications we performed as the first treatment method in simple biliary tract leaks and to reveal the power of endoscopic methods in the management of biliary tract leaks. The study also aims and to contribute to the literature on endoscopic management by creating a preliminary idea in patient follow-up.
When we evaluated the entire patient population, we found that the female patient population occupied consitituted a larger proportion with of 56.40%. 51.30% of the patients had comorbid diseases in the preoperative period.
Acar T et al. [8] achieved 81% success rate in leak management with endoscopic procedure, while Çelik M et al. [12] achieved 89% success rate. When we evaluated the results of our endoscopic interventional procedures, we also achieved a high success rate of 89.70%. Acar T et al. [8] found that the most common presenting complaint of patients after leakage was
bile coming from the drain, and we also found that this was the most common presenting complaint.
According to Fasoulas K et al. [13], the transition time to ERCP after surgery was long. Because of the multidisciplinary approach, it is inevitable that there is inevitably lost time for communication and information. Martinez-Lopez S et al. [14] evaluated patients with idiopathic biliary tract injury after laparoscopic cholecystectomy and found the that there is a need for more invasive procedures and longer hospitalization time in patients with late presentation. In our clinic, ERCP is performed by general surgeons and ERCP is planned in the early period in cases of bile leakage. Our early results are similar to the literature.
Conclusion
In idiopathic biliary tract leaks after laparoscopic cholecystectomy surgery, endoscopic interventional procedures in the Amsterdam type A stage are much less invasive and have a high chance of success. ERCP procedure can be used as the first choice as a reliable and effective method in bile duct leaks.
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 comparable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
References
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2. Siiki A, Ahola R, Vaalavuo Y, Antila A, Laukkarinen J. Initial management of suspected biliary injury after laparoscopic cholecystectomy. World J Gastrointest Surg. 2023;15(4):592-9.
3. Nuzzo G, Giuliante F, Giovannini I, Ardito F, D’Acapito F, Vellone M, et al. Bile duct injury during laparoscopic cholecystectomy: results of an Italian national survey on 56 591 cholecystectomies. Arch Surg. 2005;140(10):986-92.
4. Schreuder AM, Nunez Vas BC, Booij KAC, van Dieren S, Besselink MG, Busch OR, et al. Optimal timing for surgical reconstruction of bile duct injury: meta-analysis. BJS Open. 2020;4(5):776-86.
5. Rustagi T, Aslanian HR. Endoscopic management of biliary leaks after laparoscopic cholecystectomy. J Clin Gastroenterol. 2014;48(8):674-8.
6. Akool MA, Al-Hakkak SMM, Al-Wadees AA. The role of endoscopic retrogradecholangiopancreatography in the management of biliary complication post-laparoscopic cholecystectomy. Open Access Maced J Med Sci. 2021;9(B):313–7.
7. Dumonceau JM, Tringali A, Papanikolaou IS, et al. Endoscopic biliary stenting: indications, choice of stents, and results: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline – Updated October 2017. Endoscopy. 2018;50(9):910-30.
8. Acar T, Acar N, Güngör F, Alper E, Gür Ö, Çamyar H, et al. İyatrojenik safra yolu yaralanmalarının endoskopik ve cerrahi yönetimi [Endoscopic and surgical management of iatrogenic biliary tract injuries.]. Ulus Travma Acil Cerrahi Derg. 2020;26(2):203-11.
9. Barbier L, Souche R, Slim K, Ah-Soune P. Long-term consequences of bile duct injury after cholecystectomy. J Visc Surg. 2014;151(4):269-79.
10. Sendino O, Fernández-Simon A, Law R, Abu Dayyeh B, Leise M, Chavez-Rivera K, et al. Endoscopic management of bile leaks after liver transplantation: An analysis of two high-volume transplant centers. United European Gastroenterol J. 2018;6(1):89-96.
11. Bismuth H, Majno PE. Biliary strictures: classification based on the principles of surgical treatment. World J Surg. 2001;25(10):1241-4.
12. Çelik M, Yilmaz H, Kılıç MC, Soykan M, Akbudak İH, Ozban M, et al. Postoperatif safra kaçağı olan olgularda endoskopik retrograd kolanjiyopankreatografi ile endoskopik sfinkterotomi ve biliyer stentlemenin etkinliği ve güvenliği [Efficacy and safety of endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy and biliary stenting in post-operative bile leaks]. Ulus Travma Acil Cerrahi Derg. 2023;29(8):904-8.
13. Fasoulas K, Zavos C, Chatzimavroudis G, Trakateli C, Vasiliadis T, Ioannidis A, et al. Eleven-year experience on the endoscopic treatment of post-cholecystectomy bile leaks. Ann Gastroenterol. 2011;24(3):200-5.
14. Martinez-Lopez S, Upasani V, Pandanaboyana S, Attia M, Toogood G, Lodge P, et al. Delayed referral to specialist centre increases morbidity in patients with bile duct injury (BDI) after laparoscopic cholecystectomy (LC). Int J Surg. 2017;44(1):82-6.
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Clinical characteristics and results of 45 patients who had adrenalectomy in our clinic
Aydemir Asdemir 1, İsmail Emre Ergin 2, Abuzer Öztürk 3, Hüseyin Saygın 1, Esat Korğalı 1
1 Department of Urology, Faculty of Medicine, Sivas Cumhuriyet University, Sivas, 2 Department of Urology, Kızılcahamam State Hospital, Ankara, 3 Department of Urology, Sivas Numune Hospital, Sivas, Türkiye
DOI: 10.4328/ACAM.22042 Received: 2023-11-10 Accepted: 2023-12-18 Published Online: 2024-01-09 Printed: 2024-02-01 Ann Clin Anal Med 2024;15(2):126-130
Corresponding Author: İsmail Emre Ergin, Clinic of Urology, Kızılcahamam State Hospital, Akyüzler Street, No: 1, 06890, Kızılcahamam, Ankara, Turkey. E-mail: emreergin55@hotmail.com P: +90 505 252 68 68 Corresponding Author ORCID ID: https://orcid.org/0000-0002-3115-0533
This study was approved by the Ethics Committee of Cumhuriyet University, Faculty of Medicine (Date: 2023-18-01, No: 2023-01/09)
Aim: Laparoscopic adrenalectomy is a widely preferred method today. In recent years, many studies have reported that laparoscopic adrenalectomy requires less analgesic, less bleeding, lower complication rates and less hospitalization compared to open surgery. This study aimed to compare the surrenalectomy data performed in our clinic.
Material and Methods: The data of surrenalectomies performed in our urology clinic between December 2010 and March 2022 were compared. Age, sex, side information, surgical method, and pathology results were recorded.
Results: Forty five patients, aged between 26 and 83, were retrospectively analyzed. Of 45 patients who underwent surrenalectomy, 1 (2.2%) was bilateral, 25 (55.5%) were right, and 19 (42.3%) were left (42.3%) adrenalectomy. Of these cases, 18 (39.6%) were male, 27 (59.4%) were female, 31 (on one side of the bilateral) (67.4%) laparoscopic operation and 15 (on the other side of the bilateral) (32.6%) of them were open operation. Postoperative histopathological results were 17 (36.95%) adrenal cortical adenomas, 8 (17.4%) benign pheochromocytomas, 2 (4.35%) malignant pheochromocytomas, 6 (13.04%) adrenal cysts, 5 (10.86%) carcinoma metastases, 2 (4.36%) myelolipomas, 2 (4.36%) benign adrenal cortical oncocytomas, 1 (2.17%) borderline adrenal cortical oncocytoma, 1 (2.17%) oncocytic adrenal cortical carcinoma, 1 (2.17%) hydatid cyst and 1 (2.17%) adrenal tissue containing areas of bleeding and necrosis.
Discussion: Histopathological results of surrenalectomy are not only significant in terms of malignancy but also important in terms of the treatment plan.
Keywords: Adrenalectomy, Adrenocortical Adenoma, Laparoscopy (Mesh Database)
Introduction
Adrenal masses have a high risk of malignancy. They may occur incidentally on radiological imaging, or it may occur with clinical and laboratory findings. Today, with the widespread use of imaging methods and diagnostic methods, the number of detection of adrenal masses has increased. Adrenal gland surgery is difficult and risky because there are critical vascular and anatomical structures around this gland [1,2]. The size and location of the mass play an important role in determining the surgical approach to adrenal masses [3]. It can be difficult to determine whether adrenocortical masses are benign or malignant. These masses may be hormone active or inactive. Indications for adrenalectomy are as follows: the adrenal mass is larger than 6 cm, it is an endocrine active tumor, the mass grows during follow-up, and there is suspicion of malignancy. Laparoscopic Adrenalectomy (LA) was first described and applied by Gagner and colleagues in 1992.
LA is a widely preferred method today. In recent years, many studies have reported that LA requires less analgesic, less bleeding, lower complication rates and less hospitalization compared to open surgery. The laparoscopic approach has become the gold standard [4]. In the study of Elfenbein et al. postoperative morbidity was significantly higher in the open surgery group. The average hospitalization time and operation time were statistically longer in the open adrenalectomy group [5]. Our aim in our study is to compare the results and effectiveness of open and laparoscopic techniques used in adrenalectomy and to emphasize the importance of the minimally invasive technique by scanning the literature.
Material and Methods
Patients who were operated on for adrenal mass in our clinic between December 2010 and March 2022 were included in the study by obtaining permission numbered 2023-01/09 from the Ethics Committee on 18.01.2023. The patients included in the study consisted of patients who underwent adrenalectomy due to adrenal mass. 45 patients were included in our study. The patients were divided into two groups according to the surgical procedure performed. One group underwent open adrenalectomy and the other group underwent laparoscopic adrenalectomy. The approach in open and laparoscopic surgery was based on the surgeon’s preference and experience. Open surgery was preferred in patients with a history of upper abdominal surgery or a mass larger than 10 cm. Demographic characteristics, size, hormone activity status, and pathological results of the mass were documented. Experienced surgeons who completed the surgical learning curve performed the operations.
This study was approved by the Ethics Committee of Cumhuriyet University, Faculty of Medicine (Date: 01.18.2023 , No: 2023-01/09).
SPSS (IBM version 21, NY, USA) program was used in statistical analysis. When comparing the averages of two groups, Independent samples t-test was used if the data were normally distributed, and Mann-Whitney U test was used if they were not normally distributed. Pearson chi-square test and Fisher’s exact probability test were used to compare qualitative data. Statistical significance was accepted as p< 0.05.
Results
Our study included 45 patients. There were 13 patients in Group (1) who had open adrenalectomy (OA) and 32 patients in Group (2) who had laparoscopic adrenalectomy (LA). Laparoscopic adrenalectomy operations were performed completely in the lateral position and completely performed transabdominally. All open adrenalectomy surgeries were performed transabdominally 10 of 13 cases are subcostal,2 median,1 paramedian incision was made. The mean age was 45,9 ± 8,9 in Group 1 and 51.0 ± 13,2 in Group 2 (p= 0.19). 78.1 % of patients who underwent LA and 46.2% of patients who underwent OA were hormone-active, and this difference was statistically non-significant (p=0.072). Tumor diameter was larger in patients treated with OA (CS: 142.76± 108.7 cm3; LA: 66.95 ± 48.4 cm3) (p=0.192) (Table 1). The most common indications for surgery in the OA and LA groups were adrenokortikal adenom/incidentaloma and pheochromocytoma, respectively. Right adrenal localization (54.3%) was more common in both group (p=0.79). Postoperative histopathological results were 17 (36.95%) adrenal cortical adenomas, 8 (17.4%) benign pheochromocytomas, 2 (4.35%) malignant pheochromocytomas, 6 (13.04%) adrenal cysts, 5 (10.86%) carcinoma metastases, 2 (4.36%) myelolipomas, 2 (4.36%) benign adrenal cortical oncocytomas, 1 (2.17%) borderline adrenal cortical oncocytoma, 1 (2.17%) oncocytic adrenal cortical carcinoma, 1 (2.17%) hydatid cyst, and 1 (2.17%) adrenal tissue containing areas of bleeding and necrosis.(Table 2)
The operation time was 122.6±21 minutes in the OA group and 105.7±39 minutes in LA (p=0.18). Decrease in hemoglobin was 1.68±1.21(g/dl) in OA and 1.14±0.98 (g/dl) in LA (p=0.11). The hospitalization period was 5.5±1.6 days in OA and 3.1±1.1 days in LA. The difference was significant (p=0.01) (Table3). Among the operated patients, only 1 patient was re-hospitalized. This patient was in the open adrenalectomy group.
Discussion
The anatomical location of the adrenal glands and adrenal lesions are usually small adrenal glands due to minimally invasive surgery increased his interest in adrenal surgery. Adrenal masses can be presented with very different clinical, laboratory and radiological data. Furthermore, adrenal masses are lesions that carry an approxiamtely 4-12% malignancy risk [6]. Open adrenalectomy requires a large incision that causes significant postoperative pain and morbidity. By laparoscopic adrenalectomy, the surgery became less invasive. Since laparoscopy started to be used in surgery, the most important disadvantage of cost is discussed. However in all endoscopic procedures, laparoscopic adrenalectomy is performed with re-usable materials thus cost is not a serious problem. Also laparoscopic surgery results in a short-term hospitalization and thus providing an early return to work. Other economic benefits on laparoscopic surgery material used with increasing experience reduction in the amount of cost reductionis another factor. A retrospective cases in our study not evaluated by billing. Although clinically laparoscopic additional cost of surgery we believe it does not.
In the years when laparoscopic adrenalectomy was first described, it was recommended not to be performed in pheochromocytoma cases because of high intra-abdominal pressure. Furthermore, it was thought that it may have an attack due to manipulation of the mass during surgery. However, laparoscopic intervention has been used in many pheochromocytoma cases to date and has been used intraoperatively. No increase in the risk of attacks was found. Of course, in this regard, the patient with pheochromocytoma who is planned to be operated on is suitable for the preoperative period. It is very important to prepare for the operation. Thanks to Preoperative alpha and beta-adrenergic blockade and intraoperative blood pressure control, hypertensive attack is prevented. Significant advantages were obtained with LA compared to OA in terms of bleeding amount, hospitalization time, postoperative pain, cosmetic and functional recovery [7]. Chapius et al. first reported a patient with Cushing’s disease in 1997 [8]. After they reported that they had performed bilateral laparoscopic adrenalectomy, bilateral pheochromocytoma and congenital adrenal hyperplasiaadrenalectomy experiences have been reported consecutively. According to these studies, it has been reported that postoperative recovery is faster in these patient groups compared to open surgery. However, bilateral adrenal glands that have reached large sizes, especially in ACTH-independent macronodular adrenal hyperplasia. The application of laparoscopic adrenalectomy is still controversial. However, there are many reports that bilateral laparoscopic adrenalectomy is safe and effective in appropriate cases [9]. We performed bilateral adrenalectomy ( one side LA, other side OA) safely in 1 patient. Our indication was carcinoma (RCC) metastasis. Our opinion on this subject istransabdominal with appropriate patient selectionor retroperitoneal methods, this technique can be safely applied by experienced surgical teams.
The malignancy rate of adrenal masses increases as the mass size increases. There are old studies that do not recommend laparoscopic surgery. The general concerns in these articles were peripheral tissue invasion, tumor perforation risk, and local or trocar site recurrences due to transplants. It has been reported in recent research that the surgical approach does not impact the oncological results in adrenocortical carcinoma. In the field of literature, the rates of marginless (R0) resections, disease-free survival, and average survival times, as well as overall and local recurrence rates, showed similarities between locally or locally advanced primary adrenocortical carcinoma and LA and OA [10]. As the diameter increases in adrenal lesions the incidence of malignancy will increase [11]. In patients undergoing open adrenalectomy (5 cm) compared to those undergoing laparoscopic adrenalectomy, high tumor size was found [12]. Nevertheless, with the increasing expertise in laparoscopic procedures, its application is also being considered for larger tumors. According to our research findings, the average tumor diameter was 142.76 ± 108.7 cm3 for patients undergoing open adrenalectomy and 66.95 ± 48.4 cm3 for those undergoing laparoscopic adrenalectomy (p=0.192). Prior to surgery, open adrenalectomy is advisable if lymphadenopathy is present, if the tumor is larger than 10 cm, if there is invasion of adjacent organs or periadrenal tissues, or if there is evidence of thrombus in the renal vein or inferior vena cava. Surgical resection for adrenal cystic lesions should be considered when bleeding and calcification are observed during radiological assessment, and when hormones are active or when there is at least a 1 cm increase in size per year [13]. In our study, surgery was performed on a total of 7 adrenal cystic lesions. Four patients were operated on with a open approach and 3 patients underwent the laparoscopic approach. When hemodynamic instability and catecholamine levels were compared, there was no difference in pheochromocytoma between laparoscopic and open adrenalectomy [14]. Hemostasis may be difficult laparoscopically if intraoperative bleeding is accompanied by a hypertensive crisis during pheochromocytoma surgery. Pheochromocytoma shows strong adhesions to surrounding tissues with a desmoplastic reaction. Laparoscopic surgery should be the preferred methodin tumors also with a high risk of malignancy because it is safe and applicable. In our study, in LA group there were 8 pheochromocytoma and 1 in OA group. The recommendations of the guidelines were taken into consideration when choosing open or laparoscopic surgical technique. Studies report that between 0% and 23% of cases are switched from Laparoscopic technique to open technique [15]. The most common cause is bleeding from small venous structures. Other causes include local or vascular invasion due to malignancy, vena cava or renal vein injuries, adjacent organ injuries, abdominal adhesions, obesity, diaphragmatic injury, İlarge size of the massand large liver [16]. Our rate of conversion to open adrenalectomy was 7%. The most common cause was bleeding.
In general, the duration of LA has been reported as slightly longer than OA [17]. However, endoscopic technic can be applied in a shorter time with the increase of experience. There has been an increasing number of publications indicating that they have completed LA in a much shorter time than open adrenalectomy [16]. The reasons for this include: 1) open adrenalectomy, especially complex large or invasive, requires surgery being applied to malignant tumors, 2) increasing laparoscopic surgery experience is demonstrated [5].The mean operation time in laparoscopic adrenalectomy performed with the transperitoneal approach was 80 to 360 minutes in the literatüre [18]. Our mean operation time was 105.7±39 minutes in the LA group and 122.6±21 minutes in the OA group. We think that the reason for this difference is that the surgical technique is preferred as OA in large masses.
Another advantage of laparoscopic adrenalectomy compared to open surgery is that the amount of intraoperative bleeding is less. Although most of the studies conducted so far have stated that the amount of bleeding is higher in open surgery. One reason for this is that open is more preferred in large masses [17]. Many studies have reported that the amount of bleeding is less in the laparoscopic approach [19]. In our cases, similar to previous studies, the amount of bleeding was less in the laparoscopic approach (p = 0.11). Other advantages of LA include shortening hospitalization and early initiation of oral food intake. Lee et al. found that hospitalization time was shorter in LA (mean, 4.1 days) than in OA (mean, 9.4 days). Bulus et al. reported the average time to resumption of oral food intake as 1.05 days in the laparoscopic approach and 2.42 days in the open approach. Consistent with existing literature, our findings indicate that patients in the LA group had shorter hospital stays and resumed oral food intake more quickly than those in the OA group. While the rate of surgical complications in laparoscopic adrenalectomies typically ranges from 5% to 10%, open adrenalectomies tend to exhibit a higher incidence of complications. Wound complications are anticipated to be more prevalent in OA compared to minimally invasive approaches [16,17]. Complications did not exhibit a notable variance across the groups. The laparoscopic group experienced atelectasis, pleural effusion, and collection at the operative site as primary complications. Notably, no laparoscopy-associated complications were recorded in any of the patients within the LA group. Among fatalities following laparoscopic adrenalectomy, the leading causes were massive bleeding, pulmonary complications, sepsis, and cardiopulmonary failure [20]. Our series experienced perioperative mortality in two patients, attributed to significant bleeding and cardiopulmonary complications. Post-hospital discharge, complications may prompt readmission. The recurrence rate varies based on the scale of surgical intervention and the specific surgical field. Following abdominal surgery, this rate ranges from 5% to 15% [21]. Beck et al. identified various risk factors for readmission post-adrenalectomy, including diabetes, surgery for primary adrenal cancer, a high ASA score, the nature of the operation, advanced age, extended operation duration, and postoperative complications [22]. In our study, one patient from the patient group who underwent open adrenalectomy was readmitted.
Limitation
The limitations of our study were that it was retrospective, the number of patients was limited, and it was conducted in a single center.
Conclusions
As a result, in our study, we found the superior features of LA compared to OA as short surgery time, short hospitalization time, less bleeding and early oral intake. When LA is performed by experienced people, complications can be prevented and it can be advantageous compared to open surgery. We believe that this increasingly applied surgery will become more preferred as experience increases.
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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Aydemir Asdemir, İsmail Emre Ergin, Abuzer Öztürk, Hüseyin Saygın, Esat Korğalı. Clinical characteristics and results of 45 patients who had adrenalectomy in our clinic. Ann Clin Anal Med 2024;15(2):126-130
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Comparison of the analgesic effects of transdermal fentanyl and intravenous patient controlled fentanyl after laparotomy
Vahap Saricicek 1, Melda Acar 2, Rauf Gul 3
1 Department of Anesthesiology and Reanimation, Private Medical Point Hospital, Gaziantep, 2 Department of Anesthesiology and Reanimation, Private Malatya Park Hospital, Malatya, 3 Department of Anesthesiology and Reanimation, Faculty of Medicine, University, Gaziantep, Turkey
DOI: 10.4328/ACAM.22054 Received: 2023-11-20 Accepted: 2023-12-22 Published Online: 2024-01-03 Printed: 2024-02-01 Ann Clin Anal Med 2024;15(2):131-135
Corresponding Author: Vahap Saricicek, Department of Anesthesiology and Reanimation, Private Medical Point Hospital, Gaziantep, Turkey. E-mail: vahapsaricicek@hotmail.com P: +90 533 549 16 64 Corresponding Author ORCID ID: https://orcid.org/0000-0001-9403-1024
This study was approved by the Ethics Committee of Gaziantep University, Faculty of Medicine (Date: 2012-12-18, No: 460)
Aim: In our study, we aimed to show whether TDF patch application is effective and acceptable in the management of postoperative pain management.
Material and Methods: In this prospective randomized study, 60 patients, aged between 18-65 years, who had undergone laparotomy, were included in the American Society of Anesthesiologists (ASA) I-II-III, after Gaziantep University local ethics committee approval. No patient was given premedication. The patients were randomly divided into two groups. TDF patch (50µg/hour) was applied to group TDF (n=30) 12 hours before the operation and removed 24 hours after the operation. Group patient-controlled intravenous fentanyl analgesia (PCA) (n=30) was administered postoperatively in the PACU with patient-controlled analgesia with Intravenous fentanyl. When group TDF had pain (VAS 4≥), 100 mg of tramadol was administered as an additional analgesic. Group TDF and Group PCA were clinically observed in the perioperative period.
Results: Resting VAS was statistically significantly better in Group PCA than Group TDF at the 2nd, 4th, 6th, 12th, and 24th hours except the postoperative 1st hour (p<0.05). Additional analgesic requirement was statistically higher in group TDF than group PCA at 1st, 2nd, 6th, 12th, and 24th hours except postoperative 4th hour (p<0.05).
Discussion: It has been concluded that IV fentanyl and PCA are more effective than TDF in the evaluation of patients in the postoperative period in terms of VAS scores, but TDF can be used as an alternative to patient-controlled analgesia for postoperative analgesia with tramadol support if necessary.
Keywords: Patient-Controlled Analgesia, Pain, Transdermal Fentanyl Patch
Introduction
One of the important causes of post-surgical anxiety is postoperative pain. Postoperative pain, which starts with surgical trauma and gradually decreases with wound healing, should be relieved quickly and effectively due to undesirable effects such as sympathetic, endocrinological and metabolic changes caused in the postoperative process and the anxiety it causes. A well-provided analgesia will increase the postoperative comfort of the patient, as well as reduce the cost and the development of complications that will lead to a longer stay in the hospital [1].
Various pain management guidelines have been developed for postoperative analgesia in the last 20 years. Patient-controlled analgesia (PCA) method used in postoperative analgesia is a contemporary method that allows the patient to provide self-analgesia. However, the cost of the device and the sets, the need for patient cooperation, the need for the patient and staff to be trained in this regard, limiting mobility and incorrect dose applications may be in question [2, 3].
Transdermal fentanyl administration is an easy and non-invasive procedure. It was studied for postoperative analgesia in the 90s and was not preferred due to its disadvantages such as inability to titrate patient-specific and insufficient in early postoperative analgesia [4, 5]. It is understood that the pharmacokinetic properties of transdermal fentanyl were not taken into account in these studies. In the study conducted by Minville et al. [6], transdermal fentanyl was applied a few hours before the operation, whereas other studies revealed that its effectiveness reached a plateau level in 14 hours and lasted up to 72 hours [7, 8].
In our study, we aimed to compare the analgesic effects of transdermal fentanyl and IV patient-controlled fentanyl after laparotomy.
Material and Methods
None of the patients included in the study wanted to quit the study or were included in then excluded from the study. Sixty patients, aged between 18 and 65, who were evaluated as I-II-III according to the American Society of Anesthesiologists (ASA) classification in the pre-anesthesia evaluation, were included in the study. Patients with kidney and liver failure, patients with cardiac problems, patients with a history of allergy to opioids and the drugs to be administered, pregnant women, patients with opioid dependence, patients with chronic lung disease, patients with dermatological disorders, those with a weight below 50 kg, over 100 kg patients and patients with psychiatric disorders were excluded from the study. The patients were randomly divided into 2 groups: Group TDF (n=30): Patients treated with transdermal fentanyl patch, and Group PCA (n=30): Patients undergoing intravenous (IV) patient-controlled fentanyl analgesia (PCA). After that, the patients were evaluated preoperatively one day before the operation, and written and verbal consent forms were obtained. In Group TDF, systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), heart rate (HR), visual analog scale (VAS), Ramsey sedation score (RSS), peripheral oxygen saturation (SpO2) and respiratory rate values were recorded. To patients in the transdermal fentanyl group (Group TDF), 50 µg/h to the anterior chest wall or arm 12 hours before the operation. A tape giving fentanyl (Durogesic 50 µg/h 5TTS Flaster, Johnson & Johnson, Istanbul, Turkey) was applied. The symptoms and signs of nausea, vomiting, bradycardia, dyspnea and itching were recorded in the patients who underwent TDF until the operation. No treatment was given to Group PCA until the operation. Neither group was given any medication or premedication in the preoperative preparation room.
Hemodynamic measurements, sedation scores and VAS values of both groups were recorded in the operating room before induction. Sedation scores of the patients were evaluated with RSS. 2mg/kg propofol (Propofol 1% Fresenius Kabi, İstanbul, Turkey), 1μ/kg fentanyl (Adilat, 0.5mg, 10ml, Vem İlaç, İstanbul, Turkey) for anesthesia induction after preoxygenation (from 10 L/min for 1 min) in the operating room ) doses, 0.6 mg/kg intravenous rocuronium bromide (myocron 10 mg, 5ml vial, Vem İlaç Istanbul, Turkey) was administered. Hemodynamic measurements were recorded before and after extubation. In the recovery unit, the duration of the modified Aldrete recovery score (ARS) ≥9 and the sedation scale were evaluated and recorded. After the patients were compiled, they were sent to the relevant service. Side effects such as hemodynamic parameters, RSS, VAS level, nausea, vomiting, pruritus were recorded at postoperative 1, 2, 4, 6, 12 and 24 hours.
In the PCA group, PCA was started with a device (Cadd Legacy 6300 ambulatory infusion pump) with a loading dose of 40 μg, a basal infusion of 20 μg / h, a bolus dose of 40 μg, and a lock-in time of 10 minutes with fentanyl. Amounts of fentanyl consumed were recorded.
Statistical analysis
SPSS for Windows v13 package program was used for statistical analysis, and p<0.05 was considered statistically significant. Kolmogorov Smirnov test was used to check the conformity of continuous variables with normal distribution. Student’s t-test was used for the comparison of normally distributed variables in 2 independent groups, and Mann Whitney U Test was used for non-normally distributed variables. The single-sample Z test was used in order not to compare the population value versus the sample. Analysis of variance with repeated measures was used in the analysis of data with more than two repeated measures. The relationship between categorical variables was tested with ᵡ² analysis. Frequency, percentage and mean±SD values are given as descriptive statistics.
Ethical Approval
This study was approved by the Ethics Committee of Gaziantep University, Faculty of Medicine (Date: 18/12/2012, No: 460). Informed written consent was obtained from the patients for this prospective randomized study. It was carried in Gaziantep University Şahinbey Training Research and Application Hospital Operating Room.
Results
60 randomized clinical trials patients were included in and completed the study. Demographic data are shown in Table 1. When these data were analyzed statistically, no significant difference was found between the groups (p>0.05). There was no significant difference between the groups in pre-induction and intraoperative measurements in terms of hemodynamic parameters such as SAP, DAP, MAP, CAD, and SPO2 (p> 0.05).
When MAP and CAD, which are among the postoperative hemodynamic parameters of the patients, were examined, no significant difference was found between the groups (p>0.05).
When the postoperative peripheral oxygen saturations of the patients were evaluated, no significant difference was observed between the groups (p>0.05).
When the postoperative respiratory rates of the patients were evaluated, no significant difference was observed between the groups (p>0.05).
In terms of postoperative VAS values of the patients, there was statistically significant differences between groups at 2nd hour (p=0.001), 4th hour (p=0.001), 6th hour (p=0.001), 12th hour (p=0.001), and 24th hour (p=0.001). It was lower in Group PCA (Table II). It was lower in Group PCA (Table 2).
The time for the Aldret recovery score (ARS) to be 9 was statistically higher in Group TDF (p=0.001) (Table 3). There was no statistically significant difference between the two groups in terms of postoperative RSS, nausea, vomiting and pruritus data (p>0.05). There was a statistically significant difference in the postoperative additional analgesic consumption at the 1st, 2nd, 6th, 12th, and 24th hours, excluding the postoperative 4th hour (p=0.001).
Postoperative total fentanyl consumption of the patients was statistically higher in group PCA at 1st-2nd-4th-6th hours compared to group TDF (p=0.001). At the 12th and 24th hours postoperatively, group TDF was higher than group PCA (p=0.001).
Discussion
In our study in which we compared the postoperative analgesic efficacy of TDF and IV PCA in elective laparotomy, there was no statistically significant difference between the groups in terms of demographic findings, preoperative and postoperative hemodynamic parameters, and RSS. Postoperative VAS values were significantly lower in Group PCA compared to Group TDF at all times except the 1st hour. Postoperative analgesia consumption was significantly lower in Group PCA than in Group TDF at all times except the 4th hour. Total fentanyl consumption was significantly higher in Group PCA than in Group TDF in the first 6 hours.
The transdermal fentanyl method is suggested to be an alternative option for patients who cannot use patient-controlled analgesia, who are not oriented, who are unable to use their hands, and who have difficulty in providing a venous route [9]. However, in studies conducted, it was observed that respiratory depression was observed in patients who were given additional opioids in cases where the TDF patch was insufficient in terms of analgesia [10]. In this study, we preferred to use tramadol as an analgesic drug as a support in cases where analgesia was insufficient due to the risk of respiratory depression.
TDF and placebo groups 8 hours before the operation and removed 24 hours after the operation [11]. Additional analgesia needs of both groups were met with IV PCA fentanyl. Compared to the placebo group, the TDF group had less pain and less need for additional analgesia [11]. In our study, we aimed to compare the effects of transdermal and IV application of fentanyl on postoperative analgesia and to show the feasibility of postoperative use of TDF as an alternative method to PCA IV fentanyl. Minville et al applied PCA analgesia to all groups after the operation and thus compared TDF fentanyl+PCA with placebo patch+PCA. This study leads to an investigation of the effect of TDF on opioid consumption in addition to PCA, rather than investigating the efficacy of TDF alone in the treatment of postoperative pain. That is, these studies investigated the safety and effectiveness of TDF compared to placebo [6]. In our study, we applied TDF to the patient approximately 12 hours before the induction of anesthesia, based on its pharmacokinetic properties. Thus, we designed to evaluate the effect of fentanyl in serum on VAS and sedation scores more healthily and reliably by providing the time required for it to reach its minimum effective concentration.
Since Varvel et al. showed that serum fentanyl level starts to increase in 4-8 hours in transdermal application, it is seen that application of TDF 1-2 hours before or just before surgery will not have a significant effect on hemodynamic and clinical parameters in operations lasting 2-3 hours [12]. In the studies, it is seen that 25 µg, 50 µg and 75 µg hourly doses are used for postoperative analgesia of TDF [13, 14]. In these studies, TDF above 50 µg/h was not preferred because it may cause respiratory depression. Generally, IV morphine was used in addition to PCA TDF in these studies. In our study, we did not combine TDF and PCA, but used it for postoperative analgesic purposes separately for each group, aiming not to overestimate respiratory depression and other side effects, and to see the effects of using a single drug with two different methods on postoperative analgesia.
Ketene et al. used tramadol as an additional analgesic in their study with 25 µg/hr, 50 µg/hr and placebo patch, looked at total analgesic consumption and found that the analgesic requirement was significantly lower in the 50 µg/hr TDF group [15]. In our study, the postoperative analgesic requirement was 1st-2nd-6th-12th-24th hours in the TDF group. There was no significant difference at the postoperative 4th hour. There was no need for additional postoperative analgesics in Group PCA. In Group TDF, it was observed that additional analgesics were needed at all times except the postoperative 4th hour. In addition, among the studies, there is no standard in terms of removing TDF in the postoperative period. It is usually removed at 24 or 72 hours [4, 15, 16].
A study examining the variation of postoperative VAS values over time proved that pain intensity decreased over time [17]. Another study showed that most patients who underwent surgery experienced severe pain in the first 24 hours [18]. In our study, the fact that the hourly fentanyl consumption in the PCA group in the first 6 hours, which is the acute period, was much higher than in the TDF group and the patients in the TDF group required additional analgesics support these findings. As a result of the studies, both resting and movement VAS values were found to be lower in the TDF group [6, 15, 19]. Contrary to these studies, Minville et al [6], who compared TDF with placebo, showed that the VAS values were lower in the TDF group and therefore more effective.
The opioids we used in the study generally have a sedative effect. Fentanyl, which is stronger than morphine, has a mild sedative effect at low doses (1-2µg/kg), while it causes deep sedation at high doses (50-150 µg/kg). Although different sedation scoring systems were used, no difference was observed between the groups [15, 19, 20].. In our study, we concluded that the sedation values measured in the postoperative period between the TDF group and the PCA group were not statistically different. In our study, when the Aldret recovery score and recovery times were compared, we found that Group PCA was statistically significantly lower than Group TDF. This may be due to the delay in the onset of PCA and the increased plasma fentanyl concentration in Group TDF. There are studies that did not find a statistically significant difference in terms of side effects in the postoperative period [11, 20-22]. Siafaka et al [23] argued that local erythema, Ketene et al [15], nausea, and Miguel et al [21] argued that respiratory depression was more common in the TDF group. According to our results, typical opioid-related side effects were observed in both groups. However, there was no statistically and clinically significant difference between the groups in terms of side effects.
Limitation
The limitations of the study are that it was performed in a single center, and the number of patients is small. However, the study has many strengths such as its prospective nature, low cost, ease of use, and the use of many parameters and scoring scales.
Conclusion
In conclusion, it was concluded that there was no significant difference between TDF and PCA in terms of intraoperative and postoperative hemodynamic monitoring, but patient-controlled analgesia with IV fentanyl was more effective than TDF in the evaluation of VAS in the postoperative period. However, we believe that effective postoperative analgesia will be provided with an additional analgesic such as tramadol when TDF is required as an alternative to patient-controlled analgesia due to its ease of use in postoperative analgesia.
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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Vahap Saricicek, Melda Acar, Rauf Gul. Comparison of the analgesic effects of transdermal fentanyl and intravenous patient controlled fentanyl after laparotomy. Ann Clin Anal Med 2024;15(2):131-135
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In vitro DNA damage prevention, antioxidant and antidiabetic activities of achillea biebersteinii/millefolium extracts and synthesized ZnO nanoparticles
Emrah Caylak 1, Gokhan Nur 2
1 Department of Biochemistry, Faculty of Medicine, Girne American University, Kyrenia, Cyprus, 2 Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Iskenderun Technical University, Hatay, Turkey
DOI: 10.4328/ACAM.22057 Received: 2023-11-22 Accepted: 2024-01-30 Published Online: 2024-01-31 Printed: 2024-02-01 Ann Clin Anal Med 2024;15(2):136-140
Corresponding Author: Emrah Caylak, Department of Biochemistry, Faculty of Medicine, Girne American University, Kyrenia, Cyprus. E-mail: emrah333@hotmail.com P: +90 544 613 49 99 Corresponding Author ORCID ID: https://orcid.org/0000-0003-0408-9690
This study was approved by the Ethics Committee of Girne American University has stated that there is no need to obtain ethics approval for this reason (Date: 2023-06-06, No: 2023/032)
Aim: In this study, DNA damage preventive effects, antioxidant and antidiabetic activities of extracts of Achillea species growing endemic in the Lapta region of Kyrenia district of Cyprus, and zinc oxide-nanoparticles/Achillea (ZnO-NPs/Ach) were investigated.
Material and Methods: We performed green synthesis of ZnO-Nps using the extract obtained from Achillea species (ZnO-NPs/Ach). We performed green synthesis of ZnO-Nps using the extract obtained from Achillea species (ZnO-NPs/Ach). Additionally, we determined the anti-DNA damage, antioxidant, and antidiabetic activities of these nanoparticles.
Results: The highest concentration of 500 μg/mL of ZnO-NPs/Ach had an excellent protective effect. It was determined that the activity of ZnO-NPs/Ach was relatively vigorous in preventing lipid peroxidation. The lipid peroxidation inhibitory activities of ZnO-NPs/A. biebersteinii and ZnO-NPs/A. millefolium were calculated as 90.87% and 89.11%, respectively. Additionally, both demonstrated high antidiabetic effects compared to the positive control acarbose.
Discussion: As zinc oxide nanoparticles obtained through green synthesis have been found to have preventive effects on DNA damage, as well as antioxidant and antidiabetic properties, this study is expected to make a valuable contribution to the medical and technological literature.
Keywords: DNA Damage Prevention, Antioxidant, Antidiabetic, Achillea Biebersteinii, Achillea Millefolium, Green Synthesis, ZnO Nanoparticles
Introduction
Studies in the health field worldwide have shown that nanoscience has made significant contributions to medicine, particularly in the diagnosis, treatment, and prevention of diseases, as well as drug development. Recently, nanoparticles have been utilized in the diagnosis and treatment of various diseases, including as antimicrobial, antioxidant, antifungal, anticancer, and antidiabetic agents. Green synthesis is the preferred method for obtaining nanoparticles due to its cost-effectiveness, environmental friendliness, ease of preparation, and controllability, as opposed to the use of decaying reaction conditions and hazardous intermediate components.
Zinc oxide nanoparticles (ZnO-Nps) are particularly advantageous compared to other metal oxide nanoparticles due to their electrical and optical properties, biocompatibility, low cost, and low toxicity. Additionally, they have the potential to exhibit antibacterial and cytotoxic effects against cancer cells. ZnO-NPs are frequently used by researchers due to their wide range of applications in medicine and health science.
The genus Achillea is cultivated in temperate zone countries, including Cyprus, Türkiye, Iran, and Pakistan. Extracts from Achillea species, such as A. biebersteinii and A. millefolium, have been traditionally used in folk medicine in those countries for their diuretic, appetizing, gas-digesting, wound healing, astringent (especially in haemorrhoids), urinary antiseptic, and antitussive properties. It is also known to be successfully applied in treating inflammatory conditions and pain, such as menstruation and postpartum discomfort [1,2].
This study aims to perform green synthesis of ZnO-Nps using the extract obtained from Achillea species (ZnO-NPs/Ach). Additionally, the study will investigate the anti-DNA damage, antioxidant, and antidiabetic activities of these nanoparticles. The results of this analysis will contribute to the field of green synthesis studies in nanotechnology.
Material and Methods
Preparation of Achillea species extracts
A. biebersteinii and A. millefolium were collected from Lapta Hill in Kyrenia, Cyprus. The plant samples were identified, and a voucher specimen was recorded and stored in the Herbarium of Girne American University for reference. The Achillea species studied were dried and powdered using an electric plant grinder. All chemicals used in the study, zinc acetate (Zn(CH3COO)2.2H2O), were purchased from Merck Company (Germany). The powdered A. biebersteinii/millefolium (200 g) was extracted using 2 L of 70% ethanol as a solvent in a 1:10 ratio for 24 hours with regular shaking. The resulting mixture was filtered using a Whatman 1 filter paper. The ethanolic extracts of A. biebersteinii/millefolium plant were stored at +4°C in a refrigerator for further research [3].
Synthesis of ZnO-NPs/Ach
Firstly, 100 mL of A. biebersteinii/millefolium extract and 500 mL of 1 MM zinc acetate solution were left at room temperature for 1 hour. The colour of the mixture changed from yellow to brown, indicating the formation of ZnO-NPs/Ach. The solution was then repeatedly centrifuged (10,000 rpm x 10 minutes) and distilled water was added. The solid particles obtained from centrifugation were filtered and dried in the oven at 50°C for 24 hours. The absorbance of ZnO-NPs/Ach was measured using a UV spectrophotometer (Shimadzu UV 1800, Japan) in the wavelength range of 200-790 nm [4].The structural characterisation and particle size examination of ZnO-NPs/Ach were done by Transmission Electron Microscopy (TEM) and Scanning Electron Microscopic (SEM) (Hitachi, Japan). In addition, the spectra properties of those were carried out by Fourier Transform Infrared Spectroscopy (FTIR) (Bruker, Germany) in the spectra range of 4000–400 cm-1. X-ray diffraction (XRD) of the ZnO-NPs/Ach was analysed using an XPert PRO diffractometer (Holland) in the 2Ɵ range of 20–80o
The preventive effect of ZnO-NPs/Ach on DNA damage
To investigate the protective effect of ZnO-Nps/Ach against DNA damage, electrophoresis was performed using PBR322 plasmid DNA (4361 base pairs) [5]. A 1% agarose gel was loaded into five wells. The first well contained plasmids and dye, while the seven wells. contained plasmids and loading dye exposed to hydrogen peroxide and UV rays for DNA damage. Plasmids, loading dye, hydrogen peroxide, and ZnO-NPs/Ach solutions were loaded from the third to seventh well in different concentrations (50-100-150-250 and 500 µg/mL). Electrophoresis was then performed to obtain images (Table 1).
Antioxidant activity of ZnO-NPs/Ach
The lipid peroxidation inhibitory activity of ZnO-NPs/Ach was determined using the thiobarbituric acid (TBA) test [6]. To prepare the ZnO-NPs/Ach solution the concentration series (50, 100, 150, 250, and 500 mg/L [w/v]) were dissolved in 97% ethanol. Next, 200 μL of ZnO-NPs/Ach, 200 μL of FeCl3, 200 μL of EDTA, 200 μL of H2O2, and 200 μL of ascorbic acid were added and mixed with a vortex. The tubes were then incubated at 37°C for 1.5 h. After incubation, 1.2 mL of 28% TBA was added and the mixture was centrifuged at 3000 rpm for 15 minutes. The remaining pellet was then filtered and 1.2 mL of TBA was added again. The tubes containing the samples were boiled for 10 minutes and then cooled to room temperature. The absorbances of the samples were measured at 532 nm using a spectrophotometer. The lipid peroxidation inhibition was calculated using the formula: inhibition = [(Acont – Asamp) / Acont] × 100 (Eq-1).
Antidiabetic effects of ZnO-NPs/Ach
To investigate the antidiabetic effects of Ach spp, we assessed the enzyme inhibition capacities of the carbohydrate digestive enzymes α-amylase and α-glucosidase [7]. For the α-amylase test, the enzyme solution was prepared by mixing 27.5 mg of alpha-amylase (Sigma Aldrich Chemical Co, USA) into 100 mL of distilled water. 1 mL of the α-amylase enzyme (1 U/mL), 0.1 g/mL ZnO-NPs/Ach and 10 mL of 6.85 mM NaCl (pH 6.9 adjusted using a phosphate buffer) were mixed and centrifuged at 8,500 rpm for 15 minutes. The liquid was separated, and a 1% starch solution of 500 μL in 0.02 M sodium phosphate buffer (pH 6.9) was added to tubes containing five different concentrations (100-500 μg/mL). The reaction was stopped using a colour reagent, 3.5-dinitrosalicylic acid-DNS, and the samples were incubated in a water bath at 100°C for 5 minutes. The tubes were then incubated at 25°C for 10 minutes. After cooling to 20°C, 10 mL of distilled water was added to each sample. Absorbance measurements were taken at a wavelength of 540 nm. The α-glucosidase inhibition capacity was also determined. Then, we incubated 1 mL of starch substrate (2% maltose or sucrose), 1 U/mL of α-glucosidase enzyme (Sigma Aldrich Chemical Co, USA), and ZnO-NPs/Ach samples (50, 100, 150, 250, and 500 mg/L [w/v]) at 37°C for 5 minutes. The mixture was then placed in a boiling water bath for 2 minutes and cooled to 20C. Absorbance values were measured at 420 20°C nm. We calculated the α-amylase and α-glucosidase inhibitor activity using Eq-1.
Ethical Approval
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article. The ethics committee of Girne American University has stated that there is no need to obtain ethics approval for this reason (Date: 2023-06-06, No: 2023/032).
Results
Synthesis of ZnO-NPs/Ach
The study synthesised ZnO-NPs/Ach from A. biebersteinii/millefolium extracts using green chemistry method. UV spectroscopy, FTIR, XRD, and SEM data were analysed. ZnO-NPs/Ach formation was analysed using a UV spectrophotometer in the 380-410 nm absorbance range, as previous studies have shown [8]. In this study, peak values were determined at 405 nm, supporting the synthesis of ZnO-NPs/Ach. The FTIR results indicate that ZnO-NPs/Ach exhibit tensile vibrations in the bands between 440 and 540 cm−1. It is common for metal nanoparticles, including ZnO oxides, to exhibit vibration frequencies below 1000 cm−1. Additionally, peaks in the 450 to 600 cm−1 range were observed for ZnO-Nps/Ach. Previous studies have reported that C-H molecules (e.g. CH3, CH2) in chemical compounds produce peaks in the range of 3500-2800 cm−1. Additionally, stress vibrations of the aromatic groups C=O and C=C in A. biebersteinii/millefolium plants are in the range of 1000-1700 cm−1 [9] (Figure 1).
XRD analysis was conducted to determine the crystal structure of the ZnO-Nps/Ach synthesized in our study. The peaks in Figure 2 were identified as 34.38, 37.22, 44.79, 49.82, 55.91, 63.04, 65.57, 68.32, and 77.34 for A. biebersteinii and 35.02, 42.21, 50.08, 57.33, 62.56, 69.26, and 76.92 for A. millefolium. The XRD peaks identified in our study were consistent with the results found in previous studies [10], verifying the hexagonal structure for the nanoparticles synthesized in cross-lattice planes (002), (100), (101), (102), (103), (110), (112), (200), and (202).
The synthesis of ZnO-Nps/Ach is confirmed by the zinc peak observed in the EDX spectrum. The carbon, potassium, and magnesium peaks, however, are attributed to bioactive components attached to the surface of ZnO-Nps. The SEM analysis determined that the synthesized ZnO-Nps/Ach are evenly distributed and not clustered in specific regions [10] (Figure 2).
Anti-DNA damage activities of ZnO-NPs/Ach
The study investigated the protective effect of ZnO-NPs/Ach against DNA damage using agarose gel electrophoresis and PBR322 plasmid DNA as target DNA. Different concentrations of zinc nanoparticles (50-100-250-150-500 μg/mL ZnO-NPs/Ach) were compared in wells. The DNA progressed in the first well but was damaged by H2O2 and UV from the second well onwards. The gel electrophoresis results indicate that the addition of 50 mg/L nanoparticles in the third well prevented DNA damage, and as the ZnO-NPs/Ach ratio increased, the DNA moved more significantly. Furthermore, the addition of ZnO-NPs/Ach after the third well prevented DNA damage as the ZnO-NPs/Ach concentration increased. The highest concentration of 500 μg/mL of ZnO-NPs/Ach in the seventh well showed an excellent protective effect. Figure 3 shows the agarose gel electrophoresis.
Antioxidant activity of ZnO-NPs/Ach
We found that the lipid peroxidation prevention activities of ZnO-NPs/Ach increased in direct proportion to the concentration. The highest inhibition value was observed at the nanoparticle level of 500 µg/mL, as determined by the TBA assay. The MDA levels of ZnO-NPs/A. biebersteinii and ZnO-NPs/A. millefolium were found to be 90.87% and 89.11%, respectively (see Figure 6).
Antidiabetic effects of ZnO-NPs/Ach
The antidiabetic effect of ZnO-NPs/Ach was compared to that of acarbose (Sigma Aldrich Chemical Co, USA), which was a standard. Acarbose inhibited the α-amylase and α-glucosidase at 64% and 88.52%, respectively. ZnO-NPs/A. biebersteinii and ZnO-NPs/A. millefolium had effects of 58.12% and 52.55%, and 94.37% and 92.57%, respectively (Table 2).
Discussion
Reactive oxygen species (ROS) formed in the body can cause rapid oxidation of target molecules, leading to lipid peroxidation in cells, among other biochemical reactions. This process can contribute to various diseases caused by oxidative stress, including neurological diseases, aging, cancer, and heart disease [11,12]. Lipid peroxidation can result in the formation of complex compounds containing reactive carbonyl compounds, such as malondialdehyde (MDA). The MDA measurement is commonly used as a marker of lipid peroxidation in studies related to oxidative stress and redox signalling, particularly in those investigating the antioxidant effects of plants. According to a study [13], medicinal plants can prevent lipid peroxidation through their interaction with ZnO. The study found that the lipid peroxidation prevention activities of ZnO-NPs/Ach increased in direct proportion to the concentration. The highest inhibition value was observed at the nanoparticle level of 500 µg/mL.
Our study aimed to determine the potential antidiabetic effect of Achillea spp., a medicinal plant used in the treatment of various diseases, including diabetes, in Türkiye and Cyprus. These plants exert their antidiabetic effects by controlling hyperglycaemia through the inhibition of enzymes such as α-amylase and α-glucosidase, as well as delaying glucose absorption [14,15]. Acarbose was used as a standard, and it was found to have a strong inhibitory activity against α-amylase and α-glucosidase when compared to ZnO-NPs/Ach.
Cancer is caused by mutations in cells. Preventing diffraction and mutation of the DNA molecule is crucial, particularly in the treatment of pathological processes such as cancer. Recent studies have focused on synthesising nanocomponents and investigating their effects on preventing DNA damage [16]. In this study, we observed that the addition of 50 mg/L nanoparticles prevented DNA damage in the third well.Additionally, we found that the DNA mobility increased as the ZnO-NPs/Ach ratio increased. Furthermore, we observed that the addition of ZnO-NPs after the third well prevented DNA damage as the ZnO-NPs/Ach concentration increased. Finally, we found that the highest concentration of 500 μg/mL of ZnO-NPs/Ach had a perfect protective effect. A study was conducted using electrophoresis of agarose gel to examine the biogenic zinc oxide nanoparticles formed by green synthesis mediated by Thymbra spicata L. The study investigated the effectiveness of DNA cleavage ability and found that the protective effect of ZnO-NPs against DNA damage increased with concentration [17].
Conclusion
Our study investigated the antioxidant effects of ZnO-NPs/A. biebersteinii and ZnO-NPs/A. millefolium, synthesized using the green method. The results showed that the nanoparticles exhibited radical quenching activity and reduced biomolecular agents in plant structure. ZnO-NPs/Ach demonstrated high antioxidant activity, particularly at a concentration of 500 µg/mL. ZnO-NPs/Ach have been found to be potent inhibitors of α-amylase and α-glucosidase, as well as having antidiabetic activity. Additionally, these nanoparticles provide high levels of protection against DNA damage. It has been suggested that ZnO-NPs/A. biebersteinii and ZnO-NPs/A. millefolium could be used as antioxidant or antidiabetic agents to protect cells against DNA damage. Zinc oxide nanoparticles may have potential in the treatment of cancer, diabetes, and other chronic diseases caused by oxidative stress. Our study’s results could be a precursor to further scientific research in the health field. More comprehensive studies should investigate the effects of Achillea plant extracts and the nanoparticles synthesized from them.
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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Emrah Caylak, Gokhan Nur. In vitro DNA damage prevention, antioxidant and antidiabetic activities of achillea biebersteinii/millefolium extracts and synthesized ZnO nanoparticles. Ann Clin Anal Med 2024;15(2):136-140
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