December 2023
The role of auscultation and ultrasonography together in confirming the placement of the endotracheal intubation tube
Alper Gok 1, Raziye Gizem Gok 1, Dogac Niyazi Ozucelik 2
1 Department of Emergency Medicine, Hatay Education and Research Hospital, Hatay, 2 Department of Social Work, Faculty of Health Sciences, Istanbul University-Cerrahpaşa, Bağcılar Research and Training Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.21592 Received: 2023-01-15 Accepted: 2023-04-29 Published Online: 2023-08-08 Printed: 2023-12-01 Ann Clin Anal Med 2023;14(12):1059-1063
Corresponding Author: Alper Gok, Department of Emergency Medicine, Hatay Education and Research Hospital, Hatay, Turkey. E-mail: dralpergok@hotmail.com P: +90 533 220 44 00 Corresponding Author ORCID ID: https://orcid.org/0009-0002-8840-9195
This study was approved by the Ethics Committee of Bakırköy Dr. Sadi Konuk Training and Research Hospital (Date: 2015-07-27, No: 2015/13/02)
Aim: The usability of ultrasonography in emergency services has increased in recent years, and this study investigated the effectiveness and usability of ultrasonography in confirming the endotracheal tube location in intubations performed in the emergency department.
Material and Methods: It is a randomized controlled prospective study conducted in Istanbul Bakırköy Dr. Sadi Konuk Training and Research Hospital Emergency Department between 15.07.2015 and 15.10.2015. Patients over 18 years of age, without trauma and head and neck deformity were included in the study. Auscultation procedure was used to confirm the intubation site in one group of patients, and bedside ultrasonography (USG) along with auscultation (transtracheal passage through the larynx and lung sliding movements were evaluated during intubation) in the other group. End-Tidal CO2 was used as the gold standard for the intubation verification method.
Results: A total of 130 patients, 60 (46.2%) women, 70 (53.8%) men, and a mean age of 69.0±17.8 years, were included in the study. While the Sensitivity, Specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) were found to be 100% in 64 patients who underwent auscultation, in 66 patients who underwent bedside USG, the sensitivity of USG was 98.3%, the specificity was 66.7%, PPV was 96.7%, NPV was 80%. Specificity, PPV and NPV increased to 100% in the same group that underwent bedside USG with auscultation. There was no statistical difference between USG and auscultation in confirming the intubation site (p>0.05).
Discussion: Bedside USG, which is used together with auscultation, is a method that has high sensitivity and specificity in confirming tube location in emergency departments, is inexpensive, radiation-free, can be used at the bedside, can be repeated, and can detect tube location errors early.
Keywords: Emergency Department, Intubation, Bedside Ultrasonografiography
Introduction
Airway management skills are indispensable tools for all treatment procedures and tools of the emergency physician [1]. The goals of airway management are oxygenation and ventilation. Achieving these goals may be as easy as repositioning the patient’s head, or may be complicated enough to require a surgical airway. Ensuring airway integrity, oxygenation, ventilation and prevention of aspiration are the mainstays of emergency airway management [2]. Indications for tracheal intubation in AS include correction of hypoxia or hypercarbia, prevention of hypoventilation that may develop, and making sure that the patient’s airway is open. Secondary indications are the preparation of the necessary route for resuscitation and diagnostic includes the paralysis that will occur during the studies [3].
Rapid-sequence intubation (RSI) is the facilitation of endotracheal intubation with the simultaneous administration of induction and neuromuscular blocking agents [4]. Endotracheal intubation is the safest way to ensure that the patient’s airway provides oxygenation and ventilation and prevents aspiration. Clinical evaluation of oxygenation and ventilation alone in chaotic AS may be unreliable. Pulse oximetry and capnography are helpful guides in the decision for tracheal intubation [5].
If the patient cannot protect the airway, the risk of aspiration increases. The role of the gag reflex in airway preservation is unclear. The gag reflex could not be demonstrated in up to 37% of healthy volunteers [6]. In patients without spontaneous swallowing, the airway is compromised and they are at risk for aspiration and may require urgent intervention [6].
The most basic way to ensure emergency airway safety is endotracheal intubation. Inadvertent esophageal intubations during the procedure are rare, but they have a serious impact on morbidity and mortality [7]. The rate of esophageal intubation was found to be 6-16%. Early recognition of esophageal intubation is very important during resuscitation [8]. Although there are many methods for confirming tube location, there is no completely reliable method [8]. All these applications have limitations, but studies have shown that quantitative capnography is the most reliable and specific method [8]. Ultrasonography (USG) is a common examination in emergency rooms and intensive care units. USG is useful in airway management because of its low cost and portability. In this study, promising results were obtained in confirming the ETT site with the use of USG [9].
The aim of this study is to determine the usability of ultrasonography in confirming endotracheal tube location in patients intubated in the emergency department.
Material and Methods
This study is a prospective randomized study and was conducted in Bakırköy Dr. Sadi Konuk Training and Research Hospital (BEAH), Emergency Medicine Clinic between 15.07.2015 and 15.10.2015.
Ethics committee approval for the study was obtained from Bakırköy Dr. Sadi Konuk Training and Research Hospital Ethics Committee. The study was carried out in accordance with the principles of the World Medical Association Declaration of Helsinki.
Inclusion criteria
Patients who applied to the emergency department for a period of three months and were intubated for medical reasons or were to be intubated due to arrest were included in the study..
Exclusion criteria
Patients under the age of 18, patients who had a trauma-related arrest, who needed intubation in the emergency department, who had tracheostomy, who had head and neck deformities, or who had anatomical deformities, were not included in the study.
Patient selection
Our study was conducted between 15 July 2015 and 15 October 2015; 130 patients with intubation indication in the Sadi Konuk Training and Research Hospital Emergency Medicine Clinic were included. While Oscultation-Capnography was applied to patients corresponding to odd numbers, USG-Ascultation-Capnography was applied to patients corresponding to even numbers, and tube location was verified in intubation. Data from both groups were discussed in the conclusion and discussion section.
Ultrasonographic evaluation method
As criteria for confirming the location of the tube with USG, the passage movement of the tube and the movements of the ventilated lung are based on sonographic observation. Transition movement of the tube was evaluated by passing the tube through the trachea or esophagus with a linear ultrasonography probe placed transversely over the suprasternal notch. The movement of the ventilated lung was evaluated by looking at the sliding movements in the lung according to the BLUE protocol. General Electric brand Vivid e model and 10 MHz linear probe were used as ultrasonography device.
Implementation of the transaction
The location of the endotracheal tube was evaluated by ultrasonography by the research assistants working in our clinic in the last year.
Patients’ complaints at the time of admission to the emergency department, demographic data, blood pressure, oxygen saturation, comorbid diseases, and Mallampati scores determined by the intubation doctor were recorded.
Intubations of patients were performed by the most senior resident doctors in the emergency department and immediately gave their own feedback to the investigator on the correctness of tube location.
All patients were followed up capnographically after and during intubation.
Statistical analysis
Statistical analyzes were performed using SPSS 16.0 for Windows. Descriptive criteria were presented as mean and percentage distribution. Statistical significance level was accepted as p<0.05. The conformity of the data to the normal distribution was checked with the Kolmogorov-Smirnov test. Student’s t-test was used to determine mean differences between groups, and Pearson’s Chi-Square test was used to compare percentile differences.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
The study was conducted in BEAH emergency department between 15.07.2015 and 15.10.2015, and a total of 130 patients were included in the study. Patients who were admitted and intubated due to trauma and patients under 18 years of age were not included in the study. Twenty-seven (20.8%) patients were evaluated as arrest and emergency intubation was performed, while 11 (8.5%) patients were intubated due to hypoxia and 92 (70.8%) patients were intubated for airway safety.
Of the 130 patients included in the study, 60 (46.2%) were female and 70 (53.8%) were male. The mean age of the patients was 69.0±17.8 (Table 1).
The mean age of the auscultation group was 73.9±14.4, and the mean age of the USG group was 64.3±19.5. The mean age of all intubated patients was 69.0±17.8 years.
In the group without USG, there were 30 (46.9%) females and 34 (53.1%) males, a total of 64 individuals. There were 30 (45.5%) women and 36 (54.5%) men, totally 66 people in the USG group.
The 27 patients who were intubated were considered as arrest. Fifty-three (40.8%) patients had general condition disorder, 34 (26.2%) had shortness of breath, 21 (16.2%) had unconsciousness, 10 (7.7%) had intoxication, 9 (6.9%) had syncope, 2 (1.5%) had chest pain and 1 (0.8%) patient had abdominal pain.
Among the intubated patients, in the Auscultation-Capnography group 28 (43.8%) patients had general condition disorder, 15 (23.4%) had dyspnea, 13 (20.3%) had impaired consciousness, 1 (1.6%) had chest pain, 2 (3.1%) patients had intoxication, 4 (6.3%) patients had syncope, 1 (1.6%) patients had abdominal. Patients in the group who underwent USG-Auscultation-Capnography, 25 (37.9%) had general condition disorder, 19 (28.8%) had shortness of breath, 8 (12.1%) had impaired consciousness, 1 (1.5%) had chest pain, 8 (12.1%) had intoxication, 5 (7.6%) patients had syncope, and no significant difference was found between the reasons for admission in both groups (p=0.368).
Vital values such as pulse, blood pressure, and saturation were not measured and were not included in the study in patients admitted with arrest and intubated.
The mean Mallampati Score of the patients was 2.85±0.59. There was a difference between the two groups in mean age and Mallampati scores (p< 0.05). The mean heart rate of the patients who were intubated was 106.2±23.3/min. The heart rate was not significantly different between the two groups. The mean saturation value of the patients was determined as 81.2±11.4. Of the patients who presented with arrest, 16 were in the group without USG and 11 were in the group with USG (Table 2).
Eleven (8.5%) of 130 intubation procedures were considered gastric intubation. In our study, capnograph was considered the gold standard in confirming the tube location. While intubation performed in 5 patients in the auscultation-Capnography combination was considered as wrong intubation, intubation in 6 patients in the USG-Oscultation-Capnography combination was evaluated as wrong. No significant difference was observed in terms of false intubation rates in both groups.
In the first group, a total of 64 patients were evaluated with the combination of auscultation and capnography. While 59 of the intubations were performed correctly, 5 of them were detected as wrong intubation and re-intubation was performed. In this group, correct intubation was detected in 59 patients, similar to the auscultation procedure data, in patients who underwent capnography, while it was evaluated as incorrect intubation in 5 patients.
In the second group, 66 patients were evaluated in the group that underwent USG-Auscultation-Capnography. USG evaluated 61 of them as correct intubation and 5 as wrong intubation. In this group, in patients who underwent capnography, different from the USG data, correct intubation was detected in 60 patients, and incorrect intubation was detected in 6 patients.
In this study, the tube was withdrawn and re-intubation was performed with the suspicion of esophageal intubation by USG during the intubation procedure in 2 patients. Afterwards, re-intubation was performed and the ETT was placed in the trachea.
A total of 130 patients were evaluated in both groups, and wrong intubation was detected in 11 of 130 patients in total. While 5 of the wrong intubations were in the Auscultation-Capnography group, the number of wrong intubations was 6 in the USG-Auscultation-Capnography group.
In patients in the first group, Sensitivity was 100% (95% CI = 96.95-100%), Specificity was 100% (95% CI = 71.51-100%), in tube location verification of gastric auscultation alone, PPV was 100% (96.95-100), NPV was 100% (71.51-100). In this group, 59 correct intubations were detected by the auscultation method, while 5 intubations were evaluated as incorrect.
In the first group, in the tube location verification of auscultation alone, Sensitivity was 100%, Specificity was 100%, PPV was 100%, NPV was 100% in the presence of air in the 4 quadrants of the lung. In this group, 59 correct intubations were detected by the auscultation method, while 5 intubations were evaluated as incorrect.
Of the 130 patients in both groups who underwent gastric auscultation and lung auscultation, correct intubation was found in 119 patients in both views, while incorrect intubation was found in 11 patients.
In the second group, true positive results were detected in 59 patients in the confirmation of tube location by ultrasonography in patients who underwent Ultrasonography-Auscultation-Capnography. True negative results were found in four patients, while 2 false positives and 1 false negative were detected.
In the second group, the sensitivity of ultrasonography was 98.3% (95% CI = 91.06-99.96), Specificity was 66.7% (95% CI = 22.28 – 95.67%), PPV was 96.72% (88.65 – 99.60%), NPV was 80% (28.36-99.49%), Test Validity was 95.4%, Positive Likelihood was 2.95 (0.95-9.15), Negative Likelihood was 0.03 (0.00-0.19).
In the second group, Sensitivity was 100%, Specificity was 100%, PPV was 100%, NPV was 100% in tube location verification when auscultation was added to USG.
Sensitivity (100%) and Specificity (100%) of auscultation were detected, and although the Sensitivity (98.3%) and Specificity (66.7%) of USG were higher, no statistical difference was found between them ( p> 0.05 ).
Discussion
The usability of ultrasonography in the emergency department has increased in recent years, and in our study, in intubation; It has been determined that ultrasonography has high sensitivity and specificity in terms of speed, accuracy and efficiency during the verification process of the endotracheal tube. Early recognition of incorrect intubation in the emergency department is of great importance in emergency airway management in terms of mortality and morbidity. There is no ideal verification method [10].
In the study by Abbasi et al., ultrasonography was performed transversely from the suprasternal notch superior to confirm the position of the intubation tube, the study lasted for about ten months in the emergency department, and the sensitivity of ultrasonography was 98% (95% CI=88.8-99.9%), the specificity was 95% in sixty patients. (95% CI=51.6-100%), positive predictive value 100% (95% CI= 91.5-100%), negative predictive value 85.7% (95% CI= 42-99.2%) [10]. Sensitivity, specificity, positive predictive and negative predictive values were found to be similar to the values in our study.
In the prospective randomized study conducted by Bunyamin Muslu et al. [14], 150 patients to be operated on in the anesthesia clinic were included, of which 75 patients were esophageal and 75 patients were tracheal intubation with direct laryngoscope. As a result, Sensitivity was 100% (95% CI, 84%-100%) and specificity was 100% (95% CI, 84%-100%) on ultrasonography. In our study, the duration of ultrasonography was found to be less than 6 seconds, and the sensitivity and specificity rates were found to be similar to each other. It was thought that the fact that the aforementioned study was conducted under elective conditions may have affected the sensitivity and specificity. Our own study was conducted in a more dynamic and unstable environment, and it is possible that physical factors may affect the efficiency and speed of intubation confirmation.
In the study of Caner et al. [15], 64 tracheal intubations and 5 esophageal were detected by looking at the sliding movements in the lungs. Sensitivity, specificity, positive predictive value, negative predictive value of transtracheal ultrasonography were 96.9% (95% CI 89.2-99.6%), 80% (95% CI 28.4-99.5%), 98.4 % (95% CI 91.4-100%), 66.7% (95% CI 18.7-96.9%), respectively. In our study, the tube location was tried to be confirmed by looking at the superior suprasternal notch and the gliding movements in the lung, and the sensitivity, specificity, positive predictive value, and negative predictive values of the USGs performed by looking at the gliding movements in both the transtracheal and lung were found to be similar.
Limitations
Ultrasonography is an experience-based method; Even though the clinicians included in the study have received ultrasonography training, there is a potential for these differences to affect the outcome of the study, as there are differences between individuals.
Conclusion
Considering similar studies, the study provided an adequate number of patients. False intubation was detected in 11 (8.5%) of 130 patients. Although ultrasonography was less effective than auscultation, there was no statistically significant difference and ultrasonography application was faster.
Although it has 100% efficiency (with high sensitivity and specificity) in our study, there is a possibility of false negative or false positive results when the auscultation method is used alone in the verification of the location of the intubation tube in places with high potential to create a dynamic, noisy and chaotic environment such as the emergency room. In order to prevent this situation, it was concluded that the combination of USG and auscultation would be a more appropriate method.
In this study, the results of transtracael USG and the results of USG in the detection of sliding movements in the lung were found to be similar to each other. In a situation where ETT needs to be placed during CPR, Transteakel USG is more advantageous than lung USG during CPR, as it does not affect the CPR application area.
In addition, it was concluded that transtracheal USG can identify false intubation earlier and more effectively in emergency departments, since it detects transtracheal passage earlier than other methods in confirming the endotracheal tube location.
USG can be applied in emergency practice as an aid to auscultation routinely used because it is easy to use, low cost and does not have harmful aspects such as radiation.
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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Download attachments: 10.4328.ACAM.21592
Alper Gok, Raziye Gizem Gok, Dogac Niyazi Ozucelik. The role of auscultation and ultrasonography together in confirming the placement of the endotracheal ıntubation tube. Ann Clin Anal Med 2023;14(12):1059-1063
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Can pan-immune inflammation value and systemic inflammatory response index be used clinically to predict inflammation in patients with cataract?
Betul Akbulut Yagcı 1, Huseyin Erdal 2
1 Deparment of Opthalmology, Aksaray University Training and Research Hospital, 2 Department of Medical Genetics, Faculty of Medicine, Aksaray University, Aksaray, Turkey
DOI: 10.4328/ACAM.21657 Received: 2023-02-17 Accepted: 2023-06-16 Published Online: 2023-07-03 Printed: 2023-12-01 Ann Clin Anal Med 2023;14(12):1064-1067
Corresponding Author: Betul Akbulut Yagcı, Deparment of Opthalmology, Aksaray University Training and Research Hospital, Aksaray, Turkey. E-mail: betul_dr@hotmail.com P: +90 505 946 95 96 (Corresponding Author ORCID ID: https://orcid.org/0000-0002-0608-9195
This study was approved by the Local Ethics Committee of Aksaray University (Date: 2023-02-02, No: 22-SBKAEK)
Aim: It is known that inflammatory processes increase the risk of cataract formation. There are no studies examining inflammatory indices in patients with cataract. Therefore, this is the first study that simultaneously investigates the systemic inflammatory response index (SIRI) and pan-immune-inflammation value (PIV) in patients with cataract.
Material and Methods: Ninety-five patients and 80 healthy controls who were examined at the Ophthalmology clinics of Aksaray University Education and Research Hospital between January 2022 and January 2023 were included in this retrospective study. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), SIRI and PIV values were calculated as indicators of the inflammatory process.
Results: The mean age of the patients was 68.3 ± 12.1 years and 54.7% of cataract patients were females. In the control group, the mean age was 66.5 ± 5.4 years, and 32.5% of the participants were females. There was no significant difference between the patient and control groups in terms of laboratory parameters (p>0.05). In addition, inflammatory indices were calculated for the patient and control groups. No statistically significant difference was found between NLR, PLR, LMR, SII, SIRI, and PIV between the groups (p>0.05).
Discussion: This study indicates that SIRI and PIV can be used in the evaluation of cataract patients. Therefore, Hemogram parameters and inflammatory indexes created with their combination may contribute to monitoring the progression of cataracts.
Keywords: Cataracts, Inflammation, Systemic Inflammatory Response Index, Pan-Immune-Inflammation Value
Introduction
Cataract is the most common cause of visual impairment, affecting millions of people around the world, and its incidence is very high, especially in developing countries [1]. Age-related cataract is a common disease, the prevalence of which increases steeply past the age of 60 years. The prevalence of cataract was reported as 8-50% between the ages of 40-59, and 20-88% over the age of 60 [2]. There have been implicated risk factors including diabetes mellitus, inflammatory diseases, aging, genetic factors, drugs, smoking, malnutrition, and radiation in cataract formation [3]. Under normal conditions, oxidant and antioxidant molecules are in balance in our bodies [4-6].
As a result of the abnormal increase of free radicals, this balance is disrupted and causes oxidative stress (OS) and is accepted as one of the main underlying causes of cataract disorder [1, 7]. The accumulation of oxidized lens components as a result of the increase in reactive oxygen species (ROS) due to aging, the decrease in endogenous antioxidants, and the decrease in the efficiency of the mechanisms involved in their repair play an important role in the formation of cataracts [3].
Inflammation occurs after surgery and pathological injury, and can cause eye diseases leading to vision impairment [8]. It has been shown that ocular inflammation significantly increases the risk of cataract formation due to various factors or as a result of systemic inflammatory processes [9]. OS and Ocular inflammation (OI) are closely related pathophysiological processes, and both processes are simultaneously found in many pathological conditions, including age-related cataracts [10]. During the inflammatory process, activated phagocytic cells such as neutrophils and macrophages may play a role in cataract pathophysiology by producing large amounts of ROS [1]. In the literature, several studies have investigated the association between systemic inflammation and cataract, reporting associations between blood biomarkers including intracellular adhesion molecule-1, interleukin-6 (IL-6), transforming growth factor-beta (TGF-β), interferon-gamma (INF-γ), calprotectin [11-14]. In the studies, inflammatory indices such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) have been reported as indicators of systemic and ocular inflammation [15]. It has been reported that a new inflammatory marker, Systemic immune-inflammation index (SII), is a prognostic indicator in various diseases such as primary open-angle glaucoma, dry eye disease, diabetic retinopathy, retinal vein occlusion and retinal artery occlusion [16-20]. Systemic inflammatory response index (SIRI) and pan-immune-inflammation value (PIV) are newly designed indexes that are considered comprehensive indicators of the immune response and systemic inflammation. The SIRI and PIV are important in the prognosis or treatment response of patients with cancers, acute coronary syndrome and several sepsis [21-24]. However, SIRI and PIV are not indexes previously evaluated in inflammatory ocular diseases. To the best of our knowledge, this is the first report evaluating NLR, PLR, LMR, SII, SIRI and PIV parameters in patients with cataract.
Material and Methods
Ninety-five cataract patients and 80 healthy controls who were examined at the Ophthalmology clinics of Aksaray University Education and Research Hospital between January 2022 and January 2023 were included in this retrospective study. The present study was conducted in accordance with the Helsinki Declaration rules, and informed consent forms were obtained from all the participants. The present study was approved by the Aksaray University Local Ethics Committee (protocol number: 22-SBKAEK).
Patients with systemic diseases, including systemic infection and inflammatory disease were excluded from the study. In addition, patients with previous ocular surgery, uveitis, glaucoma, pseudoexfoliation syndrome, and retinal disease were excluded. The patient group had a best-corrected visual acuity (BCVA) of 20/40 or less with the Snellen chart. In anterior segment examination with a biomicroscope, the patient group had a senile cataract grade above 3, and dilated fundus evaluation was normal. The age- and sex-matched healthy group had BCVA of better than 20/25 with the Snellen chart. In the healthy group, the anterior segment and fundus examination were normal. In addition, patient and healthy groups were classified according to the presence of diabetes mellitus (DM). Demographic information, hemogram and biochemical parameters of the study and healthy groups were collected from the hospital automation system. The hemogram parameters, low-density lipoprotein (LDL), and serum C-reactive protein (CRP) levels were assessed. Neutrophil, lymphocyte, platelet and monocyte levels of groups were used in the complete blood parameters. The NLR, PLR, LMR, SII, SIRI and PIV, respectively, were calculated as follows: the ratio of neutrophils to lymphocytes, platelets to lymphocytes, lymphocytes to monocytes, that of platelets x (neutrophils/lymphocytes), (neutrophils x monocytes)/lymphocytes and (neutrophils x platelets x monocytes)/lymphocytes.
Statistical Analysis
IBM SPSS 22 was used for the statistical analysis of the groups. The Kolmogorov-Smirnov test was used to determine whether the data were normally distributed or not. Categorical variables were expressed as numbers and percentages, and differences between groups were determined using the chi-squared test. Continuous variables were compared using Student’s t-test and expressed as means ± standard deviation. Values that did not fit the normal distribution were compared using the Mann-Whitney U test. A statistically significant p-value was accepted as <0.05.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
The mean age was 68.3 ± 12.1 years, and 54.7% of cataract patients were females. In the control group, the mean age was 66.5 ± 5.4 years, and 32.5% of the participants were females. There was no statistically significant difference between the groups in terms of age and gender (Table 1).
Diabetes mellitus was present in 42% of the cataract patients and 24% of the control group. A statistically significant difference was found between the two groups in terms of DM (p=0.01). The median (min-max) outcomes of the hemogram parameters and indexes between the groups are shown in Table 2.
There was no significant difference between the patient and control groups in terms of laboratory parameters (p>0.05). In addition, inflammatory indices were calculated for the patient and control groups. No statistically significant difference was found between NLR, PLR, LMR, SII, SIRI, and PIV indices between the groups (p>0.05, Table 2).
Discussion
To the best of our knowledge, this is the first study to examine hemogram parameters and novel inflammatory indices including NLR, PLR, LMR, SII, SIRI, PIV together in patients with cataract. In the present study, we aimed to compare hemogram parameters and calculated novel inflammatory indices between patient and control groups. Hemogram parameters and inflammatory indices were not significantly different between the two groups.
Studies have reported that the risk of age-related cataracts increases with OI as a result of local factors or a combination of systemic inflammatory conditions [11, 13]. Klein et al. reported that markers of inflammation, including intracellular adhesion molecule-1 and IL-6, were significantly associated with age-related cataracts [11]. In another study, Chen et al. reported that inflammatory cytokines such as IL-2, and IFN-γ were significantly increased in age-related cataract and inflammatory cataract patients [13]. Erdal et al. reported that calprotectin levels were statistically significant compared to the patient and control groups in their study, in which they determined the levels of calprotectin, an inflammatory marker, in patients with cataract. They reported that NLR and PLR levels were not different in cataract patients compared to the control group. They also hypothesized that the determination of increased serum calprotectin levels can be used to assess the severity and follow-up of the disease [14].
Clinical laboratory indicators and markers of systemic inflammatory status, including NLR, PLR, LMR, and SII, have been proposed as prognostic indicators in a variety of diseases in multiple disease studies [15]. Tang et al. indicated that in the primary open angle glaucoma group, NLR, PLR and SII levels were significantly increased compared with the control group (p < 0.001). However, they showed that the LMR value was lower in the primary open-angle glaucoma patients with respect to controls [16].
In another study, Ozarslan et al. found that the mean NLR, PLR and SII levels were significantly higher in dry eye patients compared to the healthy group [17]. In addition, Kocamis et al. showed an association of pseudophakic cystoid macular edema with NLR, PLR and SII in eyes without risk factors after phacoemulsification surgery [25]. In a study conducted by Erbeyli et al. they reported that SII levels were significantly higher in patients with diabetic macular edema compared to patients without diabetic macular edema [18]. Consistent with other studies, it has been reported that NLR and SII values are significantly higher in patients with retinal vein occlusion and central retinal artery occlusion compared to the healthy group [19, 20].
SIRI and PIV are newly designed indexes that are considered easily calculable and comprehensive indicators of immune response and systemic inflammation. They are not previously evaluated in inflammatory ocular diseases. Han et al.’s study of 1724 patients with acute coronary syndrome reported that SIRI was significantly associated with major adverse cardiovascular conditions [24]. A meta-analysis encompassing 15 studies revealed that cancer patients with higher PIV levels had a significantly increased risk of death compared to those with lower PIV levels [23].
Conclusion
In conclusion, SII, SIRI and PIV is a new inflammatory indexes that can be used in the evaluation of patients with cataracts. Consequently, measurement of hemogram parameters and inflammatory indexes created with their combination may contribute to monitoring the progression of the cataracts.
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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4. Erdal H, Ciftciler R, Tuncer SC, Özcan O. Evaluation of dynamic thiol-disulfide homeostasis and ischemia-modified albumin levels in patients with chronic lymphocytic leukemia. J Investig Med. 2023; 71(1):62-66.
5. Erdal H, Özcan O, Turgut FH, Neşelioğlu S, Erel Ö. Evaluation of dynamic thiol-disulfide balance and ischemia modified albumin levels in patients with chronic kidney disease. The Medical Journal of Mustafa Kemal University 2022; 13(47): 237-42.
6. Erdal H, Bekmezci M. Evaluation of Dynamic Thiol/Disulfide Homeostasis and Ischemia-Modified-Albumin Levels in Cord Blood of Newborns to Patients with Oxytocin-Induced Labor. Aksaray University Journal of Sport and Health Researches 2022; 3(2):193-202.
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9. Minkus CL, Pistilli M, Dreger KA, Fitzgerald TD, Payal AR, Begum H, et al. Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study Research Group. Risk of Cataract in Intermediate Uveitis. Am J Ophthalmol. 2021; 229:200-9.
10. Biswas SK. Does the Interdependence between Oxidative Stress and Inflammation Explain the Antioxidant Paradox? Oxid Med Cell Longev. 2016;2016:5698931.
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12. Kubo E, Shibata T, Singh DP, Sasaki H. Roles of TGF and FGF signals in the lens: tropomyosin regulation for posterior capsule opacity. Int J Mol Sci. 2018;19 (10):3093.
13. Chen W, Lin H, Zhong X, Liu Z, Geng Y, Xie C, et al. Discrepant expression of cytokines in inflammation- and age-related cataract patients. PLoS One. 2014;9(10):e109647.
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16. Tang B, Li S, Han J, Cao W, Sun X. Associations between Blood Cell Profiles and Primary Open-Angle Glaucoma: A Retrospective Case-Control Study. Ophthalmic Res. 2020;63(4):413-22.
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Betul Akbulut Yagcı, Huseyin Erdal. Can pan-immune inflammation value and systemic inflammatory response index be used clinically to predict inflammation in patients with cataract? Ann Clin Anal Med 2023;14(12):1064-1067
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Evaluation of percutaneous blind liver needle biopsy results in chronic hepatitis B patients in a state hospital without interventional radiology
Filiz Kurklu Bozkır 1, Ilhami Celik 2
1 Deparment of Infectious Diseases and Clinic Microbiology, Aksaray University Training and Research Hospital, Aksaray, 2 Department of Infectious Diseases and Clinic Microbiology, Kayseri City Hospital, Kayseri, Turkey
DOI: 10.4328/ACAM.21718 Received: 2023-04-07 Accepted: 2023-08-21 Published Online: 2023-08-25 Printed: 2023-12-01 Ann Clin Anal Med 2023;14(12):1068-1071
Corresponding Author: Filiz Kurklu Bozkir, Deparment of Infectious Diseases and Clinic Microbiology, Aksaray University Training and Research Hospital, Aksaray, Turkey. E-mail: dr.filizkurklu@hotmail.com P: +90 505 574 90 48 Corresponding Author ORCID ID: https://orcid.org/0000-0002-5114-8828
This study was approved by the Ethics Committee of Aksasary University (Date: 2021-04-26, No: 2021/04-23)
Aim: The aim of the present study is to retrospectively evaluate the results of patients who underwent percutaneous blind liver biopsy in a clinic without interventional radiology between 2016 and 2018.
Material and Methods: A total of 54 patients who underwent liver biopsy for chronic hepatitis B between June 2016 and June 2018 in our hospital were included in this study. Demographic data such as age, sex, alanine aminotransferase (ALT), aspartate aminotransferase (AST), HBeAg, Anti-HBe, HBV DNA levels were obtained from the hospital automation system and liver biopsy results were obtained from the pathology recording system.
Results: Mortality or any other major complications (such as organ perforation, massive bleeding, or hemoperitoneum) were not observed in this study. However, liver tissue could not be removed in 3 patients. The number of patients with normal ALT (<40 U / L) was 45 (83.3%). The pathology of 31 (68.7%) of these patients was fibrosis ≥2 and/or HAI≥6. Oral antiviral therapy was started in 40 patients. HBV DNA of 33 (82.5%) patients whose treatment was initiated was found to be negative at the 6th month of the treatment.
Discussion: Liver needle biopsy is still used as the gold standard in the diagnosis and treatment of chronic hepatitis B patients. Percutaneous blind liver needle biopsy can be performed in chronic hepatitis B patients when there is no interventional radiology in the diagnosis. In addition, it was thought that liver biopsy should be performed in patients with high HBV DNA even if ALT values were normal.
Keywords: Liver Needle Biopsy, Chronic Hepatitis B, Gold Standard
Introduction
Hepatitis B virus (HBV) affects a significant portion of the population and is characterized by high mortality and morbidity. It is known that approximately 2 billion people in the world have encountered hepatitis B virus (HBV), and approximately 25% of them are infected with HBV [1]. Our country is a medium endemic region for hepatitis B. Current treatments do not eradicate the virus, suppress virus replication, prevent the progression of the disease to cirrhosis and hepatocellular carcinoma (HCC), and reduce the risk of liver-related death [2,3]. There is no indication for treatment of patients with HBV DNA below 2000 IU/ml, negative HBeAg, normal aminotransferases, and normal or minimal liver histopathology. However, over time, reactivation may be seen in these patients with the increase of HBV DNA level and aminotransferases and treatment may be indicated, so follow-up is important. The prognosis and management of the disease in chronic viral hepatitis are closely related to the determination of the extent of liver fibrosis. Although there have been improvements in non-invasive diagnostic methods such as Fibrotest and Fibroscan in recent years, liver needle biopsy (IB) is still the gold standard for determining the extent of liver fibrosis in patients with chronic hepatitis B (CHB) and histopathological follow-up of response to treatment [4]. The first percutaneous liver biopsy was performed by Paul Ehrlich in Germany in 1883, and the aspiration method was developed by Menghini towards the end of the 1950s. Today, percutaneous liver needle biopsy is performed with this technique in many centers [5,6]. As in every interventional procedure, some complications or erroneous sampling can be observed in liver biopsy. The most common complication is pain, which usually disappears within 1-2 hours after the procedure. Bleeding, peritonitis, biliary tract damage, pneumothorax, and hemothorax are rare complications that can be seen after liver biopsy. In order to prevent these, it is recommended to perform blood tests of the patients before the procedure and to be carried out in an experienced center, to follow the patients for 6 hours after the procedure, and to follow up patients at risk for a longer period of time by hospitalization. Contraindications to ICP include serious bleeding disorder (increased prothrombin time, platelet count <60000), the presence of ascites, morbid obesity, the presence of vascular lesions such as hemangioma, the presence of infection in the area to be biopsied, and uncooperative patient [7,8].
In this study, blinded percutaneous liver needle biopsy results were evaluated retrospectively and it was thought that this method can be applied for diagnosis and treatment of CHB patients in a center without interventional radiology.
Material and Methods
A total of 54 patients who underwent percutaneous blinded liver needle biopsy due to CHB between June 2016 and June 2018 in our clinic were included in this study. Demographic characteristics of the patients, aspartate aminotransferase (AST), alanine aminotransferase (ALT), platelet (PLT) and HBV DNA levels, histological activity index (HAI) according to Ishak scores in liver biopsy, and initiation of hepatitis B treatment with fibrosis were reached and recorded from the hospital automation and pathology registry system. Before the liver biopsy was performed, detailed information about the procedure and its complications was given to all patients by the physician who will perform the procedure, and written informed consent was obtained from the patients. Complete blood count, active partial thromboplastin time and prothrombin time/INR were requested from all patients before the procedure. Before the procedure, local anesthesia (1% lidocaine) was applied under the skin. The sample was taken by aspiration technique by entering through the marked intercostal space with a 17-gauge Menghini type biopsy needle (Hepafix®, B. Braun Melsungen AG 34209 Melsungen, Germany). After the procedure, the patients were hospitalized in our clinic and observed for 24 hours. The present study was approved by Aksasary University Human Research Ethics Committee (protocol number: 2021/04-23 Date: 26.04.2021).
At the end of this period, the patients without complications were discharged. IBM SPSS Statistics for Windows.Version 26.0 (Statistical Package for the Social Sciences, IBM Corp, Armonk, NY, USA) was used for statistical analysis.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Of the 54 patients included in the present study, 13 (24%) were female and 41(76) were male. The mean age was 40.2 ± 7.9 years (19-60). In a retrospective examinations, complications did not develop in any of the cases. In addition, liver tissue could not be obtained in 3 patients (5.5%). According to liver biopsy results, oral antiviral therapy was started in 40 (78.43%) patients with HAI score ≥6 and/or fibrosis score ≥2. As an oral antiviral treatment, tenofovir disoproxil fumarate was started in 22 patients and entecavir was started in 18 patients. Since biopsy material could not be obtained in 3 patients, and 8 patients did not meet the criteria for initiation of treatment in our country, a total of 11 (21.56%) patients were not treated.
Discussion
Chronic hepatitis disease can cause serious complications such as cirrhosis and HCC (hepatocellular carcinoma) that can result in death. The main purpose of treatment in CHB is the eradication of cccDNA (covalently closed circular DNA) and HBsAg from hepatocytes. However, today, there is no drug that can eradicate the virus in cccDNA in hepatocytes [9]. With current treatments, the aim is to achieve permanent viral suppression and biochemical and histological improvement, and to prevent long-term complications such as cirrhosis and/or hepatocellular carcinoma. In order to start treatment in CHB patients, it is necessary to show the HBV DNA level and liver histopathology of the patients [10,11]. Liver needle biopsy is still used as the gold standard technique to evaluate liver histopathology in CHB patients.
Liver needle biopsy was first applied by Paul Ehrlich in Germany in 1883. Today, it is frequently used in the diagnosis and follow-up of many liver diseases [5]. Since ICP is an invasive diagnostic method and rarely causes complications that may result in death, one of the most important issues discussed is the question of performing biopsy with blind biopsy or ultrasonography. In the study by Cadranel et al. from France, biopsies were performed with ultrasonography in 56% of 2084 patients [12]. In a retrospective study by Flemming et al., 100 hepatitis patients who underwent ultrasonography-guided and blind biopsy method were compared and no difference was found in terms of staging and grading [13]. In this study, all cases were performed as blinded percutaneous needle biopsy. For a healthy evaluation, at least 4-6 portal areas and 10-15 mm of liver material are required, and this is related to the experience of the physician [14]. In this study, 3 (5.5%) patients were excluded because sufficient biopsy material could not be obtained. Since ICP is an invasive procedure, it may cause some complications. Factors such as the biopsy technique, the experience of the healthcare personnel, and the suitability of the biopsy needle used determine the incidence and severity of complications. Intra-abdominal hemorrhage, hemobilia, biliary peritonitis, pneumothorax are among the complications and bleeding is the most important cause of death. Therefore, the bleeding parameters of the patient should be closely monitored before and after the biopsy. Supportive treatment with appropriate blood products should be applied in patients at risk of bleeding. ICP should not be performed in unsuitable patients [7].
In the study by Younossi et al., the rate of blinded percutaneous liver needle biopsy was 4%; 2% of complications were observed in liver biopsy performed with ultrasonography [15]. In the study by Pasha et al., 2.2% of complications were observed in blind biopsy and 0.5% in ultrasound guidance [16]. In the study by Reddy et al., pain was the most common complication (0.056-22%), and biliary peritonitis (0.03-0.22%) was also observed [17]. The pain is pleuritic, peritoneal, and diaphragmatic and usually responds to analgesics and lasts less than 2 hours. Severe, prolonged pain unresponsive to analgesics is indicative of serious complications such as intraperitoneal hemorrhage or chemical peritonitis. In a study by Piicino et al., 4 cases of hemobilia were observed [18]. In this study, no complications developed in any of the patients, and liver tissue could not be obtained in 3 patients (5.5%).
In studies conducted in HBe Ag-negative patients with normal ALT and high HBV DNA, significant liver damage was detected [19]. In our country, in a study conducted by Dağtekin H. et al., biopsy was performed in patients with normal ALT values, negative HBe Ag, and HBV DNA values above 2000 IU/mL, and it was determined that 56% of the patients required treatment [20]. In this study, the number of patients with normal ALT (<40 U/L) values was 38 (83.3%), and 26 (68.4%) patients had fibrosis ≥2 and/or HAI ≥6. Since this rate is high, even if the ALT value is normal, it suggests that the patient should be evaluated in terms of the necessity of treatment with a liver biopsy in patients with elevated HBV DNA. As a result, a limited number of patients could be included in the study since it was a single-center study. However, in this study, blind percutaneous liver needle biopsy performed for diagnosis and treatment in chronic hepatitis B patients was evaluated as a method that can be used in suitable patients because it does not require devices and techniques such as simultaneous fluoroscopy and ultrasonography, does not develop complications, and allows histopathological diagnosis in 51 (94.4%) patients. We think that it still maintains its importance.
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.
References
1. Yong-Yuan Zhang, Ke-Qin Hu. Rethinking the pathogenesis of hepatitis B virus (HBV) infection. J Med Virol. 2015; 87(12):1989-99.
2. Akarca S, Baykam N, Güner R, Günşar F, İdilman R, Kaymakoğlu S, et al. Eliminating Viral Hepatitis in Turkey: Achievements and Challenges.Viral Hepat J. 2022; 28(2):47-54.
3. Tosun S. Viral hepatitlerin ülkemizdeki değişen epidemiyolojisi. Ankem Derg. 2013; 27(2):128-34.
4. Kose S, Ersan G, Tatar B, Adar P, Erturk Sengel B. Evaluation of percutaneous liver biopsy complications in patients with chronic viral hepatitis. Eurasian J Med. 2015; 47(3):161-4.
5. Karacaer Z, Karadağ F, Durmuş G, Çiçek H, Parlak E, Arı A. et al. Percutaneous Liver Needle Biopsy Methods Can Be Safe and Effective in Patients with Viral Hepatitis.Viral Hepat J. 2017;23(3):65-70.
6. Montanari NR, Ramírez R, Aggarwal A, Buuren N, Doukas M, Moon C, et al. Multi-parametric analysis of human livers reveals variation in intrahepatic inflammation across phases of chronic hepatitis B infection. J Hepatol. 2022;77(2):332-43.
7. Tapper EB, Lok AS. Use of liver imaging and biopsy in clinical practice. N Engl J Med. 2017;377(8):756-68.
8. Zhang M, Zhang H, Cheng X, Whang X, Xu H, Gao X, et al. Liver biopsy of chronic hepatitis B patients indicates HBV integration profile may complicate the endpoint and effect of entecavir treatment. Antiviral Res. 2022; 204:105363.
9. European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017; 67(2):370-98.
10. Wilson EM, Tang L, Kottilil S. Eradication strategies for chronic hepatitis B infection. Clin Infect Dis. 2016; 62(4):318-25.
11. Crossan C, Tsochatzis EA, Longworth L, Gurusamy K, Papastergiou V, Thalassinos E et al. Cost-effectiveness of noninvasive liver fibrosis tests for treatment decisions in patients with chronic hepatitis B in the UK: systematic review and economic evaluation. J Viral Hepat. 2016; 23(2):139-49.
12. Cadranel JF, Rufat P, Degos F. Practices of liver biopsy in France: results of a prospective nation wide survey. For the Group of Epidemiology of the French Association for the Study of the Liver (AFEF). Hepatology. 2000; 32(3):477-81.
13. Flemming JA, Hurlbut DJ, Mussari B, Hookey LC. Liver biopsies for chronic hepatitis C: should nonultrasound-guided biopsies be abandoned? Can J Gastroenterol. 2009; 23(6):425-30.
14. Coral GP, Antunes ADP, Serafini APA. Araujo FB, Mattos A. Liver biopsy: importance of specimen size in the diagnosis and staging of chronic viral hepatitis. Rev Inst Med Trop Sao Paulo. 2016; 58:10.
15. Younossi ZM, Loomba R, Anstee QM, Rinella ME, Bugianesi E, Marchesini G, et al. Diagnostic modalities for nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and associated fibrosis. Hepatology. 2018; 68(1): 349-60.
16. Pasha T, Gabriel S, Therneau T, Dickson ER, Lindor KD. Cost-effectiveness of ultrasound guided liver biopsy. Hepatology. 1998; 27(5):1220-6.
17. Reddy KR, Beavers KL, Hammond SP, Lim JK, Falck-Ytter YT. American Gastroenterological Association Institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2015; 148(1):215-9.
18. Craxì A, Piccinino F, Ciancio A, Iannacone C, Deodato B, Golotta C, et al. Real-world outcomes in patients with chronic hepatitis C: primary results of the PROBE study. Eur J Gastroenterol Hepatol. 2014;26(4):388-95.
19. Al-Qahtani AA, Al-Ashgar HI, Al Mana H, Al-Ahdal MN, Soliman Ali A, Hasanain AF et al. Impact of liver biopsy on the decision to treat patients with chronic hepatitis B genotype D virus infection. Intervirology. 2014; 57(5):248-53.
20. Dağtekin H, Tabak F, Mete B, Sonsuz A, Mert A, Özaras R et al. Determination of Liver Disease in Incidentally Detected HBsAg Positives. Viral Hepatitis J. 2012; 18(2):52-8.
Download attachments: 10.4328.ACAM.21718
Filiz Kurklu Bozkır, Ilhami Celik. Evaluation of percutaneous blind liver needle biopsy results in chronic hepatitis B patients in a state hospital without interventional radiology. Ann Clin Anal Med 2023;14(12):1068-1071
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Evaluation of COVID-19-related fear/stress and associated factors in patients with axial spondyloarthritis and rheumatoid arthritis
Hüseyin Kaplan, Gizem Cengiz, Emre Şenköy, Senem Şaş
Department of Physical Medicine and Rehabilitation, Division of Rheumatology, Faculty of Medicine, Erciyes University, Kayseri, Turkey
DOI: 10.4328/ACAM.21749 Received: 2023-05-07 Accepted: 2023-10-21 Published Online: 2023-11-10 Printed: 2023-12-01 Ann Clin Anal Med 2023;14(12):1072-1076
Corresponding Author: Hüseyin Kaplan, Department of Physical Medicine and Rehabilitation, Division of Rheumatology, Faculty of Medicine, Erciyes University, Kayseri, Turkey. E-mail: huseyinkaplan@erciyes.edu.tr P: +90 507 573 28 65 Corresponding Author ORCID ID: https://orcid.org/0000-0002-3292-0907
This study was approved by the Ethics Committee of Erciyes University (Date: 2021-11-24, No: 2021/753)
Aim: In this study, we aimed to evaluate COVID-19-related fear and stress in individuals with axial spondyloarthritis and rheumatoid arthritis and their relationship with clinical and psychological factors.
Material and Methods: The study included patients diagnosed with axial spondyloarthritis (axSpA; n = 69) and rheumatoid arthritis (RA; n = 31). Demographic information, clinical characteristics, laboratory results, and COVID-19 vaccination data of all patients were recorded. Fear and stress due to COVID-19, quality of life (QoL), anxiety, depression, and disease activity were assessed with appropriate questionnaires/scales.
Results: The fear of COVID-19 scores had a weak significant correlation with RA quality of life (RAQoL), anxiety, depression, and vaccine doses. While the COVID stress scores showed a moderate correlation with RAQoL, they had a weak correlation with disease activity and disease duration of RA, age, body mass index (BMI), and anxiety. In linear regression analyses, anxiety was the only predictor with a significant effect on the scores of both COVID-19 fear and stress. Total number of vaccine doses and age were predictors of the fear of COVID-19 scores and the COVID stress scores, respectively.
Discussion: Anxiety affected fear and stress related to coronavirus disease, while the number of vaccine doses and age might differentially affect these two negative emotions.
Keywords: Anxiety, COVID-19, Pandemic, Psychological Processes, Rheumatic Diseases
Introduction
The disease named Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, first appeared in December 2019 in Wuhan, China [1]. In March 2021, the World Health Organization declared this infection a global pandemic. Afterwards, the virus spread rapidly all over the world in multiple waves, infecting millions of people and causing the death of some [2].
A wide spectrum of clinical signs and symptoms has been observed in COVID-19 infection, ranging from asymptomatic or mild flu-like presentation to severe clinical image that requires hospitalization and respiratory support, or even death. Some risk factors identified in the general population and associated with worse outcomes are advanced age, gender, and the presence of chronic disease [3]. In this context, comorbidities in individuals with or without rheumatic diseases (RDs) significantly affect the prognosis of COVID-19 infection [4]. At the time of the first outbreak of the COVID-19 pandemic, there were concerns that the immunological changes in RDs and the medication used for treatment would worsen the outcomes of COVID-19 infection. After the introduction of vaccines, this concern has been replaced by a different one: the possibility of lower seroconversion rates in RDs through a similar mechanism [5].
Studies on COVID-19 are not limited to clinical-related topics, such as disease processes or mortality, but other topics have been studied, for example, its effects on psychological health. Since the beginning of the pandemic, survey studies have shown that many people face problems that threaten individual health, such as fear of contracting COVID-19 disease, anxiety, depression, and posttraumatic stress disorder [2]. To better understand the effects of the COVID-19 pandemic on mental health, different scales have been developed worldwide, including the fear of the COVID-19 scale and the COVID stress scale, which have been validated in Turkish [6-8].
Therefore, the current study aimed to evaluate COVID-related fear and stress, as well as their associations with disease activity, QoL, anxiety, depression, hospital visits, and COVID-19 vaccination status in patients with axial spondyloarthritis (axSpA) and rheumatoid arthritis (RA). As far as we know, our study is the first to measure the impact of COVID-19 on mental health symptoms with two different scales and to address other factors that may affect the results of these scales.
Material and Methods
Study population
This study had a cross-sectional design and was conducted between January 2022 and June 2022 in the Department of Rheumatology, Faculty of Medicine, Erciyes University. Patients with axSpA meeting the 2009 classification criteria of the Assessment in Spondyloarthritis International Society and patients meeting the 2010 RA classification criteria of the American College of Rheumatology and the European League Against Rheumatism were included in the study. Demographic features, disease and treatment-related data (rheumatic diagnosis, disease duration, and medication), comorbidities, smoking status, and COVID-19 vaccination information of all patients were recorded. Laboratory data to calculate disease activity scores [erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)] were documented. The number of outpatient clinic visits between March 1, 2020 and December 31, 2021 was calculated for each patient. The exclusion criteria were the following: age < 18, a diagnosis of neurological and/or psychiatric disease, and incomplete laboratory data.
Measurements
Disease activity
The bath ankylosing spondylitis disease activity index (BASDAI) and the ankylosing spondylitis disease activity score (ASDAS) were used to evaluate disease activity in axSpA patients. On the other hand, the disease activity score (DAS)-28, the clinical disease activity index (CDAI), and the simplified disease activity index (SDAI) were calculated in the case of RA.
QoL
QoL of axSpA and RA patients was assessed with ASQoL [9] and RAQoL [10], respectively. In addition, the short form-36 (SF-36) was used as a common QoL scale for both groups. Eight SF-36 subheadings, summarized under two headings as physical and mental component summary (PCS and MCS for short, respectively), were evaluated as previously described [11].
Hospital Anxiety and Depression Scale (HADS)
This 4-point Likert scale contains 7 questions for each component, i.e., anxiety and depression. Total scores of 0–7 represent “normal”, 8–10 “suspicious conditions”, and ≥11 “abnormal” [12].
The fear of COVID-19 scale
It evaluates the fear of COVID-19 using 7 items and has been validated in Turkish [13]. It is a Likert-type scale with five options in each question (1: “strongly disagree”; 5: “strongly agree”) with possible total scores in the range of 7–35. Higher scores represent more fear.
The COVID stress scale
It was validated in Turkish [8] and evaluates COVID-19-related stress during the pandemic. It includes 8 subheadings and a total of 36 items that are evaluated on a 5-point Likert scale. In our study, scoring was performed as previously described [8]. Higher scores represent more stress.
Ethics statement
After obtaining permission from the Ministry of Health (2021-10-22T15) for the study, it was also approved by the Erciyes University Clinical Research Ethics Committee (Date: 24 November 2021; Approval No.: 2021/753). We acted in accordance with the Declaration of Helsinki and obtained written informed consent from all patients.
Statistical analyses
The normality of data distribution was tested using the Shapiro-Wilk test. Descriptive statistics for numerical variables were expressed as mean ± standard deviation or median (interquartile range [IQR]), while those for categorical variables were expressed as numbers and percentages. Between the two independent groups, the independent samples t-test was used to compare normally distributed data, and the Mann–Whitney U test was used for non-normally distributed data. The correlation between the scores of the scales evaluating fear or stress of COVID-19 and demographic, clinical, and QoL data was evaluated with the Spearman correlation analysis. Linear regression analysis (univariable and multiple models) was used to identify the predictors that affect the COVID-19 fear and stress scores. SPSS for Windows (version 23.0, IBM Corp., Armonk, NY, USA) was used for the statistical analysis. All p-values < 0.05 were considered statistically significant.
Results
A total of 100 patients (69 axSpA and 31 RA) met the inclusion criteria. The mean age of the sample was 44.92 ± 10.26, and 57% of the patients were female. The female gender was higher in the RA patients than in the axSpA (p < 0.001). While in the RA group the mean disease duration (p = 0.004) and the median number of COVID-19 vaccine doses (p = 0.015) were higher, the rate of smokers (p = 0.042) and the number of hospital visits (p = 0.020) were higher in the axSpA group. Other demographic, clinical, and treatment-related features of the patients are shown in Table 1. As for QoL, the mean ASQoL score was 7.53 ± 5.71 and the mean RAQoL score was 13.16 ±8.44. We did not find any significant difference between axSpA and RA patients in terms of QoL, anxiety, depression, fear of COVID-19, and COVID-19 stress (p > 0.05 for all; Table 2). As for the relationships between the collected data and COVID-related impacts, there was a weak correlation between the fear of COVID-19 scores and RAQoL (r = 0.3904, p = 0.030), anxiety (r = 0.3028, p = 0.002), depression (r = 0.3066, p = 0.002), and the number of COVID-19 vaccine doses (r = 0.3131, p = 0.003). While the COVID-19 stress scores showed a moderate relationship with RAQoL (r = 0.5311, p = 0.002), they weakly correlated with age (r = 0.3459, p < 0.001), body mass index (r = 0.2073, p = 0.039), disease duration (r = 0.2047, p = 0.041), SDAI (r = 0.3835, p = 0.033), CDAI (r = 0.3612, p = 0.046), and anxiety (r = 0.2115, p = 0.035) (Data not shown).
In linear regression analyses, we first applied a univariate model to identify candidate predictors (Table 3). Then, we included the candidate predictors in a multiple model. After adjusting for the effects of other factors (age, body mass index, comorbidity status, and the number of hospital visits) in the enter model, anxiety (β: 0.358, 95% confidence interval (CI): 0.234-0.817, p = 0.001) and COVID vaccine doses (β: 0.230, 95% CI: 0.391-3.271, p = 0.013) were the two predictors that had a significant effect on the fear of COVID scores. When we evaluated the COVID-19 stress scores with a similar method, age (β: 0.289, 95% CI: 0.179-1.401, p = 0.012) and anxiety (β: 0.286, 95% CI: 0.772-2.809, p = 0.001) were the two significantly effective predictors after adjusting for the effects of other factors (body mass index, disease duration, and the number of COVID vaccines) in the enter model (for all; data not shown). In correlation analyses, there was a moderate-to-strong correlation between anxiety, depression, and both PCS and MCS of the SF-36 scale (Data not shown). Therefore, depression, PCS, and MCS, which were less associated with the scores of COVID-19-related fear and stress compared to anxiety, were not included in the multiple model.
Discussion
This study revealed that anxiety was an important predictor for both fear of COVID-19 and COVID-19 stress scores in individuals with two different major rheumatic diseases (AxSpA or RA) during the COVID-19 outbreak. In addition, the number of COVID-19 vaccine doses notably affected the fear of COVID-19 scores, and age significantly affected the COVID-19 stress scores.
After the rapid spread of severe acute respiratory syndrome coronavirus 2 over the world, the combination of high mortality, negative effects on health systems, and economic consequences had devastating effects on humanity [14]. Indisputably, death is the most negative outcome of the pandemic. However, the pandemic has brought with it consequences in physical, psychological, economic, and social aspects for all humanity that cannot be ignored. Considering the past pandemic experiences, speculations concerning the effects of COVID-19 on psychological health have been formed. For example, after the Severe Acute Respiratory Syndrome outbreak in 2003, the prevalence of psychological problems such as post-traumatic stress disorder, anxiety, and depression increased [14-16].
As the COVID-19 outbreak began to show its effects in different countries, healthcare professionals carried out studies focusing on the mental health or psychological responses of individuals and/or patient groups with different characteristics. Fear, one of the reactions that normally allows us to survive, can reach harmful dimensions as a result of various negative situations (e.g., social isolation, uncertainty, financial problems, loss of family members due to COVID-19, being part of a high-risk age group, having a chronic disease, etc.), such as the COVID-19 pandemic, and can seriously affect rational decision making [17]. Warren et al. [16] reported that anxiety sensitivity was associated with COVID-19 fear. On the other hand, Asmundson et al. [18] showed that the scores on the COVID stress scale were affected by mood disorders (e.g., anxiety disorder, panic disorder, etc.). They also revealed that these scores were higher in the early stages of the pandemic and decreased after the spread of vaccines in the later stages. In the current study, anxiety scores correlated with the scores of the COVID-19 fear and stress scales. Additionally, as determined by the regression analysis, anxiety was a significant risk factor for COVID-19 fear and stress. This result is compatible with the above- mentioned studies showing that anxiety was associated with COVID-19-related fear and stress. Scores obtained from both the emotional status and COVID-19 scales did not differ significantly in axSpA and RA patients. In both diseases, it can be said that anxiety affects COVID-19 fear and stress similarly. There was also a weak relationship between the COVID-19 vaccine doses and the COVID fear scores. Moreover, the number of COVID-19 vaccine doses was an important predictor of COVID-19 fear scores. This finding may be related to the fact that patients request more vaccine doses if they experience more fear, in line with the results presented by Håkansson et al. [19].
Previous studies on inflammatory rheumatic diseases revealed that psychiatric comorbidities are related to higher disease activity and worse QoL due to changes in pain tolerance [20]. Higher levels of isolation during the pandemic resulted in worse self-reported disease activity and social and mental well-being in these patients [21]. Hassan et al. [20] reported that factors such as disease activity, disease duration, and functional status had an impact on the QoL of RA patients during the pandemic. Additionally, they identified a strong relationship between fear of COVID-19 and psychological symptoms. However, Bhatia et al. [22] emphasized that it is not clear whether this situation is due to disease-related parameters of RA patients who are at high risk for deterioration of mental health during the pandemic. In our study, the scores obtained from the scales assessing QoL, mood, and COVID-19 fear/stress were similar in both rheumatic diseases. Disease activity of RA measured by SDAI and CDAI weakly correlated with COVID-19 stress. However, there was a moderate positive relationship between RAQoL and COVID-19 stress. The potential of RAQoL to affect disease activity scores should also be considered. As a result, QoL in RA patients might have a greater effect on COVID-19 stress than disease activity. Moreover, the further isolation during the pandemic may have affected the QoL of these patients.
Age is thought to play a remarkable role in the perceived risk of COVID-19 infection. Mistry et al. [23] noted that elderly people in Bangladesh had a significant fear of COVID-19 and needed mental support. Conversely, Andrade et al. [24] reported a higher fear of COVID-19 in younger individuals. In our study, age and the COVID-19 stress scores had a low positive correlation, while age was a predictor of the COVID-19 stress scores with a significant effect in the multiple linear regression model. Due to the increased possibility of comorbidities in older age [25], we examined whether comorbidities affected the evaluated scale scores, but no significant effect was found. The exposure of the elderly to isolation may have also impacted COVID-19-related stress. As we mentioned earlier, isolation due to the pandemic could have increased stress by decreasing QoL [21].
The strength of the study is that it provides multidimensional assessments of COVID-19-related fear and stress, taking into account factors such as disease activity, QoL, anxiety, depression, hospital visits, and vaccination status. However, this study has some limitations. First, most of the collected data were based on self-report scales and questionnaires. Additionally, healthy volunteers were not included as a control group. Last, the fact that our study was cross-sectional and did not contain similar data from the pre-pandemic period prevented us from making relevant comparisons.
Conclusion
This study showed that anxiety is an independent risk factor for COVID-19-related fear and stress scores in individuals with AxSpA and RA. Age and COVID-19 vaccine doses were other important predictors affecting the fear of COVID-19 and COVID-19 stress scores, respectively. COVID-19-related fear or stress, QoL, anxiety, depression, disease activity, and the number of vaccine doses potentially interact with each other, and there is confusion as to which are pre-existing and which might trigger the other(s). The overall health of this patient group is the common goal for rheumatologists, and factors, including the pandemic, that possibly affect all sub-components of health should continue to be investigated to improve rheumatic patients’ well-being.
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.
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Hüseyin Kaplan, Gizem Cengiz, Emre Şenköy, Senem Şaş. Evaluation of COVID-19-related fear/stress and associated factors in patients with axial spondyloarthritis and rheumatoid arthritis. Ann Clin Anal Med 2023;14(12):1072-1076
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Can analgesia with intercostal catheter be an alternative to epidural analgesia for thoracotomy? A prospective study
Cigdem Yıldırım Guclu 1, Başak Ceyda Meco 1, Ahmet Onat Bermede 1, Suheyla Karadag Erkoc 1, Bulent Mustafa Yenıgun 2, Bengi Safak 1, Aysegul Guven 1
1 Department of Anesthesiology and ICU, 2 Department of Thoracic Surgery, Faculty of Medicine, Ankara University, Ankara, Turkey
DOI: 10.4328/ACAM.21769 Received: 2023-05-27 Accepted: 2023-07-03 Published Online: 2023-10-14 Printed: 2023-12-01 Ann Clin Anal Med 2023;14(12):1077-1080
Corresponding Author: Suheyla Karadag Erkoc, Department of Anesthesiology and ICU, Faculty of Medicine, Ankara University, Ankara, Turkey. E-mail: suheylakaradag@hotmail.com P: +90 506 39948 39 Corresponding Author ORCID ID: https://orcid.org/0000-0001-5086-5916
This study was approved by the Ethics Committee of Ankara University Faculty of Medicine (Date: 2018-12-10, No: 20-1370-18)
Aim: Thoracic epidural analgesia is known as the gold standard for a thoracotomy. An intercostal nerve block may be an alternative, but there are limited data in the literature about analgesia provided by intercostal catheters. This study was designed to compare the efficacy of thoracic epidural analgesia and analgesia provided by an intercostal nerve block in thoracotomy.
Material and Methods: Patients undergoing open thoracotomy were included in the study and divided into two groups. In the intercostal catheter group, the surgeon placed the intercostal catheter into the intercostal space, and in the epidural catheter group, an anesthesiologist placed the epidural catheter at the end of the surgery. A blinded anesthesiologist recorded the postoperative pain follow-up using the visual analog scale (VAS) score at rest, during movement, and during coughing. Standard monitoring and anesthetic protocols were applied to all patients.
Results: In total, 102 patients were included in this study. There was a significant difference between the groups in the VAS values at rest both at 12 and 24 hours (p:0,004). The VAS values during movement showed differences only at the 48th hour of follow-up. The VAS score for chest tube removal time showed no difference.
Discussion: Postthoracotomy pain is one of the most challenging problems for thoracic anesthesiologists and surgeons. Epidural analgesia is the gold standard; however, further studies are needed to prove the effectiveness of alternative methods. The results of this study suggest that an intercostal nerve block with a catheter can be a good alternative to thoracic epidural analgesia.
Keywords: Thoracic Surgery, Postoperative Pain, Intercostal Block, Thoracic Epidural Block
Introduction
Thoracotomy is one of the most painful surgical procedures performed. Surgical incisions, rib damage, drains, suturing techniques, and chest tubes may cause postoperative pain [1]. Providing analgesia after thoracotomy is essential not only for analgesia but also to aid respiratory mechanics during recovery. Many protocols have been used for postoperative analgesia, including systemic analgesics and regional methods. Although epidural analgesia is known as the gold standard for pain relief after thoracic surgery, it may result in some undesirable systemic effects, such as hypotension. Thoracal epidural analgesia (TEA) has been found to be superior to systemic opioids in terms of pulmonary function and analgesia. However, there are limited data regarding analgesia provided by intercostal catheters in the literature.
An intercostal block (ICNB) is often placed by the surgeon under direct visualization of the nerve bundle at the conclusion of the case as an adjunct in multimodal postthoracotomy analgesia. The short analgesia time limits the use of ICNB because of the high systemic absorption of local anesthetic drugs in the intercostal space. Although ICB has been shown to be superior to systemic opioids alone, it has been found to be inferior to TEA [1].
This randomized prospective, single-center study was designed to compare the postoperative analgesic effects of ICNB and TEA in patients undergoing elective thoracotomy. The main objective of this study was to compare the VAS scores between the two techniques.
Material and Methods
Patients included in the study underwent open thoracotomy over the six-month period after Ethics Committee approval. The exclusion criteria were age <18 years, <40 kg, body mass index (BMI) >35 kg/m2, bleeding diathesis, opioid use, allergy to drugs to be used in the study and multicostal incisions.
The 102 included patients, aged 18-75 years and classified ASA I-II, were divided into two groups by sequential randomization. The Ethics Committee of the Ankara University University Medical Faculty approved the study protocol (20-1370-18, 10.12.2018) and (the clinical trial number NCT03721250). Written informed consent was obtained from all patients.
Demographic data, preoperative medications, and the surgical and medical histories of the patients were obtained and recorded. In the operating room, standard monitoring was performed using electrocardiography (ECG), noninvasive blood pressure measurement, and oxygen saturation measurement. In addition, bispectral index monitoring was used to ensure standardization for anesthesia maintenance. After induction with fentanyl, lidocaine, propofol, and rocuronium, patients were intubated with a double-lumen tube, and tube placement was controlled with a bronchoscope. Anesthesia was maintained with desflurane at a BIS level of 50-55. During anesthesia maintenance, rocuronium and fentanyl (1 mcg/kg) were administered hourly. During skin incision closure, paracetamol (1 g, IV) was administered to all patients. For the intercostal catheter group (Group ICNB, Group I), the surgeon placed the intercostal catheter in the intercostal space by direct visualization at the end of surgery, which was mostly at T5 level. The incisions were of similar width. For the epidural catheter group (Group TEA, Group II), an anesthesiologist placed the epidural catheter between the T6-8 epidural space and administered the test dose of 40 mg lidocaine. After extubation of the patient, analgesic infusion was started in the intercostal group. In the epidural group, the infusion was started with the movement of the patient’s legs to confirm that there was no motor block. The dose of bupivacaine used as an analgesic was set at 400 mg/day for both groups; the infusion rate of analgesic was the same in both groups. To reduce the risk of postoperative nausea and vomiting, 4 mg of ondansetron was administered intravenously at the end of surgery. A blinded anesthesiologist recorded the intraoperative and postoperative data, and postoperative pain was evaluated using the visual analog scale (VAS). Paracetamol, diclofenac, and dolantin were ordered as rescue analgesics when the VAS score was > 4. Catheters in both groups were removed as the chest tube was removed. VAS scores were recorded at rest, during movement, and during coughing at 30 minutes and 1, 2, 6, 12, 18, 24, 48, and 72 hours after the procedure. The amount of each analgesic administered during the postoperative period was recorded. Patients were asked about their satisfaction after catheter removal, in order to get a yes or no answer.
According to a published study using postoperative pain assessed by VAS scores as the primary outcome variable, the expected difference between the means was calculated as 1.2 with a standard deviation of 1.5. Assuming the power of our study to be 80% and an alpha error of 0.05, the sample size was calculated as 45.
The data collected from the patients were entered into Epidata. The VAS pain score data recorded at successive time points (1, 2, 6, 12, 24, and 48 h after surgery) for patients in each group were compared using the Mann-Whitney U test. STATA 11 (Stata Corp., College Station, Texas, USA) was used as the statistical software. The results were considered statistically significant at p <0.05 [2].
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
A total of 102 patients (54 in the ICB group and 48 in the TEA group) were included in this study. The demographic characteristics were similar in the two groups (Table 1).
VAS scores were recorded at rest, during movement, and during coughing at 30 min and at 1, 2, 4, 6, 12, 24, and 48 hours after the procedure. There was no significant difference between the two groups in the use of analgesics in the postoperative period.
There was a significant difference among groups in VAS pain scores recorded at rest at the 12th hour (4.5±1.3 for Group 1 and 6.2±2.3 for group 2, P=0.004), 24th hour (2.5±1.6 for Group 1 and 4.4±1.7 for Group 2, P=0.004) and 48th hour (0.8±1.2 for Group 1 and 3.4±1.3 for Group 2, P=0.043) (Table 2).
The VAS values during movement showed differences only at one time interval. At the 48-hour follow-up, the VAS score was 2.6±19 for Group 1 and 4.3±1.4 for Group 2, and the p- value was 0.003. Other recorded VAS values were not significantly different between the two groups (p>0.05) (Table 3).
Cough had a strong impact on pain in the postthoracotomy patients. According to our results, the patient’s pain assessment during coughing did not differ between the groups (p values was > 0,05 in all time periods)
Mean VAS scores during the chest tube removal procedure were statistically different (0.54 ± 1.05 for Group 1 and 0.8±0.8 for Group 2, p=0.043). Patient satisfaction was significantly different between Group 1 and Group 2 (9.15 ± 1.04 and 7.47±1.9, respectively, p=0.00).
There were no statistically significant differences among the groups in terms of the first analgesic requirement (p=0.463), maximum VAS score (p=0.524), or total opioid requirement (p=0.255). No serious catheter-related complications were observed in either group.
Discussion
Postthoracotomy pain is one of the most challenging problems for thoracic anesthesiologists and surgeons. Pain related to thoracotomy is due to skin incision, chest wall pleural damage, rib retraction, and chest tubes. Maintaining effective analgesia not only provides pain reduction but also helps recover respiratory dynamics during postoperative period. Epidural analgesia is known to be the gold standard; however, further studies are needed to prove the effectiveness of alternative methods such as intercostal catheter block, which can also provide analgesia during thoracotomy.
This study concluded that intercostal catheters may be an alternative analgesic method in thoracotomies. The study found that placement of the intercostal catheter was easier than placement of the epidural catheter when performed by direct visualization. In addition, intercostal catheters may have been advantageous in terms of potential complications and intercostal blockages did not have systemic effects as concluded in other studies [2].
Many multimodal analgesic regimens have been used, such as nonsteroidal anti-inflammatory drugs, NMDA receptor antagonists, acetaminophen, gabapentinoids, opioids, thoracic epidural analgesia, intercostal nerve blocks, paravertebral blocks, erector spinae plane blocks, and serratus anterior block [1,3]. Intravenous analgesic regimens containing fentanyl alone do not provide sufficient efficacy in preventing postthoracotomy pain, and patients require high-dose rescue analgesics. The effective use of regional techniques is important in multimodal analgesia [4].
Thoracic epidural analgesia was the gold standard until other less invasive methods began to play a role in analgesia management. In addition, adverse events experienced with thoracic epidural have led to the search for an alternative method that provides effective analgesia. In addition to being more invasive, thoracic epidural analgesia has some unwanted side effects, such as intradural puncture, respiratory failure, dura perforation, bradycardia, hypotension, nausea and vomiting, itching, urinary retention, and catheter-related infection [5]. In addition, difficulties may be encountered in epidural catheter placement due to anatomical factors, such as scoliosis or previous spinal operations. Compared with thoracic epidural catheters, intercostal catheter replacement is much easier. Because the intercostal nerve block inhibits intercostal nerve transmission at the distal portion of the intercostal nerve, no systemic side effects are expected.
An intercostal nerve block can be performed at more than one level for postthoracotomy pain, and it can be equivalent to TEA in the first 24 hours. Long-term analgesia can be achieved with continuous infusion of local anesthetic provided by an intercostal catheter. Wurnig et al. showed that TEA was superior to ICNB after the first 24 h. In this study, the VAS scores were similar among the groups, except for three-time intervals. In particular, the VAS values recorded during movement and coughing were similar [6] .
A study by Vilvanathan et al. did not show a statistically significant difference between TEA and ICNB, but opioid infusion was included in their protocol [2]. In our clinical practice, we want to reduce opioid use in postoperative pain management especially in postthoracotomy patients; therefore, we used opioids only as rescue analgesics.
Debreceni et al. compared ICNB and TEA in thoracotomies and found that the TEA group needed fewer narcotics for breakthrough pain and showed lower VAS scores. They found no differences in pulmonary function between the groups. They concluded that TEA is superior to ICNB after thoracotomies [7].
In the study by Luketich et al., analgesia provided by ICNB was equivalent to that provided by TEA. The absence of the disadvantages encountered with TEA makes ICNB a good alternative [8]. In our study, ICNB was found to be superior at some time intervals, which supports ICNB as an alternative analgesic method.
Rice et al. concluded that ICB is comparable to TEA as an intercostal block for thoracotomy when liposomal bupivacaine is used in ICNB. Liposomal bupivacaine is effective for 72 hours and can be used instead of a catheter. They pointed out that TEA requires monitoring that can incur additional costs [9].
Kawagoe et al. performed a study using robotic thoracic surgery, which compared TEA with ICNB with IV PCA. They found that TEA was superior to ICNB for analgesia [4].
Concha et al. compared 5-segment intercostal block IV PCA morphine with PCA bupivacaine and fentanyl infusions through thoracic epidural catheters. They concluded that an intercostal block with bupivacaine plus intravenous PCA morphine is a good alternative to thoracic epidural analgesia for postthoracotomy pain management [10]. We have studied open thoracotomies, which are more painful than robotic thoracotomies. This difference in pain level between the two types of surgical interventions may be a factor in the superiority of TEA.
A study by Sagiroglu et al. compared TEA and ICNB in postthoracotomy patients that used morphine as rescue medicine. Their results concluded that better pain control was achieved with the thoracic epidural technique [11]. The results of our study showed that, especially during coughing and movement, which may be related to more pain, the ICNB method was as effective as TEA.
During the design period of our study, we decided that continuous pain treatment was crucial for thoracic surgery, that patients require effective analgesia until their chest tube is removed. Therefore, we compared these two continuous methods. In our study, the results showed that continuous ICNB can be as effective as TEA. At some postoperative time periods, ICNB was even superior to TEA.
Limitations
Our study had limitations. Because we prioritized analgesia, there were no hemodynamic records of hypotension, which may be caused by TEA. We did not evaluate the cost, postoperative complications, length of stay, or respiratory dynamics using pulmonary function tests. Also, pain perception of patients may differ, so when assessing pain at the 12th hour, a confusing result was obtained.
Conclusion
In conclusion, postthoracotomy pain management is an important issue for both anesthesiologists and surgeons. Unsatisfactory pain control can ruin all work and may result in chronic pain. Performing ICNB is easier and safer than performing TEA. The results of our study show that analgesia provided by intercostal blockage and maintenance of analgesia with a catheter can be an alternative method to epidural analgesia for thoracotomy.
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. Marshall K, McLaughlin K. Pain Management in Thoracic Surgery. Thoracic Surgery Clinics 2020;30(3):339-46.
2. Vilvanathan S, Kuppuswamy B, Sahajanandan R. A Randomized Control Trial to Compare Thoracic Epidural with Intercostal Block Plus Intravenous Morphine Infusion for Postoperative Analgesia in Patients Undergoing Elective Thoracotomy. Annals of Cardiac Anaesthesia. 2020;23 (2):127-33.
3. Kelsheimer B, Williams C, Kelsheimer C. New Emerging Modalities to Treat Post-Thoracotomy Pain Syndrome: A Review. Mo Med. 2019;116(1):41-4.
4. Kawagoe I, Hayashida M, Satoh D, Kochiyama T, Fukuda M, Kishii J. Postoperative analgesia in patients undergoing robot-assisted thoracic surgery: a comparison between thoracic epidural analgesia and intercostal nerve block combined with intravenous patient-controlled analgesia. Ann Palliat Med. 2021;10(2):1985-93.
5. Leslie K, Myles P, Devereaux P, Williamson E, Rao-Melancini P, Forbes A, et al. Neuraxial block, death and serious cardiovascular morbidity in the POISE trial. Br J Anaesth. 2013;111(3):382-90.
6. Wurnig PN, Lackner H, Teiner C, Hollaus PH, Pospisil M, Fohsl-Grande B, et al. Is intercostal block for pain management in thoracic surgery more successful than epidural anaesthesia? Eur J Cardiothorac Surg. 2002;21(6):1115-19.
7. Debreceni G, Molnár Z, Szélig L, Molnár TF. Continuous epidural or intercostal analgesia following thoracotomy: a prospective randomized double-blind clinical trial. Acta Anaesthesiol Scand. 2003; 47(9):1091-5.
8. Luketich J, Land SR, Sullivian EA, Alvelo-Rivera M, Ward J, Buenaventura PO, et al. Thoracic Epidural Versus Intercostal Nerve Catheter Plus Patient-Controlled Analgesia: A Randomized Study, Ann Thorac Surg 2005;79(6):1845-50.
9. Rice DC, Cata JP, Mena GE, Rodriguez-Restrepo A, Correa AM, Mehran RJ. Posterior Intercostal Nerve Block with Liposomal Bupivacaine: An Alternative to Thoracic Epidural Analgesia. Ann Thorac Surg. 2015;99(6):1953-60.
10. Concha M, Dagnino J, Cariaga M, Aguilera J, Aparicio R, Guerrero M. Analgesia after thoracotomy: epidural fentanyl/bupivacaine compared with inter- costal nerve block plus intravenous morphine. J Cardiothorac Vasc Anesth. 2004; 18(3):322-6.
11. Sagiroglu G, Baysal A, Kiraz O, Meydan B, Taşçı A, Iskender I. Comparison of continuous use of thoracic epidural analgesia and intercostal block for pain management after thoracotomy. Kardiochirurgia i Torakochirurgia Polska/Polish J of Thorac and Cardiovasc Surg. 2013;10(3):244-50.
Download attachments: 10.4328.ACAM.21769
Cigdem Yıldırım Guclu, Başak Ceyda Meco, Ahmet Onat Bermede, Suheyla Karadag Erkoc, Bulent Mustafa Yenıgun, Bengi Safak, Aysegul Guven. Can analgesia with intercostal catheter be an alternative to epidural analgesia for thoracotomy? A prospective study. Ann Clin Anal Med 2023;14(12):1077-1080
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Culture results of lumbar puncture samples in the emergency ward: A descriptive study
Mehmet Fatih Korcak 1, Arzu Denizbasi 2, Ozge Ecmel Onur 2
1 Department of Emergency Medicine, University of Health Sciences, Bursa Yuksek Ihtisas Training and Research Hospital, Bursa, 2 Department of Emergency Medicine, Faculty of Medicine, Marmara University, Istanbul, Türkiye
DOI: 10.4328/ACAM.21785 Received: 2023-06-09 Accepted: 2023-08-24 Published Online: 2023-09-05 Printed: 2023-12-01 Ann Clin Anal Med 2023;14(12):1081-1085
Corresponding Author: Mehmet Fatih Korcak, Department of Emergency Medicine, University of Health Sciences, Bursa Yuksek Ihtisas Training and Research Hospital, Yildirim, Bursa, Türkiye. E-mail: mehmetfkorcak@gmail.com P: +90 542 335 55 20 Corresponding Author ORCID ID: https://orcid.org/0000-0001-5883-6618
This study was approved by the Ethics Committee of Marmara University Medical Faculty (Date: 2015-10-02, No: 09.2015.260)
Aim: This study aimed to present diagnostic procedures in patients admitted to an emergency department who underwent lumbar puncture (LP) due to suspected bacterial meningitis.
Material and Methods: The study included patients admitted to the emergency department between 01 January 2013 and 31 December 2015. Patients who underwent lumbar puncture with a differential diagnosis of acute bacterial meningitis (ABM) were included in the study. The hospital patient registry was searched for the procedure “Spinal tap” in the emergency room (ER).
Results: Of the 412 patients, 50.5% (n=208) were children aged <9 years. The median age was 9 years, ranging from 0 to 93. The sex distribution was as follows: 183 (44.4%) females and 229 (55.6%) males. Of the 875 112 admissions to the ER, 412 (4.7 per 1000) underwent a spinal tap due to suspected ABM. A seasonal variation was observed in the number of applications with November and December having the maximum frequencies. In 297 (72.1%) cerebrospinal fluid (CSF) samples, bacterial infection was suspected. Of the 381 samples (92.4%) sent for culture, 10.0% (n=41) were positive. The most commonly encountered pathogens were S. aureus and skin flora (both 56.1%, n=23). Computed tomography investigation was prescribed before the LP procedure to 276 patients (67.0%).
Discussion: Turkey should introduce clear policies in managing patients requiring spinal taps in the emergency wards, including the conditions to prevent contamination and ordering computed tomography. Necessary training should be planned for the hospital staff from these perspectives.
Keywords: Lumbar Puncture, Bacterial Meningitis, Cerebrospinal Fluid, Emergency Room
Introduction
Background/rationale
Meningitis is an infectious disease characterized by infection of leptomeninges and underlying subarachnoid cerebrospinal fluid (CSF). Meningitis is the most common cause death frominfectious diseases. It is estimated that one million cases of bacterial meningitis occur each year worldwide, of which 200,000 die Case fatality rates vary with age at the time of illness and the species of bacterium causing infection. The mortality range is 3%–19% in developed countries and 37%–60% in developing countries. Up to 54% of survivors remain disabled due to bacterial meningitis [1].
Acute meningitis is a clinical condition in which meningeal symptoms occur within hours or days. Chronic meningitis, on the other hand, may take weeks. Headache is usually the earliest symptom, followed by confusion or coma [2]. The etiological distribution of meningitis varies considerably depending on age, geographical differences, season, sensitivity to certain factors, genetic structure, socioeconomic conditions, and local endemic factors [3]. In spite of the advances in diagnosis and antimicrobial therapy, meningitis continues to be one of the important causes of permanent sequelae in humans [4].
The main purpose in a patient with meningitis is to diagnose and start effective treatment as soon as possible. Immediate empirical antimicrobial therapy should be initiated after the CSF culture sample is taken, and then appropriate treatment should be performed according to the clinical and laboratory findings [3,5]. Thus, interventions in the emergency ward and the reliability of the diagnostic procedures are of utmost importance.
Objectives
We hypothesized that the proportion of spinal taps ordered in our hospital and their results are similar to the literature. This study aimed to present diagnostic procedures in patients admitted to the emergency department who underwent lumbar puncture (LP) due to suspected bacterial meningitis.
Material and Methods
Study design
The study was conducted in a cross-sectional plan. Study reporting was done following the STROBE guidelines [6]. The research protocol was approved by the Local Ethics Committee at Marmara University Medical Faculty (IRB number: 09.2015.260; Date: 02 October 2015).
Setting
The investigation was performed at the Emergency Wards of the Marmara University Pendik Education and Research Hospital during January 2016. The study hospital is a tertiary care health center in Istanbul with 600 inpatient bed capacity. The emergency department welcomes annually around 300 000 patients (http://actad.tip.marmara.edu.tr/genel-bilgiler/).
Participants
The study comprised patients admitted to the emergency department between 01 January 2013 and 31 December 2015. Patients who underwent lumbar puncture with a differential diagnosis of acute bacterial meningitis (ABM) were included in the study. The hospital patient registry was searched for the procedure “Spinal tap” in the emergency room (ER). Patients who underwent lumbar puncture due to reasons other than suspected bacterial meningitis (subarachnoid hemorrhage, central nervous system malignancies, demyelinating diseases, Guillain-Barré syndrome) were excluded from the study. Data from 412 patients were analyzed (Figure 1).
Variables
The study data were obtained from the hospital’s electronic medical records. The primary outcome variable of the study was culture positivity. The secondary outcome was the type of the pathogens grown in the culture. Other variables studied were age, sex, study date, computed tomography (CT) investigation before LP, and duration of hospitalization.
Bias
To prevent bias, data was collected by one researcher and approved by another investigator. Additionally, error checking and debugging were made after entering data into the computer.
Study size
The required sample size was calculated based on a 10.5% expected positivity in the CSF cultures. Given an unknown population and a margin of error of 3%, a sample size of 402 cases is required to estimate positive cultures in the study population with a confidence interval of 95%.
Statistical methods
Data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 25.0 software (SPSS Inc., Chicago, IL, USA). The results were presented as frequencies, percentages, means, and standard deviations (SD). The Kolmogorov–Smirnov test was performed to test if the numerical variables were normally distributed. The independent samples t-test or One-way ANOVA was used to compare data meeting parametric assumptions. The Mann-Whitney U or Kruskal-Wallis tests were used for skewed variables, and the Chi-Square test was used for categorical variables. A p value of <0.05 was considered statistically significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Participants
Of the 412 patients, 50.5% (n=208) were children aged <9 years, 12.6% (n=52) were adolescents (age 10-19 years), 26.5% (n=109) were adults (age 20-64), and 10.4% (n=43) were elderlies (>64 years). Their median age was 9 years, ranging from 0 to 93. The sex distribution was 183 (44.4%) females / 229 (55.6%) males.
Descriptive data
Of the 875 112 admissions to the ER, 412 (4.7 per 1000) underwent a spinal tap due to suspected ABM. The number of applications ranged from 22 to 52 per month, with November and December having the maximum frequencies (Figure 2).
Outcome data
All patients underwent a direct microscopic investigation of the CSF; 297 (72.1%) of the samples were suspected of bacterial infection. However, 381 (92.4%) of the CSF samples were sent for culture. Of the samples sent for culture, 10.0% (n=41) were positive. Only one pathogen could be isolated from most of the samples. Nevertheless, two agents were grown from 11 samples (26.8%), and three pathogens grew in one case (2.4%). The distributions of the pathogens grown are seen in Table 1. Culture positivity was 11.2% (n=19) among females and 10.4% (n=22) among males; the difference was not statistically significant (Chi-Square=0.073; p=0.787). Additionally, a computed tomography investigation was prescribed before the LP procedure to 276 patients (67.0%).
The median duration of hospitalization was 2 days (min. 1, max. 72 days). Patients with S. aureus and H. influenza grown had significantly longer hospitalization times compared to others (Table 2). There was no difference between the age groups concerning the duration of hospitalization (F=0.210; p=0.890). Also, no difference was found between sex and length of hospitalization (Z=1.742; p=0.082).
Discussion
Key results
Applications to the emergency service (ER) ending in lumbar puncture ranged from 22 to 52 per month. The highest frequencies were observed in November and December. In the ER, a spinal tap was performed at a rate of 4.7 per 1000 patients. Direct microscopic examination was performed to all CSF samples, and 92.4% were sent for culture. 10.0% of the culture results returned positive. A single pathogen was isolated from most samples. However, 29.2% of the samples had more than one pathogen grown.
Interpretation
Köse et al. [7] reported a mean age of 45 among adult ABM patients with a male/female distribution of 54.3%/47.8%. In the study conducted by Erdem et al., the mean age of patients diagnosed with ABM over age 50 was found 63 years [8]. Studies on pediatric patients in Turkey reported the median age as 3.5 with a boy/girl ratio of 1.29:1 [9] and a mean age of 4.74 with an equal male/female ratio [10].
It has been already proven that bacterial meningitis has a seasonal pattern. Countries in the African meningitis belt, for example, are known for peak incidence during the dry season. A persistent seasonality was detected in 96% of the 51 time-series from 38 countries, demonstrating a seasonal peak during the winter months in both hemispheres [11]. It was hypothesized that there is a potential relationship between climate and the seasonality of bacterial meningitis across a broad geographic range [12]. We agree with the postulation that climatic conditions may facilitate pathogen invasion by damaging the nasopharyngeal mucosa [13].
The final diagnosis of ABM is made by CSF culture. Bacterial growth in culture medium was reported as 60-80% [14]. In Turkey, causative agents could be isolated from cultures ranging from 38.6% [18], 45.4% [10] to 92.5% [11]. In a retrospective study by Ghotaslou et al. [15] from Iran, the most frequent etiologic pathogens of ABM were reported as S. pneumoniae, H. influenzae, Enterobacter spp, and N. meningitidis. In the retrospective study from Greece, covering the years 1974 to 2005 in the pediatric age group, N. meningitidis ranked first among all age groups throughout the years, whereas unspecific bacteria (Streptococcus spp, Enterobacter spp, Salmonella spp., and Rickettsiae spp) and H. influenzae, S. pneumoniae were included in the etiology of ABM as other causative pathogens [16].
When we look at the distribution of pathogens in our patients with CSF culture, Staphylococcus spp was the most common species. The Staphylococcus spp. infection colonizes the mucosa and skin, causes a wide range of skin and soft tissue infections, bacteremia, infective endocarditis, osteomyelitis, splenic abscesses, sepsis, and septic shock in patients having prosthetic valves or being immune compromised [17]. As a cause for ABM, Staphylococcus spp. is frequently encountered after head trauma and neurosurgical operations, and less frequently secondary to bacteremia [18]. In our study, Staphylococcus spp. and skin flora were the most frequently grown bacteria in the CSF cultures. Keeping in mind that this result has a negative impact of the patients and the culture outcomes, we may conclude that the study hospital has unsuitable conditions for lumbar puncture and that the spinal tap procedures are performed in insufficiently sterile conditions.
In a study performed by Arda et al. [19], the frequency of agents causing ABM in decreasing order was determined as S. pneumoniae, N. meningitidis, and Staphylococcus aureus. In another study by Erdem et al. [8] in adult patients over 50 years of age, the causative pathogens were mentioned as S. pneumoniae, Listeria monocytogenes, and Staphylococcus epidermidis. On the other hand, in the study of Köse et al. [7], the following frequencies were reported: S. pneumoniae, Acinetobacter spp, and Listeria monocytogenes.
In studies performed in Turkey among pediatric patient groups, the most common pathogens were N. meningitidis followed by S. Pneumoniae; Haemophilus influenzae type B was not observed in any patient [9]. After the ceftriaxone molecules were introduced to Turkey in 1988, the prevalence of S. pneumoniae, a highly resistant bacteria to penicillin, started to decrease [20]. Furthermore, between 1974 and 1986, 295 patients were diagnosed with ABM, and in 76.4% of these patients, N. meningitidis was the causative pathogen; a majority of the cases were reported from military units. The incidence of ABM due to N. meningitidis ceased after 1995, with the introduction of routine vaccination in the military units [21].
In this study, 276 patients (67.0%) underwent cranial CT imaging before LP. However, the CT scan time is accused of prolonging the LP procedure and delaying the diagnosis and antibiotic initiation [22]. A prospective study of 307 cases by Hasbun et al. [23] reported that CT scan causes a 2-hours delay in diagnosing ABM and one-hour delay in starting treatment. In 2009, Sweden revised its guidelines and removed cranial CT from the list of initial tests to be performed in impaired mental status [24]. This policy change shortened the duration of IV antibiotic treatment by approximately 1-2 hours and resulted in a 7-12% reduction in mortality. Besides, the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) published in 2016 [25] recommends cranial CT before lumbar puncture in the following conditions: Glasgow Coma Scale (GCS) <10, presence of focal neurological deficits (except cranial nerve palsy), presence of a recently developed seizure, severe mental state deterioration, and severely impaired immune system. We believe that Turkey requires an urgent policy change from the perspective of correctly utilizing CT investigations.
Limitations
Study data collection was based on the hospital’s electronic patient registry. Thus, we could not obtain information on the basis of which the doctors came to the diagnosis of ABM. Likewise, we could not retrieve the exact count of spinal tap indications. More reliable and less missing data could be obtained if the data were collected directly on-site. However, given the long duration of the study period, this was not feasible.
Conclusion
ABM is an infectious disease with high morbidity and mortality requiring early diagnosis and treatment. Therefore, meningeal irritation findings should be investigated in patients presenting with headache, fever, nausea, vomiting, and change of consciousness. Our study demonstrated that despite the relatively high number of lumbar punctures performed in the hospital the proportion of positive findings was comparatively low. There were clues suggesting that lumbar punctures under emergency service conditions were not performed under sterile conditions. Turkey should introduce clear policies in managing patients requiring spinal taps in the emergency wards, including requirements to prevent contamination and ordering computed tomography. Necessary trainings should be planned for the hospital staff from these perspectives.
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.
References
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2. Tunkel AR, Hasbun R, Bhimraj A, Byers K, Kaplan SL, Scheld WM, et al. 2017 Infectious Diseases Society of America’s clinical practice guidelines for healthcare-associated ventriculitis and meningitis. Clin Infect Dis. 2017;64(6):e34–65.
3. Bennett JE, Dolin R, Blaser MJ. Principles and practice of infectious diseases. vol. 1. Elsevier Health Sciences; 2014. p. 1097-137. e8.
4. Aneja S. Acute bacterial meningitis–early diagnosis and complications. Indian J Pediatr. 2015;82(4):303–5.
5. Hersi K, Kondamudi NP. Meningitis, Treasure Island (FL): 2018.
6. Von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: Guidelines for reporting observational studies. PLoS Med 2007;4:1623–7.
7. Köse S, Göl B, Atalay S, Akkoçlu G. [Evaluation of Five-Year Meningitis Cases in Tepecik Training and Research Hospital, Izmir, Turkey] (in Turkish). KLIMIK Derg 2013;26:54.
8. Erdem H, Kilic S, Coskun O, Ersoy Y, Cagatay Y, Onguru P, et al. Community-acquired acute bacterial meningitis in the elderly in Turkey. Clin Microbiol Infect. 2010;16(8):1223-9.
9. Ceyhan M, Ozsurekci Y, Gürler N, Karadag E, Camcioglu Y, Salman N, et al. Bacterial agents causing meningitis during 2013–2014 in Turkey: A multi-center hospital-based prospective surveillance study. Hum Vaccin Immunother. 2016;12(11):2940-5.
10. Işıkay S, Yılmaz K. [Acute bacterial meningitis in childhood: evaluation of 20 cases] (in Turkish). Gaziantep Med J 2013;19:93–8.
11. Paireau J, Chen A, Broutin H, Grenfell B, Basta NE. Seasonal dynamics of bacterial meningitis: a time-series analysis. Lancet Glob Heal 2016;4:e370-7.
12. Agier L, Deroubaix A, Martiny N, Yaka P, Djibo A, Broutin H. Seasonality of meningitis in Africa and climate forcing: aerosols stand out. J R Soc Interface 2013;10:20120814.
13. Greenwood B. Manson Lecture. Meningococcal meningitis in Africa. Trans R Soc Trop Med Hyg 1999;93:341–53.
14. Brouwer MC, Tunkel AR, van de Beek D. Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. Clin Microbiol Rev 2010;23:467–92.
15. Ghotaslou R, Yeganeh-Sefidan F, Salahi-Eshlaqi B, Ebrahimzadeh-Leylabadlo H. Etiology of acute bacterial meningitis in Iran: A systematic review. Acta Med Iran 2015;53:454–61.
16. Theodoridou MN, Vasilopoulou VA, Atsali EE, Pangali AM, Mostrou GJ, Syriopoulou VP, et al. Meningitis registry of hospitalized cases in children: epidemiological patterns of acute bacterial meningitis throughout a 32-year period. BMC Infect Dis 2007;7:101.
17. Pintado V, Meseguer M, Fortun J, Cobo J, Navas E, Quereda C, et al. Clinical study of 44 cases of Staphylococcus aureus meningitis. Eur J Clin Microbiol Infect Dis. 2002; 21(12):864-8.
18. Aguilar J, Urday-Cornejo V, Donabedian S, Perri M, Tibbetts R, Zervos M. Staphylococcus aureus meningitis: case series and literature review. Medicine (Baltimore) 2010;89:117–25.
19. Arda B, Sipahi OR, Atalay S, Ulusoy S. Pooled analysis of 2,408 cases of acute adult purulent meningitis from Turkey. Med Princ Pract 2008;17:76–9.
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22. Gopal AK, Whitehouse JD, Simel DL, Corey GR. Cranial computed tomography before lumbar puncture: a prospective clinical evaluation. Arch Intern Med 1999;159:2681–5.
23. Hasbun R, Abrahams J, Jekel J, Quagliarello VJ. Computed tomography of the head before lumbar puncture in adults with suspected meningitis. N Engl J Med 2001;345:1727–33.
24. Glimåker M, Johansson B, Grindborg Ö, Bottai M, Lindquist L, Sjölin J. Adult bacterial meningitis: earlier treatment and improved outcome following guideline revision promoting prompt lumbar puncture. Clin Infect Dis 2015;60:1162–9.
25. Van de Beek D, Cabellos C, Dzupova O, Esposito S, Klein M, Kloek AT, et al. ESCMID guideline: diagnosis and treatment of acute bacterial meningitis. Clin Microbiol Infect 2016;22(Suppl.3):S37-62.
Download attachments: 10.4328.ACAM.21785
Mehmet Fatih Korcak, Arzu Denizbasi, Ozge Ecmel Onur. Culture results of lumbar puncture samples in the emergency ward: A descriptive study. Ann Clin Anal Med 2023;14(12):1081-1085
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Effects of pesticides on testes at ultrastructural and hormonal levels
Nejat Ünlükal 1, Gülten Karabay 2, Attila Dağdeviren 2, Nilüfer Bayraktar 3, Ayşe Canan Yazıcı Güvercin 4, Mustafa Agah Tekindal 5
1 Department of Histology and Embryology, Selcuk University, Konya, 2 Department of Histology and Embryology, Başkent University, Ankara, 3 Department of Medical Biochemistry, Başkent University, Ankara, 4 Department of Biostatistics, Tınaztepe University, Izmir, 5 Department of Biostatistics, Faculty of Medicine, Izmir Kâtib Çelebi University, Izmir, Turkey
DOI: 10.4328/ACAM.21809 Received: 2023-07-03 Accepted: 2023-08-07 Published Online: 2023-08-25 Printed: 2023-12-01 Ann Clin Anal Med 2023;14(12):1086-1091
Corresponding Author: Nejat Ünlükal, Department of Histology and Embryology, Selcuk University, 42131, Konya, Turkey. E-mail: nunlukal@selcuk.edu.tr P: +90 332 224 39 16 Corresponding Author ORCID ID: https://orcid.org/0000-0002-8107-4882
This study was approved by the Ethics Committee of Başkent University (Date: 2009-08-25, No: DA 09/30)
Aim: Endocrine disruptors damage the functions of hormones in the body by imitating or blocking them. They and their metabolites change hormone levels and functions in the body. Pesticides constitute a significant group of endocrine disruptors. It is known that Profenofos, and 4-chloro-2-methylphenoxyacetic acid (MCPA) have negative effects on male genital system. However, studies about the effect on ultrastructural size are limited. Therefore, it is intended to compare the effect of MCPA and Profenofos on the ultrastructural level of the testes.
Material and Methods: There were three groups in the study (control, Profenofos, MCPA), each of which included ten fourteen-week-old male rats. Electron microscopy and biochemical investigation were performed on the excluded tissues of the testes.
Results: In histopathologic investigations, spermatogenesis was healthy in the control group. Structural degenerations were observed on spermatogenic cells and Sertoli cells in the profenofos group. The gaps among spermatogenetic cells, cellular degeneration (i.e. structural damage) in the MCPA group was more obvious than in the Profenofos group. Considering the biochemical results, a significant decrease in testosterone level was observed in the animals receiving both profonefos and MCPA.
Discussion: Profenofos and MCPA prevent the healthy continuation of spermatogenesis and therefore may cause infertility.
Keywords: Electron Microscopy, Endocrine Disrupter, Infertility, MCPA, Pesticides, Profenofos, Testes
Introduction
A pesticide is any substance or mixture of substances used in animal husbandry, agriculture, and public health to repel, kill, or keep under control unwanted organisms (pests) such as insects, rodents, fungi, bacteria, and weeds. However, pesticides have toxic effects on the environment and beneficial living organisms. Pesticides also cause toxic effects on humans by leaving residues in soil, water, and food [1]. The toxic effects of pesticides on humans are separated into acute and chronic. The effects of acute poisoning range from nausea, vomiting, and dizziness to death. Chronic exposure gives rise to reproductive toxicity, endocrine system disorders [2, 3].
Profenofos and 4-chloro-2-methylphenoxyacetic acid (MCPA) are pesticides classified as class II (moderately) toxic substances by WHO [(avaible at : https://apps.who.int/iris/handle/10665/332193)]. Profenofos is an organophosphate class insecticide, and MCPA is a chlorophenoxy derivative herbicide [4]. Studies have proven that chlorophenoxy compounds are teratogenic and embryotoxic [5]. Bilateral and unilateral tubular degeneration was noticed in the testes of rats exposed to MCPA. Profenofos causes inhibition of platelet-activating factor acetylhydrolase (PAF-AH). PAF-AH is vital for brain development and testes. PAF-AH inhibition results in severe impairment of spermatogenesis. In studies conducted in rabbits, it was observed that Profenofos disrupts testicular structures, reduces body and testicular weight, creates gaps in seminiferous tubules, leads to destruction and hypertrophy of Leydig cells, and it was concluded that it is an endocrine disrupting chemical [6]. The use of Profenofos in combination with other pesticides increases its genotoxic and cytotoxic effects [7].
Material and Methods
This study was approved by Başkent University Animal Experiments Local Ethics Committee (Project Date: 25.08.2009; Project No: DA 09/30) and supported by Başkent University Research Fund. In the study, three groups of 14-week-old rats were formed with ten male rats in each group. On the first day, 0.5 ml of blood was taken from the tail veins of all animals to measure serum testosterone levels. Profenofos and MCPA doses were selected based on doses which are known to have cytotoxic effects [8, 9].
Group 1 (Control Group): In this group, only distilled water was administered via gavage. They were allowed free access to food and water for one month under normal conditions.
Group 2 (Profenofos Group): In this group, Profenofos (Pestanal, 45632-Fluka, Sweden) was administered to the subject by gavage at a dose of 17 mg/kg on certain days and hours twice a week for one month.
Group 3 (MCPA Group): In this group, MCPA (25190, Fluka, Sweden) was administered by gavage at a dose of 190 mg/kg every day on the specified day and time for one month.
All animals were sacrificed after anesthesia with 60 mg/kg ketamine and 10 mg/kg xylazine. Testicular tissue samples removed from the rats were cut into small pieces and placed in phosphate-buffered 2% glutaraldehyde fixative solution (pH 7.4) for electron microscopy examination. Blood samples taken from the animals on the first and last day were sent to the biochemistry laboratory to measure serum total and free testosterone levels. The tissue samples were fixed with glutaraldehyde and osmium tetroxide, embedded in Araldite, and blocked. From the blocks, 70-90 nm sections were taken on copper grids with a Leica ultramicrotome. The sections were stained with uranyl acetate and lead citrate and photographed under the LEO 906E EM.
All statistical analyses were performed with the IBM SPSS 21.0 package program. Before the analyses, the normality of the data was checked by the Shapiro-Wilk test and Q-Q graphs. Differences between initial and final measurements were analyzed by the Wilcoxon test, and the Kruskal-Wallis test analyzed differences between groups at each measurement time. Pairwise comparisons for parameters found to be significant after the Kruskal-Wallis test were analyzed by Dunn’s test with Bonferroni correction. A significance level of 5% was taken for statistical tests.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Electron Microscope Examination
TEM examination of tissue samples from the control group showed that spermatids, Sertoli cells and Leydig cells at different developmental stages exhibited normal structure, intercellular structures were preserved, and tissues were in normal course. The formation of heterochromatin-rich acrosomal vesicles was observed in round spermatids (Figure 1-A). In spermatids at an advanced stage of development, the nuclear chromatin is condensed, and the centrioles are located at the opposite pole of the developing acrosomal vesicle. In contrast, in spermatids approaching spermiogenesis, the midpiece is fully formed and the mitochondria are regularly arranged (Figure 1-B). Sertoli cells in the basal lamina of the seminiferous tubule and Leydig cells in the interstitial area were found to have normal structures (Figure 1-C). Sertoli cell located in the basal lamina was distinguished by its euchromatin-rich nucleus and prominent nucleolus, while mitochondria and a few electrons-dense granules were observed in the cytoplasm (Figure 1-D). Electron micrographs showed that Leydig cells in the interstitial connective tissue had a natural structure and were located close to capillaries (Figure 1-E). As a result of these findings, the spermatogenesis process was considered healthy.
TEM examination of tissue samples from the Profenofos group showed that some seminiferous tubules retained their normal structure, while others showed significant structural changes. It was observed that acrosome vesicle developed in some round spermatids in the tubules that preserved their integrity. The basal lamina lost its homogeneous structure. It was noted that in the tubules, where structural damage was observed, prominent spaces were formed between the spermatogenic cells, and the integrity of seminiferous epithelium could not be preserved (Figure 2.A). Significant swelling and cristaelysis were observed in the mitochondria of spermatids in the spermatogenesis stage, while the residual bodies in the cell cytoplasm were determined (Figure 2.B). While it was observed that the nucleus of the Sertoli cell lost its normal structure and was rich in heterochromatin in places, swollen cristaelysis mitochondria and residual bodies were observed in the cytoplasm (Figure 2.C). It was observed that the basal lamina of the seminiferous tubule exhibited a wavy appearance in some areas; unlike the control group, there were occasional separations. While residual body formation, large lipid droplets, and widespread vacuolization were observed in the cells forming the walls of these tubules, it was noted that mitochondria had abnormal shapes such as bagels or notches with swelling and cristaelysis. The cytoplasm of Leydig cells in the intermediate connective tissue was less intensely stained (electron-permeable), with cristaelysis mitochondria and autophagic vacuoles (Figure 2.D). Moreover, with regard to the structural damage caused by Profenofos application in cells forming the spermatogenic series, it was observed that Profenofos application caused significant structural disruptions in Sertoli cells. Based on this thin section finding, it was determined that the blood-testes barrier was disrupted, and Profenofos negatively affected the spermatogenesis process.
In the testicular thin sections of the MCPA- administered experimental group, gaps were observed, as in the Profenofos group, between the cells forming the seminiferous tubule epithelium. In some of the spermatogenic cells, chromatin was found to be condensed under the nucleus membrane. The basal lamina of the seminiferous tubule showed a wavy appearance and regional thickening (Figure 3.A). In different field examinations, irregularities in the basal lamina were observed, although damage to the seminiferous tubule wall was less. Cristaelysis and intercellular dilatation were observed in the mitochondria of spermatogonium and spermatocytes. In this group, vacuolization was observed in the electron-dense cytoplasm of Leydig cells in the interstitial area (Figure 3.B). In tubules, where structural damage was evident, gaps between primary spermatocytes, vacuoles in their cytoplasm, and irregularities in cell borders were detected (Figure 3.C-D). Although late spermatids should normally be associated with Sertoli cells, they were observed to be discrete in some tubules (Figure 3.E). Accumulation of lipid droplets in the cytoplasm of some of the late spermatids was remarkable (Figure 3.F). In addition to degeneration in the spermatogonium, cristaelysis, swelling and vacuolization were observed in mitochondria. It was determined that intercellular spaces were enlarged, and spermatocyte junctions were expanded (Figure 3. G). In the examinations, increased collagen fibers were observed in the intermediate connective tissue (Figure 3.H-I). Apoptosis was detected in some of the MCPA- administered Leydig cells, apart from the Profenofos group. (Figure 3. J). Gaps between the spermatogenic cells, cellular degeneration, and structural damage in the cells were slightly more evident in the MCPA- administered group compared to the Profenofos group.
Biochemical Examination
There was no statistically significant difference between the initial (3.46 ± 1.73 pg/ml) and final (2.07 ± 2.80 pg/ml) measurements of free testosterone in the control group (p=.309), while there was no statistically significant difference between the Profenofos group (6. 33 ± 3.64 pg/ml vs. 1.85 ± 1.40 pg/ml, p=.011) and MCPA group (3.59 ± 1.98 pg/ml vs. 2.49 ± 2.16 pg/ml, p=.020). Similarly, there was no statistically significant difference between the initial measurements of total testosterone (223.91 ± 112.44 ng/ml) and the final measurements (109.11 ± 77.79 ng/ml) in the control group (p=.720). Total testosterone levels were significantly decreased in the Profenofos group (369.10 ± 234.62 ng/ml vs. 108.18 ± 53.88 ng/ml, p=.013) and MCPA group (222.85 ± 102.01 ng/ml vs. 201.62 ± 164.79 ng/ml, p=.045). On the other hand, while there was no statistically significant difference between the groups in the initial free testosterone values (p=.076), the final free testosterone level was significantly higher in the MCPA group than in the Profenofos and control groups (all p<.05), and the free testosterone level in the Profenofos group was significantly lower than in the control group (p<.05). However, for total testosterone, there was no statistically significant difference between the groups at both initial and final measurements (p=.265 and p=.141, respectively).
Discussion
The effects of organophosphates on spermatogenesis are well known. A study was conducted on rats to determine the effect of Profenofos on spermatogenesis at the ultrastructural level. Degenerative alterations were found in the testicular epithelium and Leydig cells [8]. There are studies reporting that Profenofos decreases sperm motility and count, and increases sperm anomalies [10, 11]. Histopathologic examination in these studies revealed an obstruction in the seminiferous tubules and decreased sperm count in the lumen.
In our study, degenerative changes in seminiferous tubule epithelium were found in electron microscopy examinations of the Profenofos group. In the seminiferous tubule cells, numerous large residual bodies, and lipid droplets, abnormally shaped, swollen and cristaelysis mitochondria with diffuse vacuolization were observed. In addition, mitochondrial degeneration and autophagic vacuoles were observed in Leydig cells in the interstitial tissue. Profenofos negatively affected spermatogenesis and large gaps were observed between the cells forming the spermatogenic series. Numerous residual bodies and advanced cristaelysis in mitochondria were also observed in Sertoli cells. Degenerative changes were also observed in the basal lamina of the seminiferous tubules, and in some tubules, the shape of the basal lamina was irregularized, and separations were observed. In Leydig cells in the intermediate connective tissue, increased matrix condensation in mitochondria, as well as swelling and vacuole formations, were observed. These degenerative structural phenomena, the biochemical and statistically significant decrease in testosterone, negatively affect spermatogenesis, prevent healthy sperm development, and may cause pesticide-mediated infertility. The decrease in serum cholinesterase was accompanied by a decrease in LH and FSH, while testosterone levels also decreased [11]. These data suggest that one reason for the significantly lower plasma testosterone level in our biochemical analysis is the decrease in gonadotropin-stimulating hormones in serum. Testosterone is secreted by interstitial Leydig cells in the testes under the influence of LH. Decreased testosterone levels may be due to direct damage to Leydig cells or decreased stimulation of these cells by LH.
Moustafa et al. treated Profenofos orally in male rats at a dose of 17.8 mg/kg twice a week for 65 days. They found that Profenofos caused significant edema between seminiferous tubules, structural damages in Leydig cells and vacuole formation in spermatogenic series cells in rat testes [8]. The effects of Profenofos in rabbit testes, such as decreased weight, shrinkage of seminiferous tubules, tumor-like structures, expansion in the interstitial space, reduction, or hypertrophy of Leydig cells were observed, and it was concluded that it is an endocrine disruptor due to the destruction of Leydig cells [6]. Our study has similarly determined gaps between the cells forming the seminiferous epithelium because of Profenofos and MCPA treatments.
In another similar study, the effects of Profenofos on male-specific cytochrome P450 (CYP) enzymes were investigated in Wistar rats. It has been reported that Profenofos, an organophosphate pesticide, is an endocrine disruptor of male specific CYP enzymes and causes a decrease in testosterone levels [12]. Our study measured free testosterone and total testosterone levels; It was determined that testosterone value decreased significantly in the Profenofos group (p<0.05).
Regarding histologic structure, the testes of rats administered with organophosphate pesticides had normal testicular structure, but congestion was found in seminiferous tubules [11]. In our study, it was observed that some seminiferous tubules in the Profenofos group preserved their natural structure, while in some seminiferous tubules, spermatogenic serial cells have severely degenerated. As a result of the experiment comparing the toxicology of MCPA and 4-chloro-2-carboxyphenoxyacid (CCPA) in rats, a decrease in the weight of epididymis and unilateral and bilateral tubular degeneration in testes were observed in rats given 190mg/kg MCPA [9].
In our study, degenerative changes were observed in the seminiferous tubule in the experimental group administered with MCPA in support of the studies mentioned above. These were cristaelysis in the mitochondria of spermatogonium and spermatocytes, along with irregularities in the seminiferous tubule basement membrane course. In these cells, there are gaps between spermatogonium and spermatocytes. Spermatids have lost their connection with Sertoli cells. Leydig cells in the interstitial area also showed abundant vacuolization. Some seminiferous tubules degenerated, while others retained their normal structure.
There are data in the literature that Profenofos causes sperm abnormalities; it has also been shown to cause a decrease in sperm motility and count. [10, 11]. Studies have shown that Profenofos covalently binds to tubulin proteins [13]. Disruption of microtubule formation because of the binding of Profenofos on α- and β-tubulin proteins may lead to disruptions or disorders in axoneme formation, which constitutes the most important part of sperm. This may explain the low motility of sperm with tail anomalies.
Conclusion
In our study we found that Profenofos and MCPA, whose acute effects we evaluated, caused irregularities in the basement membrane course of the seminiferous tubules and the formation of gaps between the seminiferous epithelial cells in the testicular tissue. In the Profenofos group, abnormally shaped mitochondria were observed in the testis cells. In the Profenofos group, Sertoli cell remnants were observed, whereas in the MCPA group, the germinal epithelium was found to have lost its connections with Sertoli cells. Cristaelysis was determined in the mitochondria of Leydig cells in the intermediate connective tissue. Statistical evaluation of free and total testosterone levels decreased significantly after administration. Although we think that this decrease is due to the endocrine-disrupting effects of MCPA and Profenofos, the mechanism is not fully understood and requires further investigation. The structural degeneration in the testicular appearance and the results of our biochemical data suggest that Profenofos and MCPA prevent the healthy functioning of the spermatogenesis process.
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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8. Moustafa GG, Ibrahim ZS, Hashimoto Y, Alkelch AM, Sakamoto KQ, Ishizuka M, et al. Testicular toxicity of Profenofos in matured male rats. Arch Toxicol. 2007; 81(12):875-81.
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13. Chu S, Baker MR, Leong G, Letcher RJ, Li QX. Covalent binding of the organophosphate insecticide Profenofos to tyrosine on α-and β-tubulin proteins. Chemosphere. 2018; 199:154-9.
Download attachments: 10.4328.ACAM.21809
Nejat Ünlükal, Gülten Karabay, Attila Dağdeviren, Nilüfer Bayraktar, Ayşe Canan Yazıcı Güvercin, Mustafa Agah Tekindal. Effects of pesticides on testes at ultrastructural and hormonal levels. Ann Clin Anal Med 2023;14(12):1086-1091
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Effect of nutritional status on the presence of malnutrition and quality of life in patients with gastrointestinal tract cancer
Mutlu Tuçe Ulker 1, Hakan Güveli 2
1 Department of Nutrition and Dietetics, Faculty of Health Sciences, Istinye University, 2 Department of Nutrition and Dietetics, Faculty of Health Sciences, Bahcesehir University, Istanbul, Turkey
DOI: 10.4328/ACAM.21816 Received: 2023-07-20 Accepted: 2023-09-12 Published Online: 2023-09-20 Printed: 2023-12-01 Ann Clin Anal Med 2023;14(12):1092-1096
Corresponding Author: Mutlu Tuçe Ulker, Department of Nutrition and Dietetics, Faculty of Health Sciences, Istinye University, 34010, Zeytinburnu, Istanbul, Turkey. E-mail: mutlutuceulker@gmail.com P: +90 535 933 78 93 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1757-5084
This study was approved by the Non-Interventional Clinical Research Ethics Committee of Bahceşehir University (Date: 2017-12-06, No: 2017-19/01)
Aim: Cancers affecting the gastrointestinal tract are common worldwide, and cancers of the stomach and pancreas have a poor prognosis. Supporting nutritional status before, during and after cancer treatment improves the effectiveness of treatment and quality of life. Malnutrition is seen in cancer patients due to loss of appetite, nausea, vomiting, diarrhea, chewing or swallowing problems, taste and smell changes, therefore malnutrition should be evaluated in all cancer patients and appropriate nutritional support should be initiated. In this study, we aimed to evaluate the effect of nutritional status on malnutrition and quality of life in patients with gastrointestinal system cancer.
Material and Methods: The cross-sectional study included 60 patients who received gastrointestinal system treatment and met the inclusion criteria. The Quality of Life Test (EORTC QLQ-C30) and NRS-2002 were administered to the patients by the investigator using a face-to-face method. Socio-demographic information, anthropometric measurements and biochemical findings were obtained from patient files with hospital permission.
Results: In the study, most of the patients were at risk of malnutrition; however, no significant correlation was found between NRS 2002 and quality of life and cancer stages. There was an inverse relationship between albumin levels and malnutrition risk (p<0.05).
Discussion: Cancer patients are at risk of malnutrition due to the heavy treatment brought by the disease, therefore, malnutrition risks should be determined in the early period, appropriate nutritional support should be provided and their quality of life should be improved.
Keywords: Malnutrition, Quality of Life, Cancer
Introduction
Cancer is a multi-stage disease of cell differentiation and death and is responsible for approximately one in six deaths worldwide; however, one-third of cancer-related deaths are associated with high body mass index, inadequate fruit and vegetable intake, physical inactivity, tobacco and alcohol use [1]. Cancers affecting the gastrointestinal tract (GI) are common worldwide and their incidence is increasing day by day; among them, gastric and pancreatic cancers have a poor prognosis and are difficult to treat [2]. Supporting nutritional status before, during and after cancer treatment increases the effectiveness of treatment and quality of life. The European Society for Clinical Nutrition and Metabolism recommends the measurement of resting energy expenditure for all cancer patients through the use of indirect calorimetry; however, in the absence of this measurement in clinical practice, nutritional requirements can be estimated as 105-126 kJ/kg/day with 12-15 g protein/kg/day [1]. GI cancer patients are at risk of malnutrition due to metabolic, physiological, physical and psychological changes associated with treatment and disease, and cancer cachexia and sarcopenia are reduced by identifying the risk of malnutrition and initiating nutritional support [3]. Malnutrition may be observed in cancer patients due to loss of appetite, nausea, vomiting, diarrhea, chewing or swallowing problems, taste and smell changes and this condition accounts for 30-50 percent of deaths in patients with GI tract cancer. In case of malnutrition screened in the early period, food intake and body weight changes should be examined and according to the European Society for Clinical Nutrition and Metabolism (ESPEN), malnutrition should be evaluated in all cancer patients and appropriate nutritional support should be initiated. Albumin, prealbumin, transferrin and retinol binding protein are biochemical parameters frequently used in the evaluation of malnutrition status. The serum albumin level is also a good marker for the assessment of malnutrition risk; however, it is insufficient alone. In addition to screening tests, nutrition-related biochemical parameters, especially albumin, C-reactive protein (CRP) and neutrophil biochemical parameters are widely used in the evaluation of malnutrition. Since these parameters vary depending on infection, dehydration, renal failure and liver dysfunction, they are not sufficient alone in the evaluation of nutritional status [4]. In addition, 10-15 percent weight loss within six months, body mass index <18.5 kg/m2, Malnutrition Screening Test (NRS-2002) score >3 and serum albumin level <3.0 also indicate the presence of malnutrition [3]. Screening of patients with early malnutrition screening and the development of appropriate nutrition plans will support the cancer treatment processes of patients. Therefore, the nutritional status of patients should be screened in the early period and appropriate intervention should be applied without wasting time. With timely and adequate nutritional support, patients’ quality of life improves, hospitalization levels decrease and complications are minimized [2]. In this study, we aimed to evaluate the effect of nutritional status on malnutrition and quality of life in GI tract cancer patients with oral food intake.
Material and Methods
Patients’ Population
The study participants were selected from patients diagnosed with GI cancer who received chemotherapy treatment at the oncology service of VM Medical Park Göztepe Hospital between January and July 2018. To be included in the study, they had to have the following characteristics (a) not have a chronic disease other than GI cancer; (b) be on an oral diet; (c) receive chemotherapy treatment; (d) be over 18 years of age. Pregnant or breastfeeding women with a cancer diagnosis other than metastasis were excluded.
The study was conducted in accordance with the Declaration of Helsinki, ethics committee approval was obtained by Bahçeşehir University Non-Interventional Clinical Research Ethics Committee with the decision dated 6/12/2017 and numbered 2017-19/01, and informed consent was obtained from each participant.
Study Design
This was a cross-sectional study, and participants were informed about the benefits and potential risks of the study at baseline. The Quality of Life Test (EORTC QLQ-C30) and NRS-2002 were administered to the patients by the researcher using the face-to-face method. Socio-demographic information, anthropometric measurements and biochemical findings were obtained from patient files with hospital permission.
Assessment of Nutritional Status and Detection of Malnutrition Risk
The NRS-2002 test was used to evaluate the malnutrition status of patients with GI tract cancer. The test includes two stages and in the first stage, the patient’s body mass index (BMI), weight loss in the last 3 months, change in food intake in the last week and the level of the disease are questioned, and if the answer to any of these four questions is ‘Yes’, the second stage of the questionnaire is started. In the second stage, the percentage of weight loss, nutrient intake and level of disease are questioned and a total score between 0-6 is given; if the patient is 70 years of age or older, the malnutrition score is calculated by adding one more point to the total score. If the total score is equal to or more than 3, there is a risk of malnutrition; if it is less than 3, there is no risk of malnutrition, but the screening test should be repeated every week [5].
Evaluation of Quality of Life
The EORTC QLQ-C30 scale for cancer patients was used to assess quality of life. This scale includes five different assessment sections (physical, functional, emotional and social) and symptom scales such as fatigue, nausea, pain and vomiting, with scores ranging from 0 to 100. The score for the first part (the symptom part) is inversely proportional to the patient’s condition and the score for the second part (the self-assessment part) is directly proportional to the patient’s level of health [4].
Statistical Evaluation of Data
SPSS (Statistical Package for Social Sciences) for Windows 16.0 program was used for statistical analysis of the data obtained. In the descriptive statistics of the data, mean, minimum, maximum values and standard deviation were used, the differences between the data were evaluated by the Mann-Whitney U Test and Spearman’s correlation analysis, and the Kruskal-Wallis test was used in the relationships between them. Significance levels were p<0.05.
Laboratory tests
Liver function tests, albumin, hemoglobin, eosinophil and lymphocyte parameters were obtained from patient files. Laboratory tests of the patients were measured and evaluated at Medicalpark Göztepe Hospital Laboratories.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
The study included 60 patients; however 5 patients were excluded from the study because they had a chronic disease as well as gastrointestinal system cancer and the study was completed with 55 GI system cancer patients.
Baseline characteristics of patients
A total of 55 patients, 25 women and 30 men were included in the study. Of the participants, 12.7% were nonliterate, 27.3% were primary school graduates, 18.2% were middle school graduates, 29.1% were high school graduates and 12.7% were undergraduate graduates. BMI values of the individuals were as follows: 23.6% were underweight, 38.2% were normal, 16.4% were overweight and 21.8% were obese (Table 1).
Disease-related data
The distribution of patients by cancer stage was as follows: 12.7% had stage 1, 30.9% had stage 2, 38.2% had stage 3 and 18.2% had stage 4. Metastasis was seen in 43.6% of the individuals who participated in the study, while 56.4% had no metastasis (Table 1).
Malnutrition risk and quality of life
According to the NRS-2002 score, 92.7% of the patients were at risk of malnutrition and 7.3% were not at risk of malnutrition. NRS-2002 and Quality of Life scores of patients with and without metastases did not differ. No significant correlation was found between NRS-2002 and Quality of Life scores and metastasis status. There was no significant difference between Quality of Life, self-assessment and NRS-2002 score according to cancer types. There was no significant difference between the Quality of Life scores of the patients according to the risk of malnutrition; however, there was a significant difference between the scores of the second part of the self-assessment scale (p<0.05). Quality of Life, self-assessment scores and NRS-2002 score swere found according to cancer stages and there was no significant difference between these values (Table 2).
Laboratory tests
There was a statistically positive and significant relationship between NRS-2002 scores and albumin levels (p<0.05). However, none of the relationships evaluated with other blood findings were statistically significant (p>0.05), ( Table 3).
Discussion
In our study, a large proportion of patients were at risk of (%92.7) malnutrition. Therefore, the nutritional status of patients should be screened in the early period and appropriate intervention should be applied without losing time. With timely and adequate nutritional support, patients’ quality of life increases, hospitalization levels decrease and complications are minimised. However, no significant relationship was found between NRS 2002 and quality of life. According to a study in which malnutrition risk screening was performed with NRS-2002 in cancer patients, 24.8% of patients were at moderate risk and 15.4% were at high risk [2].
In the study evaluating the effects of nutritional intervention on patients’ quality of life in GI cancer patients receiving chemotherapy treatment, quality of life scores of the patients in the intervention group were found to be higher after the intervention compared to the control group (p<0.05) [6]. In another study evaluating the quality of life scores of patients with GI tract cancer, it was reported that quality of life scores decreased with prolonged duration of chemotherapy treatment (p<0.05) [7]. In our study, no significant difference was found between quality of life, self-assessment score and NRS-2002 scores according to cancer stages. This showed that cancer stage alone was not only effective in determining the quality of life of the patients, but also many different physiological and psychological conditions affected the quality of life. According to the risk of malnutrition, there was no significant difference in the quality of life score of the patients; however, there was a significant and inverse relationship between the sub-section of self-assessment scores.
In cancer patients over 30 years of age, with gastrointestinal system cancer, stage III or IV, receiving radiotherapy or chemotherapy, quality of life and self-assessment scores were evaluated and it was reported that the quality of life of the patients was inversely related to their malnutrition status and symptoms [8]. In our study, no significant difference was found between Quality of Life, Self-Assessment Scores and NRS2002 Malnutrition Screening Test Score according to cancer stages. The Quality of Life scores of patients with and without malnutrition risk did not differ, but there was a significant difference between the Self-Assessment scores of the patients (p<0.05). This shows that not only cancer stage is effective in determining the quality of life of patients, but many psychological and biological conditions affect the quality of life, and the psychological support received by patients with gastrointestinal system cancer participating in our study may be effective for life expectations and health beliefs.
In a study evaluating the preoperative malnutrition risks and quality of life of patients with GI tract cancer, a significant inverse correlation was found between malnutrition status and quality of life (p<0.05) [9]. In our study, the Quality of Life scores of patients with and without malnutrition risk did not differ; however, there was a significant difference between Self-Assessment.
In a study evaluating the effect of oral nutrition intervention on postoperative malnutrition status and quality of life in patients with GI tract cancer, the group receiving oral nutrition intervention for three months showed a significant difference in BMI values and improved quality of life compared to the control group (p<0.01) [10].
Low serum albumin levels have been reported to be a positive marker for the detection of malnutrition risk with the NRS2002 malnutrition screening test in cancer patients [11]. In a study evaluating the effect of nutritional support for 6 weeks on the malnutrition status and quality of life of 96 esophageal cancer patients receiving chemotherapy and radiotherapy treatment, serum albumin levels and quality of life were significantly higher in the intervention group compared to the control group [12]. In our study, most of the patients were malnourished and there was a statistically significant relationship between NRS 2002 scores and albumin levels (p<0.05). However, none of the relationships evaluated with other blood findings were statistically significant.
Conclusion
Nutritional status in patients with GI cancer leads to malnutrition and worsening of the quality of life. Studies evaluating the presence of malnutrition and its relationship with quality of life in these patients are limited, and there is a need for studies that examine survival rates and quality of life of patients with GI cancer with wider parameters and include more participants.
Limitation
Due to the strict inclusion criteria in our study, the number of patients was small and should therefore be considered as a pilot study.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main 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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Mutlu Tuçe Ulker, Hakan Güveli. Effect of nutritional status on the presence of malnutrition and quality of life in patients with gastrointestinal tract cancer. Ann Clin Anal Med 2023;14(12):1092-1096
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A 10-year bibliographic analysis of extracorporeal membrane oxygenation (ECMO) literature
Ali Kemal Erenler 1, Ahmet Öztürk 1, Serkan Günay 1, Ahmet Baydın 2
1 Department of Emergency Medicine, Hitit University, Erol Olçok Education and Research Hospital, Çorum, 2 Department of Emergency Medicine, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey
DOI: 10.4328/ACAM.21818 Received: 2023-07-11 Accepted: 2023-08-21 Published Online: 2023-08-24 Printed: 2023-12-01 Ann Clin Anal Med 2023;14(12):1097-1103
Corresponding Author: Ali Kemal Erenler, Department of Emergency Medicine, Hitit University, Erol Olçok Education and Research Hospital, 19040, Merkez, Çorum, Turkey. E-mail: akerenler@hotmail.com P: +90 532 447 55 63 F: +90 364 219 19 38 Corresponding Author ORCID ID: https://orcid.org/0000-0002-2101-8504
Aim: Extracorporeal membrane oxygenation (ECMO) is a life support device providing extracorporeal artificial support to the respiratory system and/or circulatory system for patients who do not benefit from conventional therapies.
Material and Methods: A bibliometric search was conducted with information obtained from the Web of Science (WoS) database. Publications on ECMO since 2014 were analyzed. Type of the articles, top authors, language, funding agencies, affiliations, countries, journals were determined. Following statistical analysis of the literature, the top 10 articles on ECMO were investigated in detail.
Results: A total of 7940 articles were involved in the study. The majority of the articles were original articles (n=6130, 77.2%). The most productive author was Brodie D (1.9%). English was the most common language. When countries were compared in terms of the number of publications and total citations, the US was the leading country in both categories (n=3103, n=42744, respectively). ASAIO Journal had the highest number of articles (n=491). The analysis of the top 10 most cited articles revealed that the majority of the articles were related to COVID-19.
Discussion: Bibliometric studies on a specific subject may shed light on the management of diseases. When the top 10 articles are considered, the use of ECMO in patients with COVID-19 dominates the scientific literature on ECMO.
Keywords: Extracorporeal Membrane Oxygenation, Bibliometrics, Publications
Introduction
Extracorporeal membrane oxygenation (ECMO) is a rescue therapy widely used in patients with cardiopulmonary emergencies [1]. Clinical use of ECMO involves severe pulmonary failure, cardiogenic shock, circulatory instability during high-risk percutaneous coronary interventions (PCI) and persistent circulatory failure after cardiac surgery. In ECMO, blood is removed from the venous system and returned to the body via either a vein or an artery after oxygenation and decarboxylation. In veno-venous ECMO, the femoral vein is cannulated so that its tip lies at the level of the renal veins or the inferior vena cava near the right atrium. After oxygenation and decarboxylation, the blood is returned to the venous system through a cannula located in the jugular vein at an adequate distance from the draining cannula. Additionally, the femoral vein and femoral artery may also be used for this purpose. In this method, a leg perfusion cannula is used to prevent limb ischemia [2]. In a report by the Extracorporeal Life Support Organization in 2021, it was stated that a 623% increase was determined in ECMO use, worldwide, since 2009 [3]. However, it also has some disadvantages such as high cost and invasive nature [1]. Also, patients undergoing ECMO are exposed to various complications that increase morbidity and mortality related to the procedure. These complications are associated with underlying critical illness, multiple invasive procedures and devices, including the ECMO cannulas, and the longer intensive care unit (ICU) stay, and consequent nosocomial infections [4].
There is a lack of knowledge on the indications and management of ECMO in the literature. Universal guidelines with expert consensus are required [5].
Scientometrics has been used as a popular statistical method for analyzing scientific literature thoroughly in a certain field [6]. The analysis of scientific information with statistical methods is also known as bibliometrics. With the increase in the number of publications in the literature, studies based on statistical and bibliometric analysis have been carried out on many important medical issues, especially in recent years. This method allows researchers to reach a summary of analysis of a great number of articles on a specific subject in a short time. Also, it gives researchers a future perspective by explaining the current status of a scientific problem. Bibliometrics reveal the most active authors, journals, institutions, countries and the most cited influential studies on a subject or a field [7]. As in other developing methods, best practices in ECMO may be established by the ECMO educational literature [8]. In this study, our aim was to determine the current status of publications about ECMO, determine gaps of knowledge in the literature and guide researchers in this field for future studies.
Material and Methods
This study was based on ECMO publications in the Web of Science© (WoS) database. This platform allows researchers to achieve scientometric and statistical information on a specific subject. We extracted articles on ECMO by entering the keyword “Extracorporeal Membrane Oxygenation” on May 15th, 2023. Publications in the last 10 years were involved. From the database, we investigated the distribution of ECMO articles according to scientific journals. The number of articles, number of citations and citations per publication for each journal were calculated. Global research productivity, international collaborations, research themes were analyzed using the scientometric method. We also analyzed abstracts and, in case, full texts of the articles. The analysis was performed by the authors independently and controversies were ended after discussions. Document types (Original article, review article, editorial material, early access, meeting abstract, proceeding paper, letter, book chapters, correction, meeting, retraction) were determined. The top 10 authors were listed. Article languages and funding agencies according to the number of publications were listed. Similarly, the top 10 countries and 20 journals according to the number of publications were listed. The impact factors of the journals were also obtained from the official sites of the journals. The number of citations and citations per publication in terms of countries and journals were identified.
In addition, we extracted the top 10 cited articles from the database and made a summary of these articles in order to make a future prediction for researchers in this field.
The data were entered into Microsoft© Excel Programme and results were presented as numbers and percentages. Since any living subject was not involved in the study, ethical approval was not required.
Results
A total of 7940 articles have been extracted since 2014. Of these articles, 6130 (77.2%) were original articles, 1043 (13.1%) were reviews, 320 (4%) were editorial materials. When the top authors according to the number of articles involved were investigated, Brodie D was the top author with 155 (1.9%) articles, followed by Combes A with 126 (1.5%) articles and Lorusso R with 120 (1.5%) articles. English was the most common language. When leading funding agencies were investigated, the United States Department of Health and Human Services (n=348) was on the top of the list, followed by National Institutes of Health Nih USA (n=342) and the National Natural Science Foundation of China (n=112). The details are presented in Table 1.
The United States (the US) was the country that published the highest number of articles (n=3103). The US was also on top in terms of total citations (n=42744) and citations per publication (n=13.7). Germany was in second place with 905 articles, 12397 citations and a ratio of 13.7 citations per publication. China made a contribution with 669 articles, 5721 citations and 8.5 citations per publication, and located in third place. Canada had the highest rate of citations per publication (n=30.3). The US was also in first place when the h-index was considered (n=84). When the first 3 years with the most articles published were investigated, it was determined that the articles intensified in 2020, 2021 and 2022 for all countries. The comparison of productivity in terms of countries is presented in Table 2.
ASAIO Journal was the most popular journal with 491 articles and 6387 citations per publication. The journal in the second place was Perfusion with 384 articles and 2246 citations per publication, followed by the Journal of Cardiothoracic and Vascular Anesthesia with 181 articles and 1536 citations. The performance of the journals is presented in Table 2.
When the top 10 articles according to citation numbers were investigated, it was determined that the majority were original articles (8/10). The article entitled “Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma” published in the Journal of American Medical Association by Shen et al. was the most cited article with 1508 citations. Of the top 10 articles, 4 were on the use of ECMO in COVID-19 patients, 2 were on ARDS and 2 were on cardiogenic shock. A summary of the top 10 articles is presented in Table 3.
Discussion
There is a lack of information on ECMO in terms of scientometrics in the literature. The use of ECMO for treating patients with pulmonary and cardiac failure is becoming more and more widespread. The principle of ECMO depends on temporarily bypassing the functions of the lungs and heart [2]. ECMO supports circulatory functions in a timely manner and provides adequate cerebral blood flow. It is well-known that, with the perfusion of vital organs, ECMO improves survival and neurological outcomes [3]. As mentioned above, there are various techniques that may be preferred for patients requiring
ECMO. It has recently been reported that while veno-arterial ECMO had a mortality rate of 55%, veno-venous ECMO had a mortality rate of 42%. There is an ongoing debate in the literature to decrease mortality and researches are ongoing to create ideal guidelines describing indications and applications of ECMO in combination with serum laboratory data [9,10]. Even though it has many advantages, patients receiving ECMO are at risk of life-threatening complications such as bleeding, thrombosis, and infection [11].
Bibliometrics, also known as the “science of science” may help researchers in this field to share and spread their experiences and knowledge in order to establish accurate guidelines.
The use of ECMO in clinical practice attracts the attention of more and more clinicians dealing with cardio-respiratory failure. Accordingly, the number of publications on ECMO tends to rise gradually each year. In a bibliometric study about ECMO, it was stated that half of the articles (n=550) about ECMO were published in the 2010s. By the 2000s, they could determine 27 publications and only 15 in the 1990s [12]. The reason for this large increase in publications may be linked to more availability and growing experience about ECMO all over the world.
As ECMO is a relatively novel model, researchers may have a great will to make publications and lead the literature in this untouched field.
In a similar but relatively old study, Wang et al. conducted a 10-year bibliometric analysis of ECMO studies and revealed that the number of articles published in the past decade has increased, especially from 2019 to 2020 [13]. This fact proves that actual bibliometric analyses on ECMO are essential to reveal the current status of ECMO applications. Recent information on ECMO may affect and guide future perspectives.
Generality of ECMO among different countries also has a property that it may show the level of development. It has been reported that the number of ECMO-related publications tends to decrease in non-developed countries. Additionally, the US has been reported to be the leading country in terms of the number of publications [12,13]. In another study, the US was the leading country in terms of COVID-19-related ECMO studies followed by Germany and Japan [7]. In our study, accordingly, the US was the leading country in both number of publications and number of citations. While Germany is in second place, China took the third row from Japan. It was reported that the attention to ECMO was gradually increasing in China [14]. With increasing funding for research and development in China, the number of scientific articles is rising in parallel.
The University of Michigan was the institution that had the largest number of publications and the highest centrality. In the above-mentioned article, when the most productive authors were investigated, Daniel B was the author who had the largest number of publications [13]. Since our study is a recent one, Brodie D was found to be the author with the highest number of publications.
In a study, the top 3 journals with the highest number of publications were ASAIO Journal (n = 36), Frontiers in Medicine (22), and Perfusion-UK (n = 20) [7]. In our study, ASAIO published the highest number of articles. According to the official website, the current Impact Factor of ASAIO journal is 2.872 with no page charge and has a decision time of less than 1 month. The journal features peer-reviewed articles on the newest and most innovative technology, organ repair, regeneration and development, preclinical testing, and clinical outcomes. There are 12 issues per year. Journals that focus on novel methods like ECMO increase their popularity and thus, the citations they get.
Another parameter to measure the importance given to scientific development is the number of citations of articles. The number of citations gained by an article is commonly used as an indicator of its importance in the literature. The impact of research on clinical practice can also be detected with the number of citations [15]. In terms of the number of citations, the USA and ASAIO journal were on the top of the list.
The ECMO literature was reported to focus on the treatment of ARDS, prevention of coagulation system-related complications, use in neonatal and pediatric patients, mechanical circulatory support for cardiogenic shock, and ECPR and ECMO during the COVID-19 pandemic [14]. Analysis of the top 10 articles revealed that most of the articles were related to ECMO in the treatment of COVID-19 patients. Eight of the 10 articles were original articles. Treatment of ARDS and cardiogenic shock were also popular subjects among researchers. It is observed that the pandemic dominated not only social life but also scientific literature.
Conclusion
In conclusion, even though it has lethal complications, ECMO use is becoming increasingly common due to its utility in patients with pulmonary failure, cardiogenic shock, circulatory instability during high-risk PCI and persistent circulatory failure after cardiac surgery. In concordance, the number of publications on ECMO is growing rapidly over the years. The need for accurate guidelines on ECMO makes the ECMO literature inevitably important. Bibliometric studies not only reveal the scientific status of ECMO but also give perspective for future studies. According to our results, the number of publications and the number of citations a country gain is parallel to the development level. Journals should focus on novel methods in order to increase their popularity among researchers. The support of educational institutions and funding agencies has an undeniable effect on determining the leader in a scientific field.
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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Download attachments: 10.4328/ACAM.21818
Ali Kemal Erenler, Ahmet Öztürk, Serkan Günay, Ahmet Baydın. A 10-year bibliographic analysis of extracorporeal membrane oxygenation (ECMO) literature. Ann Clin Anal Med 2023;14(12):1097-1103
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The relationship between physical activity level, gastrointestinal complaints and quality of life in patients with familial Mediterranean fever
Ayşenur Yılmaz 1, Halil Yılmaz 2, Zeynep Dündar Ök 3, Serdar Kaymaz 4, Bilge Başakçı Çalık 5, Mustafa Çelik 6, Veli Çobankara 3
1 Department of Physical Therapy and Rehabilitation, Hitit University, Çorum, 2 Department of Gastroenterology, Denizli State Hospital, Denizli, 3 Department of Rheumatology, Pamukkale University Training and Research Hospital, Denizli, 4 Department of Rheumatology, Pamukkale University, Denizli State Hospital, Denizli, 5 Department of Physical Therapy and Rehabilitation, Pamukkale University Training and Research Hospital, Denizli, 6 Department of Gastroenterology, Pamukkale University Training and Research Hospital, Denizli, Turkey
DOI: 10.4328/ACAM.21821 Received: 2023-07-17 Accepted: 2023-08-21 Published Online: 2023-08-26 Printed: 2023-12-01 Ann Clin Anal Med 2023;14(12):1104-1108
Corresponding Author: Ayşenur Yilmaz, Department of Physical Therapy and Rehabilitation, Faculty of Health Sciences, Hitit University, Çorum, Turkey. E-mail: fzt.aysenurgungor@gmail.com P: +90 543 283 38 19 Corresponding Author ORCID ID: https://orcid.org/0000-0002-2357-0351
This study was approved by the Non-Interventional Clinical Research Ethics Committee of Pamukkale University (Date: 2021-03-02, No: 05)
Aim: In this study, we aimed to examine the relationship between physical activity (PA) level, gastrointestinal complaints, and quality of life (QoL) in patients with Familial Mediterranean Fever (FMF) and to compare them with healthy individuals.
Material and Methods: The study included patients diagnosed with FMF and healthy volunteers. Thirty-six FMF patients aged between 18-50 years and 38 healthy subjects were included in the study. The short form of the International Physical Activity Questionnaire (UFAA short form) was used to determine the PA levels of individuals. QoL was evaluated using the Short Form-36 (SF-36), and the Gastrointestinal Quality of Life Index (GIQLI) was used for gastrointestinal complaints.
Results: The mean age of the FMF patients (women=28 and men=8) was 41.27±14.19 years, which is comparable to that of the healthy individuals (43.26 ± 10.72 years; women=32; men=6) (p >0.05). When the group results were compared, there was a significant difference in UFAA short form, SF-36, and GIQLI (p<0,05). A significant correlation was found between UFAA short form and SF-36, GIQLI in FMF patients (p<0,05).
Discussion: It was observed that as the PA level of FMF patients decreased, their gastrointestinal complaints increased and their quality of life decreased. Therefore, recommendations should be made to increase PA levels in FMF patients.
Keywords: Familial Mediterranean Fever, Gastrointestinal Complaints, Physical Activity Level, Quality of Life
Introduction
Familial Mediterranean Fever (FMF) is a chronic inflammatory disease. FMF patients have fever and inflammation of the serous membranes with recurrent attacks. [1]. The most common symptom is abdominal pain. Today, the most effective treatment of FMF is with lifelong colchicine. The most common side effects of colchicine are diarrhea and nausea [2].
In addition, FMF is a chronic disease. Chronic diseases lead to the loss of various functions over time [3]. They cause many psychiatric disorders such as depression and anxiety, both by reducing the quality of life and their direct biological effects [4-6]. For this reason, it is known that gastrointestinal system functional diseases such as Irritable Bowel Syndrome (IBS) and dyspepsia are more common during the course of chronic diseases [7,8]. However, there are no data in the literature showing the frequency of these disorders in FMF. Chronic disease is not the only reason for the expectation that digestive system complaints will be seen more frequently in patients with FMF. There are studies in the literature that plasma serotonin 2 levels are low in FMF patients [9,10]. In the pathogenesis of IBS and similarly dyspepsia, along with psychosocial factors, dysregulation in serotoninergic functions is also involved. Plasma serotonin levels were found to be low in constipation-predominant patients with IBS. Plasma serotonin levels were found to be high in IBS patients with diarrhea [11]. Based on these data, it can be thought that constipation-predominant IBS may be seen more frequently in FMF patients. Although there are digestive system complaints related to both the disease itself and the drug used in the treatment, there are not many studies on the frequency of digestive system disorders in these patients.
Physical activity (PA) and exercise have some benefits and risks for the gastrointestinal tract. Vigorous exercise inhibits gastric emptying, inhibits gastrointestinal absorption, and causes many gastrointestinal symptoms. However, moderately intense exercise is well tolerated and has beneficial effects on inflammatory bowel disease, liver disease, constipation, diverticulosis, and gallstones. PA also increases gastric emptying and reduces the relative risk of PA levels of patients and digestive system complaints in FMF. Considering the benefits of PA, individuals should be encouraged to engage in optimal PA for healthier individuals and healthier societies. It is clear that this is necessary for prolongation of life expectancy and quality of life (QOL) [13]. Since FMF is a chronic disease, it negatively affects the quality of life. A decrease in the level of PA is also expected. However, there is no study examining the effect of PA levels on QOL in FMF patients.
Our aim is to examine the relationship between PA level, gastrointestinal complaints and QOL in patients with FMF and to compare them with healthy individuals.
Material and Methods
Participants
Individuals aged 18 years and over who were treated with the diagnosis of FMF in Pamukkale University Hospital Rheumatological Diseases Polyclinic, as well as volunteers who met the inclusion criteria without any known additional disease were included in the study. The study included 36 FMF patients aged 18 years and older who were treated with the diagnosis of FMF in Pamukkale University Hospital Rheumatological Diseases Polyclinic, who voluntarily agreed to participate and met the inclusion criteria in the study, and 38 healthy controls of the same age group without any known additional disease. Our study was carried out between March 2021 and June 2023. Patients meeting the inclusion criteria were included. Written consent was obtained from all patients. Permission for our study was given by Pamukkale University Non-Interventional Clinical Research Ethics Committee dated 02.03.2021 (no. 05). Informed consent forms were signed by FMF patients who agreed to participate in this study. We evaluated FMF patients face to face.
Inclusion and exclusion criteria
Individuals over the age of 18, who did not have any additional disease other than FMF, who were oriented and cooperative, who agreed to participate in the study, and who did not have a neurological or physical disease that would prevent them from performing PA were included in the FMF group (FMFG). In the control group (CG), healthy people over 18 years of age, oriented and cooperative, who agreed to participate, and who did not have any problems that would prevent them from performing PA were included. Those with diseases such as Diabetes Mellitus (DM), hypothyroidism, colon cancer, a recent surgery to affect mobility, diagnosed gastrointestinal disease, the integrity of the gastrointestinal tract, and the use of drugs that can change the gastrointestinal motility were not included in the CG and FMFG.
Evaluation Methods
Patient information regarding age, height, weight, gender, disease duration, age of diagnosis, duration of attacks, family history for FMF. The symptoms of the FMF patients were noted.
Demographic data were recorded after obtaining consent from the patients. Socio-demographic characteristics of the patients were determined by a face-to-face patient evaluation form. The short form of the International Physical Activity Questionnaire (UFAA) was used to determine the PA levels [14]. QoL was assessed using Short Form-36 (SF-36) [15]. The Gastrointestinal Quality of Life Index (GIQLI) includes 36 parameters. Parameters, the answers were divided into 5 degrees using a Likert scale and scoring was done (0-4; 0: worst and 4: best) [16].
Statistical analysis
It was seen that the effect size obtained in the reference study was at a strong level (d=1.04) [4]. Based on the results of the reference study, as a result of the power analysis we made by assuming that we could achieve a lower effect size (d=0.8), it was calculated that 95% power could be achieved at the 95% confidence level, when at least 70 people (at least 35 people for each group) were included in the study. The data were analyzed with the SPSS package program. Continuous variables were presented as mean ± standard deviation and categorical variables as numbers and percentages. In the comparison of differences, the significance of the Man-Whithney U Test was used when the non-parametric test assumptions were not met, and Spearman’s Correlation analysis was used when the non-parametric test assumptions were not met.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Of the 39 FMF patients, 1 patient was deemed ineligible for this study and 2 patients declined to participate. As a result, 36 FMF patients were analyzed. Of the 40 healthy individuals, 2 were deemed ineligible for this study. As a result, 38 healthy individuals were analyzed (Figure 1).
Thirty-six patients with FMF (men=8 / women=28) and 38 healthy individuals (Men=6 / women=32) were included (p=0.560). The mean age of the patients with FMF was 41.27±14.19 years, which was comparable to that of the healthy individuals (43.26 ± 10.72) (p >0.05). There was no significant difference in terms of age, weight, height and body mass index (BMI) (p > 0.05). A significant difference was found between the groups in terms of IPAQ, SF36, and GIQLI results (p < 0.05). The results are shown in Table 1.
The evaluation of all participants’ results showed a highly positive relationship between IPAQ and physical function (r = 0.563, p = 0.000), physical role (r = 0.462, p= 0.005), general health (r = 0.256, p= 0.132), bodily pain (r =0.407, p=0.014), vitality (r = 0.683, p= 0.000), social functioning (r = 0.317, p= 0.059), emotional role (r = 0.313, p= 0.064) and mental (r = 0.646, p= 0.000) in patients with FMF. The evaluation of all participants’ results showed a highly positive relationship between IPAQ and GIQLI (r = 0.726, p=0.000) in FMFG. The relationship between IPAQ, SF36, and GIQLI in patients with FMF is presented in Table 2.
Discussion
Chronic diseases cause both physical and mental problems. In this case, it impairs the quality of life [5-7]. At the same time, lack of PA is a condition that increases gastrointestinal complaints [17,18]. It is very important to improve the QOL in patients.
This is the first study to examine the relationship between PA level, and gastrointestinal findings. As a result of our study, we determined that gastrointestinal system (GIS) symptoms increased as PA decreased. At the same time, we found that the PA level of FMF patients was lower than that of healthy individuals, their GIS findings were higher, and their quality of life was more impaired.
As a result of this study, physical function, physical role, bodily pain and vitality of SF36 were lower in FMF patients than in health controls. Previous studies have shown that the quality of life of pediatric and adult FMF patients is impaired [19,20]. Our findings on quality of life are consistent with previous studies. Decreased quality of life may be associated with episodes of illness, and PA may also be associated with symptoms of depression, anxiety, and GIS symptom [4-6].
We determined that their PA was lower than that of healthy individuals. In a study, it was reported that the level of depression and fatigue in FMF patients was higher than in healthy individuals [4]. This can reduce the PA level in people and reduce their desire to exercise. At the same time, musculoskeletal symptoms are common in FMF patients. Arthritis, arthralgia, and myalgia can mostly affect the knee or hip [21]. Since the attacks in these patients are painful and physical exertion ultimately causes attacks, this forces patients to a sedentary lifestyle [22]. This can cause a decrease in PA. Therefore, patients with FMF have more problems in performing activities of daily living than healthy individuals due to their low level of PA. In a study, it was reported that the exercise capacity of patients with FMF also decreased [23]. . In the study Babaoğlu et al., patients with FMF were physically inactive during the attack [22]. In addition, the EULAR (Europa League Against Rheumatism) recommendations stipulated that FMF patients should be informed by physicians that physical stress triggers FMF episodes [24]. All this lowers the level of PA. Therefore, the level of PA was evaluated. In this study, the PA level in patients with FMF was found to be lower than in healthy individuals. There are not many studies comparing PA with healthy individuals [23]. In the previous study, a decrease was found in exercise capacity and PA level [24].
Joint pain is the third most common clinical finding of FMF after abdominal pain and fever. Episodic abdominal pain, which generally lasts less than 72 hours, is frequently seen in the course of FMF with a frequency of 89.2–93.7% [1]. Constipation and abdominal pain are seen in FMF. However, it is sometimes difficult to distinguish abdominal pain from an attack of FMF or from organic GIS disorders with visceral inflammation [25]. In addition, studies have previously found FMF to be associated with a higher risk of inflammatory bowel disease [7,8]. It was uncertain whether MEFV mutations were the cause [1,7,8]. Complaints such as constipation and diarrhea have been reported in FMF patients [20].
Limitation
Limitations of the current study were the small number of patients and the fact that most of the patients were under colchicine treatment. Colchicine treatment has controlled most of the FMF symptoms and we cannot be know whether colchicine has a positive or negative impact on GIS symptoms. There are no studies examining the relationship between PA and GIS findings in FMF patients. However, it was observed that low PA levels negatively affected the QOL and increased GIS complaints [18]. For this reason, we think that GIS findings in FMF patients should be considered and studies should be conducted to increase the PA levels in FMF patients.
Conclusion and Recommendations
It was seen that as the PA level of FMF patients decreased, their gastrointestinal complaints increased and their QOL decreased. Therefore, recommendations should be made to increase PA levels in FMF patients. At the same time, it was observed that gastrointestinal complaints of FMF patients were higher than in healthy individuals. It is important to evaluate these patients’ GIS complaints.
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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2. Özdoğan H. Ailevi Akdeniz Ateşi Tedavisi ve Prognozu (Familial Mediterranean Fever Treatment and Prognosis). Turkiye Klinikleri J Int Med Sci. 2006;2(8):51-6.
3. Anderson E, Durstine JL. Physical activity, exercise, and chronic diseases: A brief review. Sports Med Health Sci. 2019;1(1):3-10.
4. Guler T, Garip Y, Dortbas F, Dogan YP. Quality of life in Turkish patients with Familial Mediterranean Fever: Association with fatigue, psychological status, disease severity and other clinical parameters. Egypt Rheumatol. 2018;40(2):117-21.
5. McDougall J, Wright V, Schmidt J, Miller L, Lowry K. Applying the ICF framework to study changes in quality-of-life for youth with chronic conditions. Dev Neurorehabil. 2011;14(1): 41-53.
6. Gagnon LM, Patten SB. Major depression and its association with long-term medical conditions. Can J Psychiatry. 2002;47(2):149-52.
7. Palsson OF, Drossman DA. Psychiatric and Psychological Dysfunction in Irritable Bowel Syndrome and the Role of Psychological Treatments. Gastroenterol Clin N Am. 2005;34(2):281-303.
8. Yildiz A, Kizil E, Yildiz A. Quality of life and psychometric evaluation of patients diagnosed with irritable bowel syndrome: an observational cohort study. Sao Paulo Med J. 2020;138(4):282-6.
9. Onat AM, Öztürk MA, Özçakar L, Üreten K, Kaymak SU, Kiraz S. Selective serotonin reuptake inhibitors reduce the attack frequency in familial mediterranean Fever. Tohoku J Exp Med. 2007;211(1):9-14.
10. Onat AM, Ozçakar L, Oztürk MA, Uçar G, Ureten K, Dagli N, et al. Plasma and platelet serotonin levels in familial Mediterranean fever. Clin Exp Rheumatol. 2007;25(4Suppl.45):S16-20.
11. Dunlop SP, Coleman NS, Blackshaw E, Perkins A, Singh G, Marsden CA, et al. Abnormalities of 5 hydroxytryptamine metabolism in irritable bowel syndrome. Clin Gastroenterol Hepatol. 2005;3(4):349-57.
12. de Oliveira LDSSCB, Souza EC, Rodrigues RAS, Fett CA, Piva AB. The effects of physical activity on anxiety, depression, and quality of life in elderly people living in the community. Trends Psychiatry Psychother. 2019;41(1):36-42.
13. Singh S, Devanna S, Edakkanambeth Varayil J, Murad MH, Iyer PG. Physical activity is associated with reduced risk of esophageal cancer, particularly esophageal adenocarcinoma: a systematic review and meta-analysis. BMC Gastroenterol. 2014;14:101.
14. Craig CL, Marshall AL, Sjöström M, Bauman AE, Booth ML, Ainsworth BE. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003;35(8):1381-95.
15. Maurischat C, Ehlebracht-König I, Kühn A, Bullinger M. Structural validity of the Short Form 36 (SF-36) in patients with rheumatic diseases. Z Rheumatol. 2005;64(4):255-64.
16. Yilmaz-Sahin S, Oztas B, Kural E, Iyigun E. Transcultural adaptation and validation of the Turkish version of the gastrointestinal quality of life index. Indian J Surg. 2022;84(4):707-14.
17. Aya V, Flórez A, Perez L, Ramírez JD. Association between physical activity and changes in intestinal microbiota composition: A systematic review. PLoS One. 2021;16(2): e0247039.
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Download attachments: 10.4328.ACAM.21821
Ayşenur Yılmaz, Halil Yılmaz, Zeynep Dündar Ök, Serdar Kaymaz, Bilge Başakçı Çalık, Mustafa Çelik, Veli Çobankara. The relationship between physical activity level, gastrointestinal complaints and quality of life in patients with familial Mediterranean fever. Ann Clin Anal Med 2023;14(12):1104-1108
Citations in Google Scholar: Google Scholar
The effectiveness of vaccination against COVID-19-related fear and psychological resilience perception
Bahar Ürün Ünal 1, Serpil İnanmaz 2, Muslu Kazım Körez 3
1 Department of Family Medicine, 2 Department of Pediatrics, 3 Department of Biostatistics, Faculty of Medicine, Selcuk University, Konya, Turkey
DOI: 10.4328/ACAM.21823 Received: 2023-07-18 Accepted: 2023-08-28 Published Online: 2023-09-13 Printed: 2023-12-01 Ann Clin Anal Med 2023;14(12):1109-1114
Corresponding Author: Bahar Ürün Ünal, Department of Family Medicine, Faculty of Medicine, Selcuk University, Konya, Turkey. E-mail: urunbahar@gmail.com P: +90 554 293 09 05 Corresponding Author ORCID ID: https://orcid.org/0000-0001-5433-168X
This study was approved by the Ethics Committee of Selcuk University Faculty of Medicine (Date: 2021-08-27, No: E121723)
Aim: In this study, it was aimed to evaluate the relationship between COVID-19-related psychological resilience perception and fear of COVID-19 before and after vaccination using the Fear of COVID-19 Scale.
Material and Methods: The study included 830 participants aged from 18 to 89 years both before and after vaccination. Participants were administered a survey that included sociodemographic data, the COVID-19 Fear scale and the Fear of COVID-19 as well as questions related to psychological resilience perception.
Results: As a result of the study, it was found that the participants’ rates of watching the news every evening, following the number of cases on a daily basis, following social media accounts, buying masks/gloves/disinfectant increased after the vaccination. While the fear levels in females and males were similar before vaccination, the fear levels of females after vaccination were found to be higher.
Discussion: It was found that while the fear levels of females and males were similar before vaccination, the fear levels in females were found to be higher than in males after vaccination. In other studies, in which fear levels were examined without making any distinction between before and after vaccination in the pandemic process, fear levels of females were found to be higher than those of males. This can be explained by the fact that females have lower psychological resilience and the risk factor of being a female in terms of various mental disorders.
Keywords: COVID-19, Pandemic, Fear
Introduction
COVID-19 emerged in Wuhan city of China in December 2019 [1]. The infection was declared to be a pandemic by the World Health Organization (WHO) in March 2020 (available: https://www.who.int/europe/emergencies/situations/covid-19). COVID-19 is an infectious disease that causes acute respiratory tract infection [2]. According to the report released by WHO on 6 April 2023, there were 762,202,069 confirmed cases and 6,893,190 deaths across the world. In Turkey, where the first case was reported on 11 March 2020, as of 6 April 2023, there were 17,004,677 confirmed cases and 101,419 deaths (available: https://covid19.who.int/region/euro/country/tr).
COVID-19 has had social, health-related, and economic repercussions in a wide area worldwide. Governments and public health made social isolation, staying at home, and quarantine compulsory [3]. The COVID-19 pandemic has directly and indirectly affected the mental health of individuals [4]. The pandemic has led to various mental disorders in individuals such as anxiety, stress, and fear [5].
The COVID-19 infection has affected individuals mentally, socially, and economically. Restrictions and the spreading speed of the infection have led to the development of fear of getting infected, worry about the future, and anxiety. In the study, it was aimed to evaluate the relationship between the fear of COVID-19 before and after vaccination through the Fear of COVID-19 Scale.
Material and Methods
After breceiving information about the study and obtaining personal consent, 830 individuals at age of 18 years and above who applied to Selcuk University Medical Faculty COVID-19 Vaccination Unit between August and October 2021, who did not have uncontrolled epilepsy, who have not been vaccinated with live vaccine, who have not been tested for tuberculosis in the last month, and who have not tested positive for COVID-19 in the last three months, were administered personal information form consisting of 20 questions about socio-demographic characteristics, 6-item psychological resilience form, and 7-item Fear of COVID-19 Scale through face-to-face interview technique. In order to identify the effectiveness of the vaccination, the Fear of COVID-19 Scale and questions on psychological resilience were repeated before and after the study.
Approval for scientific research to be conducted in Selcuk University Medical Faculty Hospital COVID-19 Vaccination Unit was taken (Decision no: 2021/418), and ethical approval was obtained from the ethics committee (27.08.2021-E121723).
Socio-demographic Information Form
The form developed by the researchers for use in the study consisted of 20 questions inquiring about the socio-demographic characteristics of the participants such as age, gender, education status, occupation, marital status, smoking status, alcohol consumption, chronic diseases, COVID-19 history, contact with a COVID-19 infected patient, PPD test history in the last month, getting vaccinated in the last two weeks, side effects experienced in previous vaccinations, presence of neurological diseases, receiving vitamin and mineral support, presence of a known allergy, and pregnancy and breastfeeding status.
Fear of COVID-19 Scale
The scale was developed by Ahorsu et al [6] to measure COVID-19-related fear levels of individuals. The Turkish validity and reliability study of the scale was conducted by Satici et al [7]. The 7-item 5-point Likert type scale (1=Strongly Disagree, 5=Strongly Agree) has a one-factor structure. Internal consistency of the scale was found to be 0.82, and the test-retest test reliability was calculated as 0.72. A high score on the scale shows a high level of fear of COVID-19.
Questions Regarding Psychological Resilience Perception
Six questions regarding psychological resilience prepared and used by Yazici Celebi [8] in his study investigating reactions to the COVID-19 pandemic in terms of psychological resilience were included in the study by taking permission from the author. These questions are:
• I watch the news on COVID-19 (coronavirus) every evening.
• I follow the number of cases on a daily basis.
• Due to COVID-19, I started to follow the social media accounts of the Ministry of Health.
• I bought masks, gloves/disinfectants due to COVID-19.
• My sleep pattern got disrupted because of the pandemic-related anxiety.
• From time to time, I find myself examining whether I display any COVID-19 symptoms.
Statistical analysis
All statistical analysis was performed using R (available: https://www.r-project.org). Tests of normality assumptions for individual items were examined with skewness and kurtosis. Tests of skewness and kurtosis are within the adequate range of ≤ |3|. Also, tests of normality assumptions for variables were checked with Shapiro-Wilk normality tests. The internal consistency reliability was evaluated using McDonald’s w coefficients. The validity of the scale was evaluated with confirmatory factor analysis. A Mixed-ANOVA was conducted to determine the effect of different demographical variables (gender, education, marital status, smoking, alcohol consumption, etc. ) over time (before and after the vaccination) of vaccinations on the COVID-19 fear scale score. Two-proportions Z-test was used to determine whether there was a statistically significant change between before and after the vaccination in the attitudes of the participants toward the COVID-19 fear.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Table 1 presents the demographical, reliability and validity statistics for the COVID-19 fear scale both before and after the vaccination. The item-total correlations for individual items were above 0.35. The average interitem correlation of the scale was 0.616 and 0.573 before and after the vaccination, respectively. The McDonald’s w values for the COVID-19 fear scale were 0.921 before and 0.892 after the vaccination. All items had standardized factor loadings above 0.50, representing “fair” to “excellent”.
The factor structure of the scales was verified using CFA. The results were assessed based on data-model fit statistics and their cut-off scores: RMSEA and SRMR values, CFI and TLI. The results of CFA for each of the scales were CFI=0.989, TLI=0.967, SRMR=0.020, and RMSEA=0.092 for fear. This indicates a satisfactory model fit.
The descriptive statistics of the socio-demographical characteristics of the participants both before and after vaccination are presented in Table 2.
There were no statistically significant two-way interactions between gender and time of vaccination, F1,828=2.043, p=.153. Considering the adjusted p-value, it can be seen that the simple main effect of gender was not significant before the vaccination (p=.282). It becomes significant after the vaccination (p=.010). The mean COVID-19 fear score was significantly higher in females compared to males after the vaccination (p=.005) but not before the vaccination (p=.141). There was a statistically significant main effect of time of vaccination both in females and males (F1,462=346.5, p<.001 and F1,366=182.5, p<.001). There was a significant decrease in COVID-19 fear score after the vaccination both in females and males (all p<.001) (Figure 1-A).
There was a statistically significant two-way interaction between education and time of vaccination, F4,825=8.759, p<.001. Considering the adjusted p-value, it can be seen that the simple main effect of education was significant before the vaccination (p=.006) and after the vaccination (p=.001). The mean COVID-19 fear score was significantly higher in primary school graduates than in illiterate participants before the vaccination (p=.001). The mean COVID-19 fear score was lower in literate (1.75 ± 0.67) participants compared to primary school graduates (2.33 ± 0.91, p=.010), high school (2.24 ± 1.10, p=.007) and university (2.20 ± 1.06, p=.015) graduates after the vaccination. There was a statistically significant main effect of time of vaccination in all education levels (all p<.001). There was a significant decrease in COVID-19 fear scores after the vaccination in all education levels (all p<.001) (Figure 1-B).
There were no statistically significant two-way interactions between marital status and time of vaccination, F1,828=0.426, p=.514. Considering the adjusted p-value, it can be seen that the simple main effect of marital status was significant before the vaccination (p=.008) and after the vaccination (p=.005). The mean COVID-19 fear score was significantly higher in married compared to single both before (p=.008) and after the vaccination (p=.005). There was a statistically significant main effect of time of vaccination in both married and single (F1,409=236.2, p<.001 and F1,419=256.2, p<.001) participants. There was a significant decrease in COVID-19 fear score after the vaccination in both married and single participants (all p<.001) (Figure 1-C).
There was a statistically significant two-way interaction between alcohol and time of vaccination, F1,828=18.576, p<.001. Considering the adjusted p-value, it can be seen that the simple main effect of alcohol was significant before the vaccination (p=.006), but not after the vaccination (p=.922). The mean COVID-19 fear score was significantly higher in consumption of alcohol compared to no consumption of alcohol before the vaccination (p=.002) but not a after the vaccination (p=.461). There was a statistically significant main effect of time of vaccination both in alcohol and non-alcohol (F1,189=105.6, p<.001 and F1,639=439.1, p<.001). There was a significant decrease in COVID-19 fear score after the vaccination both in alcohol and non-alcohol (all p<.001) (Figure 1-D).
Following the vaccination, the participants’ rates of watching the news every night, following the number of cases on a daily basis, following social media accounts, buying mask/gloves/disinfectant, and disrupted sleeping patterns statistically significantly increased, while their rate of thinking that they displayed COVID-19 symptoms decreased (Table 3).
Discussion
The participants’ rates of watching the news every evening, following the number of cases on a daily basis, and following social media accounts after vaccination were found to be high. This situation may suggest that the participants of the study have reached a more conscious point in terms of the pandemic.
It was determined that the participants’ rate of buying mask/gloves/disinfectant statistically significantly increased. In a study conducted, the use of personal protective equipment was also found to be high [9].
It was determined that the participants’ rate of disrupted sleep patterns statistically significantly increased after vaccination. This situation can be attributed to the fact that the time allocated for sleep indirectly decreased as a result of the increase in the participants’ rates of watching the news every evening, following the number of cases on a daily basis, and following social media accounts after vaccination. In addition, working from home, staying at home, and curfews may have affected individuals’ routine sleep durations. Fast spread of the infection and high mortality rate might have affected individuals’ stress levels and disrupted their sleeping patterns. Besides, in the study conducted by Kirac et al., the anxiety related to being infected with COVID-19 positively affected postponing sleep. It was also concluded that females had higher anxiety and postponed sleep [10].
It was found that while there was an increase in the individuals’ rate of thinking that they were showing COVID-19 symptoms before vaccination, this rate decreased after vaccination. The participants stated that they believed in the protective effect of the vaccine. This situation was considered to be related with not checking the symptoms after vaccination. Moreover, in the study conducted by Yazici Celebi, it was determined that when asking if they were showing symptoms, females compared to males and married individuals compared to single individuals checked the symptoms at a higher rate [8].
It was found that while the fear levels of females and males were similar before vaccination, the fear levels of females were found to be higher than males after vaccination. No study was encountered in the literature that examined the effect of the vaccine on fear levels of females and males. In other studies, in which fear levels were examined without making any distinction between before and after vaccination in the pandemic process, fear levels of females were found to be higher than those of males. This can be attributed to females having lower psychological resilience and the risk factor of being a female in terms of various mental disorders. In the study conducted by Pak Gure, the fear of being infected with COVID-19 was found to be higher in females [11]. Kimter found that psychological resilience level of males was significantly higher than that of females [12]. In the study conducted by Erdogan Yuce et al., stress level of females was determined to be higher compared to that of males [13]. In the study by Tonbul, gender factor was found to have positively affected psychological resilience [14]. In various studies conducted, females were found to have higher levels of fear of being infected with COVID-19 in comparison to males [15-17].
In the present study, fear levels of married individuals after vaccination displayed a relative decrease, but it was not statistically significant. Similarly, the fear levels of single individuals displayed a relative decrease after vaccination compared to the level before vaccination, but the decrease was not statistically significant. However, the fear levels of married participants were statistically significantly higher both before and after vaccination compared to the fear levels of single participants. This high level of fear among married individuals can be attributed to higher family responsibilities and the presence of children increasing their fear level. On the other hand, in the study conducted by Bayulgen et al., no significant difference was found in the pandemic process between marital status and anxiety score [18]. In the study they conducted, Aydin et al. could not find a difference between marital status and having a child in scale scores [19].
In many of the studies that have been conducted, levels of fear have been reduced with higher levels of education, but in the present study, we did not find such a result, which could have been affected by social media use, information provided by the Ministry of Health on television, and rates of watching the news. In the study conducted by Arapcioglu et al., the fear of being infected with COVID-19 was found to be higher in nurses compared to doctors [20]. In the study they conducted, Doshi et al. found higher levels of fear of being infected with COVID-19 in individuals with low level of education [21]. Arisoy et al. found that as education level decreased, the fear of being infected with COVID-19 increased [17]. In the study conducted by Huang et al., no significant difference was found between educational status and anxiety [22]. Memis Dogan et al. found low anxiety levels among university graduates during the pandemic period [23]. In the study by Pak Gure et al., it was concluded that the fear of being infected with COVID-19 increased in individuals with high levels of education [11]. In the study conducted by Bozdag, it was determined that as education level increased and precautions were taken against COVID-19, psychological resilience level increased [24]. In all these studies, the effect of education level in the period when the studies were conducted independently of the effect of vaccination was evaluated.
Uncertainty about the effect of alcohol on COVID-19 before vaccination may have elevated fear levels in individuals. It can be stated that this situation may have decreased the fear of being infected with COVID-19 in alcohol consumers after vaccination along with the trust in the vaccine.
As all parameters in the present study were evaluated in a general sense throughout the pandemic process and the distinction between before and after vaccination was not encountered in the literature with a few exceptions, the data in this regard were limited. Being one of the few studies in the literature in this regard and the wide population of the study contributed to the value of the study.
Conclusion
Vaccination is the most effective and easiest protective health service that can be provided to save the lives of millions of individuals. Through vaccination, we can contribute to preventable COVID-19 infection related mortality and morbidity as well as the fear cause by the infection and psychological resilience.
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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Bahar Ürün Ünal, Serpil İnanmaz, Muslu Kazım Körez. The effectiveness of vaccination against COVID-19-related fear and psychological resilience perception. Ann Clin Anal Med 2023;14(12):1109-1114
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Investigation of the effect of fuziline on end-organs in balb-c mice with cardiac damage caused by high dose dobutamine
Yasemin Hacanlı 1, Ezhar Korkmaz Ersöz 1, Mehmet Salih Aydın 1, Muhammet Emin Güldür 2, Reşat Dikme 3, Mahmut Padak 3, Evren Büyükfirat 4
1 Department of Cardiovascular Surgery, Faculty of Medicine, Harran University, Sanliurfa, 2 Department of Pathology, Islamic Science and Technology University, Gaziantep, 3 Department of Perfusion Techniques Program, Faculty of Health Services, Harran University, Sanliurfa, 4 Department of Anesthesia and Reanimation, Faculty of Medicine, Harran University, Sanliurfa, Turkey
DOI: 10.4328/ACAM.21840 Received: 2023-08-02 Accepted: 2023-09-06 Published Online: 2023-09-19 Printed: 2023-12-01 Ann Clin Anal Med 2023;14(12):1115-1119
Corresponding Author: Yasemin Hacanlı, Department of Cardiovascular Surgery, Faculty of Medicine, Harran University, Sanliurfa, Turkey. E-mail: yaseminhacan@hotmail.com P: +90 506 700 27 00 Corresponding Author ORCID ID: https://orcid.org/0000-0002-4427-8149
This study was approved by the Local Ethics Committee of Harran University (Date: 2023-03-10, No: 01-09)
Aim: Inotropes cause an increase in cardiac output because they increase cardiac contractility through different mechanisms of action. However, they also have vasodilatory or vasoconstrictive effects that vary depending on the substance and dose. In this study, we histopathologically investigated the level of damage in end-organ tissues and the effect of fuziline on these organs in mice with cardiac injury induced by high doses of dobutamine.
Material and Methods: Thirty-two adult male Balb-c mice weighing approximately 18-20 g were included in the study. They were randomly divided into four groups (n=8): Group 1 (sham, n=8), Group 2 (dobutamine, n=8), Group 3 (dobutamine + fuziline, n=8) and Group 4 (fuziline, n=8). CK-MB as a biochemical parameter for damage assessment was analyzed in all groups. Histopathological examination was performed for the presence of necrosis, inflammation and edema in the tissues of the end-organs.
Results: CK-MB was found statistically significant between the groups (p<0.05). When the end-organ tissues of all groups were histopathologically compared for the presence of necrosis, inflammation and edema, no significant difference was observed and no damage was detected.
Discussion: Dobutamine, which is frequently used as a positive inotropic agent in cardiovascular surgery, was observed not to cause any damage to the end-organs. In addition, we believe that the absence of any tissue damage in mice in the group given only fuziline demonstrates the safety of fuziline.
Keywords: Cardiac Damage, Fuziline, Dobutamine, Antioxidant
Introduction
High blood pressure, high cholesterol and smoking play an important role in the formation of cardiovascular diseases (CVD). Despite this, the main factor is oxidative stress [1]. Oxidative stress results from the deterioration of the balance between oxidant-antioxidant in favor of oxidants. CVD, causes DNA damage, neuro-degenerative and the formation of disorders such as diabetes [2]. CVD includes peripheral artery disease, coronary heart disease, rheumatic heart disease, etc. [3]. The use of inotropes is recommended in cases of end-organ dysfunction caused by hypoperfusion in patients with CVDs [4]. Dobutamine, preferred as a positive inotropic agent, activates α1 and β1 receptors to increase cardiac output and regulate mean arterial pressure [5]. However, care should be taken in dose adjustment. Therefore, an overdose may cause the development of tachycardia [6]. Today, safer and more cost-effective alternatives are being investigated in the treatment of CVDs. In this respect, medicinal plants are of great importance [7]. Among these medicinal plants, those with components such as flavonoids, carotenoids and polyphenols have been shown to inhibit CVD [8].
Flavonoids are beneficial compounds with cardiovascular, antioxidant, anti-inflammatory etc. activities [9]. Fuzi, contains compounds such as flavonoids and alkaloids in its chemical content [10]. Fuziline is one of the components of fuzi, and in terms of side effects, fuzi’s other components, mesaconite, aconite and hypaconite, have fewer side effects than diterpenoids. It is safer [11].
In our study, we aimed to investigate histopathologically the level of end-organ damage (lung, liver, kidney and spleen) tissues and the effect of fuziline on these organs in mice with cardiac injury induced by high dose of dobutamine.
Material and Methods
Ethical Approval
Our study was conducted with the scientific committee approval of Harran University Animal Experiments Local Ethics Committee, dated 10-03-2023, session numbered 2023/001, and with decision 01-09.
Creation of Animal Groups and Damage Model
For our study, 32 adult male mice of the balb-c genus weighing 18-20 grams (gr) were included in the study. They were randomly (n=8) divided into four groups. In the cages created in such a way that the transparent feed-water attachments that can be seen inside can be reinforced, they were maintained in a dark environment with a relative humidity of 50%, where the temperature was 22 ±2 0 C, 12 hours of light and 12 hours of darkness. Mice were fed under standard conditions. Group 1 (Sham, n=8) was fed standard mouse chow and mains water for 15 days. Group 2 (dobutamine, n=8) were injected mice intraperitoneally (IP) with 40 micrograms (μg)/mouse/day of dobutamine for 15 days. Group 3 mice were injected with dobutamine + fuziline, n=8. For the first week mice were administered dobutamine 40 μg/mouse/day as IP. For the next week, in addition to dobutamine, 3 milligrams/kilogram (mg/kg) of fuziline was administered IP every day. Group 4 (fuziline, n=8) mice were injected with 3 mg/kg of fuziline IP for 15 days. One mouse from the fuziline group died on the eighth day. On the eighth day, all groups underwent). After detecting damage in the dobutamine+fuziline group, fuziline injection was started. The total working time was 15 days. Feeding of 31 mice was interrupted 8 hours before sacrifice. At the end of the experimental period (Day 16), all mice were sacrificed under deep anesthesia (Ketamine 90 mg/kg and xylazine 10 mg/kg-IP). Blood samples and end organ tissues were collected.
Preparation of Dobutamine
Sigma brand dobutamine (250 mg) was used to induce cardiac injury. 1.6 ml dobutamine was completed to 100 ml with saline. Each mouse was injected with 0.1 ml of the IP route each day.
Preparation of Fuziline
Sigma brand fuziline was purchased from the distributor of Interlab company in Turkey. Fuziline (0.96 mg/kg) was dissolved in 1.6 ml of dimethyl sulfoxide (DMSO). Each mouse was injected with 0.1 ml IP every day.
CK-MB (Creatine kinase myocardial band) study preparation
Blood collected from the mice hearts was transferred into biochemistry tubes with yellow caps. Centrifugation was performed at 4000 rpm for 10 minutes. The resulting plasma was transferred to Eppendorf tubes and stored at -80 ° C until the working day. During the working day, the Ependorfs were thawed at room temperature. The CK-MB value was measured with the Atellica Siemens device and the Atellica Siemens® commercial kit.
Histopathological Examination of End-Organ Tissues
End-organ tissue samples from mice were detected by placing them in 10% formaldehyde. The appropriate samples were embedded in paraffin after four hours of tissue monitoring in a Leica Bond-Max Immunohistochemistry tissue tracker. Four micrometer (μm) thick sections were obtained from the end-organs of each mouse and stained with hemotoxylin eosin (He) stain. Histopathological (Hex400) examination examined the presence of necrosis, inflammation and edema in end-organ tissues.
Statistical analysis
SPSS Windows version 24.0 package program was used for statistical analysis and p<0.05 was considered statistically significant. The suitability of the data for a normal distribution was tested by the Kolmogorov-Smirnov and Shapiro-Wilk tests. Comparisons between the groups were analyzed using ANOVA (one-way analysis of variance) test and Post-Hoc multiple comparisons (Bonferroni test) in the studied parameter. As descriptive statistics, mean±standard deviation was used for numerical variables and numbers and percentages were used for categorical variables.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
When CK-MB (ng/mL) levels were compared between groups, there was a significant correlation between Sham and Dobutamine (p=0.000), Dobutamine and Fuziline (p=0.000), Dobutamine+Fuziline and Dobutamine groups (p=0.04). It was found statistically significant (p<0.05) (Table 1).
When all groups were compared histopathologically in terms of necrosis, inflammation and edema, no significant difference was observed. In the histopathological examination of end-organ tissues of dobutamine-injected and dobutamine+fuziline groups, regular alveoli (blue arrow) and bronchial (green arrow) structures were observed in all lung tissues of both groups (Figures 1A and 1B).
Histopathological examination of the liver tissue showed regular structure in portal areas, hepatic veins and hepatocytes (Bile duct blue arrow and congestive vascular structure green arrow, Figures 1C and 1D).
When all the right and left kidney tissues were examined, a regular structure was observed in the glomerular structures, kidney tubules and pelvicalyceal system (glomerulus blue arrow and tubule green arrow, Figures 1E and 1F).
On the histopathological examination of the spleen tissue, regular red pulp (green arrow) and white pulp (blue arrow) structures were observed (Figures 1G and 1H).
In addition, as a result of the histopathological examination of end-organ tissues of the sham and fuziline groups no damage was found in the lung (Figures 2A and 2B), liver (Figures 2C and 2D), kidney (Figures 2E and 2F) and spleen (Figures 2G and 2H). In the histopathological examination of the end-organ tissues of 31 mice belonging to four groups, no necrosis, inflammation and edema were detected in all tissues.
Discussion
Inotropes are agents that increase cardiac output in various ways. They show different activities depending on the substance and dose. In general, they have a positive effect on hemodynamics and regulation of symptoms. Therefore, their use in patients with acute and advanced heart failure (HF) is critical. Despite these positive effects, they can also lead to increased mortality due to side effects and misuse. Dobutamine is preferred as a positive inotropic agent to eliminate blockages, despite the possibility of reducing survival in patients with HF [12]. When using high doses [10 μg/kg/minute (min)], it shows inotropic and chronotropic activity; at low doses (5μg/kg/min), it causes mild vasodilator and inotropic function that contributes to the development of hypotension [13]. Tang et al. examined the effect of long-term use of dobutamine (10.0 μg/kg) on septic myocardial dysfunction and injury by performing cecal ligation and puncture in rats. While the probability of survival in rats with dobutamine is positively affected, no effect was observed on maintaining low levels of myocardial dysfunction and myocardial injury after sepsis [14]. In a study of female rats, dobutamine was administered to female rats at doses of 5, 10, and 20 ug/min/kg at weeks 1 and 6 before and after spinal cord injuries above T6. As a result of the study, an increase in heart rate, ejection fraction and cardiac output was observed with dobutamine infusion before spinal cord injuries above T6, while a decrease in end-diastolic volume was observed. Spinal cord injuries above T6 were followed by dobutamine supplementation at 6 weeks, which led to an increase in heart rate, ejection fraction and cardiac output, as well as an increase in pulse volume [15]. In their study of rats with and without spinal cord injury, Fernandes and colleagues administered dobutamine at different doses such as 20, 50 and 100 μg/kg. Rats with spinal cord injury had reduced their struggle with cardiac stress and increased the incidence of arrhythmias with increasing doses of dobutamine [16]. In the study on female pigs, 1, 3, 10 and 30 μg/kg/min were given as continuous infusions without dobutamine loading dose. Dobutamine was announced to increase right ventricular pressure and function, but at the expense of increased mechanical work at the highest doses, exhibiting an unfavorable hemodynamic profile [17]. In their study, Mert et al. administered dobutamine at doses of 5, 10, and 15 μg/kg/min in a total of 73 patients with HF. It has been observed that ventricular arrhythmias are triggered in this way. Even, 4 patients were excluded from the study because they could not handle high doses of dobutamine administration [18]. In our previous study with dobutamine, mice were given a dobutamine dose of 40 μg/mouse/day for fifteen days. This dose appeared to cause cardiac damage [19].
According to the data of studies conducted in recent years, it has been revealed that the use of phytochemicals is the right approach to prevent CVD [20]. Fuzi, thanks to compounds such as flavonoids and alkaloids in its chemical content [10] , stands out with its protective feature against CVD by showing anti-oxidative [21] and anti-inflammatory [22] activities.
The derivation of Fuzi [21] and the polysaccharides obtained from the purified part FZPS-1 exhibit antioxidant effects by the elimination of superoxide radical, hydroxyl radical and nitrite from the environment [22]. Fuziline and some other diterpenoids were used in the study on mice for the treatment of CVD. Zhao et al.’s investigations involving fuziline, mesaconite, neolin, and hypoconite have proven that these diterpenoids exert significant analgesic effects. In terms of harmful effects, fuziline has been observed to have fewer side effects than other diterpenoids. In addition, the maximum dose of fuziline administration was stated as 1 g/kg [11]. In the study investigating the protective efficacy and mechanisms of fuziline on in vitro and in vivo myocardial injury, the protection of fuziline against myocardial injury has been clearly demonstrated and it has been suggested that it can be used as a therapeutic agent [23].
Limitation
According to our literature review, the lack of studies examining the effect of dobutamine on end organs in terms of dose and duration is our limitation.
Conclusion
According to our literature review, the effect of dobutamine on end organs has not been investigated histopathologically. In our study, CK-MB level was examined as a result of high dose injection of dobutamine, which is frequently used as a positive inotropic agent in cardiovascular surgery, and it was determined that cardiac damage occurred in dobutamine and dobutamine+fuziline groups. However, when the last organ tissues were examined histopathologically, no damage was detected. In addition, we believe that the absence of any tissue damage in the mice in the group given only fuziline demonstrates the safety of fuziline.
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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Download attachments: 10.4328.ACAM.21840
Yasemin Hacanlı, Ezhar Korkmaz Ersöz, Mehmet Salih Aydın, Muhammet Emin Güldür, Reşat Dikme, Mahmut Padak, Evren Büyükfirat. Investigation of the effect of fuziline on end-organs in balb-c mice with cardiac damage caused by high dose dobutamine. Ann Clin Anal Med 2023;14(12):1115-1119
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Evaluation of beractant, poractant alfa and calfactant use in newborns with respiratory distress syndrome: A single-center retrospective study
Cengizhan Ceylan 1, Seyma Tetik Rama 2, 3, Ayse Huzeyme Cınar 2, Murat Konak 4, Saime Sundus Uygun 4, Mehmet Ozturk 5, Hanifi Soylu 4
1 Departmant of Clinical Pharmacy, Faculty of Pharmacy, Selcuk University, Konya, 2 Departmant of Pharmacology, Faculty of Pharmacy, Selcuk University, Konya, 3 Department of Department of Pharmacology, Graduate School of Health Sciences, Ankara University, Ankara, 4 Departmant of Neonatology, Faculty of Medicine, Selcuk University, Konya, 5 Departmant of Radiology, Faculty of Medicine, Selcuk University, Konya, Türkiye
DOI: 10.4328/ACAM.21849 Received: 2023-08-08 Accepted: 2023-09-12 Published Online: 2023-09-21 Printed: 2023-12-01 Ann Clin Anal Med 2023;14(12):1120-1124
Corresponding Author: Cengizhan Ceylan, Department of Clinical Pharmacy, Faculty of Pharmacy, Selcuk University, Konya, Türkiye. E-mail: c.ceylan20@gmail.com P: +90 543 367 02 44 Corresponding Author ORCID ID: https://orcid.org/0000-0003-4164-9212
This study was approved by the Local Ethics Committee of Selcuk University Faculty of Medicine (Date: 2022-04-12, No: E-70632468-050.01.04-267676)
Aim: Surfactant production by type II pneumocytes starts at 24-25 weeks of gestation and reaches optimum level at 36-37 weeks. The aim of this study was to retrospectively evaluate the efficacy of three different surfactant preparations on the respiratory functions of preterm infants.
Material and Methods: This study was carried out retrospectively in newborns with respiratory distress syndrome who received inpatient treatment and used surfactant in the Neonatal Intensive Care Unit of Selcuk University Faculty of Medicine, Department of Pediatrics, in 2017-2021. The study group included 111 preterm infants diagnosed with RDS, with a delivery week of 32 and below, who were administered one of three different animal-derived surfactant preparations (poractant alfa, calfactant and beractant).
Results: In this study, poractant alfa was applied to 48.65% (n=54) of the patients, calfactant to 13.51% (n=15), and beractant to 37.84% (n=42) of the patients due to RDS. There was no statistically significant difference between the three different surfactant groups in terms of maternal drug use, antenatal steroid use, which affect the development of RDS in newborns. Gender, type of birth, gestational age, maternal age, 1-min Apgar scores, and 1-, 3-, 5-, and 7-day FiO2 levels did not differ between the three groups.
Discussion: The efficacy of poractant alfa, beractant and calfactant used in newborns with RDS is similar.
Keywords: Respiratory Distress Syndrome, Surfactant, Poractant Alfa, Calfactant, Beractant
Introduction
Pulmonary surfactant is a complex surface-active material found on the alveolar fluid surface of the lungs, which reduces the air-water surface tension in the lungs, facilitating breathing and preventing alveolar collapse [1, 2]. Surfactant production by type II pneumocytes starts at 24-25 weeks of gestation and reaches optimum level at 36-37 weeks [3]. Therefore, immature lungs cannot produce enough surfactant in infants born before 36 weeks of gestation, and diffuse alveolar collapse occurs in the lungs as a result of surfactant deficiency [4]. Respiratory distress syndrome (RDS) is one of the main causes of respiratory failure in premature infants due to insufficient maturation of the lungs and lack of surfactant [5]. Serious complications of RDS include pneumothorax, pulmonary hemorrhage, intraventricular hemorrhage, and bronchopulmonary dysplasia [6]. Tachypnea, subcostal and intercostal retractions, nasal flare, and cyanosis immediately after birth are some of the clinical signs of RDS. Severe cases may require intubation and mechanical ventilation. Diffuse, symmetrical, reticulogranular structures that typically mimic the ground-glass appearance are seen on the chest radiograph. In the management of newborn RDS, a skilled multidisciplinary care team should deliver the best possible respiratory support. For airway and alveolar expansion, adequate oxygenation and ventilation should be provided. Treatment of RDS in preterm newborns with exogenous surfactant replacement therapy significantly reduces the incidence of morbidity, mortality, pulmonary air leak, and pneumothorax. Also, it was found that surfactant treatment in newborns with pneumonia or sepsis showed better gas exchange compared to newborns who did not receive surfactant treatment. Antenatal corticosteroid therapy accelerates fetal lung maturation by increasing the activity of enzymes responsible for surfactant biosynthesis, thus reducing the incidence of neonatal mortality and brain injury. Recommendations of the European Guidelines (2019 update) for Management of Neonatal RDS in Preterm Infants on surfactant administration: premature infants with RDS should be given animal-derived surfactant preparation as soon as possible. CPAP (continuous positive airway pressure) should be initiated early in infants of gestational age less than 30 weeks. If the preterm neonates need mechanical ventilation, it should be targeted for the shortest possible time. If evidence of RDS persists, such as the need for mechanical ventilation, a second, sometimes third dose of surfactant should be administered. Randomized trials show that multiple-dose surfactant treatment strategies lead to a reduction in pneumothorax incidence and mortality compared to single-dose administration.
For now, there are three animal-derived surfactants approved by the Food and Drug Administration for the treatment of newborns diagnosed with RDS in Turkey: poractant alfa (Curosurf ®) in 1998, calfactant (Infasurf ®) in 1998 and beractant (Survanta ®) in 1991. The aim of this study was to retrospectively evaluate the efficacy of three different surfactant preparations on the respiratory functions of preterm infants.
Material and Methods
Study design
This study was carried out retrospectively in newborns with respiratory distress syndrome who received inpatient treatment and used surfactant in the Neonatal Intensive Care Unit of Selcuk University Faculty of Medicine, Department of Pediatrics, in 2017-2021.
The diagnosis of RDS in newborns with clinical manifestations of respiratory distress was evaluated by chest radiography. The diagnosis of RDS was confirmed by ground glass appearance in the lung and blood gas analysis. Surfactant replacement therapy was administered to each patient according to the European Consensus Guidelines [9]. The first doses of poractant alfa 200 mg/kg (recurrent dose of 100 mg/kg if needed), calfactant 100 mg/kg and beractant 100 mg/kg were injected into the trachea via an orogastric tube through an endotracheal tube.
The clinical course of postnatal RDS, newborn delivery type, RDS scoring based on neonatal chest X-ray interpretation, Apgar scores, FiO2 need, oxygen and mechanical ventilation needs, the day of starting oral feeding and the length of stay in the hospital were recorded. Then, the efficacy of three different natural surfactant preparations was evaluated in line with these parameters.
Statistical analysis
Statistical analyses were performed with SPSS (Statistical Package for the Social Sciences) statistical software. One-way analysis of variance (ANOVA) test was applied for continuous variable data for those with normal distribution. The results were considered significant at p<0.05 at 95% confidence interval.
Ethical Approval
This study was approved by the local ethics committee of the Selcuk University Faculty of Medicine (Date: 2022-04-12, No: E-70632468-050.01.04-267676).
Results
The study group included 111 preterm infants diagnosed with RDS, with a delivery week of 32 and below, who were administered one of three different animal-derived surfactant preparations (poractant alfa, calfactant and beractant) (Figure 1). Patients who died within the first three days were not included in the study groups.
In this study, poractant alfa was applied to 48.65% (n=54) of the patients, calfactant to 13.51% (n=15), and beractant to 37.84% (n=42) of the patients due to RDS.
In this study, parameters such as gender (male or female), delivery type (normal spontaneous vaginal delivery (NSVD) or cesarean delivery), maternal age, gestational age, birth weight, Apgar scores and FiO2 values were compared according to three different surfactant preparations administered to newborns with RDS (Table 1). Accordingly, 49 of 54 patients in Group-I, 11 of 15 patients in Group-II, and 38 of 42 patients in Group-III were born by cesarean section, and there was no statistical difference between the groups in this respect. The mean birth weight of the neonates was found to be 1135.09 in Group-I, 1509.7 in Group-II and 1368.4 in Group-III. A statistically significant difference was found between the groups in terms of mean birth weight. The mean Apgar scores at the 1-min were found to be 5 in Group-I, 6 in Group-II and 5 in Group-III. No statistically significant difference was found between the groups in Apgar scores at the 1- and 5-min. Gender, type of birth, gestational age, maternal age and 1-, 3-, 5-, and 7-day FiO2 levels did not differ between the three groups. There was no statistically significant difference in clinical course in terms of tachypnea, cyanosis, moaning while breathing and retraction in newborns treated with surfactant. Details of other evaluated parameters are given in Table 1.
The presence and absence of morbidity parameters such as sepsis, pulmonary hemorrhage, pneumothorax, as well as mortality in newborns with RDS in treatment with different surfactant preparations were evaluated (Table 2). Accordingly, sepsis was positive in 24 of 54 patients in Group-I, 7 of 15 patients in Group-II, and 20 of 42 patients in Group-III. No statistically significant difference was found between the groups between sepsis positive and negative. Pulmonary hemorrhage was was found to be positive in 5 of 54 patients in Group-I, 1 of 15 patients in Group-II, and 1 of 42 patients in Group-III. No statistically significant difference was found between the groups between pulmonary hemorrhage positive and negative. Mortality, which is one of the most important parameters for our study, was evaluated among the groups, was found in 12 of 54 patients in Group-I, 0 of 15 patients in Group-II, and 7 of 42 patients in Group-III. Antenatal steroid use was was found in 20 of 54 patients in Group-I, in 4 of 15 patients in Group-II, and in 20 of 42 patients in Group-III. No statistically significant difference was found between the groups in terms of antenatal steroid use. There was no statistically significant difference in the presence of sepsis, mortality pulmonary hemorrhage, and pneumothorax in the patient groups treated with various surfactants. Regarding maternal drug and prenatal steroid use, both of which have an impact on the development of RDS in neonates, there was no statistically significant difference between the three distinct surfactant groups. Details of other evaluated parameters are given in Table 2.
According to different surfactant preparations applied to newborns with RDS, extubation in the first 3 days, reintubation in 14 days, mechanical ventilation time in the first 28 days, time of dependence on oxygen, time of application of nasal continuous positive airway pressure (NCPAP), day of initiation of oral feeding and hospital stay time were evaluated. When the patients who were extubated in the first 3 days were evaluated, 29 of 54 patients in Group-I, 7 of 15 patients in Group-II and 21 of 42 patients in Group-III were positive. When the total mechanical ventilation time between the groups was compared, it was found that the mean was 18.93 in Group-I, 17.87 in Group-II and 16.26 in Group-III. The mean RDS scores on day 1 were found to be 2.07 in Group-I, 1.69 in Group-II and 1.82 in Group-III. There was no statistically significant difference in terms of extubation in the first 3 days, reintubation in 14 days, NCPAP administration time, mechanical ventilation time in the first 28 days, oxygen dependent time, day of initiation of oral feeding and hospital stay time between groups of newborns with RDS treated with different surfactants. RDS scoring and the presence of pneumothorax were evaluated by examining the chest radiographs of newborns with RDS treated with different surfactant preparations within the first 3 days. Details of other evaluated parameters are given in Table 3.
Discussion
The severity of RDS, a pulmonary insufficiency syndrome, rises throughout the first two to three days of life and starts immediately after or shortly after birth. Clinically, RDS is characterized by early respiratory distress, including cyanosis, moaning, retraction, and tachypnea. Blood gas analysis can show that respiratory failure is developing, and air bronchograms and the distinctive “ground glass” appearance on chest X-rays can confirm the diagnosis. If left untreated, death occurs due to progressive hypoxia and respiratory failure. RDS is due to structural immaturity of the lung combined with alveolar surfactant deficiency. Although there are studies worldwide to compare the effectiveness of surfactant types used in newborns, studies in our country are limited.
In a study conducted by Yılmaz et al., comparing the efficacy of Poractant alfa, Beractant and Calfactant preparations, sepsis and mortality rates were found to be lower in patients treated with Calfactant. However, in a study by Trembath et al. in which they compared beractant, calfactant, and poractant alfa, there was no difference in outcomes, including air leak, bronchopulmonary dysplasia, and mortality. The researchers thought that surfactants included in previous studies did not show real differences in the efficacy of surfactants in terms of mortality and outcomes and this was related to the variation in outcomes attributed to different institutions. It is considered to be an advantage that the sample size of the calfactant group is larger in the study by Yılmaz et al. In another study conducted in our country, mortality rates of newborns with RDS using poractant alfa and beractant were found to be similar. In our study, no significant difference was found between the sepsis rates of the patients treated with 3 different natural surfactant preparations. No mortality was observed in the group receiving calfactant treatment. This is thought to be related to the high birth weight of the newborns in the calfactant group and their lower numbers compared to the other groups.
In our study, it was observed that the oxygenation of the patients using surfactant improved and their respiratory support requirements decreased, but no significant difference was found between the natural surfactants used. In a randomized controlled study conducted in Iran, pneumothorax and pulmonary hemorrhage were found statistically significant among surfactants [15].
The results of observational studies and clinical studies have shown that antenatal steroids can reduce the need for prophylactic and early surfactant replacement in infants born after 27 to 28 weeks of gestation [16]. In our study, when the relationship between different surfactant preparations and RDS incidence in antenatal steroid use in newborns at and below 32 weeks of gestation was examined, no significant difference was found (p>0.05).
In a study comparing the use of poractant alfa and beractant, no statistical significance was found among surfactants in terms of Apgar scores, maternal preeclampsia, mode of delivery, pneumothorax and hemorrhage [17]. The results are in agreement with the data in our study.
In a randomized controlled study conducted by Mishra et al., no relationship was found between the duration of hospital stay and the surfactants used [18]. In our study, there was no significant difference (p>0.05) in terms of length of hospital stay and initiation of oral feeding for three different groups.
Another study revealed no difference between surfactants in terms of oxygen consumption, extubation age, problems, hospital stay, and death [19]. The results of our study are compatible with other studies.
In order to provide more reliable data in the comparison of three natural surfactants, randomized controlled studies that keep the sample size as large as possible are needed. In studies comparing 3 natural surfactant preparations, which have already been studied, the samples are quite small. Maximum care should be taken in patient selection. It is thought that more care should be taken when matching the socio-demographic and clinical characteristics of patients treated with different surfactant preparations.
Conclusion
The efficacy of poractant alfa, beractant and calfactant used in newborns with RDS is similar. Studies with homogeneous patient populations between groups are needed to compare efficacy more comprehensively.
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.
References
1. Han S, Mallampalli RK. The role of surfactant in lung disease and host defense against pulmonary infections. Ann Am Thorac Soc. 2015;12(5):765-74.
2. Ji J, Sun L, Luo Z, Zhang Y, Xianzheng W, Liao Y, et al. Potential therapeutic applications of pulmonary surfactant lipids in the host defence against respiratory viral infections. Front Immunol. 2021;12:730022.
3. Joshi S, Kotecha S. Lung growth and development. Early Hum Dev. 2007;83(12):789-94.
4. Pickerd N, Kotecha S. Pathophysiology of respiratory distress syndrome. Paediatrics and Child Health. 2009;19(4):153-7.
5. Chen IL, Chen HL. New developments in neonatal respiratory management. Pediatr Neonatol. Jul 2022;63(4):341-7.
6. McPherson C, Wambach JA. Prevention and treatment of respiratory distress syndrome in preterm neonates. Neonatal Network. 2018;37(3):169-77.
7. Wirbelauer J, Speer C. The role of surfactant treatment in preterm infants and term newborns with acute respiratory distress syndrome. J Perinatol. 2009;29(2):S18-22.
8. Vento G, Tana M, Tirone C, Aurilia C, Lio A, Perelli S, et al. Effectiveness of treatment with surfactant in premature infants with respiratory failure and pulmonary infection. Acta Biomed. 2012;83(Suppl. 1):S33-6.
9. Sweet DG, Carnielli V, Greisen G, Hallman M, Ozek E, Plavka, et al. European consensus guidelines on the management of respiratory distress syndrome–2019 update. Neonatology. 2019;115(4):432-50.
10. Soll R, Özek E. Multiple versus single doses of exogenous surfactant for the prevention or treatment of neonatal respiratory distress syndrome. Cochrane Database Syst Rev. 2009;(1). DOI: 10.1002/14651858.CD000141.pub2.
11. Dumpa V, Avulakunta I, Bhandari V. Respiratory management in the premature neonate. Expert Rev Respir Med. 2023;17(2):155-70.
12. Yılmaz FH, Tarakçı N, Gültekin ND, Yücel M, Keçeci R, ÖZtürk ENY, et al. Comparison of the Efficacy of Three Natural Surfactants in Preterm Turkish Newborns with Respiratory Distress Syndrome. Journal of Pediatric Research. 2021;8(2):124-30.
13. Trembath A, Hornik CP, Clark R, Smith PB, Daniels J, Laughon M. Comparative effectiveness of surfactant preparations in premature infants. J Pediatr. 2013;163(4):955-60.e1.
14. Dizdar EA, Sari FN, Aydemir C, Oğuz SS, Erdeve O, Uras N, et al. A randomized, controlled trial of poractant alfa versus beractant in the treatment of preterm infants with respiratory distress syndrome. Am J Perinatol. 2012;29(2):95-100.
15. Mussavi M, Mirnia K, Asadollahi K. Comparison of the Efficacy of Three Natural Surfactants (Curosurf, Survanta, and Alveofact) in the Treatment of Respiratory Distress Syndrome Among Neonates: A Randomized Controlled Trial. Iran J Pediatr. 2016;26(5):e5743.
16. Polin RA, Carlo WA. Surfactant replacement therapy for preterm and term neonates with respiratory distress. Pediatrics. 2014;133(1):156-63.
17. Gharehbaghi MM, Yasrebi S. Comparing the efficacy of two natural surfactants, Curosurf and Alveofact, in treatment of respiratory distress syndrome in preterm infants. International Journal of Women’s Health and Reproduction Sciences. 2014;2(4):245-8.
18. Mishra A, Joshi A, Londhe A, Deshmukh L. Surfactant administration in preterm babies (28-36 weeks) with respiratory distress syndrome: LISA versus InSurE, an open-label randomized controlled trial. Pediatr Pulmonol. 2023;58(3):738-45.
19. Patel DV, Bansal SC, Shah M, Patel CL, Patil K, Nimbalkar SM. Natural Versus Synthetic Surfactant Therapy in Respiratory Distress Syndrome of Prematurity. Indian J Pediatr. 2022;89(11):1086-92.
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Cengizhan Ceylan, Şeyma Tetik Rama, Ayse Huzeyme Cınar, Murat Konak, Saime Sündüs Uygun, Mehmet Ozturk, Hanifi Soylu. Evaluation of beractant, poractant alfa and calfactant use in newborns with respiratory distress syndrome: A single-center retrospective study. Ann Clin Anal Med 2023;14(12):1120-1124
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Evaluation of the relationship between helicobacter pylori infection diagnosed by gastric biopsy and benign prostatic hyperplasia and prostate cancer
Ersin Kuloğlu 1, Ahmet Cumhur Dülger 2
1 Department of Internal Medicine, 2 Department of Gastroenterology, Faculty of Medicine, Giresun University, Giresun, Turkey
DOI: 10.4328/ACAM.21857 Received: 2023-08-10 Accepted: 2023-09-12 Published Online: 2023-09-18 Printed: 2023-12-01 Ann Clin Anal Med 2023;14(12):1125-1129
Corresponding Author: Ersin Kuloğlu, Department of Internal Medicine, Faculty of Medicine, Giresun University, Giresun, Turkey. E-mail: ersinkuloglu.28@hotmail.com P: +90 554 397 39 14 Corresponding Author ORCID ID: https://orcid.org/0000-0002-8499-1926
This study was approved by the Clinical Research Ethics Committee of Giresun Training and Research Hospital (Date: 2023-03-13, No: 05)
Aim: It is believed that the systemic inflammation caused by the Helicobacter pylori (HP) bacterium’s cag-A and vac-A virulence factors, along with the effects of apoptosis and local growth factors on an atherosclerotic background, may play a role in the development of chronic prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer (PCa) in the prostate gland. This study aimed to evaluate the relationship between HP infection diagnosed through the invasive diagnostic method of gastric biopsy and BPH and prostate cancer.
Material and Methods: A total of 140 patients with dyspepsia, who underwent transurethral prostatectomy (TUR-P) due to coexisting benign prostatic hyperplasia or prostate cancer, as well as patients diagnosed with BPH and/or PCa who did not undergo TUR-P, were retrospectively included in our study. A control group of 100 patients with similar dyspeptic complaints but without prostate disease in the same age group was formed. Gastric biopsy results of both groups were evaluated for HP, intestinal metaplasia, and gastric atrophy.
Results: Our study showed no statistically significant differences in the distribution of HP infection, intestinal metaplasia, and gastric atrophy among patients with dyspepsia based on the presence of BPH or prostate cancer (p>0.05).
Discussion: Although it is hypothesized that HP may have an etiological role in BPH and prostate cancer, it cannot be definitively stated that it directly contributes to the etiology.
Keywords: Helicobacter Pylori, Benign Prostatic Hyperplasia, Prostate Cancer, Inflammation, Dyspepsia
Introduction
Helicobacter pylori (Hp) is a spiral-shaped, gram-negative bacterium approximately 3.5 microns long and 0.5 microns wide [1]. Age, ethnicity, gender, geography, and socioeconomic status are factors that influence the incidence and prevalence of Hp infection. Hp prevalence is higher in developing countries and lower in developed countries. Additionally, there is variation in Hp prevalence between urban and rural populations within the same country. The worldwide prevalence of Hp is over 50% [2]. In recent years, the increasing development of resistance to first-line antibiotics has made biopsy-based diagnosis necessary even in regions where Hp is endemic, regardless of the presence of alarming symptoms [3].
Hp plays a role in the pathogenesis of several gastrointestinal-related diseases, including Functional Dyspepsia (Non-Ulcer Dyspepsia), Gastroesophageal Reflux Disease (GERD), Gastritis, Peptic Ulcer, Gastric Cancer, and Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma [4]. Hp is also involved in the etiology of extra-gastrointestinal pathologies originating from vascular, respiratory, liver, skin, and renal sources. Direct exposure to the bacterium and pathogenic antigens initiates inflammation, leading to cytokine release, which explains its role in the development of extra-gastrointestinal diseases. Studies suggest that Hp may affect the prostate gland, potentially contributing to chronic inflammation and neoplastic diseases in the prostate gland [5]. A study conducted in the United States in 2013 found a positive correlation between Hp infection and low androgen production in the male population [6].
Hp’s major virulence factors are the vac-A (vacuolating cytotoxin gene A) and cag-A (cytotoxin-associated gene A) antigens. The cag-A antigen, being more virulent than vac-A, is responsible for Hp’s development of local and systemic inflammatory responses. The cag-A gene induces the production of inflammatory mediators such as TNF-alpha, IFN-gamma, IL-1beta, IL-6, IL-8, and IL-10, leading to chronic inflammation and systemic inflammatory responses. It is believed that this systemic inflammation, along with apoptosis and the effects of local growth factors, may contribute to the development of atherosclerotic conditions, potentially playing a role in chronic prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer (PCa) in the prostate gland [7].
Reviewing the literature, it can be noted that studies have been conducted to evaluate the relationship between BPH, prostate cancer, and Hp infection based on this mechanism. In this context, in our country, where Hp positivity is endemic in dyspeptic patients, we aimed to conduct a study evaluating the relationship between Hp infection diagnosed by invasive gastric biopsy diagnostic method and BPH and prostate cancer.
Material and Methods
Approval for our study was obtained from the Giresun Training and Research Hospital Clinical Research Ethics Committee (Decision No. 05 dated March 13, 2023).
Patients who presented to the departments of Internal Medicine and Gastroenterology between January 03, 2022, and December 30, 2022, and underwent transurethral prostatectomy (TUR-P) due to benign prostatic hyperplasia and/or prostate cancer accompanied by dyspepsia, as well as patients diagnosed with benign prostatic hyperplasia and/or prostate cancer accompanied by dyspepsia who did not undergo TUR-P, were retrospectively included in the study. Patients with acute and chronic prostatitis were not included. Patients underwent upper gastrointestinal endoscopy and gastric biopsy procedures. Gastric biopsies were evaluated for the presence of accompanying Hp infection, intestinal metaplasia, and gastric atrophy. The results of gastric biopsy were evaluated in a total of 140 patients meeting these criteria and 100 patients (control group) with similar dyspeptic complaints but without prostate disease in the same age group.
Data analysis was performed using the Statistical Package for the Social Sciences (SPSS) 26.0 Statistics software. The normal distribution of numerical variables of the patients was assessed by examining the skewness values. It was observed that platelet, lymphocyte, hemoglobin, potassium, C-reactive protein (CRP), hematocrit, and mean corpuscular volume (MCV) values complied with the rules of normal distribution, with reference values taken within ±1.5. The Chi-square test was used to compare age and pathological findings based on the presence of prostate disease and the implementation of transurethral prostatectomy. An independent Sample T-test or Mann-Whitney U test was used to compare age, total PSA, and laboratory parameters based on the presence of prostate disease and the implementation of TUR-P. Pearson’s or Spearman’s correlation tests were used to examine the relationships between the implementation of TUR-P and age, total PSA, laboratory, and pathological findings. The correlation coefficient was considered low for values between 0.00-0.30, moderate for values between 0.30-0.70, and high for values between 0.70-1.00. The significance levels for all analyses were conducted considering p-values of 0.05 and 0.01.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
A total of 240 patients with dyspeptic symptoms were included in our study. Among them, 41.7% of the patients did not have prostate disease, while 58.3% had either benign prostatic hyperplasia (BPH) or prostate cancer (PCa). The comparison of patients’ age, total PSA, and gastric pathology findings based on the presence of prostate disease is shown in Table 1.
Among patients with dyspeptic symptoms and no prostate disease, 73% were aged 70 or younger, while 27% were aged 70 or older. Among patients with dyspeptic symptoms and prostate disease, 62.9% were aged 70 or younger, and 27% were aged 70 or older. The mean age of patients without prostate disease was 63.67 years, while the mean age of patients with prostate disease was 69.76 years. According to these findings, there was no significant difference in age distribution based on the presence of prostate disease in patients with dyspeptic symptoms (p>0.05). However, a significant difference was observed in the mean age between patients with dyspeptic symptoms and prostate disease (p<0.05).
Out of the prostate patients, 87.9% (123 patients) had BPH, 12.1% (17 patients) underwent TUR-P, and 25% (35 patients) had co-existing prostate cancer. The mean total PSA value among these patients was 1.92.
Among patients without prostate disease, 41% (41 patients) had Hp infection, 32% (32 patients) had intestinal metaplasia, and 19% (19 patients) had gastric atrophy. Among patients with prostate disease, 47.9% (67 patients) had Hp infection, 27.3% (38 patients) had intestinal metaplasia, and 23.5% (32 patients) had gastric atrophy. Based on these findings, no significant difference was observed in the distribution of Hp infection, intestinal metaplasia, and gastric atrophy based on the presence of prostate disease in patients with dyspeptic symptoms (p>0.05).
Table 2 presents the comparison of laboratory parameters among patients based on the presence of prostate disease.
There was no significant difference in platelet, WBC, urea, creatinine, ALT, AST, sodium, potassium, and calcium values based on the presence of prostate disease (p>0.05). However, a significant difference was observed in lymphocyte, hemoglobin, and glucose values (p<0.05). The mean lymphocyte value in patients without prostate disease was 1870/mm3, hemoglobin 12.9 g/dL, and glucose 97.50 mg/dL. In patients with prostate disease, the mean lymphocyte value was 2080/mm3, hemoglobin 13.6 g/dL, and glucose 106 mg/dL. According to these results, patients with prostate disease had significantly higher mean values of lymphocytes, hemoglobin, and glucose compared to those without prostate disease (p-values for lymphocytes, hemoglobin, and glucose were 0.021, 0.021, and 0.001, respectively).
A total of 140 patients with dyspeptic symptoms and prostate disease were included in our study as the case group. It was found that 87.9% of them did not undergo TUR-P, while 12.1% underwent the procedure. The comparison of age, TSH, PSA, and pathology findings between patients who underwent TUR-P and those who did not is presented in Table 3.
Among patients who did not undergo TUR-P, 65.9% were aged 70 or younger, while 34.1% were aged 70 or older. Among patients who underwent TUR-P, 41.2% were aged 70 or younger, and 58.8% were aged 70 or older. The mean age of patients who did not undergo TUR-P was 66.32, while the mean age of patients who underwent TUR-P was 70.24. According to these findings, no significant difference was observed in age distribution and mean age between patients with dyspeptic symptoms and prostate disease based on the implementation of TUR-P (p>0.05).
Among patients who did not undergo TUR-P, 48% (59 patients) had Hp infection, 27.6% (34 patients) had intestinal metaplasia, 24.4% (30 patients) had gastric atrophy, and 21.1% (26 patients) had co-existing prostate cancer. Among patients who underwent TUR-P, 47.1% (8 patients) had Hp infection, 23.5% (4 patients) had intestinal metaplasia, 11.8% (2 patients) had gastric atrophy, and 52.9% (9 patients) had prostate cancer. The mean total PSA value in patients who did not undergo TUR-P was 1.25, while it was 0.02 in patients who underwent TUR-P. Based on these results, no significant difference was observed in the distribution of Hp infection, intestinal metaplasia, and gastric atrophy, and no significant difference was observed in the distribution of prostate cancer and total PSA based on the implementation of TUR-P in patients with dyspeptic symptoms and prostate disease (p>0.05). However, the presence of prostate cancer was found to be significantly higher in patients who underwent TUR-P (p:0.011). Additionally, the total PSA value was significantly lower in patients who underwent TUR-P compared to those who did not (p:0.01).
There was no significant difference in platelet, lymphocyte, WBC, hemoglobin, glucose, urea, creatinine, ALT, AST, sodium, potassium, calcium, neutrophil, and ferritin values based on the implementation of TUR-P (p>0.05).
Discussion
In our study, no statistically significant difference was observed in the distribution of Hp infection, intestinal metaplasia, and gastric atrophy based on the presence of BPH or prostate cancer in patients with dyspeptic symptoms (p>0.05). Additionally, no significant difference was found in the distribution and mean values of age, Hp infection, intestinal metaplasia and gastric atrophy among dyspeptic patients with or without TUR-P (p>0.05).
Upon reviewing the literature, it was observed that there were no studies conducted on the population of dyspeptic patients specifically evaluating the relationship between BPH/prostate cancer and Hp infection, intestinal metaplasia, and gastric atrophy based on gastric biopsies obtained during upper gastrointestinal endoscopy. Thus, our study is considered the first to evaluate these relationships.
When reviewing the literature regarding the assessment of the relationship between Hp infection and BPH/prostate cancer, it was found that the evaluation method typically involves molecular tests (real-time PCR) and/or immunohistochemical methods to assess the presence of Hp in the prostate tissue obtained from patients undergoing TUR-P or open prostatectomy.
In a study conducted at Istanbul Fatih Sultan Mehmet Training and Research Hospital, 113 patients who underwent TUR-P due to BPH between June 2012 and June 2013 were included. The presence of Hp was evaluated using real-time PCR in prostate tissue samples. In this study, Hp was detected in 1.8% of cases (2 patients), and chronic prostatitis was observed in 58.4% of cases (66 patients). The study concluded that the molecular detection of Hp in prostate tissue may suggest that Hp could contribute to the development of chronic prostatitis and BPH through inducing inflammation, thus requiring further investigations [7].
Another study in Iran included a total of 160 patients who underwent TUR-P or open prostatectomy due to BPH. Real-time PCR was used to assess the presence of Hp DNA in prostate tissues, and Hp was detected in 1.87% of cases (3 patients) [8].
At Sultan Qaboos University, Al-Marhoon et al. conducted a study with 100 patients, of whom 78% had BPH and 19% had prostate cancer. Immunohistochemical methods were used to assess the presence of Hp in prostate tissues, and Hp was not detected. However, using real-time PCR, Hp was detected in 5 patients. The Hp antigen test in the stool was also positive in these 5 patients. Based on similar studies, no statistically significant difference was observed between the presence of Hp DNA in prostate tissue and the development of BPH and prostate cancer (p>0.05). The absence of a direct statistically significant relationship could be attributed to the lack of favorable environmental conditions for Hp to survive in the prostate gland [8].
In a study conducted by Christopoulos and Stamatiou in Greece, they evaluated the relationship between Hp infection and prostate diseases, including chronic prostatitis and BPH leading to prostate cancer, from 1960 to 2010 using PubMed and Medline databases. They found a hypothesis-level association between Hp infection and the development of prostate cancer in the context of chronic prostatitis and BPH. However, their study did not provide statistically significant and experimentally based evidence for this association [9].
Conclusion
These studies that rely on the detection of Hp DNA in prostate tissue using molecular methods have certain limitations, such as the high cost of the molecular technique and the inclusion of a small number of patients, which may limit their generalizability. Further research with larger sample sizes and more comprehensive evaluation methods is warranted to gain a better understanding of the potential relationship between Hp infection and BPH/prostate cancer. Departments of Internal Medicine, Gastroenterology and Urology should conduct multidisciplinary studies in this field.
Limitation
In our study, we did not detect the presence of Hp in the prostate tissues of patients who underwent TUR-P using molecular or immunohistochemical methods. However, it is important to note that our study had some limitations, including the lack of molecular testing for Hp infection and the relatively small sample size of 140 patients.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Funding: None
Conflict of interest
The authors declare no conflict of interest.
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Download attachments: 10.4328.ACAM.21857
Ersin Kuloğlu, Ahmet Cumhur Dülger. Evaluation of the relationship between helicobacter pylori infection diagnosed by gastric biopsy and benign prostatic hyperplasia and prostate cancer. Ann Clin Anal Med 2023;14(12):1125-1129
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Effect of birth mode on IL-17 receptor expression in cord blood-derived CD4+ T lymphocytes
Melek Buyukkinacı Erol 1, 2, Durmus Burgucu 2, 3
1 Department of Gynecology and Obstetrics, Private Melek Büyükkınacı Erol Obstetrics and Gynecology Clinic, 2 Department of Gynecology and Obstetrics, The Mediterranean Stem Cell And Cellular Therapies Research Group, 3 Department of Physiology, Akdeniz University Technopark Babylife Cord Blood Bank and Human Cell-Tissue Production Center, Antalya, Turkey
DOI: 10.4328/ACAM.21866 Received: 2023-08-14 Accepted: 2023-09-16 Published Online: 2023-09-21 Printed: 2023-12-01 Ann Clin Anal Med 2023;14(12):1130-1132
Corresponding Author: Durmuş Burgucu, Department of Physiology, Akdeniz University Technopark Babylife Cord Blood Bank and Human Cell-Tissue Production Center, Akdeniz University, 07070, Antalya, Turkey. E-mail: dburgucu@akdeniz.edu.tr P: +90 242 226 16 80 F: +90 242 226 16 79 Corresponding Author ORCID ID: https://orcid.org/0000-0003-3980-982X
This study was approved by the Clinical Research Ethics Committee of Akdeniz University Faculty of Medicine (Date: 2017-12-06, No: 712)
Aim: The Interleukin 17 (IL-17) family of cytokines plays a crucial role in host defense against microorganisms and the development of inflammatory diseases. The IL-17 receptor family, consisting of IL-17RA, IL-17RB, IL-17RC, IL-17RD, and IL-17RE, is central to the IL-17 signaling pathway. Emerging evidence suggests that birth mode might influence the development of the immune system and the risk of immune-related disorders. This study aimed to investigate the potential effect of birth mode on the expression of IL-17 receptor family members (IL-17RA, IL-17RB, and IL-17RC) in cord blood-derived CD4+ T lymphocytes.
Material and Methods: Cord blood samples were collected from volunteer pregnant women who had either vaginal deliveries or cesarean sections (n=20 each). Mononuclear cells were isolated, and CD4+ T lymphocytes were analyzed for the expression of IL-17 receptor family members using flow cytometry. Mean fluorescence intensity (MFI) was used to quantify receptor expression levels.
Results: The expression level of IL-17RA was significantly higher in the vaginal delivery group compared to the cesarean section group (p<0.05). However, there was no significant difference in the expression levels of IL-17RB and IL-17RC between the two groups.
Discussion: The findings of this study suggest that birth mode might have an impact on the expression of IL-17 receptor family members in cord blood-derived CD4+ T lymphocytes. Notably, IL-17RA expression was notably higher in infants born through vaginal delivery, indicating a potential role of birth mode in shaping immune system development. This study provides novel insights into the potential association between birth mode and IL-17 receptor expression in cord blood-derived CD4+ T lymphocytes. The observed differences in IL-17 receptor expression levels highlight the need for further research to elucidate the mechanisms underlying the interaction between birth mode and immune system development.
Keywords: IL-17 Receptors, Birth Mode, Cord Blood, CD4+ T Lymphocytes, Сord Blood
Introduction
The Interleukin 17 (IL-17) family is an important cytokine family involved in host defense against microorganisms and the development of inflammatory diseases. The IL-17 receptor family consists of five members (IL-17RA, RB, RC, RD, and RE), each of which shares a series of homologies with their ligands [1]. Studies comparing the impact of birth mode, an important factor in neonatal immune system development, have been conducted in different geographic locations. Particularly, the cesarean section delivery is highlighted for its potential to disrupt the transmission of the maternal microbiome and jeopardize infant intestinal microbiome programming [2-3]. It has been shown that this condition negatively affects immunological development and increases the risk of allergic diseases [4]. Cord blood (CB) is widely used as an alternative source of hematopoietic stem cells for diseases requiring hematopoietic stem cell transplantation (HSCT). Cord blood collection, storage under laboratory conditions, and release when needed are routinely applied. Cord blood banking can be performed autologously and allogeneically in Turkey, known as the ‘Turkish Model’. In a previous study conducted by our group, the release rate for clinical use was found to be between 0.41% and 0.99% [5]. This rate varies worldwide, and many banks do not publish their release rates [6]. In recent years, cord blood has also been preferred as a source of mesenchymal stem cells with potential applications in regenerative and reparative medicine [7]. Additionally, studies on lymphocyte subsets derived from cord blood for cellular immunotherapy are ongoing [8]. The aim of this study is to compare the expression levels of IL-17 receptor family members IL17RA, IL17RB, and IL17RC in CD4+ lymphocytes isolated from cord blood obtained from individuals who had vaginal or cesarean section deliveries. The aim of the study is to evaluate the potential impact of birth mode, which is believed to play a role in immunological development, on IL17 receptor expression.
Material and Methods
Cord blood samples obtained from pregnant volunteers who gave birth within the stipulated timeframe, in accordance with the Ministry of Health’s Cord Blood Banking Regulation (Official Gazette Date:05.07.2005 Official Gazette Number:25866), were subjected to cellular and microbiological quality control tests as stipulated by relevant regulations. For this purpose, leftover cord blood samples from 2 ml EDTA-containing specimen samples were utilized for immunophenotypic analyses. Additional sampling was not performed in this study. Expression levels of IL17RA (R&D Human IL-17RA/IL-17R APC-conjugated Antibody FAB177A), IL17RB (BD Pharmingen™ Alexa Fluor® 647 Rat Anti-Mouse IL-17 Receptor B Cat No:565866), and IL17RC (Human IL-17RC Alexa Fluor® 647-conjugated Antibody Catalog #: FAB22691) were evaluated by flow cytometry in mononuclear cells isolated from cord blood obtained from volunteer pregnant women (n=20) who consented to participate in the study. After immunophenotyping, lymphocytes were gated in the FSC/SSC histogram, and CD4+CD3+ cells were analyzed for IL17 receptor expression. Expression levels were calculated as mean fluorescence intensity (MFI). Statistical analysis was conducted using SPSS 21 program. The Mann-Whitney U test was used for group comparisons, and p<0.05 was considered significant. The study was approved by the Akdeniz University Faculty of Medicine Clinical Research Ethics Committee on 06-12-2017 with decision No. 712.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
While the expression level of IL17RA was significantly higher in the vaginal delivery group compared to the cesarean group (P<0.05), no difference was detected in IL17RB and IL17RC expressions (Table 1, Figures 1, 2).
Discussion
This study was conducted to reveal the effect of birth mode on IL-17 receptor family members for the first time. Our findings emphasize the potential influence of birth mode on this cytokine family by showing significantly higher IL17RA expression in the vaginal delivery group compared to the cesarean group. This result can be considered an important step in better understanding the impact of birth mode on immune system development, disease pathophysiology, and allergic diseases. These findings could contribute to future health strategies by helping us understand the effects of birth on the immune system. Interestingly, the lack of an effect of birth mode on IL17RB and IL17RC expression levels might suggest that these receptors could have a less determining role in immunological development. However, these results need further support through additional research. Detailed studies on the activation and signaling pathways of IL-17 receptor family members could help us better understand their specific roles and functions. Different subsets of lymphocytes, especially T cells and natural killer cells, derived from cord blood have been shown to play an important role in immune system development and regulation [8-9]. Therefore, cell-based therapies using these subsets hold potential for future cancer immunotherapy and the treatment of other immunological diseases [10-11]. This new information allows us to assess the effects of different cell types present in cord blood on the immune system in a broader context. Our findings could offer a more comprehensive understanding of the interactions between these cell types and immune system regulation, taking into consideration the differences that could arise from factors such as genetics and environmental influences.
Conclusion
This study has taken an important step in examining the effects of normal vaginal delivery and cesarean section on the expression levels of IL-17 receptor family members. Our findings, by showing increased IL17RA expression in vaginal delivery, demonstrate the potential influence of birth mode on immune system development. However, the limitations of this study should also be considered. The sample size was limited, and the focus was on cord blood samples only. Future studies should examine the effects of different birth modes on immune development more comprehensively, using larger and more diverse sample groups. In conclusion, this study examining the expression levels of IL-17 receptor family members based on birth mode could contribute to a better understanding of immune system development and diseases.
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.
References
1. Kurtzberg J, Troy JD, Page KM, El Ayoubi HR, Volt F, Maria Scigliuolo G, et al. Unrelated Donor Cord Blood Transplantation in Children: Lessons Learned Over 3 Decades. Stem Cells Transl Med. 2023;12(1):26-38.
2. Sanchez-Petitto G, Rezvani K, Daher M, Rafei H, Kebriaei P, Shpall EJ, et al. Umbilical Cord Blood Transplantation: Connecting Its Origin to Its Future. Stem Cells Transl Med. 2023;12(2):55-71.
3. Burgucu D. Effect of smoking on the hematopoietic stem cell count in cord blood. Ann Clin Anal Med 2021;12(Suppl. 1): S83-5.
4. Wang X, Gong S, Zhu W, Fu H, Sun H. A systematic review and meta-analysis of cord blood collection practices. Transfusion. 2019;59(6):1993-2004.
5. Salge-Bartels U, Huber HM, Kleiner K, Volkers P, Seitz R, Heiden M. Evaluation of Quality Parameters for Cord Blood Donations. Transfus Med Hemother. 2009;36(5):317-24.
6. Naseri Mobaraki S, Abroun S, Atashi A, Kaviani S. Evaluation of Expansion and Maintenance of Umbilical Cord Blood CD34+ Cells in The Co-Culture with Umbilical Cord Blood-Derived Mesenchymal Stem Cells in The Presence of Microcarrier Beads. Cell J. 2023;25(3):184-93.
7. Omori A, Chiba T, Kashiwakura I. Relationship between radiosensitivity of human neonatal hematopoietic stem/progenitor cells and individual maternal/neonatal obstetric factors. J Radiat Res. 2010;51(6):755-63.
8. Kudo Y, Minegishi M, Seki O, Takahashi H, Suzuki A, Narita A, et al. Quality assessment of umbilical cord blood units at the time of transplantation. Int J Hematol. 2011;93(5):645-51.
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10. Berrien-Elliott MM, Jacobs MT, Fehniger TA. Allogeneic natural killer cell therapy. Blood. 2023;141(8):856-68.
11. Pan K, Farrukh H, Chittepu VCSR, Xu H, Pan CX, Zhu Z. CAR race to cancer immunotherapy: from CAR T, CAR NK to CAR macrophage therapy. J Exp Clin Cancer Res. 2022; 31;41(1):119.
Download attachments: 10.4328.ACAM.21866
Melek Büyükkınacı Erol, Durmus Burgucu. Effect of birth mode on IL-17 receptor expression in cord blood-derived CD4+ T lymphocytes. Ann Clin Anal Med 2023;14(12):1130-1132
Citations in Google Scholar: Google Scholar
Comparative analysis of short-term therapeutic efficacy: Radiofrequency microtenotomy vs. Steroid injection in lateral epicondylitis
Ahmet Yurteri 1, Mahmut Sert 2
1 Department of Orthopedics and Traumatology, Konya City Hospital, Konya, 2 Department of Orthopedics and Traumatology, Medicana Hospital Bahçelievler, Istanbul, Turkey
DOI: 10.4328/ACAM.21882 Received: 2023-08-17 Accepted: 2023-10-31 Published Online: 2023-11-06 Printed: 2023-12-01 Ann Clin Anal Med 2023;14(12):1133-1137
Corresponding Author: Ahmet Yurteri, Department of Orthopedics and Traumatology, Konya City Hospital, Konya, Turkey. E-mail: op.drahmetyurteri@gmail.com P: +90 553 502 20 58 Corresponding Author ORCID ID: https://orcid.org/0000-0001-5242-0275
This study was approved by the Ethics Committee of Selcuk University (Date: 2023-09-01, No: 2023/4482)
Aim: The aim of this study was to compare the retrospective short-term therapeutic efficacy of radiofrequency microtenotomy (RFMT) and steroid injection in lateral epicondylitis.
Material and Methods: Data from lateral patients with epicondylitis who had undergone conservative treatment for at least six months but experienced no improvement in pain were retrospectively reviewed. Patients meeting the inclusion criteria were divided into two groups: those who underwent radiofrequency microtenotomy and those who received steroid injections. Grip strength, pincer strength, Visual Analog Scale (VAS), Disabilities of the Arm, Shoulder and Hand (DASH), and Mayo Elbow Performance Score (MEPS) were compared for both groups at preoperative and postoperative 1st, 3rd, and 6th months.
Results: When comparing postoperative 1st-month VAS, DASH scores, and grip strength measurements of both groups, significant differences were observed, while there were no significant differences in MEPS and pincer strength measurements (p=0.028, p=0.018, p=0.001, p=0.082, p=0.169, respectively). Although there were no significant differences in the postoperative 3rd-month VAS, MEPS, grip strength, and pincer strength measurements between the two groups, a significant difference was found in DASH scores (p=0.237, p=0.185, p=0.382, p=0.979, p=0.030, respectively). Significant differences were observed in the postoperative VAS, DASH, MEPS, grip strength, and pincer strength measurements between both groups (p=0.001 for all tests).
Discussion: RFMT method provided more favorable clinical and functional outcomes compared to steroid injection at the end of the sixth month. These results suggest a strong potential for RFMT in the treatment strategy for lateral epicondylitis. However, comprehensive studies involving larger patient groups and longer follow-up periods are required to determine the exact role of RFMT
Keywords: Lateral Epicondylitis, Radiofrequency Microtenotomy, RFMT, Steroid Injection, Treatment Efficacy, Clinical Outcomes
Introduction
Lateral epicondylitis, also known as tennis elbow, is a condition seen in adults and is present in about 1-3% of cases. It involves lesions around and at the origin of the common extensor tendon [1, 2]. Particularly in histological sections at the origin of the extensor carpi radialis brevis tendon, non-inflammatory angiofibroblastic tendinosis and myxoid degeneration have been identified [3]. Treatment ranges from activity limitation to surgical intervention, encompassing a wide spectrum. However, there has been no consensus that any one treatment is superior to others as the gold standard therapy [4, 5]. Steroid injections have been used since the 1950s, however, it is known that although they reduce symptoms in the first 6 weeks, their effectiveness becomes limited after the 3rd month [6].
In recent years, RFMT has been introduced as an alternative treatment for lateral epicondylitis (LE). Despite debates about its effectiveness, it has been reported to be a safe method in human trials. The aim of this study is to compare the clinical outcomes of steroid injection and RFMT in the treatment of LE.
Material and Methods
Ethical Approval and Study Protocol
Our study was reviewed and approved by Selcuk University Ethics Committee on September 1, 2023 (Decision No: 2023/4482). Between August 1, 2021, and February 1, 2023, patients diagnosed with lateral epicondylitis were examined at the Orthopedics and Traumatology Clinic of Hakkari State Hospital by a single orthopedic surgeon who had received at least five years of orthopedic training. Among these patients, those who underwent RFMT and steroid injection by the same orthopedic surgeon were included and divided into two groups. Age, side, gender, grip and pincer strength measurements at preoperative, postoperative 1st month, postoperative 3rd month, and postoperative 6th month, as well as VAS, DASH, and MEPS scores of both groups were evaluated and compared with each other. The measurements of grip strength and pincer strength are shown in Figure 1.
Patients and Inclusion/exclusion criteria
Inclusion criteria comprised patients diagnosed with lateral epicondylitis who had been experiencing pain aggravated by wrist dorsiflexion with tenderness over the common extensor origin for at least six months. These patients had initially received NSAID treatment and had undergone epicondyle straps application; however, they exhibited no improvement in their symptoms. Among these cases, those who underwent RFMT or steroid injection were included in the study.
Exclusion criteria involved patients with a history of ipsilateral upper extremity or cervical surgery that could affect the study results. Patients who did not adhere to the specified clinic follow-up dates and those diagnosed with seronegative/seropositive/crystal-induced inflammatory arthropathies were also excluded.
RFMT and Steroid Injection Procedure
Both procedures were performed under local anesthesia, and a 2 mg/kg PRILOC %2 (VEM Pharmaceuticals, Çankaya/ANKARA) was administered to the procedure area. For RFMT, a 2 square centimeter area was identified over the tender lateral epicondyle. The probe tip was inserted perpendicular to the skin at 2-millimeter intervals, and the duration of the procedure was 0.5 seconds. As for the steroid injection, following the administration of local anesthesia to the affected area, a 20 mg DEPO-MEDROL (PFIZER PFE Pharmaceuticals, Ortaköy/Istanbul) injection was administered. After the procedures, patients were monitored for a minimum of 30 minutes for the possibility of acute complications. Figure 2 demonstrates the RFMT process.
Postop Rehabilitation
Patients were advised to avoid active movement of the affected upper extremities and to use splints for up to 48 hours post-procedure. After 48 hours, they were permitted to engage in active movement and apply loads. All patients who underwent the procedure were recommended to abstain from using NSAIDs and smoking for at least 6 months after the procedure.
Statistical Analysis
SPSS 26.0 (Statistical Package for the Social Sciences) program was used for data analysis (Graph Pad Software, Inc., La Jolla, CA). Fisher’s exact test and the chi-square test were used to evaluate categorical variables (gender, affected side). Skewness and kurtosis values were examined to determine whether continuous variables (age, grip strength, pincer strength, VAS, DASH and Meps scores at postoperative 1st, 3rd and 6th months) fit a normal distribution. Statistical analysis of “One-Way Analysis of Variance” was used when comparing the parameters of both groups with each other. “Repeated Measures ANOVA” statistical analysis was used when comparing the postoperative values of the groups with the preoperative values. The minimum (min), maximum (max), median, mean and standard deviation (SD) values of these parameters were recorded and the level of significance was determined as p-value < 0.05 in all tests.
Results
The clinical and functional scores of 80 patients who met the inclusion criteria were analyzed. Clinical follow-up of the enrolled patients was conducted at postoperative 1st, 3rd, and 6th months. Of the 80 patients, 40 underwent RFMT while the remaining 40 received steroid injections. The mean age of the RFMT group was 44.05 ± 10.71, and for the steroid injection group, it was 42.45 ± 9.51. There were no significant differences between the two groups in terms of age, gender, and affected side (p=0.482, p=0.823, p=0.412).
No significant differences were observed in preoperative VAS, DASH, MEPS, grip strength, and pincer strength measurements for both groups (p=0.537, p=0.728, p=0.904, p=0.447, p=0.986). Significant differences were observed in postoperative 1st-month VAS, DASH, and grip strength measurements for both groups, while no significant differences were found in MEPS and pincer strength measurements (p=0.028, p=0.018, p=0.001, p=0.082, p=0.169). There were no significant differences in postoperative 3rd-month VAS, MEPS, grip strength, and pincer strength measurements between the two groups, but a significant difference was observed in DASH scores (p=0.237, p=0.185, p=0.382, p=0.979, p=0.030). When comparing postoperative VAS, DASH, MEPS, grip strength, and pincer strength measurements between the two groups, significant differences were found (p=0.001, p=0.001, p=0.001, p=0.001, p=0.001). Data including measurements and comparisons for both groups are provided in Table 1.
Comparing the preoperative and postoperative 1st-month measurements of the RFMT group, no significant differences were observed in terms of VAS, DASH, MEPS, grip strength, and pincer strength (p=0.420, p=0.202, p=0.949, p=0.249, p=0.949). Similarly, comparing the preoperative and postoperative 3rd-month measurements of the RFMT group, no significant differences were observed in terms of VAS, DASH, MEPS, grip strength, and pincer strength (p=0.127, p=0.270, p=0.774, p=0.152, p=0.774). However, comparing the preoperative and postoperative 6th-month measurements of the RFMT group, significant differences were observed in terms of VAS, DASH, MEPS, grip strength, and pincer strength (p=0.001, p=0.002, p=0.009, p=0.009, p=0.001). Data illustrating the RFMT group’s preoperative measurements compared to measurements at different postoperative months are provided in Table 2.
Comparing the preoperative and postoperative 1st-month measurements of the steroid injection group, significant differences were observed in terms of VAS, DASH, MEPS, grip strength, and pincer strength (p=0.012, p=0.012, p=0.03, p=0.001, p=0.047). When comparing the preoperative and postoperative 3rd-month measurements of the steroid injection group, significant differences were observed in terms of VAS, DASH, MEPS, and grip strength, while no significant difference was seen in pincer strength measurements (p=0.007, p=0.050, p=0.018, p=0.027, p=0.703). Comparing the preoperative and postoperative 6th-month measurements of the steroid injection group, no significant differences were observed in terms of VAS, DASH, MEPS, grip strength, and pincer strength (p=0.518, p=0.393, p=1.000, p=1.000, p=1.000). Data illustrating the steroid injection group’s preoperative measurements compared to measurements at different postoperative months are provided in Table 2.
Discussion
In this study, the effectiveness of RMFT and steroid injection was evaluated in patients who had previously undergone non-invasive conservative treatments but did not achieve success. The clinical and functional evaluations of patients who underwent two different treatment methods (RMFT and steroid injection) were presented during the preoperative and postoperative periods. Initially, it was noted that there were no significant differences between the preoperative measurements of both groups. This indicates that patients in both groups were evenly distributed. In this study with a substantial amount of data, two key findings particularly stand out. The first observation is that in the 1st month after steroid injection, there was a significant improvement in VAS, DASH, and grip strength measurements compared to the RMFT group, reflecting positive clinical and functional scores. We believe this could be attributed to the rapid regression of symptoms due to the anti-inflammatory effects following steroid injection.The second significant finding is that in the 6-month mark, RMFT appears to be superior to steroid injection across all parameters. We attribute this result to the effective triggering of angiogenic and regenerative healing processes by the RMFT method, and we speculate that the limited effectiveness of steroid injection treatment in the long term plays a role in this outcome.
There are publications reporting that RF-based microtenotomy is a treatment method that achieves healing through tissue fragmentation and angiogenic effects [7, 8]. It has been suggested that in tissues treated with this method, the presence of angiogenic stimulants such as fibroblast growth factor and vascular endothelial growth factor can lead to regeneration and healing [9]. Harwood and colleagues showed an increase in vascular endothelial growth factor (VEGF) levels after radiofrequency application in rabbits with an Achilles tendinosis model [10]. In the same study, they also reported that the increase in basic fibroblast growth factor or VEGF led to an increase in type 1 collagen and extracellular matrix molecules, resulting in increased tendon strength. Takahashi et al., in a study evaluating radiofrequency effectiveness in rats, demonstrated rapid degeneration and ablation of nerve fibers, resulting in decreased early postoperative pain in tendinosis treatment [11]. RMFT may contribute to the reduction of pain in the early stages by promoting the degeneration of pain-causing nerve fibers. In fact, Waseem and colleagues have pointed out that neurogenic inflammation exists in the pathogenesis of lateral epicondylitis due to the presence of substance P and calcitonin gene-related peptide (CGRP) in the tendon. In our study, we believe that the success of RFMT treatment at the sixth month supports this theory, as it may be due to the degeneration of nerve fibers and suppression of neurogenic inflammation. Moreover, we have confidence that the long-term effectiveness of angiogenesis induced by RFMT will undoubtedly surpass that of steroid injection treatment. Additionally, harnessing the angiogenesis in the tendon could lead to complete healing in the patient over the long term through regenerative processes.
The results of the first patient group treated with radiofrequency in lateral epicondylitis were reported by Tasto and colleagues [9]. They reported positive improvements in patients’ functional and clinical scores. Similarly, in our study, we observed improvements in clinical scores among lateral epicondylitis patients. Meknas and colleagues, in a study published in 2008 comparing RFMT to open surgery, reported that RFMT was more effective in the short term compared to open surgery and yielded similar results in the long term [12]. Furthermore, in a study by Meknas and colleagues in 2013, where they reported at least 5 years of follow-up on the same patient group, they stated that patients benefited from RFMT in the long term [13].
One of the drawbacks of RFMT application is that it may incur higher costs compared to other conservative methods (such as steroid injections, epicondylitis bands, NSAIDs, etc.) due to the additional cost of probes. Additionally, skin depigmentation, adipose tissue atrophy, and tendon weakening, which are known side effects of steroids mentioned in the literature, have not been reported in our literature searches for RFMT treatment [14]. While this study did not include a patient group undergoing arthroscopic or open extensor tendon release, it is noteworthy that RFMT treatment offers the advantage of not requiring regional or general anesthesia, unlike the other two treatments. Despite the study’s limitations, which include its retrospective nature and a relatively small patient group, we believe that considering its role as an alternative treatment for LE, a common condition causing workforce loss, is essential before opting for surgical intervention.
Conclusion
Our findings demonstrate that the RFMT method yields more favorable clinical and functional results compared to steroid injection at the six-month mark. These results indicate that RFMT holds promise as a safe and significant component of lateral epicondylitis treatment strategies. We recommend its implementation before considering surgical interventions in cases where other conservative treatments have been applied but failed. However, to determine the precise position of RFMT in the lateral epicondylitis treatment algorithm, more comprehensive studies encompassing larger patient groups and longer follow-up periods are required. Such studies will shed light on the long-term effectiveness of RFMT, its impact on different patient profiles, and its comparative efficacy against other treatment methods. These comprehensive data will allow for a more detailed and reliable assessment of RFMT’s role in lateral epicondylitis treatment protocols.
Limitation
There are a few limitations to our study. Firstly, its retrospective and small-scale nature. A prospective study with a larger patient group would undoubtedly yield more data and provide stronger results. Secondly, the inclusion of pre- and post-operative radiological imaging (such as MRI or ultrasound) for patients could contribute significantly to the study.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and Human Rights Statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
References
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2. Lenoir H, Mares O, Carlier Y. Management of lateral epicondylitis. Orthop Traumatol Surg Res. 2019;105(8):S241-S6.
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6. Olaussen M, Holmedal Ø, Mdala I, Brage S, Lindbæk M. Corticosteroid or placebo injection combined with deep transverse friction massage, Mills manipulation, stretching and eccentric exercise for acute lateral epicondylitis: a randomised, controlled trial. BMC Musculoskelet Disord. 2015;16(1):1-13.
7. Eick OJ. Temperature controlled radiofrequency ablation. Indian Pacing Electrophysiol J. 2002;2(3):66.
8. Nakagawa H, Ikeda A, Sharma T, Govari A, Ashton J, Maffre J, et al. Comparison of in vivo tissue temperature profile and lesion geometry for radiofrequency ablation with high power–short duration and moderate power–moderate duration: effects of thermal latency and contact force on lesion formation. Circulation: Arrhythmia and Electrophysiology. 2021;14(7):e009899.
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10. Harwood F, Bowden K, Amiel M, Tasto J, Amiel D. Structural and angiogenic response to bipolar radiofrequency treatment of normal rabbit Achilles tendon: A potential application to the treatment of tendinosis. Trans Orthop Res Soc. 2003;28:819.
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Download attachments: 10.4328.ACAM.21882
Ahmet Yurteri, Mahmut Sert. Comparative analysis of short-term therapeutic efficacy: Radiofrequency microtenotomy vs. Steroid injection in lateral epicondylitis. Ann Clin Anal Med 2023;14(12):1133-1137
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The comparison of effectiveness of aerobic exercise and aerobic exercise with kinesio taping treatments in fibromyalgia syndrome
Buminhan Seferoglu
Department of Physical Medicine and Rehabilitation, Erzurum City Hospital, Erzurum, Turkey
DOI: 10.4328/ACAM.21883 Received: 2023-08-18 Accepted: 2023-09-18 Published Online: 2023-09-29 Printed: 2023-12-01 Ann Clin Anal Med 2023;14(12):1138-1142
Corresponding Author: Buminhan Seferoglu, Department of Physical Medicine and Rehabilitation, Erzurum City Hospital, 25240, Erzurum, Turkey. E-mail: bsefer@gmail.com P: +90 532 247 17 47 Corresponding Author ORCID ID: https://orcid.org/0000-0002-5636-8387
This study was approved by the Ethics Committee of Ataturk University, Medical Faculty (Date: 2011-05-13, No: 05/02)
Aim: The aim of this study is to determine the effectiveness of aerobic exercise and aerobic exercise with kinesio taping treatment approaches in patients with Fibromyalgia Syndrome (FM) as well as to evaluate the superiority of these treatment approaches overto each other.
Material and Methods: Forty patients diagnosed with FM according to the American College of Rheumatology (ACR) 1990 criteria for the classification of FM were included in this study and the patients were randomly divided into two equal groups. Aerobic exercise program was performed for 8 weeks in the first group and aerobic exercise program for 8 weeks with 15-day kinesio taping treatment was performed in the second group.
Results: When the superiority of the two treatment approaches to each other was compared, aerobic exercise with kinesio taping treatment was more effective than only aerobic exercise treatment in reducing the severity of pain (p<0,001), fatigue (p<0,05) and sleep disturbance (p<0,05), improving the physical functioning (p<0,05) and improving the physical functioning and bodily pain (p<0,05) subscales of Short Form-36 (SF-36).
Discussion: Results of the study suggested that aerobic exercises are an effective treatment method on reducing the symptoms and level of depression, improving the physical functioning and quality of life in patients with FM and the kinesio taping method provides a significant benefit in these patients. Further studies are needed to determine the effectiveness of kinesio taping in the treatment of FM.
Keywords: Fibromyalgia, Aerobic Exercise, Treatment
Introduction
Fibromyalgia syndrome (FM) is a clinical syndrome with an unclear etiology characterized by chronic generalized body pain, fatigue, sleep disorder, multiple somatic and cognitive problems [1].
The prevalence of FM in the overall population was reported to be 2.7%. FM is more often seen in women than men and the female/male ratio is 3:1 [2]. The risk factors for FM include female gender, advanced age, family history, low education and income level, and rheumatological diseases. On the other side, the distribution of childhood FM between genders is equal. The patients are mostly diagnosed between 30-60 years of age. Its prevalence increases with age, and the most dramatic increase occurs between 5th-6th decades [3,4]. The disease onset in children is usually between 11-15 years of age. It has been also reported in the population studies that FM develops more frequently in subjects with low education and socioeconomic level [5].
Many studies have demonstrated that exercise is beneficial in patients with FM [6-8]. There is strong evidence that aerobic exercises are effective in reducing pain, the number of tender points and depression levels and improving life quality [9,10]. Therefore, aerobic exercises are accepted as one of the most important treatment methods in patients with FM. Walking, swimming, cycling, dancing and aquatic (in water) exercises can be given as examples of primary aerobic exercises recommended for the treatment of FM. It has been noted in the studies that aerobic exercise performed at 60%-70% of the maximum heart rate for 20-30 minutes in 2-3 days weekly is the most effective treatment program for reducing the symptoms [11,12]. Aerobic exercise workout should start with a warming-up period and end with a cooling-down period. Warming-up and cooling-down periods take 5-10 minutes.
Kinesio taping is a special taping technique developed by Kenzo Kase, a Japanese specialist chiropractor and acupuncturist, in 1973 and has been used in our country in recent years. The standard tapes limit the joint movements, decelerate the healing process of the damaged tissue due to compressive effect in some cases and do not support deep tissues such as fascia. Dr. Kase developed kinesio tape as a result of 2-year research starting at the beginning of the 1970s based on the idea that more successful treatment outcomes can be obtained using a taping method similar to structural features and flexibility of the human skin without limitation of the joint movements. Kinesio taping practice is a supportive treatment method implemented combined with other treatment methods in orthopedic injuries, muscular injuries due to excessive effort and muscular fatigue, sportive injuries, neurological and rheumatological diseases, lymphedema and all kinds of painful conditions. The major contraindications of kinesio taping include allergy to polyacrylate adhesives, active cellulitis or skin infection in the application site, open wound, malignancy and deep vein thrombosis. It should be used carefully in cases of diabetes mellitus, kidney disease, congestive heart failure, coronary artery disease, skin sensitivity and pregnancy. It has been noted that the pain-reducing effect of the band is sourced from its increasing blood and lymph circulation by enlarging the space between skin and muscle, particularly through its lifting effect [13]. The main advantages of kinesio taping are non-invasiveness, simplicity, low cost, easy removability by the patient if necessary, and the absence of serious side effects. However, there is a limited number of evidence-based studies addressing the effects of kinesio taping application in the tender points of the patients with FM.
In our present study, we investigated the effectiveness of aerobic exercise alone and together with kinesio taping as treatment approaches in reducing symptoms and depression levels, as well as increasing physical functions and life quality in patients with FM, besides, we evaluated the superiority between these treatment approaches.
Material and Methods
The study was approved by the Ethics Committee of Ataturk University, Medical Faculty (Date: 2011-05-13, No: 05/02) and was conducted as a prospective, randomized and single-centered study between June 2011 and February 2013 in the Department of Physical Medicine and Rehabilitation, Ataturk University Medical Faculty. The study included 40 patients who met the inclusion criteria (18-60 years of age, diagnosis of FM according to the 1990 ACR FM classification criteria, sedentary lifestyle, signing the informed consent form). The exclusion criteria were allergic skin disease, having a cardiovascular, pulmonary, orthopedic or neurological disease inhibiting exercising, malignant tumoral disease, mental or psychotic disease, pregnancy.
The 40 patients who met the inclusion criteria of the study were numbered according to admission order and randomized into two groups. In the first group, only aerobic exercise group was applied for 8 weeks, while in the second group, aerobic exercise group for 8 weeks together with kinesio taping treatment program was applied for 15 days. The patients were evaluated by filling the Visual Analogue Scale (VAS-pain, VAS-fatigue, VAS-morning stiffness, VAS-sleep problem), Fibromyalgia Impact Questionnaire (FIQ), Beck Depression Inventory (BDI) and Short Form-36 (SF-36) and counting the tender points.
In the first group, assigned as the aerobic exercise group, a program of moderate-intensity aerobic walking exercise was applied for 3 days per week for 8 weeks for 20, 30 and 40 minutes during the first 2, between 3-5 weeks and during the last 3 weeks, respectively. The first and last stages of each exercise program were set as warming-up and cooling-down periods. In the second group, assigned as kinesio taping group together with aerobic exercise, the same aerobic exercise with an addition of kinesio taping treatment on the tender points was applied for the last 15 days. Muscle taping technique was used as the taping technique. Inhibition was implemented on the muscles with tender points and taping treatment was usually performed with 15%-25% stretch tension, while paper-off tension was used in some of the taping applications, and usually Y-strip was preferred, while some applications were performed using X-strip. The tapes were replaced once every 3-5 days according to the condition of the patient (sweating, skin structure, friction status). Thereby, the bands were assured to stay on the patients for 15 days.
SPSS v21 software was used for statistical analysis of the study data. The comparison between the demographic characteristics of the groups was carried out using the Mann-Whitney U (MWU) test and the Chi-Square test. Chi-Square and Fisher’s Exact Test were applied to compare the baseline symptoms and findings between the groups. The Wilcoxon Signed Rank Test (WSRT) and MWU test were preferred for the intragroup and intergroup comparisons of the baseline VAS values, FIQ, SF-36 and BDI scores, respectively. The statistical significance level was accepted as p<0.05 and two-tailed probability.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
All 40 patients included in the research were female and mean age of the patients was 35.23±10.26 years. Regarding baseline assessments, VAS-Pain, VAS-Morning Stiffness, VAS-Sleep problem, the number of tender points, FIQ, SF-36 and BDI scores were found to be homogeneous between groups, whereas only VAS-Fatigue scores were not homogeneous.
Aerobic exercise applied in the patients with FM was found to be effective in reducing the severity of pain, fatigue and morning stiffness (p<0.001), decreasing sleep problem (p<0.01) and the number of tender points (p<0.001), recovery of physical dysfunction (p<0.001), elevation of the life quality (p<0.05) and lowering depression level (p<0.001) as the treatment approach (Table 1). Similarly with application of aerobic exercise, kinesio taping technique administered together with aerobic exercise was detected to be effective in reducing the severity of pain, fatigue and morning stiffness (p<0.001), decreasing sleep problem and the number of tender points (p<0.001), recovery of physical dysfunction (p<0.001), elevation of the life quality (p<0.01) and lowering depression level (p<0.001) as the treatment approach (Table 2). The analysis of our study results regarding the superiority between two treatment approaches revealed that kinesio taping applied together with aerobic exercise was more effective in reducing pain (p<0.001), fatigue (p<0.05) and sleep problem (p<0.05), in recovery of physical dysfunction (p<0.05) and improving the subscale scores of physical condition and body pain in SF-36 survey (p<0.05) than the treatment of aerobic exercise alone (Table 3).
Discussion
Patients with FM are mostly females and the diagnosis is usually diagnosed between 30-60 years of age, and the prevalence of the disease increases with age. The mean age of our patients was 35.23±10.26 years, and this age group is the most common age interval for FM according to the literature [3-4].
While aerobic exercises, strengthening and stretching-relaxing exercises, Tai-Chi, Qigong and Yoga are applied for the treatment of FM, we preferred aerobic exercises in our study considering their strongest evidence regarding efficacy in the treatment [10,14,15]. However, there are also studies, which showed no significant difference between aerobic and other types of exercises [16,17]. The literature review showed that the duration of aerobic exercises ranges between 5 and 32 weeks in the studies conducted on aerobic exercises for the treatment of FM, whereas, it was most commonly found to be applied for 8-16 weeks. For these reasons, we applied a program of aerobic walking exercise for 8 weeks scheduled as 20, 30 and 40 minutes during first 2, between 3-5 weeks and during last 3 weeks, respectively.
In the literature, there are only a limited number of studies carried out with kinesio taping for the treatment of FM. It was considered that kinesio taping plays its role in pain-relieving by providing analgesic effect through activation of gate control mechanism and descendant inhibitory mechanisms via sensorial stimuli and regulation of superficial and deep fascia functions, therefore kinesio taping was used in the similar painful conditions. We preferred treatment program of kinesio taping in our study considering the fact that kinesio taping can be used also for the treatment because of its pain-relieving effect. We decided to apply kinesio taping together with aerobic exercise because it is a newly tried treatment method in the treatment of FM.
It has been observed in the literature review of many studies similar to our study that aerobic exercises were effective in reducing the severity of pain, fatigue, morning stiffness and sleep problems, recovery of functional dysfunction, elevation of life quality and lowering depression level [9,10,15-18].
There are some studies in the literature, which have researched the efficacy of particularly aerobic walking exercises in the treatment of FM similar to our study. Holtgrefe et al. have reported in their study on the patients with FM that aerobic walking exercises provided a significant improvement in FIQ score, similar to our study [19]. Kayo et al. have noted in their 28-week study comparing aerobic walking exercises with stretching exercises that aerobic walking exercises yielded significant improvement in VAS-Pain, FIQ and all SF-36 subscales similar to our study [15].
Some studies were encountered in our literature review, which showed that aerobic exercises were not effective on some parameters in contrast to our study. Munguía-Izquierdo and Legaz-Arrese have applied aquatic exercises once weekly for 16 weeks in the aquatic exercise group and compared the results with control group. Although, a significant improvement was observed in the aquatic exercise group in terms of pain and number of tender points, no superiority of aquatic exercise group over the control group could be demonstrated [19]. Harden et al. have implemented a 30-minute daily aerobic home exercise program for 12 weeks and reported that aerobic exercises provided no significant improvement in VAS-Pain and depression scores [20]. Salek et al. applied aerobic exercises for 16 weeks in addition to the use of tricyclic antidepressants and analgesics, and compared the results with the group that used only tricyclic antidepressants and analgesics. A significant improvement was monitored in both groups in terms of pain scores and the number of tender points, however, no significant difference could be shown between the groups and therefore they stated that aerobic exercises yielded no additional contribution in FM [21]. Redondo et al. compared aerobic exercises with cognitive behavioral therapy after application for 8 weeks, although they monitored significant improvement in the aerobic exercise regarding FIQ and body pain subscale of SF-36 survey, they observed no improvement in BDI and also they detected no significant difference between two treatment groups [22].
There are a limited number of studies on the use of kinesio taping in FM. Vayvay et al. in their study compared laser and kinesio taping treatments used in patients with FM and encountered that kinesio taping treatment applied together with exercise provided significant improvement in the scores of nocturnal pain, FIQ and BID, whereas no significant improvement could be determined in SF-36 score [23]. Espí-López et al. showed that implementation of kinesio taping significantly decreased pain levels in the head, neck and shoulder regions of the individuals with FM and improved patient comfort [24]. Toprak Çelenay et al. have compared the efficacies of stabilization exercises implemented alone and together with kinesio taping treatments in the patients with FM, they have reported in their study that kinesio taping treatment provided significant improvement in the scores of VAS-Pain, VAS-Fatigue, FIQ, Nottingham Health Profile (NHP), BDI and Jenkins Sleep Scale (JSS) and was significantly superior to application of the stabilization exercise alone in terms of VAS-Pain, VAS-Fatigue, stiffness, decreasing the number of lost work days as well as increasing the number of the days with good feeling and elevating energy level [25]. In our literature review, we have encountered no similar study, which researched whether kinesio taping treatment provided any benefit in the treatment of FM by analyzing the superiority of aerobic exercise together with kinesio taping treatment to the application of aerobic exercise alone.
Conclusion
The results of our study showed that aerobic exercise is an effective therapeutic method in the treatment of FM and that kinesio taping therapy provides a remarkable improvement, however, further studies are needed to determine the efficacy of kinesio taping therapy in the treatment of FM. New studies with more cases and longer follow-up periods are recommended. Our study is important with respect to showing the impact of kinesion taping therapy on the treatment outcomes in FM and guiding further studies on this subject in the future.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or 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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Buminhan Seferoglu. The Comparison of Effectiveness of Aerobic Exercise and Aerobic Exercise with Kinesio Taping Treatments in Fibromyalgia Syndrome. Ann Clin Anal Med 2023;14(12):1138-1142
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Association of multicentricity and prognostic factors of papillary microcarcinoma
Ibrahim Ali Ozemir, Medeni Şermet
Department of General Surgery, Faculty of Medicine, Istanbul Medeniyet University, Goztepe Prof. Dr. Suleyman Yalcin City Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.21909 Received: 2023-08-26 Accepted: 2023-10-20 Published Online:2023-11-07 Printed: 2023-12-01 Ann Clin Anal Med 2023;14(12):1143-1147
Corresponding Author: Ibrahim Ali Ozemir, Department of General Surgery, Faculty of Medicine, Istanbul Medeniyet University, Goztepe Prof. Dr. Suleyman Yalcin City Hospital, Goztepe, Istanbul, Turkey. E-mail: draliozemir@hotmail.com P: +90 505 803 21 25 Corresponding Author ORCID ID: https://orcid.org/0000-0001-8693-9358
This study was approved by the Ethics Committee of Istanbul Medeniyet University, Goztepe Education and Research Hospital (Date: 2023-07-12, No: 2023/0432)
Aim: Multicentric presentation of thyroid papillary microcarcinoma (PMC) is a common feature and difficult to predict preoperatively. The aim of this study was to assess the prognostic importance of the multicentric distribution of papillary microcarcinoma.
Material and Methods: A total of 1356 patients who underwent thyroidectomy between 2011 and 2019 were analyzed. Of the 483 (%35.6) patients with papillary thyroid cancer in the final pathology, macro-carcinomas were excluded and 161 (11.9%) patients with only PMC were included in the study. Patients with solitary PMC (Group 1) and multi-centric PMC (Group 2) were compared statistically in terms of prognostic factors such as tumor size, presence of lymphovascular invasion, presence of tumor capsule invasion and extra-thyroidal extension. Thyroglobulin levels and the presence of loco-regional recurrence were monitored during the follow-up period.
Results: Solitary PMC was found in 106 (65.8%) of 161 patients, and multicentric MPC was found in 55 (34.2%) patients. Tumor sizes were compared, and a larger mean tumor size was detected in Group 2 (6.4±2.2 mm vs. 5.6±2.5 mm) (p<0.05). Prognostic factors such as the presence of capsule invasion and extra-thyroidal extension were found to be significantly higher in Group 2 (30.9% vs. 16.3% and 12.7% vs. 2.8%, respectively) (p<0.05). Extra thyroidal extension was detected at a much higher rate (18.5%) in the subgroup of multicentric patients with bilateral involvement (p<0.01). There was no statistical difference between groups in terms of biochemical incomplete response and loco-regional recurrence.
Discussion: Poor prognostic factors such as large tumor size, capsule invasion and extra-thyroidal extension are more common in patients with multicentric PMC, especially in those with bilateral involvement.
Keywords: Papillary Microcarcinoma, Multicentricity, Prognosis, Extra-Thyroidal Extension
Introduction
Papillary thyroid carcinoma (PTC) is the most common histopathologic type of thyroid cancers [1]. Papillary microcarcinoma (PMC) is defined as papillary tumors less than 1 cm in diameter by the World Health Organization [2]. According to the Surveillance, Epidemiology, and End Results (SEER) database, the incidence of papillary thyroid carcinoma has more than doubled since 1995 [3]. Due to technical improvements, the detection of smaller thyroid tumors (< 1 cm) by ultrasonography (USG) also contributed to the increase in the incidence of thyroid cancer [4]. Although the widespread use of fine-needle aspiration biopsy (FNAB) has improved the accuracy of preoperative diagnosis of PMC, the majority of PMCs are still detected incidentally in surgical specimens as a result of final pathological evaluation [5]. Patients with PMC usually have an excellent prognosis, but some of the patients may show aggressive behavior, such as loco-regional recurrence, distant metastasis, and death in 0.6% of cases [6,7]. The management of solitary PMCs varies from active surveillance to lobectomy/total thyroidectomy. On the other hand, multicentric PMCs may require total thyroidectomy with or without RAI treatment [8]. PMC has a wide spectrum of treatment options because it is difficult to predict the course of the disease. Higher recurrence rates have been reported to be associated with lymph node metastases, extra-thyroidal extension, and multicentric involvement [9]. The multicentricity of PMC ranges from 9.2 to 32%, and the presence of contralateral disease ranges from 8.1 to 25.6% [10]. Multicentric involvement of PMC in one thyroid lobe has a significant risk for the presence of contralateral PMC focuses. Multicentricity has been reported to be a risk factor for lymph node metastasis and increased cancer recurrence [11].
The aim of this study was to evaluate the association between multicentricity and poor prognostic factors in patients with PMC.
Material and Methods
Patients who underwent lobectomy or total thyroidectomy with or without central lymph node dissection between 2011 and 2019 at the General Surgery Clinic of Istanbul Medeniyet University, Goztepe Prof. Dr. Suleyman Yalcin city Hospital were included in the study. Patients underwent thyroidectomy due to thyroid cancer or suspected thyroid cancer, thyrotoxicosis, or compression symptoms such as dysphonia, dysphagia, or dyspnea. Patients with solitary or multicentric papillary microcarcinoma (<10 mm) among patients with papillary thyroid cancer according to the pathology report were included in the study, while patients with macro-carcinoma (>10 mm) were excluded from the study. Patients with a family history of thyroid carcinoma and/or radiation exposure were excluded from the study.
Patients with PMC were also divided into two groups: solitary PMC and multicentric PMC. Solitary PMC patients were classified as “Group 1”, while multicentric PMC patients were classified as “Group 2”.
Solitary and multicentric PMC patients were statistically compared in terms of demographic data, and clinical findings such as nodule status, hormonal status, presence of thyroiditis and tumor size. The presence of lymphovascular invasion (LVI), tumor capsule invasion, extrathyroidal extension, and lymph node metastasis ratios were detected according to pathological evaluation and compared between groups. Also, whether the tumor diagnosis was detected preoperatively by FNAB or incidentally after surgery was compared between groups. During the follow-up period, biochemical incomplete response (Suppressed thyroglobulin >1 ng/ml) and loco-regional recurrence rates, as well as mortality rates were determined by monitoring serum suppressed thyroglobulin value and neck ultrasonography of the patients.
This retrospective research was approved by the local ethics committee on 12.07.2023 with the decision No. 2023/0432. Informed consent was obtained from each study participant.
Results are expressed as mean ± standard deviation. SPSS 20.0 (SPPS Inc., Chicago, IL, USA) was used for the statistical analysis. The Mann-Whitney U test, Chi-square test, and Kruskal-Wallis test were used to for statistical analysis. A p-value <0.05 was considered statistically significant.
Results
The study included 1356 patients who underwent thyroidectomy between 2011 and 2019. Papillary cancer was detected in 483 (35.6%) patients. Among papillary cancer patients, those with a tumor >10 mm were excluded, and 161 (33.3%) patients with PMC (<10 mm) were included in the study. Of the patients, 133 (82.6%) were female and 28 (17.4%) were male, with a mean age of 47.2 ± 12.9 years. According to the nodule status, 125 (77.6%) patients had multinodular goiter and 36 (22.4%) patients had nodular goiter. Hyperthyroidism was detected in 14 (8.7%) of the patients, while 147 (91.3%) patients had euthyroid status preoperatively. While the diagnosis of papillary cancer was made preoperatively with FNAB in 86 (53.4%) patients, PMC was detected incidentally in 75 (46.6%) patients. The presence of thyroiditis in extra-nodular thyroid tissue was detected in 58 (36.1%) patients. The mean tumor size of the patients was 5.9 ± 2.4 mm. Thyroid capsule invasion was detected in 34 (21.1%) patients, lymphovascular invasion in 8 (4.9%) patients, and extrathyroidal invasion in 10 (6.2%) patients. Central lymph node dissection was performed in 16 (9.9%) patients, and lymph node metastasis was detected in only 4 (2.5%) of them (Table 1).
During the mean follow-up period of 62 months, biochemical incomplete response was detected in 17 (%10.6) patients, loco-regional recurrence was observed in 2 (%1.2) patients, and mortality was observed in 2 patients due to non-disease- related. In 7 of 17 patients with an incomplete biochemical response, millimetric residual thyroid tissue was identified in the ultrasonography examination, lymph node metastasis was detected in 2 patients, and no pathological findings were found in 8 patients. When the index operation reports of patients with loco-regional recurrence were examined, it was found that metastatic lymph nodes were dissected in the central region in the first operation in one of the patients, and the primary tumor pathology of the other patient was poorly differentiated carcinoma. No disease-related mortality was detected in any of the patients during the follow-up period (Table 1). Solitary PMC (Group-1) was found in 106 (65.8%) of 161 patients, and multicentric PMC (Group-2) was detected in 55 (34.2%) patients. While multicentric distribution was located in a single lobe in 28 (50.1%) patients, bilateral involvement was detected in 27 (49.9%) patients. There was no difference between the groups in terms of demographic data such as age and gender. Likewise, no difference was found between the two groups in terms of nodule status, presence of thyrotoxicosis, and thyroiditis (Table 2).
Patient groups were compared in terms of tumor size; we detected that tumor sizes were statistically significantly larger in Group 2 (6.4±2.2 mm vs. 5.6±2.5 mm) (p<0.05). We compared the groups according to tumor diagnostic methods, whether the tumor was detected by suspicious findings on preoperative USG and FNAB, or by postoperative pathological evaluation. It was observed that the preoperative diagnosis rate was statistically higher in the multicentric group. Thirty-seven (67.3%) of the patients were diagnosed with FNAB preoperatively in the multicentric group, while it was diagnosed in 49 (46.2%) solitary PMC cases (p:0.011) (Table 2). Our study reveals that 43.1% of PMCs diagnosed by preoperative USG were multicentric.
In a subgroup analysis, patients with multicentric tumors were compared based on whether the tumor distribution was unilateral or bilateral. It was detected that the mean tumor size was statistically significantly higher in patients with bilateral involvement (5.9±2.4 mm. vs. 7.1±1.8 mm) (p<0.01) (Table 2).
The presence of capsule invasion, which is one of the poor prognostic factors for thyroid cancer, was found to be 30.9% in Group 2, while it was 16.3% in Group 1. The presence of capsule invasion was statistically significantly higher in patients with multicentric PMC (p:0.015). Extrathyroidal extension is accepted as another poor prognostic factor for thyroid cancer, and was also found to be significantly higher in Group 2 (12.7% vs. 2.8%) (p:0.013). Moreover, the presence of extrathyroidal extension increased up to 18.5% in the patients with bilateral multicentric involvement of PMC (p<0.01).
Lymph node metastases were detected in 2 of 8 patients in each group who underwent central lymph node dissection by detecting suspicious lymph nodes on USG or preoperatively. There was no statistical difference between the groups in lymph node metastases (p: 0.886) (Table 2).
Although incomplete biochemical response was detected more in Group 2, there was no statistically significant difference (%14.5 vs. %5.6). While both loco-regional recurrences were detected in Group 1, no statistically significant difference was found.
Discussion
Papillary cancer is the most common type of thyroid cancer, and the Surveillance, Epidemiology and End Results (SEER) database shows that thyroid cancer incidence has more than doubled over the past 2-3 decades [3]. It has been stated that the increase in the incidence of thyroid cancer is mainly due to PMCs [1,12,13], defined by the World Health Organization as thyroid cancer less than 10 mm in diameter [2]. PMCs constitute up to 42.8% of papillary thyroid cancer patients in studies with large case series [14,15].
According to the literature, multicentricity and other poor prognostic features are less common in PMC patients than in PTC patients [15]. Multicentric distribution of PMC is an important situation for surgeons and clinicians, as it may require completion of thyroidectomy after lobectomy [7]. In addition, there are publications in the literature that multicentricity is a poor prognostic factor for papillary thyroid cancers. According to the ATA guideline, if multicentricity is accompanied by extrathyroidal extension in PMC patients, the risk score of patients is elevated to the “intermediate risk group” [7,16].
USG is the most effective imaging method to detect thyroid carcinomas. Its diagnostic accuracy increases if the tumor has microcalcification, border irregularity, extrathyroidal extension, and/or lateral lymph node metastases, while the diagnostic value of USG decreases in case of smaller tumor size [7]. Lu C. et al. stated that USG evaluation is not sensitive enough to detect multicentric PTC [17]. However, in this study, we revealed that the rate of papillary cancer diagnosis by preoperative USG was higher in multicentric PMC patients. Moreover, this study revealed that 43.1% of PMCs diagnosed preoperatively by USG were multicentric. We think that this is due to the larger mean tumor size in the multicentric PMC group compared to solitary PMC patients.
As tumor size increases, the multicentric distribution of PMCs and even the bilateral involvement rates increase. Accordingly, the need for completion of thyroidectomy may be higher in this patient group.
Some studies have stated that multicentric PTC occurs at older ages [16], but in our study, a statistically significant difference was not detected between the groups in terms of age in PMC patients.
Lin et al. [16] stated that the rate of central lymph nodes metastasis was higher in multicentric PMC patients compared with solitary PMC group (20.6% vs. 13.0%, respectively, p:0.001). Loco-regional recurrence rates were also found to be higher in multicentric PMCs (15.9% vs. 5.6%, p<0.05) in the same study. In this study, no statistically significant difference was found in terms of central lymph node metastasis in multicentric and solitary PMC cases.
The presence of LVI is accepted as an independent risk factor for loco-regional recurrence, lymph node metastasis and disease-free survival [18,19]. Kim et al. [20] stated that LVI was found in 33% of PTC patients. Uludağ et al. [15] detected LVI in 14.2% of PMC patients. In this study, LVI was found in 5.7% of multicentric PMC patients versus 3.6% of solitary PMC patients. There was no statistical difference between the groups.
Other poor prognostic factors for PTC patients are the presence of extrathyroidal extension (ETE) and/or capsule invasion. The presence of ETE in PMC patients has been reported in the literature at rates ranging from 2 to 21% [7,15]. In this study, ETE occurred in 12.7% of multicentric PMC patients, while 2.8% of solitary PMC patients had ETE, and the difference between groups was statistically significant. The presence of capsular invasion was found to be 30.9% and 16.3% between multicentric and solitary PMC groups, respectively, with a statistically significant difference.
Lin et al. [16] found that the loco-regional recurrence rate was 9.5% in multicentric cases and 5.6% in solitary cases in the thyroid papillary cancer population that they followed for about 8 years, but they did not detect a statistically significant difference. On the other hand, Zhang et al. [21] found a significant increase in the rates of lateral and cervical lymph node metastasis in the case of multicentric thyroid papillary cancers after 10 years of follow-up. Grodski et al. evaluated PMC patients in their study and detected that the overall recurrence rate was 3.5% with a median time to recurrence of 10.3 years. The majority of recurrences were loco-regional with distant recurrence occurring in 0.6% [9]. In our study, we detected loco-regional recurrence in only two patients (1.2%) with solitary PMC in approximately 5 years of follow-up.
Current guidelines recommend completion of thyroidectomy in cases of multicentric PMC that have undergone lobectomy [6,22]. Our study also supports the necessity of completing thyroidectomy in this patient group.
Conclusion
This study is important because it contains a homogeneous group of 161 patients with only micropapillary cancer, thus we can more clearly reveal the prognostic effect of multicentricity in PMC. In conclusion, this study revealed that tumor size is a significant factor in the occurrence of multicentric and bilateral involvement of PMC. Multicentricity increases the rate of poor prognostic factors such as the presence of capsule invasion, the presence of LVI and the presence of ETE in PMC patients. However, there was no difference detected between multicentric or solitary PMC in terms of either biochemical incomplete response or loco-regional recurrence.
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. Lombardi CP, Bellantone R, De Crea C, Paladino NC, Fadda G, Salvatori M, et al. Papillary Thyroid Microcarcinoma: Extrathyroidal Extension, Lymph Node Metastases, and Risk Factors for Recurrence in a High Prevalence of Goiter Area. World J Surg. 2010;(34): 1214-21.
3. Bernet V. Approach to the patient with incidental papillary microcarcinoma. J Clin Endocrinol Metab. 2010; 95(8): 3586-92.
4. Neuhold N, Schultheis A, Hermann M, Krotla G, Koperek O, Birner P. Incidental papillary microcarcinoma of the thyroid further evidence of a very low malignant potential: a retrospective clinicopathological study with up to 30 years of follow-up. Ann Surg Oncol. 2011;18(12): 3430-6.
5. Iscan Y, Sormaz IC, Tunca F, Giles Senyurek Y. Multicentricity is More Common in Thyroid Papillary Microcancer with a Preoperative Diagnosis Compared to Incidental Microcancer. Eur Thyroid J. 2019;8(5): 256-61.
6. Pacini F, Schlumberger M, Dralle H, Elisei R, Smit JW, Wiersinga W. European Thyroid Cancer Taskforce. European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur J Endocrinol. 2006; 154(6): 787-803.
7. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26(1):1-133.
8. Ito Y, Miyauchi A, Oda H. Low-risk papillary microcarcinoma of the thyroid: A review of active surveillance trials. Eur J Surg Oncol. 2018; 44(3): 307-15.
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10. Roti E, Degli Uberti EC, Bondanelli M, Braverman LE. Thyroid papillary microcarcinoma: a descriptive and meta-analysis study. Eur J Endocrinol. 2008; 159(6): 659-73.
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12. Burgess JR, Tucker P. Incidence trends for papillary thyroid carcinoma and their correlation with thyroid surgery and thyroid fine-needle aspirate cytology. Thyroid. 2006; 16(1):47-53.
13. Leenhardt L, Grosclaude P, Cherie-Challine L. Increased incidence of thyroid carcinoma in France: a true epidemic or thyroid nodule management effects? Report from the French Thyroid Cancer Committee. Thyroid. 2004;14(12):1056-60.
14. Noguchi S, Yamashita H, Uchino S, Watanabe S. Papillary microcarcinoma. World J Surg. 2008;32(5):747-53.
15. Kartal K, Aygün N, Uludağ M. Clinicopathologic differences between micropapillary and papillary thyroid carcinoma. Sisli Etfal Hastan Tip Bul. 2019;53(2):120-4.
16. Lin JD, Chao TC, Hsueh C, Kuo SF. High recurrent rate of multicentric papillary thyroid carcinoma. Ann Surg Oncol. 2009;16(9): 2609-16.
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19. So YK, Kim MJ, Kim S, Son YI. Lateral lymph node metastasis in papillary thyroid carcinoma: A systematic review and meta-analysis for prevalence, risk factors, and location. Int J Surg. 2018;50: 94-103.
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21. Zhang XJ, Yang T, Li SH, Liu D, Xu DB, Li H, et al. Multicentric papillary thyroid carcinoma: a clinical analysis of 221 patients. Int J Clin Exp Pathol. 2016;9(5):5680-6.
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Ibrahim Ali Ozemir, Medeni Şermet. Association of multicentricity and prognostic factors of papillary microcarcinoma. Ann Clin Anal Med 2023;14(12):1143-1147
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Evaluating the risk factors of venous thromboembolism patients
Esra Arslan Aksu 1, Songül Özyurt 2
1 Department of Chest Diseases, Faculty of Medicine, Samsun University, Samsun, 2 Department of Chest Diseases, Faculty of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey
DOI: 10.4328/ACAM.21922 Received: 2023-08-30 Accepted: 2023-10-28 Published Online: 2023-11-06 Printed: 2023-12-01 Ann Clin Anal Med 2023;14(12):1148-1151
Corresponding Author: Esra Arslan Aksu, Department of Chest Diseases, Faculty of Medicine, Samsun University, Samsun, Turkey. E-mail: dresraarslan07@gmail.com P: +90 549 458 44 45 Corresponding Author ORCID ID: https://orcid.org/0000-0003-0448-1801
This study was approved by the Ethics Committee of Recep Tayyip Erdoğan University (Date: 2021-19-08, No: 2021-147)
Aim: Pulmonary thromboembolism (PTE) is a serious health problem; nevertheless, diagnosing this disorder using today’s technology is easier than it was in the past. However, identifying the risk factors associated with PTE and providing proper prophylaxis is as important as diagnosing it. In the present study, it was aimed to identify risk factors for pulmonary embolism and to determine, which patients will should receive special attention for prophylaxis.
Material and Methods: This study included 355 patients with venous thromboembolism. Patient risk factors were evaluated, such as vital signs, laboratory findings, clinical symptoms, diagnosis and treatment methods, mortality rates, Wells scores, and PESI scores were evaluated.
Results: Immobilization was the most common risk factor (42.5%) among the patients. Previous surgery (32 patients, 9%) and cancer (69 patients, 19.4%) were among the most common risk factors. In 44 patients (12.4%), no risk factor was identified. There was a significant correlation between pulmonary arterial pressure and PESI scores, and mortality.
Discussion: In conclusion, iIt is vital to avoid delays in diagnosing and treating common diseases with high mortality rates, such as VTE and PTE. However, prevention is as important as diagnosis and treatment.
Keywords: Venous Thromboembolism, Risk Factors, Clinical Findings, Mortality
Introduction
The average incidence rate of venous thromboembolism (VTE) is 23-–269/100,000 per year [1–3]. Mortality secondary to VTE has decreased due to the development of early diagnosis and treatment methods, along with the commonplace evaluation of risk factors and correct prophylaxis. Identifying risk factors associated with VTE, as well asand effective and accurate prophylaxis, are as important as the primary treatment of the disease.
Various risk factors have been identified that increase susceptibility to VTE. The most commonly reported risk factors include prior history of VTE, surgery, active cancer, major trauma, hospitalization, long flights, immobility, obesity, and concomitant heart diseases [4-–11]. Other risk factors include pregnancy, oral contraceptive use, puerperium, and chronic inflammatory diseases such as inflammatory bowel diseases [12-–14].
In addition to environmental and acquired factors causing VTE, hereditary risks also exist. Hereditary conditions causing hypercoagulopathy play an important role in pulmonary thromboembolism’s (PTE) pathogenesis. The most common hereditary conditions include protein C deficiency, protein S deficiency, antithrombin-III deficiency, factor-V Leiden mutation, and hyperhomocysteinemia.
This study evaluated the risk factors, epidemiologic characteristics, diagnosis, and treatment methods for patients diagnosed with PTE in our clinic.
Material and Methods
The data of 355 patients with PTE admitted to our hospital were analyzed. The age, gender, comorbid conditions, and risk factors of the patients were evaluated. In addition, data regarding diagnostic test results, post-diagnostic treatments, complications, laboratory results, Wells and PESI scores, and mortality were analyzed. Comparisons between paired independent groups that did not show normal distribution were made using the Mann-–Whitney U test. The difference between mortality rates was determined using the ratio test. Data were analyzed using IBM’s SPSS 20.0 program. A significance level of p < 0.05 was considered statistically significant.
Statistical Method
Data were analyzed in IBM SPSS 20.0. Comparisons of two independent groups that did not show normal distribution were tested with the Mann-Whitney U test. The difference between mortality rates was tested with the ratio test. A p- value <0.05 was considered statistically significant.
Ethical Approval
Every stage of the study was carried out in accordance with ethical principles. Ethical approval was obtained from the ethics committee (Date: 2021-19-08, No: 2021-147).
Results
Among the 355 patients included in the study, 241 (60.3%) were female, and 141 (30.7%) were male. The average age of the patients was 70 years. When the vital signs of the patients were analyzed, it was found that the mean respiratory rate of the patients was 23 (+/– 5), the mean systolic blood pressure was 117 (+/– 22) mmHg, the mean diastolic blood pressure was 70 (+/–12) mmHg, the mean pulse rate was 97 (+/– 17) bpm, and the mean temperature was 36.7 °C.
The patients’ mean arterial blood gas values were 72.4 mmHg for PO2, 33.1 mmHg for PCO2, a pH of 7.4, and 91.4% saturation. Dyspnea was the most common complaint (91.5%) during hospitalization. Other symptoms and complaints recorded while the patients were hospitalized are presented in Table 1. Exactly 58 (16.1%) of the patients were smokers.
No risk factors were detected in 44 patients (12.4%). The most common risk factor was immobilization. The patients’ risk factors are shown in Table 2.
Precisely 24 patients (6.8%) had a low Wells score, 228 patients (64.2%) had a moderate Wells score, and 103 patients (29%) had a high Wells score. Exactly 260 patients (73.2%) were found to have PESI scores indicating high risk. There was a significant correlation between PESI scores and mortality.
Thoracic CT angiography was the most commonly used diagnosis method. Exactly 338 (95.2%) patients were diagnosed with thoracic CT angiography. Apart from CT angiography, ten patients were diagnosed using scintigraphy, three were diagnosed by clinical examination, and four by Doppler USG. Tomography results indicated thrombus in the main pulmonary artery in 125 patients (36.9%), thrombus in the lobar vessels in 203 patients (59.9%), segmental thrombus in 251 patients (74.4%), and subsegmental thrombus in 147 patients (43.5%). The most common radiologic finding besides pulmonary embolism was atelectasis (109, 32.3%). Other concomitant findings were pleurisy, diaphragmatic elevation, mosaic perfusion, consolidation, and pulmonary infarction. Deep vein thrombosis was detected in 133 (45.5%) patients who underwent lower extremity venous Doppler. Echocardiographic examination showed right ventricular dysfunction in 154 (43.4%) patients. The mean pulmonary artery pressure of the patients was 40 mmHg.
Patients diagnosed with PTE received standard heparin (72, 20.3%), low molecular weight heparin (242, 68%), thrombolytic therapy (36, 10.1%), and vena cava inferior filter (5, 1.4%) as initial treatment methods. Major bleeding was observed in seven patients (2%) after being administered thrombolytics. Fifteen (7.1%) of the patients expired, mainly due to PTE, while other patients succumbed to myocardial infarction, malignant diseases, cerebrovascular diseases, sepsis, or heart failure. The hospital mortality rate was 10.4%.
Discussion
If not promptly diagnosed and treated, VTE is a common disease with high mortality and morbidity. Prevention of this disease is as important as timely diagnosis. Understanding the risk factors of VTE and applying appropriate prophylaxis can help prevent the occurrence of the disease and, thus, its mortality and morbidity. There are different risk factors for PTE, and scoring systems based on these factors help doctors diagnose VTE. The Wells Criteria, Modified Wells Criteria, Geneva Score, and Modified Geneva Score are the most commonly used scoring systems for diagnosing VTE [15]. Due to its specific parameters, the Wells Criteria, an empirical probability scoring system, is the easiest to apply in clinical practice. In this study, 64.2% of the patients were found to have a moderate probability of embolism.
The current study analyzed the data and risk factors of PTE patients admitted to our clinic. The mean age of the patients in this study (70) was roughly middle-aged, similar to previous studies [16]. However, compared to other studies, the mean age of the patients was higher. In previous studies, the risk of thrombosis was shown to increase with age. The results of the present study also supported this finding [17,–18].
While risk factors for PTE are examined by considering genetic and acquired factors, the causative factor is not determined in half of all cases [19]. However, in this study, the number of cases where no risk factor could be detected (12.4%) was lower than in prior studies. Acquired risk factors for PTE include prolonged immobilization, a recent operation or trauma, and a history of thrombophlebitis. Similar to previous studies, immobilization was found to be the most common risk factor in the current study [20].
The most common clinical manifestations of PTE include acute onset dyspnea, chest pain, tachypnea, and tachycardia. However, these symptoms are not specific to pulmonary embolism. Similar to the literature, the most common symptoms in this study were acute onset dyspnea (91.5%) and chest pain (27.5%).
As prior studies have shown, patients with PTE may have lung radiograph results that do not indicate PTE. PTE’s The most common lung radiograph indicators of PTE are linear atelectasis, diaphragmatic elevation, pleural effusion, and parenchymal infiltration [21]. In this study, the most common direct radiographic finding was linear atelectasis, with a rate of 32.3%. Other common findings were diaphragmatic elevation and infiltration. One of the most commonly used methods in diagnosing PTE is thoracic CT angiography. Prior studies have reported widely varying sensitivity and specificity values for thoracic CT angiography in diagnosing PTE . This wide range of sensitivity and specificity is believed to be related to the experience of the individual taking and interpreting the images. Thoracic CT angiography was performed in 95.2% of our patients, and filling defects were most commonly observed in the segmentary arteries (74.4%). The main pulmonary artery thrombi rate was 36.6% in this study, and, in correlation, right ventricular dysfunction was observed in the echocardiographic examination results of 43.4% of the patients. Mean pulmonary artery pressure (PAB) was measured as 40 mmHg. There was a significant correlation between PAB and mortality. Median PAB values were found to be higher in patients who eventually expired.
Different from other studies conducted on VTE risk factors, the treatment methods applied to the patients were examined in the current study. DMWH treatment was found to be the most common initial treatment. Current guidelines and prior studies similarly recommend standard heparin or DMWH as a treatment for PTE. In addition, 10% of the patients were given thrombolytic therapy. Precisely 7.1% of the patients diagnosed with thromboembolism lost their lives due to PTE. When considered together, these data points clearly show the importance of reperfusion therapy in treating PTE. The PESI index predicts mortality due to PTE and determines its severity. The PESI index scores of the study’s patients participating in the study were also evaluated. As a result, 260 patients (73.2%) were found to have PESI scores indicating high risk. There was a significant correlation between PESI scores and mortality. Patients with high PESI scores had a significantly increased mortality rate.
Conclusion
It is vital to avoid delays in diagnosing and treating common diseases with high mortality rates, such as VTE and PTE. However, prevention is as important as diagnosis and treatment. To prevent such diseases, it is necessary to identify risk factors and apply the proper prophylaxis. This study examined these risk factors, their frequencies, and diagnosis and treatment methods.
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
1. Pomero F, Fenoglio L, Melchio R, Serraino C, Ageno W, Dentali F. Incidence and diagnosis of pulmonary embolism in Northern Italy: a population-based study. Eur J Intern Med. 2013; 24(7): 77-8.
2. Wong P, Baglin T. Epidemiology, risk factors and sequelae of venous thromboembolism. Phlebology. 2012; 27(2): 2-11.
3. Johansson M, Johansson L, Lind M. Incidence of venous thromboembolism in northern Sweden (VEINS): a population-based study. Thromb J. 2014; 12(1):6.
4. Ageno W, Haas S, Weitz JI, Goldhaber SZ, Turpie AGG, Goto S, et al. GARFIELD-VTE investigators. Characteristics and Management of Patients with Venous Thromboembolism: The GARFIELD-VTE Registry. Thromb Haemost. 2019; 119(2): 319-27.
5. Lehnert P, Lange T, Møller CH, Olsen PS, Carlsen J. Acute Pulmonary Embolism in a National Danish Cohort: Increasing Incidence and Decreasing Mortality. Thromb Haemost. 2018;118(3): 539-46.
6. EINSTEIN–PE Investigators; Büller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, Minar E, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012; 366(14): 1287-97.
7. Keller K, Hobohm L, Ebner M, Kresoja KP, Münzel T, Konstantinides SV, et al. Trends in thrombolytic treatment and outcomes of acute pulmonary embolism in Germany. Eur Heart J. 2020; 41(4): 522-9.
8. Jiménez D, J de Miguel-Díez, Guijarro R, Trujillo-Santos J, Otero R, Barba R, et al. RIETE Investigators. Trends in the Management and Outcomes of Acute Pulmonary Embolism: Analysis From the RIETE Registry. J Am Coll Cardiol. 2016; 67(2): 162-70.
9. Barco S, Schmidtmann I, Ageno W, Bauersachs RM, Becattini C, Bernardi E, et al. HoT-PE Investigators. Early discharge and home treatment of patients with low-risk pulmonary embolism with the oral factor Xa inhibitor rivaroxaban: an international multicentre single-arm clinical trial. Eur Heart J. 2020; 41(4): 509-18.
10. Golemi I, Cote L, Iftikhar O, Brenner B, Tafur A, Bikdeli B, et al. Registro Informatizado de Enfermedad Tromboembólica Investigators. Incidence of major adverse cardiovascular events among patients with provoked and unprovoked venous thromboembolism: Findings from the Registro Informatizado de Enfermedad Tromboembólica Registry. J Vasc Surg Venous Lymphat Disord. 2020; 8(3): 353-9.
11. López-Reyes R, Nauffal D, Ballester M, Martín-Antorán JM, de Sousa MS, Riera-Mestre A, et al. RIETE investigators. Venous thromboembolism in patients immobilised at home. Eur Respir J. 2015; 45(6): 1728-31.
12. Anderson FA Jr, Spencer FA. Risk factors for venous thromboembolism. Circulation. 2003; 10723(1): 9-16.
13. Lobo JL, Garcia-Fuertes JA, Trujillo-Santos J, Merah A, Blanco-Molina MÁ, Casado I, et al. RIETE Investigators. Anticoagulant therapy for venous thromboembolism in patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2018; 30(5): 526-530.
14. Kourlaba G, Relakis J, Kontodimas S, Holm MV, Maniadakis N. A systematic review and meta-analysis of the epidemiology and burden of venous thromboembolism among pregnant women. Int J Gynaecol Obstet. 2016; 132(1): 4-10.
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Esra Arslan Aksu, Songül Özyurt. Evaluating the risk factors of venous thromboembolism patients. Ann Clin Anal Med 2023;14(12):1148-1151
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Surprises after laparoscopic cholecystectomy: Incidentally detected gallbladder malignancies
Alper Varman
Department of General Surgery, Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey
DOI: 10.4328/ACAM.21951 Received: 2023-09-07 Accepted: 2023-11-22 Published Online: 2023-11-27 Printed: 2023-12-01 Ann Clin Anal Med 2023;14(12):1152-1155
Corresponding Author: Alper Varman, Department of General Surgery, Faculty of Medicine, Necmettin Erbakan University, Hocacihan Mahallesi, Abdulhamid Han Caddesi, Selçuklu, Konya, Turkey. E-mail: alp.varman@gmil.com P: +90 554 818 23 34 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1918-5143
This study was approved by Necmettin Erbakan University Meram Medical Faculty Ethics Committee (Date: 2023-11-03, No: 2023/4605)
Aim: Accidental gallbladder cancers have started to increase all over the world with the spread of laparoscopic cholecystectomy. The aim of this study is to evaluate gallbladder malignancies in patients who were not diagnosed with preoperative malignancies undergoing laparoscopic cholecystectomy for benign reasons in our clinic, accompanied by literature.
Material and Methods: Cases of laparoscopic cholecystectomy performed in our clinic between 2010 and 2019 with the preliminary diagnosis of gallstones, chronic cholecystitis, delayed acute cholecystitis or benign gallbladder polyps were retrospectively reviewed. Demographic data such as age, gender and comorbidities of the patients were recorded. Patients with preoperative gallbladder or liver malignancy were excluded from the study.
Results: Incidental gallbladder malignancy was detected in 11 of 5100 cases in the histopathological examination of cholecystectomy material. Nine cases were recalled and reoperated, and then transferred to oncology for chemotherapy. Two cases were followed nonoperatively.
Discussion: Cholecystectomy operation is one of the most performed surgeries in a number of general surgery clinics and is mostly performed for benign reasons. For this reason, the process of following up and evaluating the histopathology results after the operation can be neglected. Today, with the widespread use of laparoscopic cholecystectomy, incidental gallbladder malignancies have increased. For this reason, pathology outcome follow-up after cholecystectomy or laparoscopic cholecystectomy operation is important.
Keywords: Gallbladder, Cholelithiasis, Adenocarcinoma
Introduction
Gallbladder cancers are malignancies with a high mortality rate. The estimated 5-year survival rate is 5-10%. Despite advances in diagnosis and treatment possibilities, surgery is still the only curative treatment option [1].
Despite the widespread use of radiological examinations such as Ultrasound and Computed Tomography, 50-70% of gallbladder cancers are diagnosed during laparoscopic cholecystectomy performed for benign reasons or in pathology reports received after cholecystectomy. Only about 30% of them are able to get a diagnosis before surgery [2-4]. These cases are called unsuspected or incidental gallbladder carcinomas.
Accidental gallbladder carcinomas are detected in 0.3-2% of all cholecystectomies and are usually at an advanced stage [5,6]. Chemotherapy, radiotherapy or chemoradiotherapy do not significantly affect survival in these patients. Complete resection is considered as the only curative treatment option. However, even in cases diagnosed at an early stage and undergoing R0 resection, 5-year survival does not exceed 10% in incidental gallbladder carcinomas [7].
Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) are used for restaging incidental gallbladder carcinomas after cholecystectomy. R0 re-resection is the gold standard treatment for tumors up to pT2. This procedure can be performed as a non-anatomical wedge resection of the gallbladder bed, or as an anatomical resection of liver segments 4b and 5 [1,7,8].
In this study, we aimed to evaluate, accompanied by the literature, the gallbladder malignancies we encountered in patients who underwent laparoscopic cholecystectomy for benign reasons in our clinic and no preoperative malignancy was detected.
Material and Methods
This study was approved by Necmettin Erbakan University Meram Medical Faculty ethics committee (Date:03.11.2023, No:2023/4605). We retrospectively analyzed 5100 cases diagnosed with gallstones, chronic cholecystitis, delayed acute cholecystitis or benign gallbladder polyps at our general surgery clinic between 2010 and 2019. Demographic data such as age, gender and comorbidities of the patients were recorded. Incidental gallbladder carcinoma was detected in 11 (0.22%) patients.
Cases with a preoperative diagnosis of malignancy, cases with mass image and wall irregularity findings that may cause suspicion of malignancy in radiological examinations, cases with intraoperative gallbladder mass or gallbladder irregularity, and cases with a macroscopic mass lesion in the examination performed on the operating table after removal of the specimen were excluded from the study.
Results
A total of 11 patients were diagnosed with coincidental gallbladder cancer. Seven of our patients were female and 4 were male. The mean age was 66.6 years (60-82). Five patients were referred to surgery with the diagnosis of acute cholecystitis, 1 patient with Mirizzi syndrome and 5 patients with cholelithiasis. Preoperative abdominal USG was performed in all patients. In addition to USG, MRCP and abdominal CT examination were performed in 4 patients, and ERCP was performed in one patient. All patients had cholelithiasis. Intraoperative gallbladder perforation was observed in 4 patients. It was observed that the gallbladder was not removed from the abdomen with an endobag in any case. As a result of histopathological examination, the presence of tumor at microscopic level in 10 patients and at macroscopic level in 1 patient was reported. Pathologically, it was reported that the surgical margin was negative in all patients. Nine of our patients were re-operated after the pathology results. Surgical necessity and treatment procedures were explained to our 2 patients who were not operated. Due to the general condition of the patient, non-operative follow-up was deemed appropriate in line with the opinions and preferences of the patients after the briefing.
Liver wedge resection was performed in 5 of 9 patients who underwent surgery. The pathology of the resection material was reported as normal. Surgical margins were clean and no metastases were observed. Liver wedge resection, lymph node dissection and trocar port excision were performed in 2 of our patients. Metastasis was not detected in the liver in these 2 patients. It was reported that there was no metastasis at the trocar port site. Of the lymph nodes, 4/16 metastases were reported in one patient and 8/12 metastases in the other. Liver wedge resection and trocar port excision were performed in one of our patients. Metastasis was not detected in the liver in this patient, either. Adenocarcinoma infiltration was seen in the trocar port. Liver wedge resection and lymph node dissection were performed in one of our patients. No metastases were detected in the liver. The lymph node was reported as 3/10 metastases. Following surgical procedures, 7 of our patients received chemotherapy and 2 of our patients received chemoradiotherapy. Only 3 of our 11 patients are still alive and have completed the 8th, 17th and 18th months after the operation. Eight of our patients died, and the average survival time was 10.5 months.
In 2 of our patients, aged 82 and 71, the tumor was detected microscopically in the fundus of the gallbladder. It was staged as T2 pathologically. No lymphovascular invasion was observed, there was no perineural invasion. A non-operative follow-up decision was taken considering the interviews with the patients with negative surgical margins and the general condition of the patients. Chemotherapy was applied to one of the patients. Our patient who received chemotherapy had a survival of 18 months.
One of our patients was a 62-year-old female patient. Radiologically, abdominal USG and abdominal CT examinations were performed, as well as MRCP and ERCP examinations for the patient. Perforation did not develop in the laparoscopic cholecystectomy performed on the patient who was diagnosed with Mirizzi syndrome with 1 cm calculus in the gallbladder with all these examinations. In the case whose gallbladder was taken out of the abdomen without using an endobag, a 2×2 cm macroscopic tumor was detected by the pathology. The tumor was observed in the fundus of the gallbladder. Lymphovascular invasion or perineural invasion was not detected in the patient with T2 pathological stage. In addition, liver wedge resection and lymph node dissection procedures were applied to the patient (Figures 1, 2). In addition, chemotherapy and radiotherapy were applied to the patient who was found to have metastasis in 3 of the 10 removed lymph nodes. The patient, who also had perimuscular invasion, died 8 months after the first operation.
Liver wedge resection and trocar site excision were performed in our 67-year-old male patient. The patient, who was diagnosed with cholelithiasis by abdominal USG, had a 1 cm calculus in the gallbladder. The use of a bag was not considered necessary in the patient who did not develop gallbladder perforation during the surgery. The tumor was microscopic and located in the fundus. Before the operation, there was palpable stiffness at the wound site in the subxiphoid area. The patient was re-operated and liver wedge resection and trocar port excision were performed. While no metastasis was detected in the liver, adenocarcinoma infiltration was observed at the trocar site. Following chemotherapy, the patient died 12 months after his first surgery.
Liver wedge resection, lymph node excision, and trocar site excision were performed in 2 patients. No metastases were observed in the trocar sites. Lymph nodes were reported as 4/16 and 7/12 metastases. While no liver pathology was observed in 1 patient, liver metastasis was detected in one patient and the surgical margin was evaluated as negative.
Discussion
Different results were obtained in various studies when incidental gallbladder carcinomas were compared with patients who underwent surgical resection after preoperative diagnosis. However, it was observed that residual tissue remained in the abdomen in the second surgery of the majority of patients with incidental gallbladder carcinoma [9-10]. In our study, malignant tissues were observed in the resection material performed in 4 of our patients. Effective use of imaging studies before re-resection is important. FDG PET-CT is one of the most important tests that can help us in this area [11].
In the study by Ando et al., 36 patients were operated and residual tissue was detected in 16 patients. Although residual tissue was completely resected in 12 of these 16 patients, R0 resection could not be achieved in 4 patients [10]. In the study by Pawlik et al., it was observed that 70 of 115 patients had residual disease [12].
When the literature is examined, the incidence of incidental gallbladder carcinomas varies between 0.4% and 1.6%. In our study, the rate was found to be 0.22%. In addition, peroperatively removed gallbladders are examined in detail on the operating table and frozen examination is performed in suspected cases [10,12,13].
Gallbladder cancers, which are more common in women, are mostly detected in older patients. Considering these values, the gender and age parameters in our study are compatible with the literature [12,13].
When tumor staging was evaluated, 72% of the patients in our study were T1, while 28% were T2. In the study by Shukla et al., the rate of T1 tumors was 25%, and the rate of T2 and T3 tumors was 75%. In another study, Pawlik et al. reported that the T1 tumor rate was 8%, the T2 rate was 92%, and the T3 rate was 92%. When the literature is scanned, it is seen that T2 tumors are detected more than T1 tumors, although there is no clear consensus in this area [12,13].
The average number of lymph nodes removed in lymph node dissection performed in patients who underwent second surgery after cholecystectomy was 4 in our study. It is seen that this ratio is 6 and 3 in the other 2 studies examined. It is thought that the current situation is caused by the difference in the number of lymph node dissections performed in the patients and the tumor stages.
When surgical resection techniques are compared in incidental gallbladder malignancies, there are publications indicating that standard hepatectomy (right hepatectomy or extended hepatectomy) does not increase survival compared to wedge resection (segments 4b and 5), and even increases postoperative morbidity and mortality [14].
Conclusion
In conclusion, laparoscopic cholecystectomy is the most commonly performed operation all over the world. Preoperative radiological examinations performed by an experienced radiologist should guide the surgery. In suspected peroperative cases, frozen section should be studied and if necessary, additional surgery should be performed in the same session. The use of an endobag while removing the gallbladder from the abdomen is the most effective method to prevent trocar site metastases. Considering the incidental gallbladder malignancies, pathology reports should be followed and the results should be evaluated.
Limitations
In none of the cases included in our study, endobag was not used while removing the gallbladder from the abdomen. New studies are needed to examine the effect of endobag use on recurrence or local invasion.
Although the number of cases is high, our study is a single-center study. Multicenter studies will be more enlightening on the subject.
Acknowledgment
I would like to thank the Asoc. Prof. Mustafa Şentürk for for guiding and inspiring with his light.
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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Alper Varman. Surprises after laparoscopic cholecystectomy: Incidentally detected gallbladder malignancies. Ann Clin Anal Med 2023;14(12):1152-1155
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