November 2023
Management of chest trauma; tube thoracostomy: A feasible option
Muhammad Ayub Jat 1, Abdul Mutalib Almadawy 2
1 Department of Surgery, Faculty of Medicine, Northern Border University, 2 Department of Specialist Thoracic Surgeon, Ministry of Health, Northern Medical Tower, Arar, Saudi Arabia
DOI: 10.4328/ACAM.21648 Received: 2023-05-23 Accepted: 2023-07-03 Published Online: 2023-07-10 Printed: 2023-11-01 Ann Clin Anal Med 2023;14(11):961-965
Corresponding Author: Muhammad Ayoob Jat, Department of Surgery, Faculty of Medicine, Northern Border University, 1321, Arar, Saudi Arabia. E-mail: dr.ayubjat@yahoo.com P: +966 535 213 066 Corresponding Author ORCID ID: https://orcid.org/0000-0001-7671-0314
This study was approved by the Ethics Committee of Northern Border University (Date: 2020-10-20, No: 10/42/H)
Aim: In this study, we aimed to determine the safety and feasibility of tube thoracostomy in the management of chest trauma and its impact on patient outcomes.
Material and Methods: This retrospective study was conducted at the Department of Surgery, Northern Medical Tower, in Arar Kingdom of Saudi Arabia for 2 years from January 2019 to December 2020. Inclusion criteria were patients who presented to the Emergency Department with chest trauma due to a motor car accident (MCA), history of falls, history of assault, etc., and they were hemodynamically stable. Exclusion criteria were hemodynamically unstable patients with obvious signs of thoracotomy. Records of all patients with chest trauma were retrieved from files. The variables of the study were the demographic data, the mechanism of trauma, the clinical assessment of patients, the duration of the chest tube, length of stay in the hospital, complications, and clinical outcomes.
Result: This study included 365 patients with chest trauma, 329 (90.14 %) males and 36 (9.86%) females with a ratio of M 9:1 F. The age of the patients ranged from 12 to 70 years with a mean age of (41.15 ± 1.5) years. Road traffic accidents were the commonest mechanism in 300 (82.19%) patients with blunt chest trauma and a stab wound in penetrating chest trauma. Head and neck injuries were the most common associated injuries. Tube thoracostomy under local anesthesia was done in 98 (27%) patients, while 267 (73%) patients were managed conservatively.
Discussion: Tube thoracostomy is a safe and feasible option in the management of chest trauma with better patient outcomes. Chest trauma resulting from road traffic accidents remains the major mechanism of chest injury among young males and active age groups.
Keywords: Chest Trauma, Rib Fracture, Tube Thoracostomy, Pneumothorax, Hemothorax
Introduction
Trauma is an important and serious problem of public health concern. As the population of KSA is relatively young, injuries have serious implications for the country’s health and prosperity; 40% of the population is 19 years old and younger [1]. The high motorization rate in Middle Eastern countries has increased the incidence of RTA-related fatalities [2]. Chest trauma is a leading cause of death in 25% of multiple trauma patients and, the percentage increases to 50% when associated with other injuries. [3]. Regardless of the mechanism, the main concerns of thoracic trauma are combined effects on both respiratory and cardiovascular functions, leading to hypoxia, hypovolemia, and decreased cardiac output through direct effects on the thoracic organs. [4] Most of these trauma patients are treated successfully conservatively in the emergency department through principles of initial trauma management (Advance trauma life support) and interventions such as intubation, ventilation, or intercostal tube drainage within the scope of practice of emergency physicians, while some patients with blunt chest trauma 10–15% and in penetrating chest trauma 15–30% underwent surgery. Moreover, to achieve optimal patient outcomes and significantly reduce morbidity and mortality, patients require aggressive management of chest injuries along with precise treatment of associated injuries. [5] The objective of this study was to determine the safety and feasibility of tube thoracostomy in the management of Chest trauma and its impact on patient outcomes.
Material and Methods
This retrospective study was conducted with 365 patients who presented to the ER department with chest trauma due to a motor car accident (RTA), a history of fall or assault admitted in Northern Medical Tower, during the period of 2 years from January 2019 to December 2020. Ethical approval was obtained from the institutional Local Committee of Bioethics (letter No. 10/42/H dated 20/10/2020). All hemodynamically stable patients with chest trauma irrespective of their age and sex were included in this study and hemodynamically unstable patients with obvious indications for thoracotomy were excluded from the study.
Records of all the patients with chest trauma admitted to the surgical department were retrieved from files in the medical records department, and the findings were recorded. The files concerned the medical history and clinical examination that was done on the patient at the time of arrival. Each of the patients in the department of accident and emergency had been resuscitated according to the latest guidelines of the Advanced trauma life support (ATLS) protocol, using integrated management by a team of specialists, including a trauma physician, general surgeon, orthopedic surgeon, and anesthetist. The patient had been subjected to a chest X- posterior-anterior view and a CT scan of the chest was done whenever indicated. Patients were also subjected to extended FAST scans, including the scan of the chest to detect hemothorax. Associated injuries to other parts of the body were also recorded from medical files. Management was recorded in the form of conservative treatment, analgesia, chest physiotherapy, tube thoracostomy, or thoracotomy. Study variables were demographic data, mechanism of trauma, clinical assessment of patients, the duration of chest tube, length of hospital stay, complications, and clinical outcomes.
Data collected were entered in a master chart and analyzed using Excel-2019 with the help of a medical statistician. Data were summarized in the form of proportions and frequency tables in an Excel -2019 spreadsheet.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
This study included 365 patients with chest trauma, among them 348 patients (95.5%) had blunt chest trauma, while 17 patients (4.5%) had penetrating chest trauma. Of 365 patients, 329 (90.14%) were males and 36 (9.86%) were females. Male: female ratio was observed to be 9:1. The maximum number of patients aged 21-40 years comprised 63% (230 out of 365). Young males are more prone to chest injuries due to more exposure to the external environment.
In this study, blunt chest trauma was more common than penetrating trauma with a ratio of 10:1. Of 348 patients who had blunt chest trauma, 312 (89.65%) were males, while 36 (10.4%) were female, and all 17 patients who had penetrating trauma were males, showing that males are more prone to both blunt as well as penetrating chest trauma. Road traffic accident RTA (82.19%) is the most common mechanism of blunt chest injury, followed by fall from a height (6%), whereas stab wound was the most common cause of penetrating trauma. Moreover, pedestrians are more susceptible to blunt trauma chest as a result of road traffic accidents compared to passengers (Table 1).
Rib fractures were the most common injury 237 in patients (64.93%) after blunt chest trauma. Secondly, the lung was injured in a significant number of cases, leading to pneumothorax in 115 (31.5%) (Figure 1), hemothorax in 80 (21.91%) (Figure 2), hemopneumothorax in 65(17.80%) and lung contusion in 38 (10.41%) (Table 2).
Among chest trauma patients, the most commonly associated injuries were head and neck injuries (45.25%), followed by musculoskeletal injuries in 21.35% i.e. clavicle fracture, upper and lower limb injuries, abdominal injuries in 11.23% and spine injury in 4.52% of patients.
Pain is the chief complaint of 348 (95.34%) patients with chest trauma, followed by complaints of breathlessness in 292 (80%) as a result of respiratory distress due to pneumothorax or hemothorax. The most common clinical finding in patients with chest trauma was tenderness in 310 (84.93%) within the injury site, decreased breath sounds in 275, (75.34%), and surgical emphysema in 36 (9.86%) patients.
In the present study, tube thoracotomy was performed only in 98 (26.84%) patients, while 267(73.16%) patients were managed conservatively in the form of NSAID, epidural and intravenous narcotics, controlled analgesia (PCA), intercostal block and chest physiotherapy (Table 3).
In this study, the maximum number of patients (43.5%) had a chest tube for a period of 6-8 days and the average duration of hospital stay was 8.5 days. No mortality was found in penetrating trauma patients, whereas six blunt chest trauma patients died, with a mortality rate of 1.64%; five of these deaths were associated with traumatic brain injury.
Discussion
With the rapid development of cities, expansion, and a remarkable increase in high-speed traffic flow, trauma in general and chest trauma, in particular, are increasing. Thus, the requirement for enhanced care, trained personnel, and sophisticated equipment for saving the life of trauma patients has increased [6]. A flail chest is a consequence of blunt chest trauma in which at least three consecutive ribs are fractured in two or more places and is associated with significant morbidity and mortality [7]. Surgical rib fixation (SRF) is a treatment for flail chest as it provides chest wall stability, a significant decrease in mechanical ventilation requirements, and prevents ventilator-acquired pneumonia [8]. In the present study, 4 cases of flail chest were observed; they required surgical rib fixation and mechanical ventilation for a short time. A study by Marasco et al. [9] reported that patients who received surgical treatment had significantly fewer days of mechanical ventilation and a shorter hospital and ICU-(LOS) length of stay.
In the present study, the majority of patients belonged to the age group of 21-40 years, which comprised 230 patients (63. 01%). Other studies by Lema et al. [10] and Khursheed SQ et al [11] also showed similar results. Our study showed a male predominance with the incidence of 90.14% and male to female ratio was 9:1. In another study by Dehgan et al. [12], they reported a male-to-female ratio of 3.34:1.7. Similar results obtained by Ekpe EE et al. [13] suggest that males and younger individuals are more likely to have more chest injuries because they are more active and mobile, which increases the risk of trauma.
In our study, 300 patients (82.19%) suffered blunt chest trauma due to road traffic accidents (RTA), which is the most common mechanism of trauma. Similar results were reported in other studies by Lema et al (81.75%), Khursheed SQ et al (91.25%) and Aymen et al (81.25%) [14]. In this study 17 patients (4.65%) suffered penetrating chest trauma by stab wound, which is the most common mechanism of injury, but in a study by Khursheed SQ et al., gunshot injury (64.28%) was the most common cause of penetrating injury, followed by stab wound injury (21.43%). The mechanism of penetrating chest injury depends on the level of civilization of crime and violence in a particular community.
In the present study, the most commonly associated injury in chest trauma patients was head injury (45.25%), followed by skeletal injury (21.35%) i.e. clavicle fracture, upper and lower limb injuries, spine injury, and abdominal injury. In a study of 52 patients by Choudhary et al. 38.4% cases of head injury and 15 % cases of skeletal injuries. were reported [15].
In this study, rib fracture was the most common type of chest injury (63 %), followed by lung injury in a significant number of cases, leading to pneumothorax in 115 (31.5%), hemothorax in 80 (21.9%), hemopneumothorax in 18%, and lung contusion was observed in 38 (10.41%) cases. In the present study, pain and tenderness in the chest wall (95. %) were the commonest finding followed by difficulty in breathing (80.2%) as a result of pneumothorax or hemothorax. Similar results were reported in a study by Khursheed SQ et al [11].
In this study, the majority of patients 267 (73.16%) were managed conservatively with observation, adequate analgesia, intravenous narcotics, epidural analgesia, monitoring, bed rest, and chest physiotherapy, while 98 patients (26.84%) underwent tube thoracostomy with no major complications. Similar results in a study by Majid al M [16] et al., in which 170 of the 226 patients (75.2%) were managed conservatively and 57 (25.2%) of the patients underwent tube thoracostomy. Most patients with chest trauma were treated with conservative management in a study by Sharma K et al. [17] (93.6%), but studies by Khan et al. [18] and Dalal et al. [19] reported that 65% of patients 90% patients with chest injuries were managed by tube thoracostomy, respectively.
In this study, we used a large-bore chest tube (36-40 Fr) in the case of hemothorax and a small bore (28 -32 Fr) in the case of pneumothorax with fewer complications. A prospective study by Inaba et al. [20] compared the outcomes of patients treated with (relatively) small bore (28–32 Fr) chest tube versus a large bore (36–40 Fr) for trauma; authors did not find differences in terms of chest tube output and associated complication [21]. In our study a maximum number of patients (45%) had chest tubes kept for 6-8 days and the average duration of hospital stay was 8.5 days. Similar results were found in a study by Novakov et al. [22], they reported a mean hospital stay duration of 8.7 days in 212 patients with chest trauma. No mortality was found in penetrating trauma patients, whereas six blunt trauma patients died, with a mortality rate of 1.72%; five of these deaths were associated with traumatic brain injury, while in another study by Mohamed L et al. [23] the mortality rate was 6.9%.
Most of the patients with mild or minor hemo/pneumothorax resolve spontaneously without exposing the patient to the risks associated with chest tube placement. However, a chest tube is compulsory for patients in respiratory distress on presentation, patients who require intermittent positive pressure Ventilation (IPPPV), patients with associated significant injuries, and patients who develop respiratory distress during conservative management.
Conclusion
Chest trauma resulting from road traffic accidents remains the major mechanism of chest injury among young males and active age groups. Thoracic trauma is an important cause of hospitalization, morbidity, and mortality. The incidence of chest trauma was higher in males than in females. Intensive care unit stay was significantly longer among patients with blunt chest trauma than with penetrating trauma.
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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Muhammad Ayub Jat, Abdul Mutalib Almadawy. Management of chest trauma; tube thoracostomy: A feasible option. Ann Clin Anal Med 2023;14(11):961-965
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Effects of iloprost and n-acetylcysteine on ischemia-reperfusion injury and thiol/disulfide hemostasis in rats
Yasin Alper Yildiz 1, Fatih Altintoprak 2, Fehmi Celebi 2, Volkan Oter 3, Gozde Cakırsoy Cakar 4, Hayrullah Yazar 5, Hüseyin Cakiroglu 6, Ali Muhtaroğlu 7
1 Department of General Surgery, Faculty of Medicine, Kastamonu University, Kastamonu, 2 Department of General Surgery, Faculty of Medicine, Sakarya University, Sakarya, 3 Department of Gastroenterological Surgery, Faculty of Medicine, Ankara City Hospital, Ankara, 4 Department of Pathology, Faculty of Medicine, Sakarya University Research and Educational Hospital, Sakarya, 5 Department of Biochemistry, Faculty of Medicine, Sakarya University Research and Educational Hospital, Sakarya, 6 Experimental Medicine Researchand Application Center, Faculty of Medicine, Sakarya University, Sakarya, 7 Department of General Surgery, Faculty of Medicine, Giresun University , Giresun, Turkey
DOI: 10.4328/ACAM.21658 Received: 2023-02-19 Accepted: 2023-07-03 Published Online: 2023-08-02 Printed: 2023-11-01 Ann Clin Anal Med 2023;14(11):966-970
Corresponding Author:Yasin Alper Yıldız, Department of General Surgery, Faculty of Medicine, Kastamonu University, Kastamonu, Turkey. E-mail: yalperyildiz@gmail.com P: +90 534 953 06 28 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6348-1927
This study was approved by the Local Ethics Committee of Sakarya University Animal Experiments (Date: 2018-09-05, No: 24)
Aim: Intestinal ischemia occurs after partial or complete obstruction of the intestinal arterial blood flow, and reperfusion injury following the restoration of blood flow. Intestinal ischemia-reperfusion [IIR] damage can cause multiple organ failure and death.
In our study, we aimed to observe the effect of ilioprost and N-acetylcysteine on ischemia-reperfusion injury and to show the effect of the Thiol disulfide mechanism in this area.
Material and Methods: Thirty Sprague Dawley rats were divided into five groups of six animals each: sham, IIR, IIR+IL, IIR+NAC and IIR+NAC+IL. Intestinal samples and blood were collected after completion of the sham or IIR protocol. Small-bowel samples were evaluated according to the Chiu score. Thiol/disulfide [DS] hemostasis was followed using a novel series of serum biomarkers. Serum concentrations of total thiol, native thiol and disulfide were also determined.
Results: The average Chiu score was lower in the IIR + NAC group than in both the IIR and the IIR + IL group, but the differences were not statistically significant. The score in the sham group was significantly lower than those of the other four groups. The level of reduced thiol and the native thiol/total thiol [NT/TT] ratios were higher in groups treated with NAC, IL or both. In the latter groups, oxidized thiol, DS/TT and DS/NT ratios were lower than in the IIR group but the differences between the three treatment groups were not statistically significant.
Discussion: The addition of IL to NAC was not more protective than NAC alone in a rat model of IIR injury. Our results suggest that markers of thiol-DS hemostasis can be used as indicators of antioxidant mechanisms in IIR injury.
Keywords: Ischaemia-Reperfusion Injury, Disulphide, Thiol, Iloprost
Introduction
Ischaemia is defined as reversible or irreversible cell or tissue death due to the depletion of cell energy stores and the accumulation of toxic substances. This is the result of an insufficient blood supply to the tissues and organs due to decreased arterial and/or venous blood flow. Ischaemia causes tissue hypoxia and thus hypoxic tissue damage [1]. However, the restoration of blood flow [reperfusion] induces even more damage [2], including the formation of reactive oxygen species (ROS) from the renewed supply of cellular oxygen [3]. Mesenteric ischaemia that develops due to the occlusion of the superior mesenteric artery (SMA) prominently affects the small intestine, which is highly susceptible to ischemia-reperfusion (IR) injury [4,5]. Iloprost (IL) is a stable prostaglandin I2 analog with pharmacokinetic properties very similar to those of the parent compound [6,7]. Previous studies have demonstrated the protective effects of IL on IR injury in different organs [8]. N-acetylcysteine (NAC) is an intracellular glutathione (GSH) precursor that increases glutathione S-transferase activity in the liver [9]. Its activities include the protection of tissues against ROS damage, by directly removing oxidants [10,11]. The beneficial effects of NAC in rats, including rat models of IR injury of the heart and liver, have been demonstrated [11,12]. Thiols (-SH) are organic compounds that contain a sulfhydryl functional group [13]. Among the thiols found in plasma are albumin and other proteins, cysteine, cysteinyl glycine, glutathione, homocysteine and γ-glutamyl cysteine thiols [14]. Oxidation of the thiol groups of these thiol-containing molecules results in the formation of reversible disulfide (DS) bonds [15]. The reversible oxidation-reduction of the thiol groups and DS bonds is referred to as thiol-DS hemostasis [16] and it can be followed using the method developed by Erel and Neşelioğlu[17], which allows each and/or all of the components to be measured and further analyzed. In this study, we used of this method to investigate the abilities of IL and NAC, alone or in combination, to prevent intestinal IR (IIR) injury in rats.
Material and Methods
Experimental Design
Ethical approval was obtained from the Local Ethics Committee on Animal Experiments of Sakarya University University on 05/09/2018 with decision No. 24. Thirty mixed-sex Sprague Dawley rats weighing 250–350 g each were divided into five groups of six animals: sham, IIR, IIR+IL, IIR+NAC and IIR+NAC +IL. Prior to the experiment, the rats were acclimated under 12 h light/12 h dark conditions, with water and standard rat food supplied ad libitum. Intestinal samples [5 cm of ileum from the distal end of the terminal ileum to the proximal ileum] and blood were collected from the sham group, which did not undergo any surgical procedures. In the IIR group, the cranial mesenteric artery [CMA] and the superior mesenteric artery (SMA) were dissected and then clamped to induce intestinal ischemia. Then the skin was closed with skin staples. After 45 min of ischemia, the abdomen of the rats was reoperated and reperfusion was induced by declamping the CMA with the skin again closed using skin staples. After 120 min of reperfusion, the abdomen was reoperated and the animals were euthanized by cervical dislocation. Intestinal samples and blood were collected. In the IL-treated rats, 2 µg IL/kg was administered intraperitoneally 30 min before reperfusion. In the NAC-treated rats, 300 mg NAC/kg was administered intraperitoneally 30 min before reperfusion. Intestinal samples and blood were collected as in the sham group.
Histopathological evaluation
Tissues separated for histopathological examination were fixed in 10% formaldehyde and sent to the Department of Pathology. After routine processing, the tissue samples were embedded in paraffin, from which sections 5 µm thick were cut and stained with hematoxylin and eosin. Sections were evaluated by light microscopy (Nikon Eclipse-Ni Y-THPL, Japan) by a pathologist blinded to the treatment groups. The tissues were classified using the system of Chiu et al. (1970), described in Table1.
Biochemical Evaluation
Thiol-DS hemostasis measurements
The concentrations of total thiol (TT, μmol/L) and native thiol (NT, μmol/L) in serum were measured and the values were used to calculate the thiol/DS ratio, an oxidative marker of hemostasis. Samples collected in capped gel tubes and transferred in a cold chain were allowed to stand for 30 min before they were centrifuged (cooled, 4000 rpm 10 min). Serum parameters of interest were analyzed using Rel assay diagnostics kits. A fully automated autoanalyzer (Beckman Coulter, chemistry analyzer AU 680, serial number: 2016024580, MishIMA K.K, Japan) in the Biochemistry Laboratory was used to measure TT, NT and DS concentrations (μmol/L), from which DS/NT, DS/TT and NT/TT ratios, as well as oxidation reduction rates, were determined.
Statistical analyses
All data were processed using IBM Statistical Package for the Social Sciences Statistics 22 (SPSS 2013). Numerical variables were analyzed using descriptive statistics [mean, standard deviation], and differences between categorical variables from more than two groups were analyzed via one-way ANOVA. A Levene test was performed to determine the presence or absence of variance homogeneity, followed by a Tukey test or Tamhane’s T2 test.
Ethical Approval
Ethics Committe approval for the study was obtained.
Results
Histopathological Results
A comparison of the Chiu scores of the five groups (Table 2) showed that they were lower in the sham group than in all other groups. Microscopic examination of the small intestine sections of the sham group showed that all were of grade 0. Thus, there were no morphological changes in the lamina propria, and ulceration, mononuclear cell infiltration, increased capillary permeability and hemorrhage were not observed (Figure 1a). In sections of small intestine with grade 1 damage (IIR+NAC and IIR+NAC+IL), subepithelial separations were present at the upper end of the villi (Figure 1b). In rats with grade 2 damage, the subepithelial separations were of moderate grade (Figure 1c). Grade 3 damage, seen in all IIR groups, consisted of deformations at the ends of the villi where the mucosal epithelium was pushed intensely upwards (Figure 1d). In rats with grade 4 damage (IIR, IIR+IL, IIR+NAC+IL), villus deformation was accompanied by dilated capillaries reaching the lamina propria (Figure 1e).
IIR scores were lower in the IIR + IL group than in the IIR + NAC and IIR + NAC + IL groups, but the differences were not statistically significant (p> 0.05). All IL groups had a higher mean Chiu score than the IIR group, but again the difference was not significant. The IIR + NAC group had a lower Chiu score than either the IIR group or the IIR + IL group, but neither difference was statistically significant (Figure 2). The Chiu score of the IIR + NAC + IL group was lower than that of the IIR and IIR + IL groups and higher than that of the IIR + NAC group, without statistically significant differences. The mean Chiu score of the IIR + NAC + IL group was significantly higher than that of the sham group.
Thiol-Disulfide Hemostasis
The results of biochemical analyses of thiol-DS hemostasis in the five groups of rats are presented in Table 3.
According to the results of one-way ANOVA, TT, NT, DS, NT/TT, DS/TT, DS/NT, the reduced thiol ratio, the oxidized thiol ratio and the thiol oxidation reduction rates differed significantly among the five groups (p < 0.05). The data were further analyzed in a Levene test followed by a Tukey test for homogeneous groups and a Tamhane T2 test for non-homogeneous groups.
TT levels (Figure 3) were lower in the IIR and IIR + IL groups than in the sham group, but without a significant difference (p> 0.05). However, they were significantly higher in the IIR + NAC and IRR + NAC + IL groups than in the other groups and in the IIR + NAC group than in either the IIR + IL or the IIR + NAC + IL group.
Similar to TT, NT levels (Figure 3) were lower in the IIR and IIR + IL groups than in the sham group but the difference was not significant (p> 0.05). The levels were significantly higher in the IIR + NAC and IIR + NAC + IL groups than in the sham and IIR groups, but significantly lower in the IIR + IL group than in the IIR + NAC group.
DS levels (Figure 3) were significantly higher in the sham, IIR + NAC and IIR + NAC + IL groups than in the IIR + IL group (p <0.05), which was slightly higher than in the IIR group. The difference between the IIR + NAC + IL group and the IIR group was significant.
The reduced thiol ratio was significantly higher in the IIR + IL, IIR + NAC, and IIR + NAC + IL groups than in the sham and IIR groups (p <0.05). It was higher, but not significantly, in the IIR + NAC group than in the IIR + NAC + IL and IIR + IL groups. The NT/TT ratio was significantly higher in the IIR + IL, IIR + NAC, IIR + NAC + IL groups than in the sham and IIR groups and was also higher in the IIR + NAC group than in the IIR + NAC + IL and IIR + IL groups, but the differences were not significant.
The oxidised thiol ratio was significantly lower in the IIR + IL, IIR + NAC, IIR + NAC + IL groups than in the sham and IIR groups (p <0.05) but the difference between the IIR + NAC + IL and IIR + IL groups was not statistically significant. The DS/NT ratio was significantly lower in the IIR + NAC, IIR + IL and IIR + NAC + IL groups than in the IIR group; significantly higher in the IIR + NAC group than in the sham group; and non-significantly lower in the IIR + NAC group than in both the IIR + NAC + IL and IIR + IL group.
The DS/TT ratio was significantly lower in the IIR + IL, IIR + NAC, IIR + NAC + IL groups than in the sham and IIR groups and non-significantly lower in the IIR + NAC group than in the IIR + NAC + IL and IIR + IL groups.
The thiol oxidation reduction rate was significantly higher in the IIR + NAC + IL group than in the IIR group, and non-significantly higher in the sham and all treated groups than in the IIR group.
Discussion
Our study uniquely evaluated thiol-DS hemostasis in a rat model of IIR injury. Although methods to reduce IR injury and prevent organ failure have been described in the literature [19], our study is the first to compare the effects of IL and NAC on reperfusion subsequent to intestinal ischemia.
The protective effects of IL on ischemic musculoskeletal damage and in heart disease, lung diseases, and IR-associated spinal cord injury have been demonstrated in several studies [20-25]. Using the Chiu score, we found that IL reduced IR injury in the small intestine compared to the untreated (IR) control, but the difference was not statistically significant.
However, our study is the first to investigate the effects of these two drugs on intestinal IR. A comparison of IL and NAC, alone or in combination, showed better histopathological results in NAC-treated groups and worse histopathological results in IL groups. This finding supports previous studies that have reported that NAC may be effective for the prevention of IIR injury. Thus, the therapeutic effects of NAC in the clinical setting merit investigation.
Whether IL and/or NAC, as antioxidants, have an effect on thiol-DS hemostasis, a new marker of oxidative stress was also examined in this study. While many clinical conditions disrupt the thiol-DS balance, it is not known whether this also occurs in IIR injury. Erel and Neselioğlu [17] showed that plasma levels of DS were higher in patients with degenerative diseases such as diabetes, obesity and pneumonia as well as in smokers, but lower in patients with proliferative diseases such as multiple myeloma, bladder cancer, colon cancer and kidney cancer
Our study revealed significant differences between groups with respect to serum markers for thiol-DS haemostasis. Specifically, TT, NT and DS levels were highest in the NAC group and lower in the NAC+IL groups. The oxidised thiol level was the lowest and the reduced thiol ratio was the highest in the NAC group, which suggests that IL reduces the effects of NAC when the two drugs are administered in combination. Our results demonstrate that utility of TT, NT and oxidized and reduced thiol ratios in assessing the degree of antioxidant activity during IIR injury. This novel finding should be examined in further studies. The limitation of this study is that the number of subjects in the study was small.
Conclusion
A combination of NAC and IL has no advantage over NAC alone in protector IIR injury. The use of the Thiol disulfide mechanism and measurement parameters in intestinal ischemia-reperfusion injury gives results related to the rate of damage. New studies are needed to increase the level of evidence of the results.
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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6. Ylitalo P, Kaukinen S, Seppäla E, Nurmi AK, Pessi T, Krais T, et al. Pharmacological effects of iloprost (ZK 36 374), a stable prostacyclin analogue, in man. Biomed Biochim Acta. 1984;43(8-9):399-402.
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9. Slusser SO, Grotyohann LW, MartinLF ,Scaduta RC. Glutathione catabolism by the ischemic rat kidney. Am J Physiol. 1990; 258(6):1546-53.
10. Conesa EL, Valero F, Nadal JC, Fenoy FJ, López B, Arregui B, et al. N-acetyl-L-cysteine improves renal medullary hypoperfusion in acute renal failure. Am J Physiol Regul Integr Comp Physiol. 2001; 281(3):730-7.
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12. Bartekova M, Barancik M, Ferenczyova K, Dhalla NS. Beneficial Effects of N-acetylcysteine and N-mercaptopropionylglycine on Ischemia Reperfusion Injury in the Heart. Curr Med Chem. 2018; 25(3):355-66.
13. Sen CK, Packer L. Thiol homeostasis and supplements in physical exercise. Am J Clin Nutr. 2000;72(Suppl.2):6530-69.
14. Turell L, Radi R, Alvarez B. The thiol pool in human plasma: the central contribution of albumin to redox processes. Free Radic Biol Med. 2013;65:244-53.
15. Cremers CM, Jakob U. Oxidant sensing by reversible disulfide bond formation. J Biol Chem. 2013;288(37): 26489-96.
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Download attachments: 10.4328.ACAM.21658
Yasin Alper Yildiz, Fatih Altintoprak, Fehmi Celebi, Volkan Oter, Gozde Cakırsoy Cakar, Hayrullah Yazar, Hüseyin Cakiroglu, Ali Muhtaroğlu. Effects of iloprost and n-acetylcysteine on ischemia-reperfusion injury and thiol/disulfide hemostasis in rats. Ann Clin Anal Med 2023;14(11):966-970
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Diagnostic and prognostic value of scd163 levels in upper gastrointestinal bleeding
Melis Dorter 1, Utku Murat Kalafat 2, Busra Bildik 3, Doganay Can 4, Serkan Dogan 2, Kader Irak 5, Basar Cander 2, Ramazan Guven 4
1 Department of Emergency Medicine, Koc University Hospital, Istanbul, 2 Department of Emergency Medicine, University of Health Science, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, 3 Departmen of Emergency Medicine, Karabuk University Training and Research Hospital, Karabuk, 4 Department of Emergency Medicine, Ministry of Health Basaksehir Cam and Sakura City Hospital, Istanbul, 5 Department of Gastroenterolog, Ministry of Health Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.21697 Received: 2023-04-01 Accepted: 2023-05-17 Published Online: 2023-07-04 Printed: 2023-11-01 Ann Clin Anal Med 2023;14(11):971-975
Corresponding Author: Melis Dorter, Department of Emergency Medicine, Koc University Hospital, Istanbul, Turkey. E-mail: melisdorter@gmail.com P: +90 530 304 88 06 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6958-6052
This study was approved by the Ethics Committee of Health Sciences University and Istanbul Kanuni Sultan Süleyman Training and Research Hospital (Date: 2019-05-16, No: KAEK/2019.06.154)
Aim: Upper gastrointestinal endoscopy (an invasive procedure) is the gold standard for diagnosing patients with suspected upper gastrointestinal bleeding. In this study, oOur aim is to determine the value of sCD163 in upper gastrointestinal bleeding.
Material and Methods: In this single-center,e cross-sectional, prospective study, we aimed to evaluate the value of sCD163 as a non-invasive marker for diagnosing and predicting upper gastrointestinal bleeding. Patients aged ≥18 years who underwent endoscopy for suspected upper gastrointestinal bleeding and presented at the emergency department of Kanuni Sultan Suleyman Training and Research Hospital in the University of Istanbul Health Science were included in the study. Statistical analysis was conducted using the SPSS Statistics 26.0 program (IBM Inc., New York, USA). The study was conducted between January 8, 2019 and January 4, 2020 with 75 participants. Of these, 41 patients had upper gastrointestinal bleeding, and 34 were healthy volunteers.
Results: In the patient group, Glasgow-–Blatchford scores and sCD163 values were calculated for those with and without bleeding-related findings. Notably, the patient group had statistically significantly higher sCD163 levels than the healthy volunteer group healthy volunteers (p < 0.05).
Discussion: sCD163 may be a useful biomarker for diagnosing upper gastrointestinal bleeding and identifying the clinical process.
Keywords: Gastrointestinal Bleeding, sCD163, Scoring, Endoscopy
Introduction
More than 75% of all gastrointestinal (GI) bleeding cases occur in the upper GI system, making this condition one of the most prevalent reasons for hospital admissions worldwide [1,2]. Patients with upper GI bleeding exhibit wide-ranging symptoms and clinical courses, ranging from asymptomatic occult bleeding to subclinical occult bleeding, anaemia and hypovolemic shock [3]. Many risk assessment scoring systems have been established to predict clinically significant outcomes, such as mortality, hospital-based intervention requirement, re-bleeding and hospitalizsation duration [4]. These scoring systems were classified into three, such as a classification that only requires endoscopic data, including endoscopic and clinical findings, and the scoring system, which is based only on clinical results [5]. In addition, some studies have reported on certain biomarkers that can may be useful for GI bleeding assessment.
One of these biomarkers is sCD163, which functions as a scavenger receptor during the endocytosis of the haemoglobin-–haptoglobin complex [6]. In this study, we aimed to investigate the value of sCD163 in diagnosing upper GI bleeding in patients who underwent endoscopy, independent of subjective parameters (e.g., the prolongation of the patient’s waiting time for interventional procedures such as endoscopy, and the suitability of the conditions in terms of diagnosis and prognosis).
Material and Methods
Determination of study groups
This single-centere, cross-sectional and prospective study was conducted in the emergency department of Istanbul Kanuni Sultan Suleyman Training and Research Hospital, University of Health Sciences.
Ethical statement: Prior to participant enrolment, the Ethics Committee of Health Sciences University and Istanbul Kanuni Sultan Süleyman Training and Research Hospital approved our study (KAEK/2019.06.154).
The study was conducted between January 8, 2019 and January 4, 2020. The study It included patients presenting to the emergency department and undergoing endoscopy with a provisional diagnosis of upper GI bleeding and healthy volunteers. Based on the parameters of the initial laboratory tests, the Glasgow-–Blatchford score was calculated.
Exclusion criteria
For the upper GI bleeding or patient group, those who were aged <18 years, who had lower GI bleeding, who had oesophageal variceal bleeding, had malignancy-induced bleeding and were unwilling to participate in the study were excluded. For the healthy control group, we excluded those who were aged under <18 years of age, were pregnant, had a known comorbiditiesy and had signs of acute infection during enrolment.
Laboratory methods
Biochemical analysis
Venous blood was collected from both groups by routine phlebotomy in a 5 mL gel tube (BD vacutainer SST II Advance; NJ, USA) and a 2 mL anticoagulant tube (K2-EDTA; Becton Dickinson, NJ, USA). Samples placed in the anticoagulant tube were examined immediately. After completing the biochemical tests used in scoring the blood samples that were placed in the gel tube, we kept the remaining portion at room temperature for 20 minutes before being centrifuged at 3500 rpm for 10 minutes to obtain serum and plasma samples. Meanwhile, the remaining serum and plasma samples were collected in Eppendorf tubes and frozen at −80°C for enzyme-linked immunosorbent assay (ELISA). From the serum, white blood cells (WBC), haemoglobin, platelets and red blood cell distribution width were analyzsed by fluorescence flow cytometry (XN-2000; Sysmex Corp., Kobe, Japan).
ELISA analysis
The CD163 protein of all samples was analyzsed by the sandwich ELISA method in the Synergy HTX BioTek instrument (Biotek Instruments, Inc., Vermont, USA) using the SUNLONG brand CD163 ELISA kit (catalogue number: SL2931Hu). The intra-assay coefficient of variability (CV) of the kit is <10%, and the inter-assay CV is 12%.
Statistical analysis
Patients’ age, sex, vital signs, medical history (chronic diseases), medication use, haemogram and biochemical parameters were recorded to calculate the Glasgow-–Blatchford score. In addition, endoscopy results were calculated and recorded using the Forrest scoring system. Especially, the CD163 levels were recorded.
Statistical analyses were completed in two study groups: the patient group (patients with upper GI bleeding) and the control group. The data were analyzsed using the SPSS Statistics 26.0 (IBM Inc., New York, USA). We present continuous variables as mean, standard deviation and median (Q1–Q3) values, and categorical variables as numbers (percentages). For the pairwise comparison of non-normally distributed continuous variables, we used Pearson’s chi-square test. The relationship between numerical variables was determined by Spearman’s correlation analysis. We also conducted receiver operating characteristic (ROC) analyses and identified the area under the curve values. Furthermore, the sensitivity, specificity and positive and negative predictive values (PPV and NPV, respectively) of sCD163 were determined by calculating the sCD163 cut-off value, and then compared between the Glasgow-–Blatchford and Forrest scoring systems. A p- value of <0.05 was considered statistically significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Out of 75 included participants, 41 were patients with upper GI bleeding, and 34 were healthy volunteers. The patient group had more males than females (73.2% [n = 30] vs. 26.8% [n = 11]), whereas the healthy volunteer group had more females than males (61.8% [n = 21] vs. 38.2% [n = 13]). The mean age was 57.54 ± 2.99 years in the patient group and 45.50 ± 2.79 years in the healthy volunteer group, showing a statistically significant difference (p < 0.05). The distribution of endoscopy results by sex showed no statistically significant difference. Moreover, 9.8% (n = 4) of participants in the patient group demonstrated normal endoscopy results. Table 1 shows the demographics of the included participants and the sex distribution of the endoscopy results.
Table 1 shows the distribution of patient history and medication use history by sex. The distribution of patient history characteristics by sex showed no statistically significant difference. In the patient group, 75.6% (n = 31) had no history of chronic disease, and only 7.3% (n = 3) had GI bleeding history. In addition, 53.7% (n = 22) had a history of taking non-steroidal anti-inflammatory drugs (NSAIDs), and 31.7% (n = 13) had a history of taking anticoagulants.
Table 1 shows the distribution of the patient group’s complaints by sex. The main complaint was melena (80% [n = 33]), followed by bloody vomiting (68.3% [n = 28]). Other complaints were hematochezia (2.4% [n = 1]), epigastric pain (2.4% [n = 1]) and syncope (2.4% [n = 1]).
Table 2 shows the minimum, maximum and mean laboratory values of the patient group. The minimum haemoglobin value was 4.20 g/dL, whereas the maximum was 14 g/dL, obtaining a mean haemoglobin value of 9.21 g/dL. Furthermore, the minimum WBC count was 2.67 103/mm3, whereas the maximum was 22.15 103/mm3. Thus, the mean WBC value of the patient group was 10.74 103/mm3.
In the patient group, the Glasgow-–Blatchford score and sCD163 values demonstrated no statistically significant difference between patients with and without bleeding findings. Those with an endoscopy result of Forrest score of 3 and normal were included in the group without bleeding. Bleeding signs were found in 24 patients, and none in 17 patients. The mean Glasgow-–Blatchford score of patients without bleeding was 12, which was higher than that of patients with bleeding findings. Although the Glasgow-–Blatchford score is clinically very useful, no correlation was found between patients with high scores and those with bleeding rates detected at endoscopy. Table 2 shows the bleeding findings and the values of the Glasgow-–Blatchford score and the sCD163 marker.
Moreover, the patient group had higher sCD163 levels than the healthy volunteer group, showing a statistically significant difference (p < 0.05) (Table 2).
Figure 1 shows the ROC analysis of the sensitivity and specificity of sCD163. Sensitivity, specificity, PPV and NPV were examined by calculating the cut-off value of sCD163 as a diagnostic marker in the examination conducted with ROC analysis. The sensitivity, specificity, PPV and NPV were 78.05%, 55.88%, 68.09% and 67.86%, respectively (Table 3). After the sCD163 results were found to be significantly different between the control group and those with and without bleeding findings, ROC and regression analyses were conducted for diagnosis confirmation. Although the difference was not significant in the regression analysis, each unit increase in sCD163 increased the bleeding risk by 1.7 times (odds ratio) (Table 3).
Discussion
In the United States, 300,000 patients are hospitalizsed yearly for upper GI bleeding. In addition, 100,000 to 150,000 patients develop upper GI bleeding during hospitalizsation [7]. Many scoring methods and guidelines are available for the diagnosis and treatment of upper GI bleeding. However, emergency medicine physicians need tools to decide between outpatient follow-up and safe discharge and between the requirement of endoscopy and observation in the emergency department.
In some studies, upper GI bleeding was more common in males than in females, and the mean age of all patients was 51-–77 years [8]. Fugarolas et al. investigated 3270 patients, and the mean age was 57 ± 16.8 years; additionally, studies conducted by Zimmerman et al. respectively [9-10]. In the present study, upper GI bleeding was also more common in males, with a mean age of 57.54 ± 2.99 years.
In patients who are diagnosed with upper GI bleeding and admitted to the emergency department, melena is generally the most common symptom on admission [11]. Lewis et al. also reported melena as the most common complaint (48%) [12]. Our study found that 80.5% of those in the patient group presented with melena and 68.3% presented with hematemesis. Thus, in our study, where some patients had more than one symptom, melena was the most common, followed by hematemesis, consistent with previous studies.
Drug use is one of the most important predisposing factors for upper GI bleeding [13]. In our study, 92.7% of those in the patient group had a history of medications that can cause upper GI bleeding, and we found NSAIDs to be the most commonly used (53.7%). In the study by Paspatis et al., 49% of patients with upper GI bleeding used NSAIDs [13]. In Turkey, Sezgin et al. found that the rate of NSAID use was 44.3% [14]. These previous results are consistent with our results.
In a study by Cheng et al. [15] Aas causes of upper GI bleeding, gastric ulcers accounted for 22% in Cheng et al.’s study, [15]. In our study, all patients from the patient group underwent endoscopy, and ulcers were detected in 90.2%. In a study by Sugawa et al., the causes of upper GI bleeding were gastric ulcer (33%), erosive gastritis (24%) and oesophageal varices (22%) [16]. Lakhwani et al. reported an incidence of peptic ulcer of 61.7% 61.7% as the rate of peptic ulcer [17]. Our study also reported peptic ulcers as the most common cause of upper GI bleeding, consistent with the literature [18].
According to Gross et al., the prevalence of ulcers by the Forrest scoring system was 18% for Forrest score 1a, 17% for 2a, 17% for 2b, 20% for 2c and 42% for 3 [19]. In Ozen et al.’s study, 3.7%, 8.9%, 10.2%, 10%, 2.3% and 64.9% of patients with bleeding ulcer had Forrest scores of 1a, 1b, 2a, 2b, 2c and 3, respectively [20]. In Cander et al.’s study, the most frequent bleeding was found in Forrest score 3, with a rate of 70% [21]. Our study identified Forrest score 3 in 31.7% of endoscopies, consistent with the previous studies. Additionally, 22% and 14.6% had Forrest scores 1b and 1a, respectively. We think that treatments used for patients until endoscopy prevent the detection of active bleeding findings.
Identifying patients’ haemoglobin level upon admission is critical for the treatment, follow-up, and prognosis of upper GI bleeding. In Kocoglu et al.’s study, the initial haemoglobin levels were within 3-–18.5 g/dL, with a mean value of 9.65 ± 2.73 g/dL [22]. In oOur study,’s the mean haemoglobin value was 9.21 ± 2.32 g/dL, consistent with the previous study. Bleeding severity, anaemia presence before bleeding and prolonged hospital stay are effective on the entry haemoglobin level [22].
Compared with other scoring systems, the Glasgow-–Blatchford scoring system is more useful in predicting the need for endoscopic treatment, clinical intervention and surgery for upper GI bleeding [23]. In our study, the Glasgow-–Blatchford scores and sCD163 mean scores were calculated according to the bleeding findings of the patient group. Waidmann et al. reported that the sCD163 level is a new independent non-invasive risk factor for death and variceal bleeding in patients with cirrhosis [24]. In a 2017 study, Fouad et al. followed up 243 patients with cirrhosis for 1 year and found that the sCD163 levels were significantly higher in patients with re-bleeding, large varicose veins or high bleeding risk. In a previous study, sCD163 correlated with hepatic venous pressure gradient and contributed to portal hypertension prediction [25]. We also investigated the level of sCD163 in patients with non-variceal upper GI bleeding and found statistical significance in the patient group compared with the healthy group.
Considering that sCD163 acts as a scavenger receptor responsible for haemoglobin sequestration, O’Reilly et al. perceived that the sCD163 levels in serum and cerebrospinal fluid in patients with intracranial haemorrhage can be used as a marker to predict poor prognosis after intracranial bleeding, peri-haematomal oedema and intracranial haemorrhage [6].
Our study has several limitations. First, in this study, patients with upper GI bleeding had chronic diseases. Although sCD163 is responsible for sequestering haemoglobin, its levels markedly increase during the inflammatory process because it is expressed in macrophages. Although people with no signs of additional illness or complaints were included in the healthy volunteer group, an inflammatory condition might have been present. Other limitations of the study include the small sample size and single-centere design.
In conclusion, although clinical intervention is critical in upper GI bleeding, early detection and prediction of the clinical course can promote early intervention and help reduce mortality. According to our study results, sCD163 may be a useful biomarker for the diagnosis of upper GI bleeding and the identification of the clinical process.
Conclusion and Limitation
sCD163 may be a useful biomarker for diagnosing upper gastrointestinal bleeding and identifying the clinical 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
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.21697
Melis Dorter, Utku Murat Kalafat, Busra Bildik, Doganay Can, Serkan Dogan, Kader Irak, Basar Cander, Ramazan Guven. Diagnostic and prognostic value of sCD163 levels in upper gastrointestinal bleeding. Ann Clin Anal Med 2023;14(11):971-975
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An outbreak of septic arthritis after arthroscopic reconstruction of the anterior cruciate ligament
Güliz Evik 1, Gülcan Türkmen 2, Fatma Bozdağ 3, Mehmet Çolak 4, Gülden Ersöz 5
1 Department of Infectious Diseases, Faculty of Medicine, Mersin University, 2 Department of Nursing, Mersin University Hospital, 3 Department of Public Health, Faculty of Medicine, Mersin University, 4 Department of Orthopaedics and Traumatology, Faculty of Medicine, Mersin University, 5 Department of Infectious Diseases, Faculty of Medicine, Mersin University, Mersin, Turkey
DOI: 10.4328/ACAM.21699 Received: 2023-03-22 Accepted: 2023-05-05 Published Online: 2023-08-05 Printed: 2023-11-01 Ann Clin Anal Med 2023;14(11):976-980
Corresponding Author: Güliz Evik, Department of Infectious Diseases, Faculty of Medicine, Mersin University, 33343, Mersin, Turkey. E-mail: gulizevik@gmail.com P: +90 536 557 09 33 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2125-3536
This study was approved by the Clinical Research Ethics Committee of Mersin University (Date: 2022-02-23, No: 148)
Aim: Acute septic arthritis after arthroscopic posterior cruciate ligament (PCL) reconstruction is uncommon but is a very critical complication. Properly sterilized surgical instruments are the most important step in preventing infection. After arthroscopic anterior cruciate ligament surgery, a cluster of 6 joint-bursa infection cases was seen in our unit. The aim of this study was to determine the socio-demographic and clinical practices that may be associated with the development of infection in the surgical site after arthroscopic cruciate ligament surgery.
Material and Methods: This was a cross-sectional study of SSIs developing after arthroscopic anterior cruciate ligament surgery in 2018 in a University Hospital. Environmental and surgical equipment samples were taken. ATP bioluminescence test was performed on these samples. When a high-risk status was detected, surveillance cultures were performed.
Results: A total of 15 procedures meeting the inclusion and exclusion criteria were evaluated. Six patients were considered to have infections, while 9 were infection-free. An examination of the surgery lists showed that 6 of the 7 patients with infection represented the first arthroscopic procedure of the day. An inquiry regarding personnel of the surgery room showed that a newly appointed nurse made a modification in the decontamination procedure of the surgical equipment.
Discussion: Incomplete sterilization of surgical equipment and environmental contamination can lead to serious infection.
Keywords: Arthroscopic Surgery, Anterior Cruciate Ligament, Septic Arthritis, Outbreak
Introduction
Infections represent a rare complication following arthroscopic anterior cruciate ligament reconstruction, with a reported incidence between 0.15% and 0.45% [1-4].
Despite these low incidence rates, early recognition of these infections has considerable clinical significance, as they may lead to severe and irreversible consequences such as graft and hyaline cartilage loss as well as arthrofibrosis. Thus, prompt initiation of treatment is essential [5].
Although septic arthritis is generally a sporadic event following arthroscopic surgery, several case series and outbreaks have been reported [6-8].
Current orthopedic practice requires the sterilization of reusable devices (critical devices) with traditional methods and the documentation of compliance with standards with respect to all decontamination steps as well as cleansing and disinfection procedures prior to sterilization. According to the disinfection and sterilization guidelines in healthcare facilities, the main sources of surgical site infections (CAE) include inadequate decontamination and microorganisms that survive in a biofilm layer that cannot be removed from the surface of surgical equipment. (available at: https://stacks.cdc.gov/view/cdc/47378)
The high percentage of compliance with manual standard applications for the use of reusable medical devices can help hospitals minimize the risk of transmitting pathogens to medical devices [10].
Orthopedic surgery requires a highly sterile environment to prevent joint infection. Ensuring that surgical instruments are sterilized is of great importance in preventing post-operative surgical infection. Although septic arthritis is relatively rare after anterior cruciate ligament reconstruction, orthopedic surgeons are likely to encounter difficult-to-treat patients.
In this study, a clustering of infections of the articular-bursa following arthroscopic anterior cruciate ligament surgery in our unit has been assessed in light of the literature.
Material and Methods
Epidemiological Investigation
This was a cross-sectional study of SSIs developing after arthroscopic anterior cruciate ligament surgery between 1 July and 31 August 2018 in a University Hospital setting. The study was approved by the Mersin University Clinical Research Ethics Committee. Due to the retrospective nature of the study, informed consent was waived. Patients over 18 years of age and undergoing elective arthroscopic cruciate ligament surgery were included. Exclusion criteria were additional procedures other than arthroscopic surgery, history of trauma or surgery within the past month, prosthetic surgery within the past year, and age under 18 years.
The dependent variable of the study was infection at the site of surgery after arthroscopic cruciate ligament surgery, while the independent variables were age, gender, room of surgery, duration of surgery, the surgeon performing the procedure, as well as the number of patient’s procedure on the daily surgery list and the number of patient’s procedure in the daily arthroscopy list.
Study data were statistically analyzed in a computer environment. Data were summarized using descriptive statistics (mean, standard deviation, minimum and maximum). Comparison between categorical variables was performed using the chi-square test, while Fisher’s exact test was used when any of the values were below five in the table. The significance of the continuous and categorical variables was investigated with the Mann-Whitney U test. A p-value of less than 0.05 was considered statistically significant.
Investigation of the outbreak
Procedures prior to and following arthroscopic surgery were subjected to a comprehensive examination in order to identify the source of infection. Surgery room, surgical sets utilized, and sterilization steps of the arthroscopic devices were assessed. Samples for microbiological cultures were obtained from all potential areas of contamination. ATP bioluminescence test was performed on the samples obtained from the surroundings such as trocars, shaver tips, set clamps, surgical stretchers, anesthesia table, computer keyboards, and mobile phones in addition to inside and outside of sterile instrument packages of the material company. When a high-risk status was detected, surveillance cultures were performed. Also, the medical personnel and their activities within the surgical environment have been observed with respect to potential risky behaviors.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Epidemiological results
Patients undergoing arthroscopic cruciate ligament surgery in a university hospital between July and September 2018 were examined. A total of 15 procedures meeting the inclusion and exclusion criteria were evaluated.
Thirteen cases (86.7%) were male and 2 (13.3%) were female, and the mean age of participants was 26.07 ± 8.51 years (min: 18, max:41). All patients underwent cruciate ligament surgery. Of these cases, 8 (53.3%) were operated in the first orthopedic surgery room, while 2 (13.4%) were operated in the second orthopedic surgery room, and others were operated in other surgical rooms (neurosurgery 1, cardiovascular surgery 1, gynecology 1, algology 2). The mean duration of surgery was 64.93 ± 17.55 minutes (min: 40, max: 105). Two procedures (13.3%) were performed by Surgeon A, 11 (73.4%) by Surgeon B, and 2 (13.3%) by Surgeon C. Ten patients (66.7%) were first on the surgery list, while 2 (13.3%) were second, 2 (13.3%) were fifth, and one (6.7%) was seventh on the surgery list. Twelve (80.0%) patients underwent the first arthroscopy on that day, and 3 (20.0%) had the second. Table 1 shows the data for the two groups.
Among patients presenting with knee pain after surgery, a microbiological sample was obtained from the knee joint in three that showed the growth of Enterobacter aerogenes in all three (resistant to amoxicillin clavulanic acid and ampicillin), Klebsiella oxytoca (resistant to amoxicillin clavulanic acid, cefoxitin, and ampicillin) in one, and methicillin-susceptible coagulase-negative staphylococcus. In the other three patients presenting with pain, erythrocyte sedimentation rate (ESR) was 43 mm/hr, 41 mm/hr, and 45 mm/hr; c-reactive protein (CRP) was 155.8mg/dl, 129.0 mg/dl, and 65.86 mg/dl, and white blood cell count (WBC) was 8.08/mm3, 14.20/mm3, and 12.22/mm3, respectively. ESR in two of the other nine operated patients was 4 mm/hr and 17 mm/hr, respectively; no post-surgery laboratory data were available in the remaining 7 patients. These subjects were contacted by phone calls and reported no symptoms. Thus, 6 patients were considered to have infections, while 9 were infection-free.
No significant association between age and infection was observed (z=-0.59, p=0.95), as was the case for the duration of surgery and infection (z=-0.932, p=0.35).
Results of the Outbreak Analysis
An examination of the surgery lists showed that 6 of the 7 patients with infection represented the first arthroscopic procedure of the day. An inquiry regarding personnel of the surgery room showed that a newly appointed nurse made a modification in the decontamination procedure of the surgical equipment, which involved sole rinsing with water and prolonged exposure to external surrounding conditions. Also, high concentrations of disinfectants were used for the sterilization procedure of the arthroscopy devices. There was no growth in samples obtained from surgical equipment and the surgery room, while E. aerogenes was isolated from the tip of the shaver. Also, no growth occurred in samples from solutions.
Table 2 shows the organisms isolated and sites of isolation in previous studies.
Discussion
Among the orthopedic procedures, hip and knee implantation surgeries are frequently performed and should be prospectively followed up with regard to surgical site infections (SSIs), as they represent major surgical operations. However, the requirement to follow the possible occurrence of SSIs prospectively is frequently overlooked in arthroscopic procedures due to the low risk of infections, leading to retrospective assessments when such infections are observed in a particular surgery unit.
Although septic arthritis is a rare occurrence following anterior cruciate ligament repair, it may lead to serious complications such as graft failure or arthro-fibrosis [1].
Infections after anterior cruciate ligament repair may arise due to a number of different causes. Reported risk factors for septic arthritis include previous surgery on the operated knee, prolonged surgery, extensive incisions, inflammation due to prolonged tourniquet application, foreign body effect due to sutures, and use of graft material [10,11].
Other potential risk factors include the use of intra-articular steroids [12].
Furthermore, failure to perform effective sterilization of surgical equipment, environmental contaminants, and noncompliance to surgery room requirements (open doors, excessive number and mobility of the personnel) facilitate the development of SSIs [13,14].
Arthroscopy devices are considered critical equipment and should be sterilized according to the recommendations of the manufacturer. Currently, most arthroscopy devices are sterilized at 134 ℃ using autoclaves. However, sterilization is performed after completing the essential steps of washing and disinfection. At this point, although ultrasonic cleansing devices are not used for the optical parts due to potential harm, they are utilized for cleaning the cannula. This step requires not only mechanical cleaning, but also the use of enzymatic solutions and disinfectants. One alternative to heat autoclaves is the use of low-heat ethylene oxide or hydrogen-peroxide gas autoclaves, although no recommendations have been provided by manufacturers. Another option is chemical sterilization, which may provide adequate sterilization with the use of high- level disinfectants such as glutaraldehyde or peracetic acid when used in the context of appropriate conditions, heat and duration [15].
Observations performed during the study showed that chemical sterilization was performed in the surgery room to avoid harm during the transfer and sterilization of optical devices and the accompanying cannula, although the surroundings were not suitable for such procedures leading to certain setbacks. The distinction between clean and dirty areas was not clearly defined, no enzymatic agents were used, and an adequate sterilization heat was not achieved despite the use of peracetic acid. In fact, the failure to detect these setbacks and to implement the required arrangements was mainly due to inadequate training and knowledge on the part of the personnel.
Investigations involving similar infections showed bacterial contamination in the samples obtained from preparatory areas. For instance, Blevins et al. reported contamination in the cannula and growth of MSSA [7]. In another study, pseudomonas was isolated from ECG probe samples [16].
In a previous study on outbreaks after arthroscopic procedures, the source of the infection was the biological load remaining in the lumen of the arthroscopic equipment. In the article by Pritish K. et al., the outbreak was found to result from tissue remnants in the arthroscopic inflow and outflow cannula as well as in the tip of the shaver due to inadequate decontamination prior to re-use [7].
Coagulase-negative staphylococci and Staphylococcus aureus represent the most common causes of septic arthritis after arthroscopic procedures. The source of contamination is very difficult or impossible to detect, since these organisms are part of the skin flora [1,11,16-19].
A review of the 11 publications examining the types of microorganisms, choice of grafting, and treatment protocols in septic arthritis cases after arthroscopic anterior cruciate ligament repair showed microbial growth in 94% of the subjects, 70% of which were due to Staphylococcus aureus and coagulase negative staphylococci [20].
However, in another outbreak report, Pritish K. et al. isolated Pseudomonas aeruginosa in their 7-case series [7].
The cases reported herein were also considered to represent an outbreak. In three of the seven patients, Enterobacter aerogenes was isolated in the joint fluid, while this was accompanied by coagulase negative staphylococci (CNS) in one case, and only CNS was isolated from another patient.
Although several causative pathogens were isolated and the source of infection was identified in our study, certain limitations should be mentioned. Since patients were not followed up in the hospital, some cases might have been unnoticed due to failure to contact with phone calls or due to mild symptomatology. Also, joint fluid sampling could not be performed in all cases, and also sampling was made only after initiation of antibiotics in some others, leading to failure to detect microbial growth. Furthermore, no genotypic comparisons could be made, since the study was retrospective in design and collected samples could not be saved; thus, only phenotypic characteristics such as antibiotic susceptibility and microbial identity could be assessed.
Limitations
The study was based on the examination of patients’ medical records. The inability to retrieve postoperative laboratory results in all patients was one of the limitations of our study. Also, the nurses’ surgery notes could not be evaluated as they could not be recorded.
Conclusion
Cleaning of medical devices is in line with standard practices, as it significantly reduces the bioburden on the surfaces of medical devices, it can be one of the most important steps for the reuse of medical devices and the prevention of outbreaks.
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.21699
Güliz Evik, Gülcan Türkmen, Fatma Bozdağ, Mehmet Çolak, Gülden Ersöz. An outbreak of septic arthritis after arthroscopic reconstruction of the anterior cruciate ligament. Ann Clin Anal Med 2023;14(11):976-980
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Clinicopathological roles of Vasobin-2 in colorectal cancers
Suat Benek 1, Ayşegül İsal Arslan 2, Kasım Çağlayan 3, Mehmet Zengin 1, Fatih Rüştü Polat 1, Tamer Sağıroğlu 1
1 Department of General Surgery, Faculty of Medicine, Tekirdağ Namık Kemal University, Tekirdağ, 2 Department of Pathology, Faculty of Medicine, Tekirdağ Namık Kemal University, Tekirdağ, 3 Department of Pathology, Ankara Training and Research Hospital, Ankara, Turkey
DOI: 10.4328/ACAM.21705 Received: 2023-03-29 Accepted: 2023-06-21 Published Online: 2023-08-03 Printed: 2023-11-01 Ann Clin Anal Med 2023;14(11):981-985
Corresponding Author: Suat Benek, Department of General Surgery, Faculty of Medicine, Tekirdağ Namık Kemal University, Tekirdağ, Turkey. E-mail: cerrahsbenek@gmail.com P: +90 507 559 88 09 Corresponding Author ORCID ID: https://orcid.org/0000-0003-0774-7695
This study was approved by the Ethics Committee of Tekirdağ Namık Kemal University (Date: 2021-04-27, No: 2021.123.04.18)
Aim: Vasohibin-2(VASH2) is a pro-angiogenic molecule synthesized from mononuclear cells. The biological characteristics of colorectal cancer (CRC) cells and their microenvironment are not known yet. In the present study, the purpose was to investigate the clinicopathological roles of VASH2 in colorectal cancers.
Material and Methods: Three-micron sections were made for Immunohistochemistry (IHC) Analysis of the paraffin block tissues of 159 patients who underwent curative surgery for CRC. Immunohistochemical staining was performed with anti-CD34 and anti-D2-40’ and anti-Vasohibin-2 antibodies as lymphatic vessel markers on vascular endothelial cells. The density of newly formed vessels in the peripheral stroma of the tumor with CD34 and D240 and the presence of VASH-2 were investigated in these vessels.
Results: It was determined in the relationship analysis of the variables that VASH2 positivity showed a positive relationship with tumor diameter (p<0.05). No significant relationships were detected with other prognostic factors. Advanced age, perineural invasion (PNI), and pathological stage were the parameters that predicted survival in the Cox Regression Analysis, in which many variables were included (p<0.05), and VASH2 positivity showed negative predictive characteristics together with CD 34 positivity (p<0.05). No relationship was detected between VASH2 expression levels and CD34 and D-240 in cancer stroma and paracancerous tissue. VASH2 expression was significantly lower in cancer stroma and VASH2, CD34, and D-240 levels were higher in paracancerous tissue; however, no relationship was detected in this respect.
Discussion: In the present study, a significant relationship was detected between VASH2 and tumor diameter. However, no statistically significant differences associated with prognosis were detected. Further studies of its other roles in the tumor microenvironment as well as the pro-angiogenic characteristics of VASH2 will help to reveal the effects of this molecule in cancer angiogenesis.
Keywords: Angiogenesis Stimulating Agents, Endothelial Cells, Immunohistochemistry, Vasohibin
Introduction
Colorectal cancer is the third most common cancer on a worldwide scale and is the second most common cause of cancer-related mortality [1]. Several hereditary and somatic mutations play roles in its development. It is generally diagnosed at an advanced stage, and only 10% of newly diagnosed cases are in the early stage [2]. In the past decade, colorectal cancer-related mortality has increased in all age groups [3]. It is estimated that 25% of newly diagnosed rectal cancers and 10-12% of colon cancers will be diagnosed under the age of 50 in the next decade [4]. Recurrence occurs in 30-50% of patients after curative treatments, and survival rates decrease in this group [5]. Its prognosis is determined according to the TNM Staging System that was established by the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC). Aside from the stage of the disease, other parameters such as biological behavior of the tumor, biomarkers, neoadjuvant or adjuvant oncological treatment preferences, and various risk factors play a role in survival. Histological characteristics such as tumor budding, perineural and lymphovascular invasion, apical lymph node invasion, lymph node involvement rate, molecular markers such as BRAF, MSI, KRAS, CDX2, and the compliance of patients with the treatment play roles in the process.
Angiogenesis is the process of the regeneration of the blood vessels in the pre-existing vascular bed, which takes place physiologically during wound healing, reproduction, and development. It is pathological in the formation of cancer. Neovascularization is required for metastasis and tumor growth. Tumors develop varying degrees of angiogenic phenotypes depending on genetic background and catalysis of the local factors such as hypoxia. The balance between oncogenes and tumor suppressor genes determines the direction of the angiogenesis process. The regulation of angiogenesis occurs between tumor cells, endothelial cells, stromal cells, and inflammatory cells with the help of inhibitory/stimulatory factors [6]. Folkman was the first author to describe and show the presence of a proangiogenic factor [7]. Many proangiogenic and antiangiogenic factors have been described so far, the most prominent among which is Vascular Endothelial Growth Factor, which is induced by hypoxia and various growth factors and cytokines (e.g., EGF, PDGF, TNF-α, TGFβ, interleukin-1β). VEGF, on the other hand, increases vascular permeability and endothelial cell proliferation inducing tube formation and providing secretion of proteolytic enzymes (e.g., plasminogen activator receptor, urokinase, uPA, and MMP1) from vascular endothelial cells. It is effective in the regulation of vascular blood flow with its effects on nitric oxide release. The lymphogenesis process is regulated by the VEGF family. Previous experimental studies have shown that VEGF-C and VEGF-D increase tumor lymphangiogenesis and metastasis process over the lymphatic pathway [8,9]. Secreted by endothelial cells as a result of VEGF stimulus, the Vasohibin 1 (VASH1) molecule, which was described by Sato, also shows antiangiogenesis activity [10]. As another member of the same family and synthesized by bone marrow-derived infiltrative mononuclear cells, Vasohibin 2 (VASH2) stimulates angiogenesis and is also involved in the regulation of the synthesis of FGF 2 and VEGF, which are the main stimulators of VASH1 production. The hypoxic environment results in the expression of hypoxia-inducible Factor 1a via VEGF secreted by all tumor cells. Hypoxia reduces the inducible effects of VEGF on Vasohibin. In vivo studies showed that the Vasohibin family plays roles in many cancer types concerning microvessel density, histological grade, vascular invasion, poor clinical characteristics, metastasis, and spread in the abdominal cavity [11].
In the group of colorectal cancer patients included in the current study, the purpose was to investigate the effectiveness of the VASH2 Family in terms of tumor size, disease stage, metastasis, tumoral histological characteristics, survival, and prognosis.
Material and Methods
The study included 192 patients who underwent colorectal resection because of colon and rectal adenocarcinoma in Tekirdağ Namık Kemal University Medical Faculty Hospital General Surgery Clinic between 2013 and 2021. Clinical and follow-up data of the patients were obtained by retrospective scanning of data files. The data on the age, gender, tumor diameter, presence of metastases, and life expectancy of the patients were obtained from the files. The pathology preparations of these 192 patients were removed from the archives and evaluated again by the pathologist using an Olympus Bx46 brand Light Microscope, and appropriate tumor blocks without necrosis and bleeding were determined. Tumor blocks of 159 patients were retrieved from the pathology block archives and included in the study.
Immunohistochemistry
Three-micron sections were made from paraffin block tissues of these 159 patients for immunohistochemistry analysis. The sections were taken on slides with a positive charge and were deparaffinized with xylol for 15 minutes after waiting for one hour in an oven at 60°C. They were passed through decreasing alcohols and washed in distilled water for hydration. The slides were then placed in Benchmark XT brand device and anti-CD34 (Roche, QBEnd/10, USA) staining was made for vascular endothelial cells, anti-D2-40 (Roche, Mouse Monoclonal Antibody, USA) was used as lymphatic vessel marker, and anti-Vasohibin-2 (Merck, Clone 5E3 Mouse Monoclonal, Japan) was used as immunohistochemical staining method.
Immunohistochemistry evaluation
The slides were evaluated by the pathologist researcher by using a Bx46 Olympus brand Light Microscope, without knowing the clinical course of the patients. The areas where colon cancer cells came into contact with or penetrated the stroma were identified carefully. In the first step, microvessels were counted after scanning the immunostained area by looking for CD34-positive signals at x40 magnification under the light microscope. Locations with the most prominent microvessels were selected. Microvessel Density (MVD) was evaluated with Light Microscopy at×200 magnification in invasive tumor areas that contained the largest number of capillaries and small venules (neovascular spots) per 1 mm2 area according to the original method. The investigation of Lymphatic Vessel Density (LVD) was performed by using the same procedure described above, searching for D2-40-positive signals. Then, immunoreactive ratios were evaluated for Vasohibin2 in tumor peri-stroma microvessels and tumoral cells (Figure 1). The density of newly formed vessels in the peripheral stroma of the tumor with CD34 and D240 and the presence of Vasohibin2 were investigated in these vessels. Vasohibin positivity was noted in neoplastic cells in some of the cases, as seen in (E).
Statistical analysis
The distribution of numerical data was analyzed with the Shapiro-Wilk test. While Pearson’s test was used for the relationship between parametric data, the Spearman Test was preferred for data showing heterogeneous distribution. The Kaplan-Meier method was used for survival curves, and the survival effect of the variables was calculated with the proportional hazards model. A p-value below 0.05 was accepted for statistical significance. All analyzes were performed with SPSS v 22 for windows software.
Ethics committee approval:
This study was approved by Tekirdağ Namık Kemal University Health Research Ethics Committee ( No: 2021.123.04.18)
Results
Among the patients, 73 (38%) were female and 119 (62%) were male. The mean age was 65 years (23-89), mean tumor diameter was 49.4 mm (1-170). The majority of the patients were recto-sigmoid cancers (n:108 – 56.2%). Tumor localizations are summarized in Figure 2.
The number of patients who were metastatic at the time of diagnosis was found to be 25 (13%). Stage 3, Stage 2 and Stage 1 patients were 73 (38%), 59 (30.7%), and 35 (18.2%), respectively. All patients underwent curative surgery, however, 6 (3.1%) patients received hyperthermic intraperitoneal chemotherapy in addition to cytoreductive surgery (hipec). Grade 2 patients were in the majority (133-69.3%) in the postoperative histological examination. Although 48 (25%) patients had Grade 1 tumors, 11 (5.7%) patients had Grade 3 tumors. The LVI rate was 56.8% (109) and the PNI rate was 31.3% (60). A total of 123 (64%) of the patients survived as of 01.11.2022 and 69 (36%) of them died. The mean follow-up period was calculated as 32 (0-77) months. A mean of 16 (3-44) CD 34+ and a mean of 5 (1-20) D240+ vascular structures were counted at 40 magnification in the re-examination performed in 159 patients. VASH2 was not expressed in 18 (11.5%) patients. The mean number of VASH2-stained vascular structures was 3 (0-20).
In the relationship analysis of the variables, it was determined that VASH2 positivity showed a positive relationship with tumor diameter (p<0.05 cc: 0.198). However, no significant relationship was detected with prognostic factors such as age, stage, PNI, and LVI (Table 1).
Advanced age, PNI, and pathological stage were the parameters that predicted survival in the Cox Regression Analysis, in which many variables were included (p<0.05). VASH2 positivity showed negative predictive characteristics together with CD 34 positivity (p<0.05) (Table 2).
The cut-off value was calculated as 65.5 in the ROC curve drawn according to age (AOC: 0.631). The cut-off value for the clinical stage was determined as Stage 3C (AOC: 0.707). The age and clinical stage-dependent survival curves are summarized in Figure 3.
Discussion
VASH2 induces angiogenesis by triggering increased VEGF levels over HIF 1α under hypoxic conditions [10]. It consists of 355 amino acids, is 55% similar to VASH1, and is found in mononuclear cells rather than endothelial cells [11]. It can stimulate tumor cells to proliferate, migrate and infiltrate. With their decreased levels, the abnormality in the vascular structure improves, and tumor growth is suppressed. It also reduces p53 levels and shows anti-apoptosis activity by reducing Bax Expression [12,13]. In the study that was conducted by Liu et al., it was emphasized that the level of VASH1, which is another member of the same family, with antiangiogenetic characteristics, exhibited a negative relationship with tumor size and a positive relationship with the presence of advanced stage and distant metastases in colon cancer patients [14]. In the study conducted by Du et al., aside from the role they play in angiogenesis, it was reported to be effective in microvessel density, histological grade of tumor, level of invasion, poor clinical outcomes, rate of metastasis, and extent of tumor spread within the abdominal cavity [12]. VASH2 is mainly expressed in cancer cells and has a prognostic significance for most cancer types [15,16,17]. However, the evaluation of plasma concentrations of VASH1 and VASH2 is at low levels. It was considered that it would be beneficial to conduct a study to elucidate whether their routine use would be beneficial in clinical practice. In light of this information, in the present study, the interaction between VASH2 and tumor size, grade level, number of metastatic lymph nodes, lymphovascular and perineural invasion level, clinical stage, relationship with age and gender, tumor localization, and survival were investigated in patients who were diagnosed with colorectal cancer and whose treatment process was completed. Positive relationships were detected between tumor size and VASH2, which showed angiogenic activity (p=0.013). No significant relationships were detected between histological grade level (p=0.816), metastatic lymph node number (p=0.151), pathological stage (p=0.185), and other parameters. Although the rate of lymphovascular and perineural invasion of the tumor (CD 34 and D2-40 positivity rate) decreased with increasing age, it was remarkable that there were no significant changes in VASH2 levels. Gender differences did not cause any differences in VASH2 levels (p=0.730). The positive relationship between VASH2 and tumor size contributed to the literature data. No relationship was detected between the presence of the tumor in the colon or rectum and different localizations in the colon and the VASH2 levels (p=0.59). Considering the VASH2 angiogenesis activity, the expected relationship between lymphovascular invasion and the number of metastatic lymph nodes was not found to be significant in the current study. Also, no relationship was detected between VASH2 expression levels in cancer stroma and cancer tissue and CD34 and D-240. VASH2 expression was significantly lower in cancer stroma. VASH2, CD34, and D-240 levels were higher in the tissue around cancer, but no relationship was detected between VASH2, CD34, and D-240.
Takahashi et al. showed that, in serousovarian cancer, VASH2 expression is a poor prognostic factor [15]. It is already known that VASH2 is involved in the epithelial-mesenchymal transition because of regulating TGF-β signaling. It also plays important roles in tumor progression through stromal activation of cancer-associated fibroblasts [16]. As well as its pro-angiogenic activity, it probably has various other roles in the tumor microenvironment. The relationship between Vasohibin expression and disease prognosis was investigated in the pancreatic, liver, breast, and many other cancer types and has been shown in many previous studies [17-19]. It was suggested that VASH2 expression induces angiogenesis, and therefore, contributes to tumor growth [20,21]. It was observed in the current study that age, perineural invasion, and pathological stage were associated with poor prognosis, but not with VASH2 expression. Similarly, contrary to expectations, no relationship was detected between the stage of the disease and the metastatic disease.
The first limitation of the study was that it had a retrospective design. A total of 25 (13%) patients had metastases (Stage 4) at the time of diagnosis in the group, and 70% of the patients were histopathologically classified as Grade 2. Intra-abdominal spread rates were not assessed. Conditions such as abdominal aortic aneurysm, peripheral vascular disease, atherosclerosis, age-related macular degeneration, association with other malignancies (ovary, esophagus, pancreas, lung, stomach, breast, hepatocellular Ca, etc.), renal functions, which were shown to be associated with the Vasohibin family, could not be studied in the patient group [22-25]. Conducting a prospective study in a more homogeneous patient group will shed light on the questions that must be answered.
The present study showed that VASH2 has a significant relationship with tumor diameter, but not with other prognostic factors. To understand the accuracy of this, prospective studies on homogeneous patient groups with similar tumor stages are needed.
Conclusion
The expression of VASH2 in the cancer cell, cancer stroma, and the area around the cancerous tissue causes a prognostic difference. Effective studies are needed to understand the factors affectingthe expression and roles they play in the microenvironment. In this way, it will be understood whether it is a predictive factor for tumor prognosis 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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7. Folkman J, Merler E, Abernathy C, Williams G. Isolation of a tumor factor responsible for angiogenesis. J Exp Med. 1971;133(2):275-88.
8. Stacker SA, Achen MG, Jussila L, Baldwin ME, Alitalo K. Lymphangiogenesis and cancer metastasis. Nat Rev Cancer. 2002;2(8):573-83.
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10. Sato Y. The Vasohibin Family. Pharmaceuticals (Basel). 2010;3(2): 433-40.
11. Sato Y. The vasohibin family: a novel family for angiogenesis regulation. J Biochem. 2013;153(1):5-11.
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Suat Benek, Ayşegül İsal Arslan, Kasım Çağlayan, Mehmet Zengin, Fatih Rüştü Polat, Tamer Sağıroğlu. Clinicopathological roles of Vasobin-2 in colorectal cancers. Ann Clin Anal Med 2023;14(11):981-985
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Investigation of oxygen saturation levels in respiratory system diseases in the covid-19 pandemic
Gülbin Aydoğdu Umaç 1, Arife Erdogan 2, Fatma Ezgi Can 3
1 Department of Manisa Provincial Ambulance Service Chief Physician, Manisa, 2 Department of Emergency Medicine, Faculty of Medicine, Izmir Bakırçay University Cigli Regional Training Hospital, İzmir, 3 Department of Biostatistics, Faculty of Medicine, İzmir Katip Çelebi University, İzmir, Turkey
DOI: 10.4328/ACAM.21722 Received: 2023-04-10 Accepted: 2023-06-16 Published Online: 2023-07-03 Printed: 2023-11-01 Ann Clin Anal Med 2023;14(11):986-989
Corresponding Author: Arife Erdogan, Department of Emergency Medicine, Faculty of Medicine, Izmir Bakırçay University Cigli Regional Training Hospital, İzmir, Turkey. E-mail: arife.erdogan@yahoo.com P: +90 531 343 97 31 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2488-2012
This study was approved by the Ethics Committee of Izmir Bakircay Unıversity (Date: 2023-02-01, No: 869/849)
Aim: In the Covid-19 pandemic, it is seen that patients remain hypoxic in the long term and their SpO2 values decrease. The aim of this study was to evaluate the SpO2 levels in cases transported to the hospital by 112 ambulance and to investigate the correlation of the data results with respiratory system diseases and COPD patients, which is the group most frequently transported to the hospital.
Material and Methods: We examined the SpO2 values of patients who were transported by 112 emergency ambulance with shortness of breath during the long period of the pandemic. We examined 270,753 patients who were transported between March-September 2020, 2021, 2022. The patients were divided into two groups according to the degree of saturation: saturation between 86-90% and below 85%.
Results: We statistically analyzed the saturation levels of the patients by year and month. There was no statistically significant relationship in terms of the number of transported cases by years and months in patients with a saturation below 85% (p=0.908). There was a significant correlation between years and months in patients with 86-90% saturation (p=0.029). There was a statistically significant relationship between the saturation levels of the cases carried by years (p=0.017). In 2021-2022, the percentage of patients with both saturation below 85% and between 86-90% increased compared to 2020 (p=0.003; p=0.015).
Discussion: According to the results of the study, the low oxygen levels of the patients who were transported to the hospital with shortness of breath increased in the 1st and 2nd years compared to the beginning of the pandemic.
Keywords: Long COVID-19 Syndrome, Dyspnea, Hypoxemia, Pulse Oximetry
Introduction
Coronavirus Disease-2019” (COVID-19) has become an epidemic in a short time and become a global concern due to being an easily transmitted disease. Signs and symptoms seen in the acute phase of the coronavirus disease are now better defined. Among them, the most common are cough, shortness of breath, fever and sometimes acute respiratory distress [1]. More than 70% of COVID-19 survivors had a disorder in one or more organs 3 to 4 months after the first symptoms [2,3]. The symptoms seen in the long term after the acute illness were have been named “long haulers”, or patients living with “Chronic COVID syndrome”, “post-COVID-19 syndrome”, or “post-acute-COVID-19’’ [4,5].
In the long COVID-19 Syndrome, extensive symptoms such as shortness of breath, chronic cough, chest tightness, cognitive dysfunction, and extreme fatigue have been reported by recovering patients [6,7]. Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by progressive airflow limitation affecting more than 5% of the world’s population. Exacerbation attacks seen in the course of the disease cause worsening of the patient’s respiratory symptoms and change of medication. Tracheobronchial infections are the leading cause of COPD exacerbations. Most of these infections are caused by viral infections.
At the beginning of the pandemic, all pulmonologists worldwide expected that COPD patients would be hospitalized more frequently for exacerbations and pneumonia, and that mortality would be higher in these patients due to complications. However, COPD patients in the patient groups admitted to the hospital in the following days were not as high as expected [8,9]
It is also predicted that this expected height will appear in the coming years of COVID. The aim of this study was to evaluate the SpO2 levels in cases admitted to the hospital by 112 ambulances and to investigate the correlation of the data results with respiratory system diseases and COPD patients, which is the group most frequently transported to the hospital.
Material and Methods
Between March and September 2020, 2021, 2022, patients who were transported to the emergency services by ambulance with suspected COVID-19 and complaints of shortness of breath were examined. Specifically, the purpose of selecting these periods is to examine population-wide saturation levels that underlie prolonged COVID-19 symptoms, using data from the onset of the pandemic, 1 year and 2 years after onset. A total of 270,753 patients were reviewed retrospectively at the specified times.
Patients diagnosed with COPD, COPD attack, asthma attack, viral pneumonia, bacterial pneumonia, lower respiratory tract disease, bronchitis, bronchiolitis were examined. The patients were evaluated according to their saturation and divided into two groups: saturation between 86-90% and below 85%. Patients with a saturation SpO2 below 85% were considered to be severely hypoxic, and patients with an SpO2 between 86-90% were considered to be moderately hypoxic. In addition, we divided the months into two groups: March-April-May and June-July-August-September to examine whether there is a difference between the months. We looked at the statistical relationship between saturation levels among these groups. The purpose of selecting these periods was to look at data from the onset of the pandemic and at 1 and 2 years after onset to address population-wide saturation levels that underlie prolonged COVID-19 symptoms.
This study was approved by the Izmir Bakircay University Ethics Committee for Non-Interventional Clinical Trials (Approval no: 869/849) (2023/02-01).
Statistical analysis
Data were evaluated in the statistical package program IBM SPSS Statistics 25.0 (IBM Corp., Armonk, New York, USA). Descriptive statistics were presented as frequency (n) and percentage (%). The Cochran-Armitage test was used to determine the relationship between years and the number of admitted cases. A value of p<0.05 was considered statistically significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
In our study, 270.753 patients who were transported to the emergency room by ambulance with the complaint of shortness of breath were examined. The number of cases transported is shown in Table 1 according to months and years. There was no statistically significant relationship in terms of the number of cases transported by years and months in patients with saturation below 85% (p=0.908). There was a significant correlation between years and months in patients with 86-90% saturation (p=0.029). In 2021, the percentage of cases admitted in both March-April-May and June-July-August-September increased compared to 2020 (p<0.001). In 2022, the percentage of cases carried in March-April-May decreased compared to 2020. The percentage of cases admitted in June-July-August-September increased compared to 2020 (p=0.027). There was no significant relationship in terms of the number of admitted cases by month between 2021-2022 (p=0.144).
The saturation levels of the admitted cases by year are shown in Table 2. There was a statistically significant relationship between the saturation levels of the admitted cases by years (p=0.017). In 2021 and 2022, the percentage of patients with both saturation below 85% and between 86-90% increased compared to 2020 (p=0.003; p=0.015, respectively). There was no significant relationship between the years 2021-2022 in terms of the number of cases transported according to the saturation level (p=0.638).
Discussion
Severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) primarily targets the respiratory system, causing respiratory and multiorgan failure [10]. Dyspnea (shortness of breath) is an important clinical finding in respiratory system diseases [11,12]. Hypoxemia in COVID-19 is similar to community-acquired pneumonia or interstitial lung disease; it results from intrapulmonary shunts, loss of lung perfusion regulation, intravascular microthromboembolism, impaired diffusion capacity, and preservation of lung mechanics [13,14].
The pulse oximeter is placed on the skin, then the skin is illuminated and SaO2 is assessed by measuring changes in the light absorption of oxyhemoglobin and reduced Hb [15]. With pulse oximetry, patients’ arterial oxygen saturation levels and respiratory functions are measured non-invasively [16]. Oxygen saturation is a vital parameter used in the initial evaluation of patients in need of oxygen. It is now described as the 5th vital sign. It is one of the most important parameters used to evaluate the need and response of patients to oxygen therapy [17]. With pulse oximetry, which is an indicator of the adequacy of ventilation, the normal O2 value (SpO2) was found to be 95-100%. The classification of hypoxia according to pulse oximetry values is carried out as follows [18]: SpO2 95-100% Normal, SpO2 91-94% Mild hypoxia, SpO2 86-90% Moderate hypoxia, SpO2<85% Severe hypoxia.
According to studies, as with other respiratory diseases, COVID-19 patients, with oxygen saturation (SpO2)<85% in room air are at high risk [19,20]. Causes of hypoxia seen in COVID-19; Impairment of lung perfusion is caused by intrapulmonary shunts, microthromboembolism and impaired diffusion capacity [21,22]. “Silent” or “happy” hypoxemia, which is a feeling of disproportionate shortness of breath with low hypoxemia, is seen in other diseases of the respiratory system and COVID-19 disease. Although the mechanism of this silent hypoxemia is not fully understood, its rates are not fully known [23].
In this study, we examined the SpO2 levels of the patients who were transported by the 112 emergency ambulance with the complaint of shortness of breath. When we examined by years, it was found that the the number of patients who were transported with severe hypoxia and moderate hypoxia in the 1st and 2nd years of the pandemic was statistically significant compared to the number of patients transported at the beginning of the pandemic. Rahman et al. showed a decrease in SpO2 levels in their study [24].
When we examined patients with SpO2<85%, no significant difference was found in the number of cases according to months and years. It was observed that the number of patients with moderate hypoxia increased in the 1st year of the pandemic compared to the beginning of the pandemic, but decreased in the winter months of the 2nd year of the pandemic compared to the beginning of the pandemic.
We can attribute this to the fact that seasonal epidemics could not show the expected effect due to the COVID-19 epidemic and personal protective measures such as mask use, social distancing and hand hygiene. Similarly, studies have found that there is a significant decrease in pneumonia and shortness of breath complaints due to all other factors during the COVID-19 pandemic [23-25].
Through statistical analysis, we’ve observed a noteworthy rise in patients’ saturation levels during the initial two years of the pandemic. This pattern of increased saturation levels was evident in two distinct groups: one where saturation levels fell below 85%, and the other where levels ranged from 86% to 90%. Notably, this rising trend was not influenced by any specific months within these years, underscoring the fact that the increase was consistent throughout this period.
The primary objective of this research, as stated in the manuscript’s introduction, is to examine the saturation levels, which are critical to understanding long-term COVID-19 symptoms, such as shortness of breath. These symptoms often necessitate hospitalization. The data under consideration for this study spans from the initial emergence of the pandemic and continues through the first and second years following the outbreak.
In the 2nd year of the pandemic, we saw that the SpO2 levels of patients who were transported with 112 decreased significantly. In COVID-19 patients, the clinic can range from asymptomatic to severe pneumonia causing acute respiratory distress syndrome (ARDS). During this period, SpO2 monitoring with pulse oximetry is recommended for patients who are in the risk group, especially for silent hypoxia in prolonged COVID-19.
Study Limitations
The most important limitation of our study was that outpatient hospital admissions were not included in the study population.
Conclusion
According to the results of the study, the low oxygen levels of the patients who were transported to the hospital with shortness of breath increased in the 1st and 2nd years compared to the beginning of the pandemic.
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. Rubin R. As Their Numbers Grow, COVID-19 “Long Haulers” Stump Experts. JAMA. 2020; 324(14):1381-3.
5. Greenhalgh T, Knight M, A’Court C, Buxton M, Husain L. Management of post-acute covid-19 in primary care. BMJ. 2020; 370: m3026.
6. Venkatesan P. NICE guideline on long COVID. Lancet Respir Med. 2021; 9(2):129.
7. Lopez-Leon S, Wegman-Ostrosky T, Perelman C, Sepulveda R, Rebolledo PA, Cuapio A, et al. More than 50 long-term effects of COVID-19: a systematic review and meta-analysis. Sci Rep. 2021;11(1):16144.
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Download attachments: 10.4328.ACAM.21722
Gülbin Aydoğdu Umaç, Arife Erdogan, Fatma Ezgi Can. Investigation of oxygen saturation levels in respiratory system diseases in the covid-19 pandemic. Ann Clin Anal Med 2023;14(11):986-989
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Investigation of peripheral natural killer cell activity in recurrent miscarriages of unknown cause
Elnare Alyazova 1, Gulchin Babayeva 2, Mehmet Cengiz Çolakoğlu 2, Jule Eriç Horasanlı 2
1 Department of Gynecology and Obstetrics, Meram Faculty of Medicine, Medova Hospital, 2 Department of Gynecology and Obstetrics, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey
DOI: 10.4328/ACAM.21747 Received: 2023-05-02 Accepted: 2023-06-12 Published Online: 2023-07-04 Printed: 2023-11-01 Ann Clin Anal Med 2023;14(11):990-994
Corresponding Author: Jule Eriç Horasanlı, Department of Gynecology and Obstetrics, Meram Faculty of Medicine, Necmettin Erbakan University, Konya,Turkey. E-mail: juleesen@gmail.com P: +90 555 479 33 94 Corresponding Author ORCID ID: https://orcid.org/0000-0002-8738-7126
This study was approved by the Ethics Committee of Necmettin Erbakan University, Medical Faculty (Date: 2022-11-06, No: 2020/2889)
Aim: Recent studies on alloimmune factors have shown that Natural Killer (NK) cells may have a role in the implantation and maintenance of pregnancy. It is unclear precisely what kind of relationship exists between uterine and peripheral blood NK cells. Our study aims to investigate the relationship between pNK cells and recurrent pregnancy loss.
Material and Methods: Among the patients who applied to the outpatient clinic at University Hospital, retrospectively, women with two or more pregnancy losses constituted the RM group, and women with two or more live births and no miscarriage formed the control group. Two or more miscarriages before 20 weeks of gestation were accepted as the criterion to consider a case of recurrent pregnancy loss.
Results: To investigate the etiology of miscarriage in RM patients, parameters associated with the cytotoxicity of pNK cells in women with RM and control fertile women were evaluated. Although the median pNK activity level was relatively higher in the recurrent low group compared to the control group, there was no significant difference between the groups in our study (p=0.448).
Discussion: The present study found no significant difference in the percentages of CD56+dim and CD56+bright pNK cells between the patient group with unexplained RM and the healthy fertile control group. There was also no significant difference in CD8 and CD158a expressions in pNK cells between the patient group with unexplained RM and the healthy fertile control group.
Keywords: Peripheral Natural Killer Cell , Recurrent Miscarriages
Introduction
Recurrent miscarriage (RM) or recurrent pregnancy loss (RPL) is an early pregnancy complication affecting approximately 1-3% of couples of reproductive age. American Society for Reproductive Medicine (ASRM) defines RM as two or more spontaneous pregnancy losses, not necessarily consecutive, before the 20th week of pregnancy [1]. the European Society for Human Reproduction and Embryology (ESHRE) defines it as three or more consecutive pregnancy losses (not necessarily intrauterine) [2]. RM’s etiology includes coagulation system disorders, genetic disorders, anatomical factors, immunological causes, hormonal disorders, and environmental causes. Immunologic causes account for 20–50% of all recurrent pregnancy losses [3].
Recent studies on alloimmune factors have shown that Natural Killer (NK) cells may have a role in the implantation and maintenance of pregnancy. Since NK cells are the predominant leukocyte population in the endometrium during implantation and early pregnancy, the most extensive studies have been conducted on these cells. NK cells are divided into peripheral NK (pNK) and uterine NK (uNK) cells. Phenotypically, they are categorized into two types:
1-CD56 positive CD16 negative NK cells (referred to as CD56 bright)
2-CD56 positive CD16 positive NK cells (referred to as CD56 dim) [4].
In the peripheral blood, the main population of NK cells (90%) is CD56 dim cells. They are potent mediators of natural cytotoxicity and are more cytotoxic than other NK subsets. These cells are in direct contact with chorionic villi in the intermittent space, and the ability of the developing fetus to evade NK cytotoxicity from these cells may determine pregnancy outcome [6–8]. The cytotoxic CD56 dim subset has been reported to be up-regulated in the peripheral blood of women with RM compared to healthy fertile women [5-7]. Uterine NK (uNK) cells are predominantly CD56 bright CD16 cells. From a histological perspective, uNK cells are much more granulated than pNK and exhibit a greater immunomodulatory role than the pNK subset, which has potent cytolytic activity [8]. The origin of uterine NK cells is still unknown. Uterine NK cells are mainly CD56 bright CD16- cells with a more immunoregulatory role. Endometrial NK (eNK) cells represent one-third of total lymphocytes in the endometrium and may be involved in embryo implantation. Once pregnancy has occurred, decidual NK (dNK) cells become the predominant subset of lymphocytes in the uterus and contribute to the maintenance of the pregnancy [9].
NK cells can be classified as NK1 and NK2 based on their distinct cytokine production profiles. The NK1 type mainly produces IFN-γ and Tumor necrosis factor α (TNF-α), while the NK2 type primarily secretes IL-4, IL-5, IL-10, and IL-13. A shift from NK1 to NK2 profile has been documented to be necessary for healthy pregnancies [10]. Indeed, peripheral blood CD56 bright NK cells of women with a history of RM were found to have proportionally lower levels of IL-4 and IL-10 and higher levels of IFN-γ and TNF-α than healthy controls, indicating an increase in the NK1/NK2 ratio [11]. On the other hand, RM patients are thought to have a more active immune system balanced by the secretion of immunoregulatory cytokines compared to healthy women, while there is an increase in NK cells producing IFN-γ and immunosuppressive TGF-β and IL4 [7].
Some studies have shown that the CD8+ NK subset is more cytolytic than its CD8- NK counterpart. Besides, NK cells with higher CD8+ expression were suggested to be more active [12, 13]. However, other studies have shown that NK cytolytic activity is directly related to CD158 a/b in NK cells [14].
NK cell function in human reproduction is currently poorly understood. Studies have shown changes in the NK cell population in recurrent pregnancy loss and infertility. It is unclear precisely what kind of relationship exists between uterine and peripheral blood NK cells. Our study aims to investigate the relationship between pNK cells and recurrent pregnancy loss.
Material and Methods
Among the patients who applied to the outpatient clinic of Necmettin Erbakan University Meram Medical Faculty Hospital Gynecology and Obstetrics Clinic between January 2020 and January 2021, women with two or more pregnancy losses constituted the RM group and women with two or more live births and no miscarriage formed the control group. Two or more miscarriages before 20 weeks of gestation were accepted as a criterion to consider a case of recurrent pregnancy loss.
A total of 30 patients aged 20-40 years with recurrent pregnancy loss were included in the study. All women had a normal parental chromosome. All of them were negative for antiphospholipid antibodies (ANA, Anti DNA, Anticardiolipin-IgM, Anticardiolipin-IgG, Antiphospholipid-IgM, Antiphospholipid Ig-G), Anti Toxoplasma-IgM, Antirubella-IgM, hypothyroidism or hyperthyroidism (free T4 and TSH values were checked). All patients had a normal HSG, and none had cervical incompetence, which was checked with the No. 8 Hegar plug on day 26 of the menstrual cycle. None of the patients presented thrombophilia criteria (Antithrombin III deficiency, Protein C deficiency, Protein S deficiency, Factor V Leiden mutation, Prothrombin 2010 mutation, MTHFR 677 mutation, MTHFR 1298 mutation). Acar K, Management Of HIgh RIsk EssentIal Thrombocythemia In Pregnant WIth Recurrent Pregnancy Loss. Selcuk Medical Journal, 2009; 25. 3: 167-170. The control group consisted of 10 women between the ages of 20 and 40 who applied to the Necmettin Erbakan University Meram Medical Faculty Hospital Gynecology and Obstetrics Clinic and had two or more births and no history of pregnancy loss. Demographic and clinical characteristics of the participants were recorded at hospital admission. The patients included in the study were selected randomly according to the order of admission to the outpatient clinic. Those included in the control group were assigned by simple random sampling.
Blood samples of all RM and control groups were analyzed at the Microgen Genetic Diseases Diagnosis Center laboratory in Ankara. The ELISA method determined NK cell activity from peripheral blood samples with the NK VUE test kit. The reference range for the activated NK test was accepted as <1800 pg/ml.
Statistical analysis: For statistical analysis, all collected data were analyzed with the Statistical Package for the Social Sciences, version 20, SPSS Inc., Chicago, IL (SPSS). The Kolmogorov-Smirnov test and histograms determined the conformity of data to normal distribution. Normally distributed continuous variables were analyzed with the independent T-test, and non-normally distributed continuous variables were analyzed with the Mann-Whitney U test. The Chi-square test was used for categorical variables. The statistical significance value was determined as P ≤0.05.
Ethical Permit of the Study: Ethical approval was received from Necmettin Erbakan University, Medical Faculty, Ethics Committee (06.11.2022, Number: 2020/2889) before the study started. All participants provided electronic informed consent.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
A total of 40 women, including 30 patients who were admitted to the Necmettin Erbakan University Meram Medical Faculty Hospital Gynecology and Obstetrics Clinic between January 2019 and January 2020 and diagnosed with recurrent pregnancy loss, and 10 healthy fertile women who applied to the same clinic between the same dates, were included in the study.
The mean ages of the RM and control groups were not statistically different, 28.2±4.4 and 30.4±2.0, respectively (p=0.462). The mean number of pregnancies was 3 (3, 12) in the RM group and 3 (3, 4) in the control group, with no statistical difference between the two groups (p=0.101).
The median NK activity levels of the groups were not significantly different, with 2145 (264, 3900) in the RM group and 1380 (500, 4000) in the control group (p=0.662). The mean number of cases with high NK activity was 17 (56.7%) in the RM group and 5 (50%) in the control group. There was no statistical difference between the two groups (p=0.714).
The median percentiles of the CD56+CD16+ subgroup were 52.3 (23.7, 70.7) in the RM group and 49.6 (23.7, 66.7) in the control group. There was no statistical difference between the two groups (p=0.574). The median percentiles of the CD56+CD16- subgroup were 47.6 (29.2, 76.23) in the RM group and 50.3 (33.2, 76.2) in the control group. There was no statistical difference between the two groups (p=0.563). (Figure 1)
The median percentiles of the CD8+ subgroup were 27.4 (1.32, 45.52) in the RM group and 24.61 (8.66, 36.10) in the control group. There was no statistical difference between the two groups (p=0.743). The median percentiles of the CD158a+ subgroup were 10.52 (2.75, 53.40) in the RM group and 9.48 (2.75, 40.21) in the control group. There was no statistical difference between the two groups (p=0.662).
The median percentiles of the CD158-CD8- subgroup were 53.58 (0.47, 75.58) in the RM group and 57.06 (31.68, 75.58) in the control group. There was no statistical difference between the two groups (p= 0.217). The median percentiles of the CD158+CD8+ subgroup were 6.86 (2.44, 27.79) in the RM group and 5.62 (4.05, 8.22) in the control group. There was no statistical difference between the two groups (p=0.381). The laboratory findings of the groups are compared in Table 2.
Discussion
In the last decade, specific properties of NK cells in peripheral blood and uterus have been studied to determine whether Natural Killer cells are associated with miscarriage. Various studies have described increased numbers of uterine and peripheral blood NK cells in women with recurrent miscarriages compared to control fertile women [6, 7]. However, its relationship with miscarriage has not yet been clarified. Patients with recurrent miscarriages may exhibit a lack of inhibition of decidua NK cells, leading to a more active state characterized by higher levels of proinflammatory cytokines. Indeed, dysfunctional cytokine production by Natural Killer cells was documented in peripheral blood, with increased interferon-γ levels and decreased Interleukin-4 [11].
Yasuhiko Ebina et al. investigated the association of NK cell activity with the etiology of recurrent miscarriage in a prospective study and the predictive value of NK cell activity for the outcome of subsequent pregnancies in these women. In that study, peripheral NK cell activity was measured in 160 women with a history of RM and compared according to the etiology of RM and pregnancy outcomes. Patients with idiopathic RM have been found to have significantly higher NK cell activity than those with a known etiology of RM. NK cell activity was higher in women with normal chromosomal karyotype who resulted in miscarriage and subsequently became pregnant again than in those who gave live birth (p<0.05). Moreover, women with NK cell activity of 33% and above had a higher risk of miscarriage with a normal chromosomal karyotype (relative risk 3.4, 95%, confidence interval 1.3 to 8.7). They concluded that an increase in peripheral NK cell activity was associated with abortions with a normal chromosomal karyotype, which may play a role in the underlying pathophysiology of RM [15]. In another study, Lee et al. reported that high NK cell activity with a cut-off value of 34.3% and above was associated with RM [16].
Chernyshov et al. evaluated the role of increased peripheral NK cell cytotoxicity (NKc) in women with IVF failure. A total of 79 APAS-negative women, including 33 patients with high NKc, were evaluated for the expression of lymphocyte subsets, intracellular cytokines (IFN-γ, IL-4, TNF-α, IL-10), activating markers (CD69, HLA-DR, CD8, KIR(CD158a), CD95 and chemokine receptors (CXCR3, CCR4) using flow cytometry. They reported that NKc levels were higher in women with implantation failure (IF) than in women with successful IVF and that implantation failure was associated with higher CD8, CD158a, and HLA-DR expression in NK cells, activating markers in T-lymphocytes, and levels of IL-4+ T lymphocyte subsets. The predictive value of a single elevated NKc for IVF success was 0.85, while adding the other two abnormal parameters caused it to fall below 0.39. The study identified elevated NKc as a negative, though not critical, factor for implantation in IVF cycles. The immune mechanism of IVF failure includes elevated NKc and several other factors, such as increased CD8 and CD158a expression in NK cells, T lymphocyte activation, and decreased Th2 parameters [17]. However, a systematic review and meta-analysis by Seshadri et al. showed that peripheral NK cell counts were higher in infertile women than in fertile controls. Additionally, in the same study, women with RM had higher numbers and percentages of peripheral NK cells than controls [18].
Despite a body of evidence regarding the relationship between NK cell cytotoxicity and female fertility, different views have been formulated regarding the relationship between the cytotoxic activity of pNK and RM [19]. Although pNK cells contribute to establishing an immune-tolerant environment for placentation, they must have a particular cytotoxic potential to fight infections under normal conditions [20]. Some studies have reported a high rate of pNK cells [21] or cytotoxicity in patients with RM [22]. However, other studies have reported conflicting results showing a lower NK cell ratio or lower pNK cytotoxicity in RM patients compared with fertile controls [23]. A large cohort study suggested that the relationship between subsequent pregnancy outcomes and pNK cytotoxicity is nonlinear and that patients with both low and high pNK cytotoxicity tend to have a high miscarriage rate [24]. Therefore, compared to fertile control, RM patients with both higher pNK cytotoxicity and lower pNK cytotoxicity should be evaluated extensively.
NK cytotoxicity is controlled by the complex interaction between inhibitory and activating receptors. When activating receptor signals are dominant, NK cells exert their cytotoxicity by secreting cytotoxic granules [25].
In the present study, parameters associated with the cytotoxicity of pNK cells were evaluated in women with RM and control fertile women to investigate the etiology of miscarriage in RM patients. Despite the relatively higher median pNK activity level in the recurrent miscarriage group than in the control group, there was no significant difference between the groups in our study (p=0.448). The RM and control groups also did not differ significantly in CD8, CD158a (KIR2DL1) expressions, and IFN-γ amount in pNK cells.
There are many limiting factors in our study. Several factors affecting the level and function of peripheral blood NK cells, namely mental stress age, and race, may affect the results. Some undetected autoimmune diseases or infections may also affect the outcome. Besides, it is unclear whether there is a similarity in cell activity between cycles with conception and without conception. There may be a change in pNK cell number and function when implantation occurs. The activity was measured only once in the present study. Furthermore, subgroups of NK cells may affect pregnancy outcomes.
Conclusion
The present study found no significant difference in the percentages of CD56+dim and CD56+bright pNK cells between the patient group with unexplained RM and the healthy fertile control group. There was also no significant difference in CD8 and CD158a expressions in pNK cells between the patient group with unexplained RM and the healthy fertile control group. Moreover, NK cell activity levels were not significantly different between the two groups.
NK cell function in human reproduction is still poorly understood. All studies collectively indicate changes in the NK cell population in recurrent pregnancy loss and infertility, with results varying depending on whether the material examined is peripheral blood, endometrium, or first-trimester decidua.
It is unclear exactly what kind of relationship, if any, exists between uterine and peripheral blood NK cells. Uterine NK cells play an essential role in early implantation, but whether anomalies cause miscarriages remains to be elucidated. In any case, many studies have shown an independent relationship between peripheral NK cells and RM.
Despite many studies suggesting pNK number or activity as markers of immunological risk in women with RM, its prognostic value remains controversial. Whether changes in NK cell number and activity are the cause or the consequence is not fully understood. Therefore, due to the many arguments in this area, studies with more extensive patient series and control groups are needed to accept or reject the role of NK cell assessment as a predictive test to screen women with infertility or RM.
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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Elnare Alyazova, Gulchin Babayeva, Mehmet Cengiz Çolakoğlu, Jule Eriç Horasanlı. Investigation of Peripheral Natural Killer Cell activity ın Recurrent Miscarriages of Unknown Cause, Case-Control Study. Ann Clin Anal Med 2023;14(11):990-994
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Clinical features and outcomes of pediatric ocular traumas
Hasan Burhanettin Kapti, Aslihan Uzun, Asena Keles Sahin
Department of Ophthalmology, Faculty of Medicine, Ordu University, Ordu, Turkey
DOI: 10.4328/ACAM.21750 Received: 2023-05-07 Accepted: 2023-06-21 Published Online: 2023-07-08 Printed: 2023-11-01 Ann Clin Anal Med 2023;14(11):995-999
Corresponding Author: Aslihan Uzun, Department of Ophthalmology, Ordu University, Training and Research Hospital, Altinordu, Ordu, Turkey. E-mail: draslihanuzun@gmail.com P: +90 537 023 21 17 (Corresponding Author ORCID ID: https://orcid.org/0000-0002-5787-3879
This study was approved by the Ethics Committee of Ordu University (Date: 2022-10-27, No: 2022-241)
Aim: In this study, we aimed to evaluate clinical features and outcomes of pediatric ocular traumas in a tertiary hospital.
Material and Methods: Medical records of children under 18 years who underwent surgery for pediatric ocular trauma between January 2018 and December 2021 were reviewed. Ocular traumas were classified according to the Birmingham Eye Trauma Terminology system.
Results: The study included 19 patients (13 males and 6 females). The mean age was 9.83±5.02 (1-17) years. The mean follow-up was 4.7±3.7 (1-12) months. Injuries were caused by sharp objects [glass (57%), wires (28.5%), and knife (14.5%)] in 6 patients, and 5 children had blunt trauma. The types of traumas were open globe (52.6%), closed globe (15.8%), eyelid laceration (15.8%), closed globe injury with eyelid laceration (10.5%) and upper canalicular laceration (5.3%). Penetrating injury was detected in 7 children and globe rupture was detected in 2 patients. One patient had an intraocular foreign body. The mean interval between trauma and surgery was 6.2±11.2 (1-48) hours. Preoperative and postoperative BCVAs were 0.38±0.43 and 0.55±0.19, respectively. A corneal scar was observed in 6 eyes, iris deformity was found in 3 eyes, persistent hypotonia occurred in 1 eye and proliferative vitreoretinopathy developed in 1 eye.
Discussion: Children who needed surgery for ocular trauma had open globe injuries, notably glass-induced penetrating eye lesions. Pediatric eye injuries may cause persistent ophthalmologic sequelae and visual loss despite proper treatment. Hence, preventing eye injuries in youngsters may prevent lifelong vision loss better than treating them thereafter.
Keywords: Blunt Trauma, Eye Injuries, Open Globe Injury, Pediatric Ocular Trauma
Introduction
Ocular traumas, which account for 8%-14% of injuries, are important causes of acquired, unilateral vision loss in children [1]. Despite medical and technological advances, pediatric eye injuries can cause significant visual morbidity and permanent sequelae. Ocular traumas also impose severe psychological, sociological, and financial burdens on society and families [2]. In addition to the primary devastating effect of injury, amblyopia is an important problem in these patients.
Children have a low capacity to recognize potential dangers and perform movements in a less concentrated manner, so they are likely to be exposed to various traumas. Eye traumas constitute 7% of all bodily injuries [3]. Although most ocular injuries can be avoided with simple, preventive measures, most of children with ocular traumas suffer from visual loss.
Ocular injuries in pediatric and adult patients differ in several ways. It is often not possible to get accurate information about the cause of the injury in children. Additionally, it is often not possible to perform a complete ophthalmologic evaluation, especially in children under 3 years of age. Furthermore, ocular healing process is also different in children and adults. Inflammatory response is stronger in pediatric patients than in adult patients, leading to high tendency of scar formation [3]. In addition, even if eye injuries, especially those that occur at a young age, are treated well, amblyopia can result in serious vision loss in children.
A thorough understanding of the causes and characteristics of ocular injuries in children can help clinicians in analyzing the condition and providing the most effective treatment. Although many studies have been conducted on pediatric ocular injuries, detailed reports are needed to improve the understanding of these potentially sight-threatening traumas. The aim of this study was to evaluate the clinical characteristics as well as visual and anatomical outcomes of ocular injuries in pediatric patients who underwent surgery and followed up in a tertiary center accepting referrals from neighboring hospitals.
Material and Methods
Medical records of all children below the age of 18 who were admitted to our Ophthalmology Department for traumatic eye injury and operated between January 01, 2018 and December 31, 2021 were retrospectively reviewed. Patients who were referred to our clinic for additional surgery and children who were referred to another center for additional surgery after primary repair were excluded. Ethical approval was obtained from Clinical Research Ethics Committee (Approval number: 2022-241) on October 27, 2022. This study was conducted in accordance with the tenets of the Declaration of Helsinki. Informed consent forms were signed by the legal guardians of all children before surgery.
Data regarding age, gender, affected eye, time elapsed between trauma and admission, trauma setting, cause of trauma, traumatizing object, type and site of injury were retrospectively retrieved from the medical records of the patients. The patients were divided into three groups according to age: < 7 years (pre-school), 7-12 years, and 13-18 years old.
Best corrected visual acuity (BCVA), initial findings and intraocular pressure (IOP) at admission, the time elapsed between injury and surgical treatment, initial surgery, BCVA after treatment, follow-up period, the need and type of second surgery, and sequelae during follow-up were recorded. The Birmingham Eye Trauma Terminology (BETT) system was used to classify ocular injuries.
Intraocular pressure measurement with applanation tonometry was performed in patients who did not have an open globe injury. Applanation tonometry was not used in children with open globe injuries. Hypotony was considered when patient’s eyes had IOP values lower than 6 mmHg, whereas ocular hypertension was considered in the eyes with IOP values higher than 21 mmHg with no evidence of glaucomatous damage to the optic nerve head.
Statistical Analysis
The Statistical Package for the Social Sciences® package program (SPSS version 20.0; IBM Inc., Chicago, IL, USA) was used for statistical analysis. The Snellen BCVA was changed to a logMAR value for statistical analysis. Categorical variables were presented as frequency and percentage, and medians and interquartile range (IQR) for non-normally distributed variables. The Kolmogorov-Smirnov test was used to see if the variables in each group had a normal distribution. Since there was no normal distribution, the Mann-Whitney U test, the Kruskal-Wallis test, and the Wilcoxon test were used to compare the data. The Chi-square test was used to look at count data and p<0.05 was considered statistically significant.
Results
The study included 19 eyes of 19 pediatric patients who underwent surgery for ocular injuries. The median age was 10 (IQR 5–13) years. Of all children, 13 (68.4%) were males and 6 (31.6%) were females. The number of boys with ocular traumas was significantly higher compared to girls (p = 0.02). There was no relationship between the trauma mechanism and gender (p=0.38). All patients had unilateral ocular injury. There was no statistically significant difference between the eyes in terms of laterality (p = 0.53). The median follow-up period was 3 (IQR 1–6) months.
Ocular injury occurred outdoors in 11 (57.9%) patients, at home in 7 (36.9%) patients, and at school in 1 (5.2%) patient. Six (31.6%) of the eye injuries were caused by penetrating injuries, and five (26.4%) of them were caused by blunt injuries. In blunt traumas, the most common causes of injury were wooden (n=2), toy (n=2), and pot handle (n=1). Glass (n=3), wire (n=2), and knife (n=1) were the causative agents in penetrating injuries. Other eye injuries occurred due to traffic accidents in 4 (21%) patients and due to falls in 4 (21%) patients. Due to blunt trauma, a globe rupture was observed in one eye, hyphema and iridodialysis in one eye, and only hyphema in two eyes. Seventeen patients (89.4%) were admitted to the hospital within the first 24 hours of trauma. The mean interval between the ocular trauma and primary repair was 3 (IQR 2–4) hours.
The patients were divided into three groups according to age: <7 years (%31.6, n=6), 7-12 years (%26.3, n=5) and 13-18 years (%42.1, n=8). In the <7 years group, the causes of ocular injuries were sharp objects (33.3%), blunt objects (33.3%), and falls (33.3%). In the 7-12 age group, the causes of injury were blunt objects (40%), falls (40%), and sharp objects (20%). However, the most common cause of injury in the 13-18 age group was a traffic accident (50%), followed by sharp objects (37.5%) and blunt objects (12.5%).
Visual acuity could not be measured in 3 eyes (15.7%), and BCVA was below 0.1 in 9 eyes (47.3%) at admission. Patients whose preoperative visual acuity could be evaluated had a BCVA of 0.6 (IQR 0.1-3) logMAR before primary repair, whereas the BCVA at the last visit was 0.2 (IQR 0-1.1) logMAR. Preoperative and postoperative BCVAs were significantly different (p = 0.01).
After surgical treatment, applanation tonometry was performed in 14 eyes (73.6%), and IOP was below 6 mmHg in 1 eye (5.2%) and above 21 mmHg in 2 eyes (11.1%). In five eyes in which applanation tonometry could not be performed, IOP was assessed using finger palpation and evaluated as normal. None of the patients with high IOP required additional surgery and IOP could be controlled using topical antiglaucomatous agents.
According to the BETT system, the most common injury type was open globe injury, which occurred in ten children (52.6%). The most common open globe injury was a penetrating injury (70%, n = 7) (Table 1).
The injury sites were full-thickness corneal, full-thickness scleral, full-thickness corneoscleral, lamellar corneal, and lamellar scleral in five (26.3%) patients, three (15.7%) patients, two (10.5%) patients, three (15.7%) patients, and one patient (5.2%), respectively (Figure 1).
Of the eyes with open globe injury, 4 (40%) had iris prolapse, 3 (30%) had hypotonia, 3 (30%) had traumatic cataracts, 2 (20%) had hyphema, 2 (20%) had superficial foreign bodies, 2 (20%) had vitreous prolapse, 2 (20%) had iridodialysis, and 1 (10%) had vitreous hemorrhage. All closed-globe injuries had hyphema. Primary repair alone was performed in 16 eyes. Anterior chamber lavage was performed during primary repair in two eyes, and foreign body removal from the anterior chamber was performed during primary repair in one eye. A second surgery was required in four patients (21%). Two patients underwent intraocular lens (IOL) implantation after cataract surgery, one underwent iridoplasty simultaneously with IOL implantation after cataract surgery, and one underwent vitreoretinal surgery for vitreous hemorrhage. At the last follow-up, corneal scarring, iris deformity, hypotony, and proliferative vitreoretinopathy (PVR) were found in six (31.6%) eyes, three (15.8%) eyes, one (5.3%) eye, and one (5.3%) eye, respectively. None of the patients had sequelae after closed globe injury, whereas all eyes with sequelae had open globe injuries at the time of presentation.
Discussion
This study examined trauma-related ocular damage in children. Number of boys was greater than girls, which is consistent with earlier studies. Boys are more energetic and risk-averse than girls, which may explain the higher ocular trauma rate [4]. The mean age of children with ocular trauma in previous studies was 5-11.9 years [5,6]. Similarly, the mean age was 9.83 years, in our study. There was no difference between the two eyes in our study similar to previous ones reporting no ocular dominance in pediatric ocular traumas [7].
At admission, visual acuity could not be assessed in 3 patients (15.7%). In similar studies, visual acuity could not be evaluated at first admission in 16%-28% of patients [8,9]. In our study, 9 patients (47.3%) had visual acuity of 0.1 or lower at presentation. Perforating injuries or globe ruptures are associated with worse visual prognosis than closed globe and adnexal injuries [10]. In our study, visual results were worse in open globe injuries than in closed globe injuries. Ten patients (52.6%) had visual acuity better than 0.5 after surgical repair. A previous study showed that 65.4% of patients achieved a visual acuity better than 0.5 after surgery [11]. The proportion of the children who achieved a visual acuity of 6/12 or better was reported in a wide range from 36% to 92%, in different studies evaluating the treatment outcomes of pediatric eye injuries [12-14]. Varieties in the design of the studies and severity of ocular injuries may have led to these different results.
In pediatric eye injuries, it is crucial to ensure globe integrity by performing surgical repair as soon as possible to prevent complications and permanent vision loss. In our study, 89.4% of patients were admitted to the hospital within the first 24 hours, and the mean interval between ocular injury and first evaluation was 6.5 hours. In a multicenter study, the rate of hospital admission within the first 24 hours was reported as 77.3%; however, a study conducted in Egypt reported a lower rate of hospital admission within the first 24 hours after injury (56%) [5,15]. Compared to previous studies, the interval between the trauma and admission to the hospital, and thus the initial evaluation, was shorter in our study.
Our research has shown that the main causes of eye injuries in the younger age groups (<7 and 7-12 years) were falls, blunt objects, and sharp objects, whereas traffic accidents were the most common cause of ocular injuries in the older age group (13–18 years). According to Saxena et al., bows and arrows were the most common cause of eye injuries among young people in India, followed by household appliances and firecrackers [16]. According to the findings of Sofi et al., the most common cause of eye injury in youngsters was wood, followed by stone and sharp objects [17]. These findings reflect the cultural and socioeconomic differences that exist between countries. It has been demonstrated that eye injuries caused by sharp objects are mostly seen in developing countries, whereas sports injuries are more common in developed countries [3].
The place where the injury occurred, differs according to the age of the children. It has been reported that childhood ocular traumas in the preschool age occur most frequently at home [8,11,13]. In our study, eye injuries most commonly occurred on the street (57.8%), which is an expected result considering the geographical location and sociocultural level of the region where this study was conducted.
Most studies on pediatric eye injuries have shown that the incidence of closed globe trauma is higher than that of open globe injury [1,11]. However, in our study, the incidence of open globe injury was higher than that of closed globe injury. This may be due to the fact that our hospital is the only tertiary care center in our province that receives many referrals from neighboring hospitals, and many patients are directly referred to our hospital without primary repair.
The most common clinical findings in the current study were corneal laceration (26.3%) and eyelid laceration (26.3%). In the Pediatric Ocular Trauma Study (POTS3), the most common clinical finding in children with eye injury was corneal laceration (40.7%), followed by eyelid laceration (30.2%) [10]. A study conducted in the USA reported that adnexal (43.7%) and corneal injuries (27.2%) were the most common ocular injuries in children [18]. Traumatic cataract associated with corneal laceration was the most important cause of vision loss after open globe injury. All children with corneal perforation eventually developed cataract in our study. It has been reported that eyelid defects, corneal opacities, cataract, posterior segment disorders, glaucoma, and phthisis bulbi may develop after pediatric ocular injuries [4]. In our study, ophthalmic sequelae (corneal scar, iris deformity, hypotony, and proliferative vitreoretinopathy) were observed in 11 (57.8%) patients in the last follow-up.
Study Limitations
There are certain limitations of this study, including the small sample size, relatively short-term follow-up period, retrospective design, and inability to evaluate visual acuity in some patients. The potential difference in group comparisons reported as “no difference” might not have been detected, since the insufficient sample size in our study increased the risk of type 2 error. However, the fact that our hospital is the only university-based tertiary center accepting referrals from neighboring hospitals enables to reach a sufficient number of cases of pediatric ocular traumas. Another limiting factor is that our study was not able to evaluate the effects of patients referred from another center on parameters such as time between injury and surgery and visual prognosis.
Conclusion
Open globe injuries, especially penetrating eye injuries caused by glass, were noteworthy in children who need surgical repair due to ocular trauma. Despite appropriate and effective management of pediatric eye injuries, patients may experience permanent ophthalmologic sequelae and vision loss. Therefore, measures to prevent eye injuries in children may be more effective in preventing permanent vision loss than any medical intervention after the injury.
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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2. Bozali E, Yalinbas Yeter D, Apa AS, Vural Ozec A, Erdogan H. Pediatric open globe injury in a university-based tertiary hospital in the Anatolian region. Clin Exp Health Sci. 2022;12(3):719-24.
3. Ayca Sari A. Childhood eye injuries and their characteristics. Turk J Ophthalmol. 2012;42(1):41-7.
4. Ozturk H, Ozen B. The clinical features and the factors affecting visual prognosis in pediatric open-globe injuries. Int Ophthalmol. 2022;42(11):3589-600.
5. Zhang Y, Feng K, Yan H. Epidemiological Characteristics of Pediatric Ocular Trauma in China: A Multicenter Retrospective Hospital-Based Study. J Ophthalmol. 2022;2022:4847027.
6. Gise R, Truong T, Parsikia A, Mbekeani JN. A comparison of pediatric ocular injuries based on intention in patients admitted with trauma. BMC Ophthalmol. 2019;19(1):37.
7. Li X, Zarbin MA, Bhagat N. Pediatric open globe injury: A review of the literature. J Emerg Trauma Shock. 2015;8(4):216-23.
8. Sul S, Gurelik G, Korkmaz S, Ozdek S, Hasanreisoglu B. Pediatric open-globe injuries: clinical characteristics and factors associated with poor visual and anatomical success. Graefes Arch Clin Exp Ophthalmol. 2016;254(7):1405-10.
9. Saksiriwutto P, Charuchinda P, Atchaneeyasakul LO, Surachatkumtonekul T, Phamonvaechavan P. Epidemiology of Pediatric Open Globe Injuries in a University Hospital in Thailand. Cureus. 2021;13(11):e19366.
10. Barry RJ, Sii F, Bruynseels A, Abbott J, Blanch RJ, MacEwen CJ, et al. The UK Paediatric Ocular Trauma Study 3 (POTS3): clinical features and initial management of injuries. Clin Ophthalmol. 2019;13:1165-72.
11. Puodžiuvienė E, Jokūbauskienė G, Vieversytė M, Asselineau K. A five-year retrospective study of the epidemiological characteristics and visual outcomes of pediatric ocular trauma. BMC Ophthalmol. 2018;18(1):10.
12. Minderhoud J, van Nispen RM, Heijthuijsen AA, Beunders VAA, Bueno de Mesquita-Voigt AMT, Moll AC, et al. Epidemiology and aetiology of childhood ocular trauma in the Republic of Suriname. Acta Ophthalmol. 2016;94(5):479-84.
13. Thompson CG, Kumar N, Billson FA, Martin F. The aetiology of perforating ocular injuries in children. Br J Ophthalmol. 2002;86(8):920-2.
14. MacEwen CJ, Baines PS, Desai P. Eye injuries in children: the current picture. Br J Ophthalmol. 1999;83(8):933-6.
15. Al Wadeai EA, Osman AA, Macky TA, Soliman MM. Epidemiological Features of Pediatric Ocular Trauma in Egypt. J Ophthalmol. 2016;2016:7874084.
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17. Sofi RA, Wani JS, Keng MQ. Profile of children with ocular trauma. JK-Practitioner. 2012;17(1-3):44-50.
18. Matsa E, Shi J, Wheeler KK, McCarthy T, McGregor ML, Leonard JC. Trends in US Emergency Department Visits for Pediatric Acute Ocular Injury. JAMA Ophthalmol. 2018;136(8):895-903.
Download attachments: 10.4328.ACAM.21750
Hasan Burhanettin Kapti, Aslihan Uzun, Asena Keles Sahin. Clinical features and outcomes of pediatric ocular traumas. Ann Clin Anal Med 2023;14(11):995-999
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Analysis of the characteristics and complications of mesiodens with cone beam computed tomography: A retrospective study
Kevser Kolçakoğlu 1, Eda Nur Güzeldemirci 2, Gizem Doğan Okur 1, Esra Kızılcı 1
1 Department of Pedodontics, Faculty of Dentistry, Erciyes University, Kayseri, 2 Department of Private Kardent Oral and Dental Health Center, Ankara, Turkey
DOI: 10.4328/ACAM.21751 Received: 2023-05-08 Accepted: 2023-06-20 Published Online: 2023-08-02 Printed: 2023-11-01 Ann Clin Anal Med 2023;14(11):1000-1005
Corresponding Author: Kevser Kolçakoğlu, Department of Pedodontics, Faculty of Dentistry, Erciyes University, 38000, Kayseri, Turkey. E-mail: kevser.kolcakoglu@gmail.com P: +90 539 257 41 07 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2596-8678
This study was approved by the Clinical Research Ethics Committee of Erciyes University (Date: 2023-03-29, No: 199)
Aim: The aim of this study was to investigate the three-dimensional characteristics of mesiodens with Cone-beam Computed Tomography (CBCT) and to analyze the eruption status, direction, shape and complications of mesiodens in pediatric patients.
Material and Methods: In the study, 473 children between the ages of 7-14 years who were diagnosed with mesiodens from the patients who applied to Erciyes University Pediatric Dentistry Department for dental examination between 2012-2020 were evaluated retrospectively. CBCT images of 122 mesiodens from 94 patients who met the inclusion criteria were analyzed. Demographic indicators, the number of mesiodens, crown shape, position, mesiodens eruption status, eruption direction, and dentition stages of the patient were recorded in patients with mesiodens. Clinical complications caused by mesiodens (diastema, eruption delay, rotation, hyperplastic follicle, cyst, root resorption) and their positions in the sagittal, frontal and axial planes were classified.
Results: The mean age of patients with mesiodens was 8.75(%1.92) years and 22 (%23.40) of the patients were female and 72 (%76.60) were male. The percentages of patients with 1 and 2 mesiodens were 70.21, 29.79%, respectively. None of the patients had three or more mesiodentes. Of the 122 mesiodentes examined, 95 were conical and conical mesiodens was the most common (77.90%). When the directions of the mesiodens were examined according to their shapes, it was seen that the conical mesiodentes were positioned more inverted (n=30) and those with tubercles were positioned vertically (n=15) (p<0.05). Type 3 mesiodens (impacted and in contact with the central incisor) (n=65,53.30%), evaluated in the sagittal plane, was found to cause more rotation (p<0.05).
Discussion: Mesiodentes are difficult to diagnose, especially when they are impacted, and can be overlooked in routine clinical dental examinations. In cases where they are not diagnosed, they can cause orthodontic problems. It is necessary to increase the awareness of dentists about mesiodens, especially when examining pediatric patients.
Keywords: Cbct, Mesiodens, Characteristics
Introduction
Supernumerary teeth are defined as “non-erupted or erupted teeth or tooth-like structures in addition to 20 primary and 32 permanent teeth” [1]. The etiology of supernumerary teeth is multifactorial because it is caused by both genetic and environmental factors [1]. The presence of fewer or more teeth is due to the effects of the maturation period [2]. There are many theories of supernumerary tooth formation, and the most common is the theory of hyperactivity of the dental lamina [2].
Supernumerary teeth can be classified according to their location (topography) in the dental arch. Supernumerary teeth located between the maxillary anterior incisors are termed mesiodens as the most prevalent form of supernumerary teeth [3]. It was reported that the prevalence of mesiodens in primary dentition is between 0.3-0.8%, while in primary dentition is between 0.1-3.8%. Mesiodentes are more common in males than in females, and they may be found in more than one, remain embedded, and usually do not cause symptoms [4]. Asymptomatic mesiodens is recognized as a result of routine clinical and radiological examination and may lead to many complications such as delayed eruption, tooth displacement, diastema, pain, and swelling in the relevant area, pathological root resorption in adjacent teeth, and cyst formation [2, 4, 5].
Radiographic examinations are of great importance in the diagnosis, differential diagnosis and examination of complications caused by mesiodens. Panoramic radiographs can be used in the diagnosis of mesiodens, but since the anterior region evaluation is insufficient in panoramic radiographs, more detailed examinations are needed [6]. Periapical and occlusal radiographs are helpful in more detailed examination, but conventional radiographic methods are two-dimensional and provide limited information. It is known that mesiodens cause various complications and may remain impacted. For this reason, it is recommended to use advanced imaging techniques for the three-dimensional evaluation of the surrounding anatomical structures and pathologies associated with the mesiodens [7]. Cone-beam computed tomography (CBCT) provides a high-resolution three-dimensional imaging of the bone structures of the head and neck region and has become widespread in dentistry due to its relatively low radiation dose [8].
In this study, it was aimed to evaluate the prevalence of mesiodens in children admitted to the Department of Pediatric Dentistry, Faculty of Dentistry of Erciyes University, and to examine the age and gender distribution of mesiodens, eruption status, direction, shape and complications by cone beam computed tomography.
Material and Methods
Ethics committee approval for this study was obtained from Erciyes University Clinical Research Ethics Committee (2023-199).
In this retrospective study, 473 pediatric patients aged 7-14 years who were diagnosed with mesiodens and had panoramic radiographs, who were admitted to Erciyes University Faculty of Dentistry, Department of Pediatric Dentistry between 2012 and 2020 were included. Of these patients, 109 pediatric patients who underwent CBCT scans were identified.
Criteria for exclusion from the study:
*scans of insufficient anterior maxilla and nasal cavity
*Scans with poor image quality that do not allow for review
*patients with syndromes that may be associated with the presence of supernumerary teeth (Cleft lip/palate, Williams and Gardner syndrome, Cleido cranial dysplasia, etc.)
CBCT images of 125 mesiodentes from 94 patients who met the inclusion criteria were analyzed.
Images were analyzed using a Dell Precision T1500 WorkStation (Dell D02M, Poland) and a 19-inch resolution, 1920×1080 pixel Dell monitor (Dell E190S, China). The measurements described below were recorded in DICOM format with the special computer software NNT (NNT Software, V9.01, New Tom, Italy) the Newton 5G CBCT device.
In this study, the presence of an extra tooth or tooth-like structure in the region between the long axis of the two maxillary central teeth was considered as mesiodens. Demographic information such as age, gender, mesiodens number, shape (conical, supplemental, tubercular), tooth position (horizontal, vertical, invert, mesioangular, distoangular), mesiodens eruption status (embedded, erupted), mesiodens eruption direction and dental examination information such as the dentition period of the patient (primary, mixed, permanent) and finally the complications caused by the mesiodens (diastema, eruption delay, rotation, hyperplastic follicle, cyst, root resorption) and their positions in 3 planes (sagittal, frontal and axial) were classified.
To minimize variability, our research assistant (E.G. and G.D.) with 3 years of experience working in our department reviewed frontal, sagittal, axial and cross-sectional CBCT scans. The control of the scans examined was done by a faculty member (E.K. and K.K) who has 12 years of clinical experience in our department. Different results were re-evaluated by the observers and common conclusions were reached. An inter-research kappa compatibility test was performed, and since the number of observers was more than 2, this value was calculated as 0.84 using ‘Fleiss’ kappa coefficient’ [9]. In the classification made by Fleiss, a Kappa value of 0.75 and above indicates excellent compatibility [10].
CBCT analysis of mesiodens position
In this study, the positions of mesiodentes in three-dimensional planes were investigated. First, the classification defined by Kim et. al [11] was modified by Goksel et al. to classify the 3D positions of the mesiodens and this classification was used in our study.
Mesiodentes were examined in 3 planes according to the following criteria:
•In the frontal plane: the mesiodistal positions of the mesiodens were examined.
Type A= straight, long axis and no inclination.
Type B= crown in midline, root in distal.
Type C= root in midline, crown in distal.
•In the sagittal plane; The superior-inferior positions of the mesiodens were examined.
Type 1 = fully erupted.
Type 2= partially erupted.
Type 3= impacted and in contact with the central incisor.
Type 4= impacted and not in contact with central incisor.
Type 5 = in contact with the nasal cavity,
Type 6 = in contact with the nasal septum.
•In the axial plane; The anteroposterior positions of the mesiodens were examined.
Type A = labial to the dental arch
Type B= in line with the dental arch
Type C= anterior to the nasopalatine canal, in contact with the nasopalatine canal
Type D= behind the nasopalatine canal, in contact with the nasopalatine canal
Type E = behind the nasopalatine canal, not in contact with the nasopalatine canal
Statistical analysis
The study was evaluated with the IBM SPSS Statistics 23 (SPSS Inc., Chicago, IL, USA) package program. Number, percentage, mean and standard deviation were used as descriptive statistical methods in the evaluation of the data. The relationship between the categorical variables was investigated with the Chi-Square Test, and the strength of the significant relationship between the groups was determined using Cramer’s V correlation coefficient.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
The mean age of the study patients was 8.75 (1.92%) years. Of the patients, 72 (76.60%) were male and 22 (23.40%) were female. The ratio of the gender to each other was 3.2:1.
A total of 122 mesiodentes were detected, including 66 (70.21%) single mesiodentes and 28 (29.79%) double mesiodentes. None of these patients had three or more mesiodentes. Of the 122 mesiodentes s examined, 95 were found to be the most common conical shape (77.90%).
Other mesiodentes weree tubercular (n=24, 19.70%) and supplemental (n=3, 2.50%). When the directions of the mesiodentes were examined according to their shapes, it was seen that the conical mesiodens was positioned more inverted (n=30) and those with tubercles were positioned vertically (n=16). The majority of mesiodentes were diagnosed in the mixed dentition (n=106, 86.90%), with 13 in the permanent dentition (10.70%) and 3 in the primary dentition (2.50%). Types of complications caused by mesiodens are shown in Table 1.
It has been identified that the number of mesiodentes causing rotation, eruption delay and root resorption in the relevant teeth is 1 (0.80%), the number of mesiodentes causing the eruption delay, rotation, the hyperplastic follicle is 2 (1.60%), and the number of mesiodens causing the eruption delay, hyperplastic follicle, root resorption is 1 (0.80%). In the 3D CBCT evaluation, the mesiodistal positions in the frontal plane were examined as Type A, Type B and Type C and their numbers were recorded. (Table 1). When mesiodentes were evaluated according to their directions on the frontal axis, it was seen that most of the mesiodentes located horizontally, vertically and inverted were Type A, the mesioangular one was Type B, and the distoangular one was Type C in the Frontal plane.
The superior-inferior positions of the mesiodens in the sagittal plane were examined (Table 1). Accordingly, the most observed position was “Type 3 (buried and in contact with the central breaker)” (n=65, 53.30%).
Most of the mesiodentes whose anteroposterior positions were examined in the axial plane were Type B (n= 87, 71.30%). The numbers and percentages of other mesiodentes are given in Table 1. None of the examined mesiodentes were Type 2 (partially erupted) (Table 1).
When the directions of the mesiodentes were examined according to their shapes, it was seen that the conical mesiodentes were positioned more inverted (n=30) and those with tubercles were positioned vertically (n=15). There is a significant relationship between shape and direction (p<0.05) (Table 2).
When Table 3 is examined, it can be seen that teeth with hyperplastic follicles cause more rotation (p<0.05). It was determined that Type 3 teeth, which were evaluated in the sagittal plane, caused more rotation (p<0.05).
Discussion
In this study, the prevalence of mesiodens was evaluated by cone beam computed tomography in children living in the Cappadocia region. In some studies, it was reported that mesiodens prevalence was more frequent in males than in females with a ratio of 2 [3, 13]. Ersin et al. also found that the mesiodens ratio in males was 3 times higher than in females [14]. Colak et al. reported that the prevalence of mesiodens was higher in females than in males [15]. In our study, the prevalence of mesiodens was found to be higher in males, similar to those reported in the majority of studies.
Anthonappa et al. underline that most of the studies on mesiodens do not refer to “the number of mesiodens observed in a person” [16]. In the study conducted by Gündüz et al., the single incidence of mesiodens was 76.8%, while the double incidence was 23.1% [17]. Kazanci et al. on the other hand, found one mesiodens at a rate of 80% and two mesiodentes at a rate of 20% [18]. In our study, similar to other studies, the probability of single (70%) mesiodens was found to be higher than the probability of double mesiodentes (29.7%). The presence of three or more mesiodentes, which was reported as “rare” in the literature, was not detected in any of the patients included in the study. The high incidence of single mesiodens in our study and the absence of three or more mesiodentes may be due to the fact that syndromic individuals were not included both in this study and in other studies.
When mesiodentes are examined in terms of their morphology, the number of “conical-shaped” mesiodentes is higher [13, 19, 20]. In our study, conical shaped mesiodens was found to be the most common with a rate of 77.90%, similar to the literature.
When assessing the position of mesiodens in the study by Mukhopadhyay et al., 62.8% vertical and 30.8% inverted mesiodentes were reported [21]. In a study by Gunduz et al., positions of mesiodentes were vertical in 55.2%, inverted in 37.6% and horizontal in 7% [17]. Similar to the studies reported in this study, the highest rate of mesiodentes was found in the vertical position (45.9%).
In the study by Ersin et al., 4.2% of the mesiodentes examined were observed in the primary, 87.5% in the mixed dentition, and 8.3% in the permanent dentition [14]. The majority of mesiodentes examined in our study were in patients with mixed dentition (86.90%). We assume that this is due to the fact that the age groups of the patients included in the study were similar, and the study was conducted in the pedodontics clinic.
In the study by Ramesh et al., it was stated that 55% of the mesiodentes erupted, 18% were half-impacted, and 27% remained impacted [22]. In our study, 113 (92.60%) of the examined mesiodentes were impacted. Tomography is requested for pediatric patients only in cases where there is difficulty in the diagnosis and treatment planning in the clinic and in surgical interventions. Elapsed, asymptomatic mesiodens and routine examinations are performed with panoramic and periapical films. The evaluation of tomography within the scope of the study may be effective in finding these results in our study.
Mesiodens can cause midline diastema, crowding, delay or obstruction in the eruption of central incisors, rotation, root resorption, and dentigerous cyst formation [11]. Kim et al. found that the most common complication related to mesiodens was delayed eruption of permanent central incisors (56.4%) [11]. However, Shih et al. reported the most common complication related to the mesiodens as midline diastema and determined the root resorption of the adjacent tooth to be 1.5% [10]. In the mesiodens examined in this study, maxilla midline diastema (12.30%), eruption delay in adjacent teeth (35.20%), rotation in adjacent teeth (16.40%), cyst (3.30%) or hyperplastic tooth follicle formation (5%) and complications such as root resorption (2.50%) in the associated teeth were observed. The results of our study support the results of Kim et al.’s study.
In our study, mesiodentes were examined in three planes. As a result, it was determined that most of the mesiodentes were located between the midlines of the central teeth, straight and uninclined in the long axis, positioned in the axial dental arch and in contact and impacted with the central teeth in the sagittal direction. Mukhopadhyay et al. reported 2.6% labial mesiodentes [21]. However, Kim et al. found that none of the mesiodens was labial to the dental arch [23]. In this study, a labial mesiodens was determined albeit less (1.6%), according to the results of study by Aoun et al., they reported that 20.5% of the mesiodentes were in contact with the base of the nose, and 49% with the nasopalatine canal [24]. In our study, the mesiodens contacting the nasal cavity was 3.30% and the mesiodens contacting the nasal septum was 1.6%. The low rate of mesiodentes contacting the nasal cavity and nasal septum in our study may be related to the fact that the mesiodens was more in contact with the central teeth in the group studied. In the study group, the fact that the mesiodens was located closer to the oral cavity and located in the arch may have affected the result in this way.
Limitations
Within the scope of this study, it was aimed to evaluate the mesiodens in three dimensions by tomography. However, complications such as being buried were overestimated. For this reason, we think that different results may be encountered in studies with a higher number and in which both panoramic and periapical and tomography are evaluated together.
Conclusion
Mesiodentes are cases that are difficult to diagnose, especially in the case of impact, and can be unnoticed in routine examinations. However, if they are not diagnosed, they can cause orthodontic problems. For this reason, it is important that they are diagnosed early and intervened in the early period to intervene in the complications. In this study, it was provided to evaluate the mesiodens in 3 dimensions in 3 planes and to deal with the complications that may occur. In this respect, we emphasize that this is important for both pediatricians and orthodontists.
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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Kevser Kolçakoğlu, Eda Nur Güzeldemirci, Gizem Doğan Okur, Esra Kızılcı.Analysis Of The Characteristics And Complications Of Mesiodens With Cone Beam Computed Tomography: A Retrospective Study. Ann Clin Anal Med 2023;14(11):1000-1005
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Could the subvastus approach be the first choice in total knee arthroplasty?
Mehmet Fevzi Cakmak, Levent Horoz
Department of Orthopedics and Traumatology, Faculty of Medicine, Kirsehir Ahi Evran University, Kirsehir, Turkey
DOI: 10.4328/ACAM.21759 Received: 2023-05-17 Accepted: 2023-06-20 Published Online: 2023-08-08 Printed: 2023-11-01 Ann Clin Anal Med 2023;14(11):1006-1010
Corresponding Author: Mehmet Fevzi Cakmak, Department of Orthopedics and Traumatology, Faculty of Medicine, Kirsehir Ahi Evran University, Kirsehir, Turkey. E-mail: drmfcakmak@gmail.com P: +90 532 207 97 59 Corresponding Author ORCID ID: https://orcid.org/0000-0001-9338-8232
This study was approved by the Ethics Committee of Kirsehir Ahi Evran University (Date: 2023-03-07, No: 2023-05/30)
Aim: Total knee replacement procedures are widely used in advanced cases of knee osteoarthritis. Medial parapatellar arthrotomy is one of the most commonly used approaches in total knee replacement. As an alternative to this approach, the subvastus approaches have been developed. The purpose of this study is to compare medial parapatellar and subvastus approaches.
Material and Methods: The study population was the archive of the orthopedics and traumatology clinic of a third-level hospital. This is a retrospective study. The study was conducted with 288 participants, including 147 MPPs and 141 SV. Range of motion, pain scores, and functional scores of the patients were recorded. The GENESIS II TKR system was performed for all participants.
Results: No significant difference was observed in terms of age, BMI values, and the operated side among the patients. No significant difference was found in KSS values between groups at the 12th week and first-year measurements. However, there were statistically significant differences observed in OKS measurements on the third and tenth days. A significant difference was observed in VAS values measured on the first and third postoperative days. The study groups were analyzed in terms of developing complications. According to the findings, no complications were observed in 136 participants in the MPP group and 129 participants in the SV group.
Discussion: Our study concluded that the SV approach should not be the first choice for TKR due to its limitations.
Keywords: Total Knee Replacement, Medial Parapatellar Arthrotomy, Subvastus Approach, Continuous Passive Motion, Range of Motion, Visual Analogue Scale
Introduction
Total knee replacement (TKR) procedures are widely used in advanced cases of knee osteoarthritis [1]. The literature reports survival rates of over 20 years, in the range of 90-95% [2]. Cost-effectiveness studies have shown that TKR procedures are cost-effective, and numerous studies have been conducted in this regard [3,4]. Accelerating the return to normal life is the primary goal in current TKR procedures. The economic and social impacts of this goal have been investigated, and the effectiveness of different protocols has been compared [5]. The goal is to reduce hospitalization time to hasten the return to normal life and facilitate early rehabilitation is the objective [6].
Complications that develop after TKR have been the subject of numerous studies. Severe pain and decreased strength in the quadriceps muscles are among the most common complications. It has been reported that the traditional medial parapatellar arthrotomy (MPP), which involves detachment of the medial portion of the quadriceps tendon from the patella, leads to painful scar tissue [7].
However, there is information indicating that this approach may cause damage to the quadriceps tendon and delay rehabilitation [7]. As an alternative to this approach, the subvastus approach (SV) has been developed. Early functional outcomes have been reported to be better with the SV approach. Different approaches have yielded varying results in the literature [8-12].
In the SV approach, the muscle incision is small, making it difficult to visualize the surgical area. As a result, difficulties in exposure are encountered, and the risk of injury to the patient remains uncertain [8].
The purpose of this study is to compare patients who underwent surgery using the minimally invasive SV and MPP approaches at our clinic.
Material and Methods
Study Population
The study population consisted of an archive of total knee arthroplasties.
Study Design and Participants
Our study was retrospective. A total of 380 patients who underwent total knee arthroplasty in the orthopedics and traumatology clinic between June 2019 and January 2022 were included in the study. Participants were selected using the SV or MPP approach and were followed up for at least one year. Participants were selected according to standard protocols, and those who did not meet the criteria were excluded from the study. The study was conducted with 288 participants, including 147 MPPs and 141 SV, with complete medical records. One week before the operation, physical examinations were performed after preoperative anesthesia examination. The participants’ demographic information, implant selection, and measurement planning were recorded before the operation.
One day prior to surgery, the range of motion (ROM), pain scores (VAS), and functional scores (KSS, OKS) of patients were recorded. Informed consent was obtained from the participants. Following standard inpatient evaluations on the first, second, and third days of the post-op period, outpatient follow-up evaluations were conducted on the 10th day, 20th day, sixth week, third month, sixth month, and the first year. Standard follow-ups were continued annually. On the first day after surgery, rehabilitation was initiated with the device adjusted to 45°. For those who tolerated the rehabilitation for 60 minutes, the device was adjusted to 75°, 90°, 105°, and 120°, respectively. Permission was granted up to 90° on the first day, and those who tolerated it were allowed to progress to 105° and 120° on the second day. The angle that participants could tolerate and the duration of their tolerance was recorded on the first, second, and third days.
Groups
– Group 1 refers to the MPP approach.
– Group 2 refers to the SV approach.
Surgical technique
MPP Approach
The GENESIS II TKR system (Smith & Nephew; Memphis, TN) was applied to all participants following standard femoral and tibial cuts. The arthrotomy was initiated five mm lateral to the vastus medialis muscle of the joint capsule and three cm above the patella and completed by leaving a five mm tissue layer between the patella and the capsule.
SV Approach
Smith and Nephew, Genesis II implantation was performed for all participants following standard femoral and tibial cuts. The posteromedial border of the vastus medialis muscle was identified by finger dissection, separated by blunt dissection, and elevated with a periosteal elevator. From the point where the muscle meets the patella, arthrotomy was initiated from the medial side, leaving approximately five millimeters away. The arthrotomy was then completed at the level of the tibial tuberosity, following the medial aspect of the patellar tendon.
Data
The research data were as follows:
-Age, BMI values, and the side on which the surgery was performed.
-Soft tissue complications have been recorded, including superficial infections, deep joint infections, hematomas, tissue degradation, and their timing and treatment processes.
-Continuous Passive Motion (CPM).
-Opioid consumption was recorded on the first day of the postoperative period, on the first, second, and third days of hospital stay, and when the first opioid need occurred.
-Visual Analogue Scale (VAS) values were measured on preoperative, postoperative first, third, and tenth days, 12th week, and the first year.
-Rehabilitation parameters were measured, including Knee Society Score (KSS) and Oxford Knee Score (OKS), at preoperative and on the postoperative 10th day and 12th week.
-Range of Motion (ROM) was measured on preoperative, postoperative third day, 10th day, 12th week, and first year.
Ethics
Ethical permissions for the study were obtained from the ethics committee of the tertiary healthcare institution where the researchers work (Date: 07 March 2023 / 2023-05/30)
Power Analysis
A power analysis was performed to determine the sample size. An effect size of d=0.75, Power(1-β)=0.90 and allocation ratio 1 were assumed. As a result, the minimum sample size was calculated as 39 people in each group.
Statistical Analysis
Analyses were conducted using SPSS 26 software. The normality of the data was examined using the Kolmogorov-Smirnov test. The Mann-Whitney U test was utilized to compare two independent groups, whereas the Friedman test was used for repeated measurements of more than two groups. In case of significant differences, Bonferroni-corrected p-values were considered in multiple comparisons. Relationships between categorical variables were examined using Chi-square tests. A significance level of p < 0.05 was deemed statistically significant in all analyses.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
According to research groups, no significant difference was observed in terms of age, BMI values, and the operated side among the patients (p>0.05). However, significant differences were identified between the ROM values measured on the third and tenth days after surgery (p<0.05). Upon examination of the findings, it was determined that the mean of the SV group was higher than the mean of the MPP group on both days
No significant difference was found in KSS values between groups at the 12th week and first-year measurements. However, there were statistically significant differences observed in OKS measurements on the third and tenth days after surgery (p<0.05). The mean value of the SV group was higher than that of the MPP group on both days (Table 1).
After the analysis, a significant difference was observed in the VAS values measured on the first and third postoperative days (p<0.05). However, there was no intergroup difference in the initial opioid requirement and daily opioid consumption values (p>0.05). Regarding VAS values, the mean of the MPP group was higher than that of the SV group on both days (Table 2).
Table 3 presents the values of CPM endurance and passive ROM. Analyses revealed significant differences in CPM values (p<0.05). Specifically, in terms of endurance, the mean value of the SV group for CPM 1, 2, and 3 was higher than the mean value of the MPP group. Similarly, in terms of passive ROM, the mean value of the SV group for CPM 1, 2, and 3 was higher than the mean value of the MPP group (Table 3).
Table 3. CPM values in groups
The study groups were analyzed in terms of developing complications. According to the findings, no complications were observed in 136 participants in the MPP group and 129 participants in the SV group. Superficial soft tissue infections were seen in five participants in the MPP group and three in the SV group, while the deep joint infection was observed in one participant in the SV group. No cases of deep joint infection were found in the MPP group. Six participants in the MPP group and eight in the SV group were reported to have developed hematomas. However, there was no statistically significant difference between the groups regarding complications (p>0.05).
Discussion
Our study’s early three-month period results observed benefits of SV approach mainly in parameters such as early rehabilitation endurance and higher range of motion values. The more harmonious patellar tracking contributed to these results [8]. In the study conducted by Grace et al. [9], the incidence of medial tilt was found to be 8% in the MPP group and 2.5% in the SV group. An objective evaluation of patellar tilt and tracking was not performed in our study. Nevertheless, the clinical outcomes of the SV group support the findings in the literature.
In the literature, findings indicate that the SV approach is particularly successful in muscle strength and pain management following surgery. Faura et al. [12] reported no difference between the measurements of the SV and MPP approaches in quadriceps peak torque. In a study [13], the SV approach was significantly superior to other approaches regarding straight leg raises and pain management in the early postoperative period. Our study observed significant improvement in the SV approach group in endurance and passive ROM measurements using VAS and CPM modalities on the first, second, and third postoperative days.
The patella is supplied by an extraosseous vascular ring [14]. The supreme genicular artery lies in the belly of the vastus medialis and is preserved by the SV approach [7]. The MPP approach disrupts the relationship between the perivascular vascular ring and the superior, superomedial, and inferomedial genicular vessels. The SV approach is thought to reduce the need for lateral retinacular release and, thus, minimize the impact on patellar blood supply [14-16].
In the study [10], which evaluated early postoperative outcomes, it was emphasized that the values of the SV group recorded on the first day postoperatively in passive flexion were superior to those of the MPP group and that this difference was statistically significant. The measurements we made on the first, second, and third postoperative days showed that SV group values were significantly better in both aspects. With respect to ROM, SV group values were significantly higher than MPP group values in measurements taken on the third and tenth postoperative days. However, the difference identified in measurements taken during the twelfth week and the first year was not statistically significant. Passive flexion of the knee joint is controversial, as it is influenced by many parameters, such as component alignment and patellar alignment [17-19].
When comparing the SV and MPP approaches in total knee arthroplasty, differences existed between flexion and extension during early rehabilitation. The SV group observed passive and active straight leg raising earlier [10]. However, our study did not evaluate an objective parameter measuring active extension.
Faure et al. [12] reported no difference in quadriceps muscle strength three months after total knee arthroplasty. However, in the first week and first month postoperatively, muscle strength was significantly higher in the SV group compared to the MPP group. However, no differences were found in VAS values between the groups on the 10th day and after. Our findings suggest that muscle strength is regained earlier in the SV approach and that postoperative pain is less on the first and third days compared to the MPP approach.
There is a consensus in the literature regarding the superiority of the SV approach in the early period. However, this finding loses its validity after the third month, which can be explained by the quadriceps tendon’s healing and the extensor mechanism’s normalization [20]. In our study, it was observed that there was no superiority of the SV approach in terms of functional scores and active knee extension after the third month.
The results of KSS and OKS evaluations were the same as the other parameters. According to the measurements taken on the 10th postoperative day, OKS values were significantly higher in the SV group. However, no difference was found between the groups in OKS and KSS evaluations after the 12th week.
In VAS analyses, a significant superiority was observed in the SV group in measurements taken on the first, second, and third postoperative days. However, the VAS values of both groups were similar after the 10th day. Although the SV group had a better first opioid requirement time and daily consumption, no statistically significant difference was found between the groups.
Berstock et al. conducted a meta-analysis by examining 11 studies [21]. The results showed that the SV group had better VAS values on the first day and ROM values on the first week. These results were statistically significant. However, no significant difference was observed in the KSS values among the examined studies, consistent with our findings. Our study found that the OKS values in the SV group were significantly better on the third- and tenth days post-surgery. However, no significant difference was observed in subsequent follow-ups.
Different results have been reported in the literature regarding complications. Peng et al. found that SV and MPP groups were similar regarding soft tissue and wound complications [22]. Li et al. found that wound healing was worse in the SV group, but there was no difference in a hematoma [23]. Our study showed that hematoma was more common, and wound healing was worse in the SV group.
The SV approach in TKR offers advantages; however, there are unpredictable perioperative challenges [24, 25]. The main issue is the difficulty and insufficiency of the visual field during surgery, which is challenging to predict preoperatively. Obesity, muscle hypertrophy, and failed proximal tibial osteotomy further complicate the SV approach [8]. We suggest avoiding the SV approach in fixed knees with advanced joint contracture, large patellar osteophytes, and severe varus deformities. The occurrence of the secondary patellar tendon and medial collateral ligament injuries is probable. These injuries are particularly associated with advanced deformation and challenging dislocation, especially during the early stages of the learning curve.
Our study has some limitations. One limitation is the retrospective design, which can disrupt randomization in patient selection and homogeneity of results. Another limitation is the one-year limit on patient follow-up. Therefore, a randomized controlled cohort study will be planned to reevaluate the results.
Conclusion
Our study concluded that the SV approach should not be the first choice for TKR due to its limitations in surgical visualization and longer learning curve. The MPP approach should be preferred for TKR because it provides a more comprehensive surgical view, an easy learning curve, and lower complication rates.
Acknowledgments: We would like to thank H. Cagdas Basat and O Utku Demir for their contributions.
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.21759
Mehmet Fevzi Cakmak, Levent Horoz. Could the subvastus approach be the first choice in total knee arthroplasty? Ann Clin Anal Med 2023;14(11):1006-1010
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Can platelet-rich plasma be as effective as corticosteroids in the treatment of frozen shoulder in rats? Experimental animal study
Javid Mohammadzadeh Azarabadi 1, Shahla Vahidfar 2, Ekin Kaya Şimşek 1, Duygu Türkbey Şimşek 3
1 Department of Orthopedics and Traumatology, Faculty of Medicine, Baskent University, 2 Department of Physical Medicine and Rehabilitation, Lokman Hekim Demetevler Medical Center, 3 Department of Pathology, Gülhane Training and Research Hospital, Ankara, Turkey
DOI: 10.4328/ACAM.21771 Received: 2023-05-30 Accepted: 2023-07-31 Published Online: 2023-08-05 Printed: 2023-11-01 Ann Clin Anal Med 2023;14(11):1011-1014
Corresponding Author: Javid Mohammadzadeh Azarabadi, Department of Orthopedics and Traumatology, Faculty of Medicine, Baskent University, Ankara, Turkey. E-mail: dr_jma_md@yahoo.com P: +90 538 038 79 83 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2393-3535
This study was approved by the Ethics Committee of Başkent University Medical and Health Sciences Research Board and Experimental Animals (Date: 2017-01-30, No: 17/02)
Aim: Frozen shoulder is an important health problem that causes significant socio-economic losses as it affects daily life. Its etiopathogenesis has not been fully elucidated. A long recovery period leads to new searches for treatment. In the treatment of frozen shoulder, corticosteroids (CS) and platelet-rich plasma (PRP) are applied, among other options. The aim of this study is to compare the effectiveness of CS and PRP in frozen shoulder.
Material and Methods: A secondary frozen shoulder model was created in rats. At the end of the eight-week waiting period, the shoulder joint was released. The rats, divided into three groups, were injected intraarticularly with saline in the first group, CS in the second group, and PRP in the third group. After a two-week waiting period, the shoulder joint range of motion of the sacrificed rats was measured. The joint capsule was evaluated histologically for synovial inflammation, type 3 collagen, capillary proliferation, subscapular bursa adhesion and fibrosis.
Result: CS and PRP application did not affect the range of motion of the joint. A significant increase in synovial inflammation a decrease in fibrosis, type 3 collagen deposition, subscapular bursa adhesion were revealed. It was observed that vascular proliferation did not change.
Discussion: CS and PRP treatment yielded similar results in the frozen shoulder animal model. While both of these treatments do not affect the range of motion of the joint, they reverse the pathological changes in a frozen shoulder.
Keywords: Frozen Shoulder, Corticosteroid, Platelet-Rich Plasma, Joint Range of Motion
Introduction
Frozen shoulder (FS), with pain and limitation in joint range of motion, is a common disorder of the glenohumeral joint, but its etiopathogenesis has not been fully elucidated. Complaints usually regress on their own in 1-3 years, but in some cases, this period has been reported to last up to 10 years [1]. It is mainly seen in individuals between the ages of 40 and 60 who are active and constitute a productive power. Considering the prolongation of the recovery period of up to 3-10 years in this disease, which severely restricts daily life, it causes significant socio-economic losses and psychological problems for both the patient and the society [1].
The pathophysiology of FS is not fully understood, but several mechanisms have been suggested. Inflammatory changes, fibrosis and capsular contracture are part of the pathological changes [2]. The pathophysiology of FS is firstly the pathological changes caused by synovial inflammation followed by the development of capsular fibrosis. But the cause of FS is still unknown. Treatment modalities for FS include drug therapy, local steroid injection, physiotherapy, hydrodistention, manipulation under anesthesia, arthroscopic capsule release, and open capsule release [3].
It has been reported that CS treatment in FS is beneficial both in relieving pain and increasing joint range of motion (JRM) [4]. PRP is a fraction of whole blood containing concentrated growth factors and proteins. Cytokines contained in PRP drive tissue healing through autocrine and paracrine effects [5]. It has been reported that PRP injections can be used as a safe and non-surgical intervention to reduce FS pain and improve shoulder mobility [6].
The aim of this study is to determine the effectiveness of CS and PRP treatments in FS and to compare the difference between them.
Material and Methods
Ethical approval was obtained for this study with the decision of Başkent University Medical and Health Sciences Research Board and Experimental Animals Ethics Committee dated 30/01/2017 and numbered 17/02.
In our study, 48 Sprague Dawley, 8-month-old female rats were used. The weight of the rats used ranged from 250 to 300 g. Before being included in the study, subjects were verified to have no gait disorders. Each animal was housed in polycarbonate cages of 8 rats in an environment where they could freely get food and water. Ambient humidity was constant at 50±10% and ambient temperature was 20±2 °C as a standard. The room in which the cages were located was illuminated for 12 hours, from eight in the morning to eight in the evening, in a day-night cycle. During the experiment, the rats were given Purina® standard rat chow. The animals were not treated with activity restriction or rehabilitation (treadmill) throughout the experiment.
The subjects were divided into three groups of sixteen. Half of the subjects in each group were used for JRM measurement (n=8) and the other half for histopathological examination (n=8).
Blood was taken from the tail vein of Group 3 subjects into 1 ml citrate tubes. After centrifugation at 700 RCF for 7 minutes, the plasma at the top of the tube was taken with an injector and prepared for intraarticular injection from the posterior left shoulder of the same rat.
All animals underwent the same standard surgical operation by the same surgeon. Preoperatively, 50mg/kg Ketamine Hydrochloride (Brema®, Bremer Pharma GMBH, Warburg – Germany) and 7 mg/kg Xylazine Hydrochloride (Alfazyne®, Alfasan International B.V., Woersen – Netherlands) were administered intraperitoneally for general anesthesia. The subjects were numbered by writing numbers on their tails. After anesthesia, the rats were weighed and the weights were noted. The left shoulder surgical field was free of hair. The subject was fixed by taping the right front and both hind legs onto the styrofoam in the prone position. The surgical site was cleaned with 10% polyvinylpyrrolidone – iodine-containing antiseptic solution (Batticon®) and covered with a sterile drape. All surgical procedures were performed under sterile conditions.
FS in rats was created in all three groups by modeling the previous study by Villa-Camacho et al. [7]. After this procedure, 10mg/kg of enrofloxacin (Baytril-K®) was given subcutaneously for three days as an antibiotic, but no anti-inflammatory drug was used. At the end of eight weeks of waiting, the sutures were cut and the shoulder was released. Intraoperatively, the range of motion of the joint was examined passively without forcing the shoulder, and the release of the sutures was confirmed.
Group 1 (Control): 1 ml of 0.9% saline solution (SF) to the left shoulder joints of rats. Group 2 (CS): 0.2 ml, single dose 0.5 mg/kg triamcinolone acetonide (Kenakort®-A retard IM/IA 40 mg ampoule, Deva İlaç, Istanbul-Turkey). Group 3 (PRP): In the same session, from the tail vein of rats. PRP obtained from the blood taken was applied intra-articularly from the posterior joint.
In the tenth week (two weeks after injection), all groups were sacrificed by administering euthanasia dose of intraperitoneal Ketamine Hydrochloride (150mg/kg). The treated left shoulders of the subjects were removed en bloc to include the forearm, humerus, clavicle and scapula. A randomly selected half of the sacrificed animals from all three groups (n=8, each group) were reserved for JRM measurement and the other half (n=8, each group) for histopathological examination.
All measurements were performed in the same way in the standard setup. For the experiment, a horizontal line was drawn on the Styrofoam, parallel to the bottom edge of the Styrofoam. Angle values were marked on the lower and upper parts of the line and divided into 2 parts as adduction (Add) and abduction (Abd).
A standard weight of 10 grams (gr) was used for all measurements. The measurements were made before the shoulder joints began to degenerate after sacrification. The tissues were kept moist by dripping saline during the procedures. JRM measurement was performed as previously described by Oki et al. [8].
Tissue samples taken by making coronal sections (parallel to the scapula) from the shoulder joints were subjected to routine histopathological procedures. It was stained with Hematoxylin-Eosin (H&E) stain to evaluate synovial inflammation, type 3 collagen, capillary proliferation, and subscapular bursa adhesion. Picro Sirius Red was stained to evaluate fibrosis. It was evaluated under the light microscope at appropriate magnification.
Statistical Analysis
SPSS 22.0 package program was used for statistical analysis of the data. Categorical measurements were presented as numbers and continuous measurements as Mean±Standard Deviation (SD). The normal distribution of the groups was examined using the Shapiro–Wilk test. Tukey’s multiple comparison test was used for JRM analysis. Fisher’s test was used to analyze histological studies.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
When the groups were compared with each other for joint range of motion, no significant difference was found between them (Table 1 and Figure 1).
Compared to the control group, synovial inflammation was significantly increased in the CS and PRP group (x2=7.273; p=0.007). There was no significant difference between the CS and PRP groups. When the groups were compared among themselves in terms of vascular proliferation, no significant difference was found (x2=1.067; p= 0.3017). Fibrosis was found to be significantly reduced in the CS and PRP groups when compared to the control group (x2=5.923; p= 0.0149). Compared to the control group, Type 3 collagen deposition was found to be significantly reduced in the CS (x2=12.44; p=0.0004) and PRP (x2=7.273; p=0.007) groups. Subscapular bursa adhesion was found to be significantly reduced in the CS (x2=5.333; p=0.02) and PRP (x2=5.333; p=0.02) groups compared to the control group (Table 1).
Discussion
In this study, it was observed that the effect of CS and PRP treatment on JRM was limited in rats with the FS model. On the other hand, it was found that synovial inflammation increased significantly, fibrosis, type 3 collagen deposition, and subscapular bursa adhesion decreased. It was observed that vascular proliferation did not change. CS and PRP act similarly in the treatment of FS.
Intra-articular CS injection is one of the FS treatment protocols [1]. It has been reported that intraarticular CS leads to rapid relief of pain and improvement of JRM [1, 9, 10]. However, in this study, it was seen that CS treatment did not change JRM. On the other hand, parameters such as synovial inflammation, fibrosis, type 3 collagen deposition and subscapular bursa adhesion, which play a role in the pathophysiology of FS, were found to have changed positively. It has been suggested that the increase in fibroblasts in the joint capsule in FS plays a role in the regulation of inflammatory and fibrotic processes [11]. Capsular fibrosis and contracture have been suggested to stiffen the shoulder capsule, limiting the range of motion [12]. In this study, it was found that synovial inflammation increased, whereas fibrosis decreased. This situation was interpreted to mean that both CS and PRP had a therapeutic effect.
It has been shown that the amount of type 3 collagen in the capsule and the adhesion to the subscapular bursa increase in the rat FS model [13]. It has been reported that the synovial fluids of FS patients have high collagen synthesis [14]. In this study, it was found that the amount of type 3 collagen decreased as a result of CS and PRP treatment. The increase in fibroblasts in the synovial fluid increases the amount of type 3 collagen. We think that the decrease in the amount of type 3 collagen shows the therapeutic effect of both CS and PRP. On the other hand, the decrease in subscapular bursa adhesion as a result of both CS and PRP treatments shows the effectiveness of both treatment methods.
Thu et al. reported that adhesive capsulitis intra-articular PRP injection may be a useful option in the treatment of patients with low therapeutic compliance, especially for exercise therapy or contraindications for CS injection or oral pain-reducing drugs [15]. In a study conducted by Feusi et al. on rats, they reported that PRP injections corrected the histological changes in the frozen shoulder [16]. The findings obtained in this study support the findings of Feusi et al. However, we found that both CS and PRP treatment did not affect JRM. According to the histological results, CS and PRP, whose therapeutic effects were also shown in this study, were not effective on JRM; It has been interpreted that physical therapy-assisted CS and PRP application could increase JRM. On the other hand, the reason why CS and PRP treatment did not make a significant difference in JRM in this study may be due to the use of a 10 g weight to measure JRM. In pilot studies, 10-13% of humeral shaft fractures were observed when 20 and 30 grams of weight were used; We evaluated the JRM using a 10- gram weight for measurements.
It is reasonable to investigate FS in an animal model to better define the etiology, pathology, and treatment, which are not fully clear. Since it is not possible to create primary FS on an animal model, it is preferred to create a secondary FS model with joint immobilization in studies. Immobilization is the second most common cause of secondary frozen shoulder after diabetes. Although it is advantageous to perform surgery on large animals such as rabbits and dogs, rats are preferred in many studies because they are easy to obtain, have more anatomical similarities to the human shoulder and are more resistant to surgical procedures. Researchers reported that the shoulder movements of rats during forward walking were similar to the abduction movements of humans [17]. The most obvious limitation of JRM in FS is in the direction of external rotation in humans. On the other hand, it is known to be in the abducent direction in the rat model [18, 19]. In our study, the improvement in the abducent direction was higher in the groups in which recovery was investigated, which is an expected result since this is the direction that rats use most in shoulder movements during walking.
Limitation
The limitation of this study is that all subjects were left in their natural course without any coercion similar to rehabilitation. In this study, there was no difference between the treatment groups and the control group in terms of JRM. We think that the JRM will increase if the subjects are forced similar to rehabilitation.
Conclusion
As a result, there is no difference between CS and PRP application in the treatment of FS, these treatments do not affect JRM, but the levels of molecules that play a role in the pathophysiology of FS have a therapeutic effect. It is thought that the use of CS and PRP application together with other options such as physical therapy in FS may increase JRM.
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. Brun SP. Idiopathic frozen shoulder. Aust J Gen Pract. 2019;48(11):757-61.
2. Koh KH. Corticosteroid injection for adhesive capsulitis in primary care: a systematic review of randomised clinical trials. Singapore Med J. 2016;57(12):646-57.
3. Cho CH, Bae KC, Kim DH. Treatment Strategy for Frozen Shoulder. Clin Orthop Surg. 2019;11(3):249-57.
4. Ladermann A, Piotton S, Abrassart S, Mazzolari A, Ibrahim M, Stirling P. Hydrodilatation with corticosteroids is the most effective conservative management for frozen shoulder. Knee Surg Sports Traumatol Arthrosc. 2021;29(8):2553-63.
5. Paoloni J, De Vos RJ, Hamilton B, Murrell GA, Orchard J. Platelet-rich plasma treatment for ligament and tendon injuries. Clin J Sport Med. 2011;21(1):37-45.
6. Harna B, Gupta V, Arya S, Jeyaraman N, Rajendran RL, Jeyaraman M, et al. Current Role of Intra-Articular Injections of Platelet-Rich Plasma in Adhesive Capsulitis of Shoulder: A Systematic Review. Bioengineering (Basel). 2022;10(1):21.
7. Villa-Camacho JC, Okajima S, Perez-Viloria ME, Walley KC, Zurakowski D, Rodriguez EK, et al. In vivo kinetic evaluation of an adhesive capsulitis model in rats. J Shoulder Elbow Surg. 2015;24(11):1809-16.
8. Oki S, Shirasawa H, Yoda M, Matsumura N, Tohmonda T, Yuasa K, et al. Generation and characterization of a novel shoulder contracture mouse model. J Orthop Res. 2015;33(11):1732-8.
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10. Wang W, Shi M, Zhou C, Shi Z, Cai X, Lin T, et al. Effectiveness of corticosteroid injections in adhesive capsulitis of shoulder: A meta-analysis. Medicine (Baltimore). 2017;96(28):e7529.
11. Akbar M, McLean M, Garcia-Melchor E, Crowe LA, McMillan P, Fazzi UG, et al. Fibroblast activation and inflammation in frozen shoulder. PLoS One. 2019;14(4):e0215301.
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13. Liu YL, Ao YF, Cui GQ, Zhu JX. Changes of histology and capsular collagen in a rat shoulder immobilization model. Chin Med J (Engl). 2011;124(23):3939-44.
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15. Thu AC, Kwak SG, Shein WN, Htun M, Htwe TTH, Chang MC. Comparison of ultrasound-guided platelet-rich plasma injection and conventional physical therapy for management of adhesive capsulitis: a randomized trial. J Int Med Res. 2020;48(12):300060520976032. DOI: 10.1177/0300060520976032.
16. Feusi O, Karol A, Fleischmann T, von Rechenberg B, Bouaicha S, Werner CML, et al. Platelet-rich plasma as a potential prophylactic measure against frozen shoulder in an in vivo shoulder contracture model. Arch Orthop Trauma Surg. 2022;142(3):363-72.
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19. Kanno A, Sano H, Itoi E. Development of a shoulder contracture model in rats. J Shoulder Elbow Surg. 2010;19(5):700-8.
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Javid Mohammadzadeh Azarabadi, Shahla Vahidfar, Ekin Kaya Şimşek, Duygu Türkbey Şimşek. Can platelet-rich plasma be as effective as corticosteroids in the treatment of frozen shoulder in rats? Experimental animal study. Ann Clin Anal Med 2023;14(11):1011-1014
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Seromucinous borderline tumor of the ovary: Correlation of MRI findings with literature
Ebru Hasbay
Department of Radiology, University of Health Sciences, Tepecik Education and Research Hospital Center, Izmir, Turkey
DOI: 10.4328/ACAM.21773 Received: 2023-06-01 Accepted: 2023-07-10 Published Online: 2023-07-22 Printed: 2023-11-01 Ann Clin Anal Med 2023;14(11):1015-1019
Corresponding Author: Ebru Hasbay, Department of Radiology, Faculty of Medicine, Tepecik Education and Research Hospital Center, Izmir, Turkey. E-mail: ebruhasbay@gmail.com P: +90 506 269 62 52 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6288-3169
This study was approved by the Ethics Committee of Health Sciences University Tepecik Training and Research Hospital (Date: 2023-06-06, No: 2023/05-08)
Aim: The aim of this study was to describe magnetic resonance imaging (MRI) findings of ovarian seromucinous borderline tumor (SMBT) and compare the findings with the literature.
Material and Methods: This retrospective study examined 13 patients (15 lesions) with seromucinous borderline tumors in terms of size, configuration, signal intensity (SI), and accompanying ovarian endometriosis. An experienced abdominal radiologist evaluated the MRI findings of SMBT.
Results: On MRI, 15 lesions were found. The mean age of the patients was 48.2±13.5 years. Their mean size was 150.1±68.4 mm. SMBTs appeared as complex cystic-solid masses. T2-weighted SI of the solid portion was hyperintense in almost all of the tumors. Endometriosis was present in 10 patients (66.7%). Asid was detected in 15.4% (n=2) of the patients, while peritoneal dissemination was evident in 30.8% (n=4) of the patients.
Discussion: More than half of tumors were accompanied by endometriosis. High T2-weighted SI of the solid portion could be a specific feature of ovarian SMBTs.
Keywords: Magnetic Resonance Imaging, Neoplasm, Ovary, Seromucinous Tumor, Endometriosis
Introduction
Seromucinous ovarian tumor is a newly defined category of ovarian epithelial tumor in the 2014 World Health Organization (WHO) Classification of Tumors of the Female Reproductive Organs [Kurman RJ, Carcangiu ML, Herrington CS. World Health Organisation classification of tumours of the female reproductive organs. International Agency for Research on Cancer; 2014], which was previously known as Mullerian mucinous borderline tumor (MMBT) and Mullerian mixed epithelial borderline tumor (MEBT).
Seromucinous tumors can be divided into benign, borderline, and malignant. Borderline tumors are the most common type of seromucinous tumors, with an incidence of 7.6% among all ovarian borderline tumors. As with other subtypes of ovarian borderline tumor, seromucinous borderline tumor (SMBT) could be a precursor lesion of a malignant tumor [1]. Like endometrioid and clear cell neoplasms, seromucinous borderline ovarian tumors are frequently associated with endometriosis [2,3]. These endometriosis-related ovarian neoplasms are now attracting attention because they show common molecular genetic changes such as inactivating mutation of the ARID1A tumor suppressor gene [4,5].
The imaging findings of seromucinous tumors have been discussed in a few reports about borderline tumors [6-8]. However, the radiological findings of SBMTs are still unfamiliar to radiologists.
The purpose of this study was to characterize the magnetic resonance imaging (MRI) aspects of SBMTs, as well as their clinicopathologic features, and to compare the results with the literature.
Material and Methods
Ethical consideration
The study protocol was approved by the Institutional Review Board (Approval number 2023/05-08, Date: 06/06/2023).
Patients
This retrospective study investigated the patients who underwent pelvic MRIs in the hospital between July 2016 and April 2023. Seventeen individuals with surgically and histologically confirmed SBMTs were included. Four individuals were excluded because they either did not have a preoperative MRI or were operated on at another hospital. Two of the 13 individuals that remained had bilateral lesions. Finally, preoperative MRI scans for 15 lesions that were included in the study were examined. Figure 1 illustrates the study design’s flow chart.
MRI scanning protocol
MRI examinations were performed with the standard protocol using a 1.5 T MRI system (Siemens Avanto, Siemens Aera, GE Optima360) with a pelvic phased-array coil. The protocol included sagittal, axial, and coronal T2-weighted images without fat saturation, axial T2-weighted fat-saturated images, and axial T1-weighted fat-saturated gradient-echo images before and after intravenous contrast administration (Gadoteric acid, Dotarem®, Guerbet, Paris, 0.1 mmol/kg).
Image analysis
As MRI findings, among the morphological features, the tumor diameter, a signal of the solid portion on T2, the ratio of the solid to cystic part, the presence of ascites, peritoneal spread and relation with the endometriosis were evaluated.
The morphological characteristics of each tumor were divided into 3 types by visual inspection: unilocular cystic with a single nodule, unilocular cystic with multiple nodules, multilocular cystic with solid.
When interpreting MRI images, the presence of “T2 shading,” was considered when the cystic portion showed lower SI on T2WI compared with a simple ovarian cyst.
‘‘T2 WI high SI solid portion ’’was defined when the solid portion of the tumor presented a high SI equal to subcutaneous fat or water.
Clinical and pathological analysis
The demographic information of patients was evaluated by reviewing the clinical records of patients, including age and tumor markers. The radiologist examined the number (percentage) of patients who exhibited increased concentrations of cancer antigen (CA) 125 (≥35.0 IU/mL) and CA-19-9 (≥37.0 IU/mL).
The pathological diagnosis was done based on the pathological reports of our hospital, including tumor subtype, location (right or left or bilaterality), coexisting pathologies such as cystic endometriosis, and histopathologic stage. The histopathologic stage was determined using the International Federation of Gynecology and Obstetrics staging system.
Statistical analysis
Research data were evaluated using the SPSS version 21.0 statistical program (IBM SPSS Statistics for Windows, Armonk, NY: IBM Corp.). The conformity of continuous variables to normal distribution was investigated using visual (histogram and probability graphs) and analytical methods (Kolmogorov-Smirnov/Shapiro-Wilk tests). For the descriptive statistics of the study, mean and standard deviation in data with normal distribution, median, minimum and maximum in data that do not fit normal distribution were shown. Numbers and percentages were used to summarize descriptive statistics for categorical variables. A p-value less than 0.05 was accepted as statistically significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
The results are summarized in Table 1. Thirteen patients (15 lesions) diagnosed with ovarian SMBTs were included in the study. The mean age of the patients was 48.2±13.5 years. It was observed that the tumor side was unilateral in 84.6% (n=11) and bilateral in 15.4% (n=2) of the patients. The mean tumor size was 150.1±68.4 mm.
Pathological examination revealed that endometriosis was present in 10 patients (66.7%). Peritoneal dissemination was found to be present in 30.8% (n=4) and acid in 15.4% (n=2) of patients.
It was observed that 84.6% (n=11) of the tumors had a solid part and the average size was 25.6±15.5 mm. The ratio of the solid part was found to be below 10% in four tumors (30.8%), between 10-30% in 6 tumors (46.2%) and over 30% in three tumors (23.1%) of all tumors. Morphological characteristics of each tumor were divided into 3 types by visual inspection: unilocular cystic with multiple nodules, multilocular cystic with solid and multilocular cystic without solid. Nine of the 13 tumors showed multiple nodules with unilocular (n = 4) or multilocular (n = 9) cystic masses. Of the 13 tumors, 2 were multilocular cystic masses without solid components.
On T2WI, the solid portion of tumors showed a high SI in 11 of 13 cases.
The median value of CEA 125 was 191.8 (10.1-1328.0), and the median value of CEA 19-9 was 78.5 ( 6-1091.0).
Discussion
The 2014 WHO Classification of Tumors of the Female Reproductive Organs introduced seromucinous tumor, which includes borderline tumors, as a new category of ovarian tumor [Kurman RJ, Carcangiu ML, Herrington CS. World Health Organisation classification of tumours of the female reproductive organs. International Agency for Research on Cancer; 2014]. According to the literature, the most common subtype of seromucinous tumor is borderline tumor [8]. This retrospective study assessed the diagnostic value of a set of MR imaging findings of SMBT. The mean age of patients with SMBT was similar to the previous study [8,9] but younger than in the study by Karpathiou et al [10]. The mean size of seromucinous borderline tumor was 150,1±68,4 cm. This study showed different results, in which the patients were older than in the previous study. Borderline tumors were more frequent on the left side with two of them having bilateral lesions. The lesion lateralization was similar to the left-sided predominance in the literature. The appearance of tumors varied in the study. All tumors showed complex cystic masses, unilocular or multilocular with solid portions. These findings were similar to previous studies.
Wu et al reported that endometriosis was found in one-third of SMBT [5]. Endometriosis was twice as frequent in the present study. A previous report showed that T2 shading is a sensitive, but not specific sign for endometriosis [11]. On the other hand, “T2 dark spots”, well-defined hypointense foci due to chronic clot retraction within the ovarian cystic lesion, have low sensitivity but high specificity for endometriosis; these could help differentiate endometriosis from hemorrhagic cysts. Endometriosis is a common disease, defined as the presence of endometrial glands and stroma outside the uterus, and is estimated to affect approximately 10% of women of reproductive age [12,13]. Malignant transformation is rare, and is estimated to occur in 0.6–0.8% of women with ovarian endometriosis [14]. Endometrioid carcinoma and clear cell carcinoma are common histological subtypes associated with endometriosis [14,15]. Seromucinous borderline tumors (SMBTs) are also considered endometriosis-related neoplasms. MR imaging features of these neoplasms are characterized by mural nodules within endometriotic cysts [14,16,17].
Seromucinous borderline tumors have a low pathological stage and long-term disease-free survival, indicating a good prognosis [1,10]. More than 80% of SMBT are diagnosed as stage I. It presents peritoneal dissemination with the frequency of less than 15% [18]. The recurrence rate and mortality are extremely low [19]. In this study, four of the patients had peritoneal involvement in the MRI, however intraoperative consultation/frozen results showed peritoneal washing cytology specimens of these groups were hypocellular and were negative for malignancy.
There are several MRI features with high specificity for the diagnosis of seromucinous borderline tumors: “papillary solid nodule in the endometriotic cyst,” “high SI solid portion on T2WI,” and “low SI core on T2WI” [7,8]. The present study also showed some of these features. “T2 shading” in the cystic portion, which suggests endometriosis and “high-SI solid portion with low SI core” were seen in all cases. The pathological features, such as gross papillary architecture, edematous stroma, and fibrous core of solid components, correspond to these radiological findings [8].
SMBT most commonly appeared multilocular cystic mass with the solid component. The ratio of solid portion was predominantly within 10-30% in 6 tumors (46.2%), which the is similar to the literature. In relation to MRI findings, ‘‘T2 WI high SI solid portion ’’ was extremely high, similar in the previous study.
Limitation
This study had several limitations. First, this study was retrospective. Second, because seromucinous borderline tumor is not common, a limited number of cases have been evaluated. Third, contrast-enhanced images were not available for some patients therefore, enhanced sequences were not evaluated. However, this was unavoidable because of the including long-term patients. Finally, patients who underwent MRI were included in the study, which might cause selection bias.
Conclusion
This study demonstrated radiologically useful findings for the recognized SMBTs. In terms of MR imaging findings intracystic fluid, high SI on T1WI and low SI on T2WI were suggestive of SMBT. Seromucinous borderline tumors had specific features such as a high SI solid portion on T2WI with low SI core with high specificity.
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.21773
Ebru Hasbay. Seromucinous borderline tumor of the ovary: Correlation of MRI findings with literature. Ann Clin Anal Med 2023;14(11):1015-1019
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High doses of methylprednisolone in patients with severe COVID-19 infection
Ahmed Farhan 1, Saira Kanwal 1, Arslan Ahmad 1, Syed Muneeb Ali 2, Naveed Ullah Khan 3
1 Department of General Medıcıne, 2 Department of Critical Care Medicine, 3 Department of Neurology, Pakistan Institute of Medical Sciences, Islamabad, Pakistan
DOI: 10.4328/ACAM.21774 Received: 2023-06-13 Accepted: 2023-07-17 Published Online: 2023-08-01 Printed: 2023-11-01 Ann Clin Anal Med 2023;14(11):1020-1024
Corresponding Author: Saira Kanwal, Department of General Medıcıne, Pakistan Institute of Medical Sciences, Islamabad, Pakistan. E-mail: drsairakanwal@gmail.com P: +92 321 248 34 51 Corresponding Author ORCID ID: https://orcid.org/0000-0002-7444-219X
This study was approved by the Ethics Committee of Shaheed Zulfiqar Ali Bhutto Medical University (Date: 2021-04-28, No: F.1-1/2015/ERB/SZABMU/771)
Aim: Hypoxemia caused by lung injury is a typical feature of SARS- CoV-2 Pneumonia. Although corticosteroids are not the definite treatment for this condition, they have proven to be effective in some cases. In this study, we aimed to determine if high doses of methylprednisolone are safe and effective in patients suffering from severe SARS-COV-2 pneumonia.
Material and Methods: In all, 78 patients were enrolled in the study. The randomized double-blinded study involved half of the patients receiving methylprednisolone and half receiving a placebo. The primary outcome, calculated by comparing the percentage of in-hospital deaths between the two groups, was not statistically significant. In the Methylprednisolone group, patients had decreased lung compliance, increased oxygen demand, and an increased risk of infections, as measured by procalcitonin levels.
Results: A total of 78 patients were divided equally to get a placebo or pulse methylprednisolone in this double-blinded, randomized control trial. The study included 64.1% (50) female participants and 35.9% (28) male participants. Serum Ferritin levels were significantly increased in the placebo group in comparison to the methylprednisolone group. Procalcitonin was increased in the methylprednisolone group. The requirement for oxygen inhalation was lower in the placebo group. The total hospital stays, and days spent on mechanical ventilation were longer in patients who survived.
Discussion: Methylprednisolone use in severe COVID-19 infections did not improve survival compared to placebo. Furthermore, methylprednisolone significantly increased the risk of infection.
Keywords: SARS-COV-2 Infection, Methylprednisolone, Mechanical Ventilation
Introduction
A worldwide pandemic caused by SARS Corona Virus 2 (SARS-CoV-2) gripped the world in 2019, infecting more than 590 million people and claiming 6.4 million lives. The majority of patients recover well, but 14% develop severe pneumonia and 5% develop critical pneumonia [1]. Lung damage, acute respiratory distress syndrome, and respiratory failure are the most common causes of death in patients. Lymphopenia with low CD4 and CD8 lymphocytes may be associated with disease activity and poor prognosis [2]. Key histological features include exudative diffuse alveolar damage, capillary congestion, and microthrombi [3,4].
Infection can be controlled by a well-adjusted immune response, but lung injury can result from an extravagant response. A cytokine storm is induced by impaired gaseous exchange and alveolar patency caused by neutrophils and macrophages, resulting in lung injury and the release of IL-1, IL-6, and TNF alpha by infected cellular debris [5]. Due to their ability to suppress immune functions by impairing the innate immune system, corticosteroids have been widely discouraged because of the fear of worsening viral transmission. However, the development of severe or critical pneumonia in patients receiving long-term maintenance doses of steroids is not associated with COVID-19 [6]. The Multinational Surviving Sepsis Guideline in COVID-19 recommends giving steroids to patients with severe COVID-19 who have ARDS on mechanical ventilation (based on very limited evidence) [7]. However, a study conducted on COVID-19 patients with the RECOVERY Trial has shown that using dexamethasone, a corticosteroid, as a treatment for severe COVID-19 requiring oxygen therapy or a mechanical ventilator improved the outcome significantly [8].
Similar to influenza, Middle East respiratory syndrome, or severe acute respiratory syndrome, steroids have a well-established role in viral pneumonias [9]. Glucocorticoids are used in pulse doses in order to combat cytokine storms leading to ARDS, disseminated intravascular coagulation, shock and death, and to reduce affliction and mortality [10]. This study aimed to evaluate the effectiveness of high-dose methylprednisolone in patients with severe SARS-CoV-2 pneumonia.
Material and Methods
The study was conducted at the Intensive Care Unit, Pakistan Institute of Medical Sciences, Islamabad, between January 2021 and December 2021, as a single-center, double-blind, randomized, controlled parallel group study. This trial was registered with the Iranian Registry of Clinical Trials (IRCT) under the number IRCT20200723048178N3. Ethical approval was granted by the Ethical Review Board (ERB) of Shaheed Zulfiqar Ali Bhutto Medical University on 28 April 2021, No. F.1-1/2015/ERB/SZABMU/771. Patients were enrolled only after informed consent. All data of the patients were kept confidential except for the researchers and the patient.
A total of 78 patients were randomized using a “simple” randomization method that considered individuals as one unit. With the help of “https://www.randomizer.org/”, a random number table was generated. Two groups of patients were labelled “controls” and “interventional”. The caregivers (ICU nurse) and patients were blinded.
Setting
This study included patients (>18 years) who were confirmed positive for SARS-CoV-2 by Real-Time Polymerase Chain Reaction (RT-PCR). The study included patients with severe COVID-19 infections. COVID-19 infection is defined as patients whose oxygen saturation is 94% on room air, whose arterial partial pressure of oxygen to fraction of inspired air ratio is 300mm Hg, whose respiratory rate exceeds 30 breaths per minute, or whose radiological images indicate a lung infiltrate of > 50% [11]. According to standard guidelines, all patients received dexamethasone 6 mg for a minimum of three days [8]. Patients with HIV infection, active tuberculosis, pulmonary tuberculosis history, creatinine clearance (CrCl) of less than 30 ml/minute, an ejection fraction of 30% or less, advanced liver disease, and methylprednisolone allergy were excluded from the study.
Data collection
Two groups of 39 people each were formed. On one arm, 1000 mg of Methylprednisolone (Solumedrol®) was infused into 100 ml of normal saline once daily for three days, diluted in 100 ml of water. The other arm received 100 ml of normal saline (placebo). Infusion bottles were numbered so that the nurse administering the fluid was unaware of which bottles contained the actual medication. Oxygen therapy, ventilator support, antiviral drugs (remdesivir), antibiotics, fluids, PPIs, and anticoagulants were all administered to the patients.
Outcomes
The primary outcome was the in-hospital mortality between the two groups after 28 days. The total duration of hospital stay, change in the inflammatory markers (i-e. C-Reactive Protein (CRP), InterLeukin-6 (IL-6)) before and after treatment with methylprednisolone, days on Mechanical Ventilation (MV), changes in the requirement of oxygen as measured by the Fraction of inspired Oxygen (FiO2), Positive End-Expiratory Pressure (PEEP), and static lung compliance (C-Diff) were the secondary outcomes.
Data Analysis procedure
Data were analyzed using SPSS version 25. The primary outcome was mortality at 28 days after enrollment. The comparisons were conducted according to the intention-to-treat principle. A total of 78 patients were included in the study.
Secondary outcomes i-e the total duration of hospital stay, change in the inflammatory markers before and after treatment with methylprednisolone, days on Mechanical Ventilation (MV), changes in the requirement of oxygen as measured by the Fraction of inspired Oxygen (FiO2), Positive End-Expiratory Pressure (PEEP), and static lung compliance (C-Diff) were measures as mean differences between the methylprednisolone and the placebo group. The same comparison was done in the discharged and death groups. This study was performed at Pakistan Institute of Medical Sciences, and all investigators were unaware of patients’ treatment assignments.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
In total, 78 patients participated in the study. Supportive care and conventional treatment were provided to all patients. Pulsed methylprednisolone was administered to half of the patients, while placebos were administered to the other half.
The study included 64.1% (50) female participants and 35.9% (28) male participants. Table 1 summarizes the baseline characteristics of study participants before and after treatment between groups.
Table 2 shows the difference in variables after the intervention. The difference was calculated by subtracting the value of a variable after the intervention from the baseline value.
There was a significant increase in ferritin levels in patients who received a placebo compared to those who received methylprednisolone (P value 0.001). Compared to the placebo group, methylprednisolone significantly increased procalcitonin levels (p-value (<0.001). FiO2 showed significant reductions in oxygen requirements in patients receiving placebo compared to methylprednisolone (p-value 0.032). Static Lung Compliance (C-stat) increased in the methylprednisolone group (p-value 0.024), but there was no effect on PEEP values in either group.
Patients with high oxygenation requirements died more frequently. This was seen as the number of deaths was more in patients whose mean change in the FiO2 values was less compared to those whose FiO2 dropped significantly. A significant reduction in peep requirements from baseline was also associated with mortality benefits (p-value 0.001). The C-Stat values, on the other hand, were positively associated with improved outcomes (p-value 0.001).
The total hospital stay and the number of days spent on mechanical ventilation were longer in patients who survived. Patients who died spent an average of 11.45±7.27 days on mechanical ventilation compared to 14.8±5.93 days in those who survived (p=0.067). Additionally, the mean length of hospital stays in patients who died was 14.16±9.45 compared to 19.15±5.8 in patients who survived (p-value 0.008).
Discussion
We found no improvement in the hospital mortality in patients receiving standard care and 1000mg of methylprednisolone for 3 days than in patients receiving standard care and placebo, rather a worsening of mortality. In terms of secondary outcome, Ferritin levels significantly increased in placebo-treated patients compared to methylprednisolone-treated patients. D-dimers and IL-6 worsened after therapy, but CRP improved but was not statistically significant. Methylprednisolone therapy significantly increased procalcitonin levels. FiO2 significantly decreased in patients receiving a placebo versus methylprednisolone (p-value 0.032). PEEP values did not change in either group and high-dose pulse therapy did not shorten hospital stays.
Although steroids have been extensively used in syndromes closely linked to COVID-19 like SARS, Middle East Respiratory Syndrome, MERS, influenza, and community-acquired pneumonia, the evidence to support or reject the use of glucocorticoids in such circumstances is weak due to the lack of RCTs [12- 15]. In viral infections, glucocorticoids are associated with favorable outcomes based on patient selection, dosage, type, and time from infection. In patients treated with systemic glucocorticoids for MERS, SARS, or influenza, viral clearance is slow [13,16,17].
The strengths of corticosteroids used in available publications are not homogeneous [18]. The two main evidentiary drugs used extensively are dexamethasone and remdesivir [19]. In a study conducted at Bellvitge University Hospital, a tertiary care hospital with 750 beds in Barcelona (Spain), similar outcomes were observed. Two groups of patients were treated with methylprednisolone 100 mg/day pulses for three days (189 patients) and dexamethasone 6 mg/day for 10 days (493 patients). In-patient hospital mortality, invasive ventilation, critical care admissions, and time spent in hospitals before discharge were significantly higher in the methylprednisolone group as depicted in our study.
Despite the improvements in CRP, the results of both the dexamethasone and methylprednisolone groups were comparable in terms of inflammatory markers. However, our study found a slight improvement in CRP, but not statistically significant, but worsening of other inflammatory markers after receiving pulse steroids. This study differed from the Spain study in that we administered pulse steroids to ICU patients who were on mechanical ventilation, whereas the Spanish study involved patients who were not on mechanical ventilation [20].
According to a Brazilian double-blind placebo-controlled trial, methylprednisolone was not advantageous in treating COVID-19 pneumonia patients with SpO2 greater than 94% at room air or in need of noninvasive or invasive ventilation. Among those given methylprednisolone 0.5 mg/kg/12h or placebo for five days, 28-day mortality rates were 37.1% and 38.2%, respectively [21].
In our study, the proportion of patients developing septic shock was higher in the pulse steroid group than in the placebo group as reflected by high procalcitonin levels in the corticosteroid-receiving group. The use of steroids in viral syndromes and influenza increases the risk of secondary bacterial and fungal infections [22].
Dexamethasone has been widely used in hospitalized patients worldwide as a result of the results of the RECOVERY trial [8]. There is a better mortality outcome for COVID positive patients who receive dexamethasone during the first week of their disease and require oxygen support. This indicates that immunopathological factors could play a role at a given stage of a disease, accompanied by active virus replication.
Since this study was conducted in a tertiary care hospital in an area requiring a high number of referred patients with severe diseases, one reason for the high mortality rate may have been the fact that patients included in our study had severe diseases and all required mechanical ventilation. The observed outcomes might have been affected by a different time and period of corticosteroid administration.
Conclusion
In this study, we found that high-dose methylprednisolone did not improve survival in patients with SARS-CoV-2 infected patients as compared to the placebo. Significant decreases in some of the inflammatory markers were seen in the methylprednisolone group as compared to placebo. Large multicentred studies with high power are required to confirm the findings in our 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. 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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Ahmed Farhan, Saira Kanwal, Arslan Ahmad, Syed Muneeb Ali, Naveed Ullah Khan. High doses of methylprednisolone in patients with severe COVID-19 infection. Ann Clin Anal Med 2023;14(11):1020-1024
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Evaluating the diagnostic efficacy of secretoneurin in ıdentifying heart failure among dyspneic patients in the emergency department
Tahir Talat Yurttaş 1, Ali Cankut Tatliparmak 2, Sarper Yilmaz 3, Asım Bedri Erdem 4, Özgür Dikme 4, Özlem Dikme 4
1 Department of Emergency Medicine, Faculty of Medicine, Istanbul Yeni Yuzyil University, 2 Department of Emergency Medicine, Faculty of Medicine, Uskudar University, 3 Department of Emergency Medicine, Faculty of Medicine, Istanbul Dr. Lutfi Kirdar City Hospital, 4 Department of Emergency Medicine, Faculty of Medicine, Istanbul Training and Research Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.21783 Received: 2023-06-07 Accepted: 2023-07-10 Published Online: 2023-07-15 Printed: 2023-11-01 Ann Clin Anal Med 2023;14(11):1025-1028
Corresponding Author: Ali Cankut Tatliparmak, Department of Emergency Medicine, Faculty of Medicine, Uskudar University, Istanbul, Turkey. E-mail: alicankut@gmail.com P: +90 216 400 22 22 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6729-5021
This study was approved by the Ethics Committee of Health Sciences University Istanbul Training and Research Hospital Ethics Committee (Date: 2021-06-04, No: 2864)
Aim: The accurate and timely diagnosis of heart failure is crucial for optimal patient management. This study aimed to evaluate the diagnostic potential of secretoneurin, a novel biomarker, in patients presenting with dyspnea to the emergency department.
Material and Methods: The study included 51 patients, 19 of whom were diagnosed with heart failure, and 32 patients without heart failure. Secretoneurin levels were measured and compared with established biomarkers, N-terminal pro-brain natriuretic peptide (NT-proBNP) and high sensitivity cardiac troponin-t (hs-cTnT), for diagnostic utility.
Results: The study findings revealed a significant elevation of secretoneurin levels in heart failure patients compared to those without heart failure (p<0.001). In addition, secretoneurin exhibited moderate discriminative properties (AUROC: 0.643, 95% CI: 0.457 – 0.828) when differentiating heart failure from non-heart failure patients. However, NT-proBNP (AUROC: 0.864, 95% CI: 0.739 – 0.99) and hs-cTnT (AUROC: 0.759, 95% CI: 0.596 – 0.922) demonstrated superior diagnostic performance.
Discussion: Secretoneurin is promising as a potential diagnostic biomarker for heart failure, with elevated levels observed in heart failure patients. Further investigations are warranted to determine its precise role and potential contribution as part of a comprehensive diagnostic approach.
Keywords: Secretoneurin, Heart Failure, Dyspnea, Diagnostic Biomarker, Emergency Department.
Introduction
In emergency medicine, expeditious and accurate diagnosis is pivotal, significantly influencing patient outcomes [1]. One such diagnostic challenge often encountered is the differentiation of dyspnea etiology in patients [2]. Amidst the plethora of possibilities, heart failure tends to be a recurrent determinant of this presentation [3]. Traditional cardiovascular biomarkers, including B-type natriuretic peptides (BNPs) signifying cardiomyocyte stress, and cardiac-specific troponins, indicating cardiomyocyte injury, have indeed found their place in contemporary clinical practice [4–6]. Yet, they fall short of providing a comprehensive understanding of the ongoing pathophysiology, particularly concerning aspects such as neuroendocrine tone and cardiomyocyte Ca+2 homeostasis. Such limitations subtly underscore the persistent need for additional, perhaps more nuanced, biomarkers in heart failure.
Secretoneurin, a derivative of secretogranin II, belonging to the chromogranin-secretogranin (granin) family of proteins implicated in cardiac pathophysiology, enters the arena of promising biomarkers [7]. Secretoneurin’s emergence arises from the proteolytic activity of PC1/3 and PC2 on secretogranin II, with their activity seen to triple in failing myocardium [8]. Circulating secretoneurin levels have been reported to elevate in heart failure patients, rendering it a potential marker of interest [9]. Furthermore, animal models have demonstrated secretoneurin’s beneficial influence on myocardial ischemia/reperfusion injury, reduction of cardiomyocyte apoptosis, promotion of angiogenesis, and improvement of left ventricular function post-myocardial infarction [10,11]. This intriguing array of attributes lends credence to the hypothesis that secretoneurin might not only be a mere bystander marker but also an active player influencing the disease process.
In light of the aforementioned considerations, this study primarily aims to elucidate secretoneurin’s diagnostic utility as a biomarker in patients presenting with undifferentiated dyspnea to the emergency department. More specifically, the study will investigate whether secretoneurin levels differ significantly between patients ultimately diagnosed with heart failure and those with alternative etiologies of dyspnea. Through this inquiry, it is hoped that the diagnostic landscape of heart failure will be further enriched, ultimately guiding more accurate and timely interventions.
Material and Methods
Study Design
This study utilized a cross-sectional design to evaluate the diagnostic accuracy of secretoneurin for heart failure diagnosis in patients presenting to the emergency department with symptoms of shortness of breath.
Selection of Participants
A total of 51 consecutive patients over the age of 18 who presented to the emergency department of Istanbul Training and Research Hospital between September 2021 and October 2021 with chief complaint of shortness of breath and Canadian Triage and Acuity Scale of 1 or 2 were enrolled in the study [12]. Patients with a known diagnosis of heart failure with reduced ejection fraction, patients undergoing cardiopulmonary resuscitation within the emergency department and patients with altered mental status were excluded from the study.
Data Collection
Clinical and laboratory data were collected from each participant upon enrollment. The variables of interest included age, sex, secretoneurin levels, procalcitonin levels, high sensitivity cardiac troponin-t (hs-cTnT) levels, C-reactive protein (CRP) levels, and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Age was recorded as a continuous variable, while sex was categorized as male or female. Secretoneurin, procalcitonin, hs-cTnT, CRP, and NT-proBNP levels were measured using standard laboratory methods.
Statistical Analysis
Descriptive statistics were used to summarize the demographic and clinical characteristics of the study population. Continuous variables were presented as mean ± standard deviation or median with interquartile range, depending on the distribution. Categorical variables were presented as frequencies and percentages. The independent t-test or Mann-Whitney U test was used to compare continuous variables between patients with and without heart failure, based on the normality assumption. The chi-square test or Fisher’s exact test was used to compare categorical variables. A p-value less than 0.05 was considered statistically significant.
Ethical Considerations
This study was conducted in accordance with the principles outlined in the Declaration of Helsinki. Ethical approval was obtained from the institutional review board of Health Sciences University Istanbul Training and Research Hospital Ethics Committee (4/6/2021 no: 2864). Informed consent was obtained from each participant prior to enrollment in the study.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Fifty-one patients were enrolled in the study and categorized into two groups based on their definitive diagnoses: heart failure (n=19) and no heart failure (n=32) (Table 1). The mean age of the study participants was 67.70 ± 12.28 years, with no statistically significant difference observed between the groups (heart failure: 70.28 ± 13.19; no heart failure: 66.10 ± 11.63; p=0.262). Of the total number of patients, 25 were female (49%), and there was no statistically significant difference in gender distribution between the two groups (p=0.691).
Regarding biomarker analysis, there was no statistically significant difference in procalcitonin levels between the heart failure group (median: 0.073, IQR: 0.05 – 0.146) and the group without heart failure (median: 0.065, IQR: 0.05 – 0.151) (p=0.676). However, the median hs-cTnT level was significantly lower in the group without heart failure (median: 0.011, IQR: 0.005 – 0.015) compared to the heart failure group (median: 0.02, IQR: 0.016 – 0.039) (p<0.001). Similarly, there was no statistically significant difference in CRP levels between the two groups (no-heart failure group median: 16.2, IQR: 6.9 – 52; heart failure group median: 18.45, IQR: 5.28 – 47.25; p=0.955). However, the median NT-proBNP level was significantly lower in the group without heart failure (median: 200.5, IQR: 85 – 661.28) compared to the heart failure group (median: 4044, IQR: 1787 – 9384) (p<0.001). Moreover, the average secretoneurin level was found to be significantly lower in the group without heart failure (mean: 132.33 ± 41.57) than in the heart failure group (mean: 158.17 ± 28.31), with a mean difference of 25.84 (95% CI: 6.12 – 45.56).
To evaluate the diagnostic utility of the biomarkers that exhibited statistically significant differences between the groups (NT-proBNP, hs-cTnT, and secretoneurin), receiver operating characteristic (ROC) analysis was performed (Table 2). The analysis revealed that the NT-proBNP level displayed excellent discriminative properties in distinguishing heart failure from no heart failure in patients presenting to the emergency department with dyspnea (AUROC: 0.864, 95% CI: 0.739 – 0.99, p<0.001). The discriminatory properties of hs-cTnT were found to be acceptable (AUROC: 0.759, 95% CI: 0.596 – 0.922, p=0.011). However, secretoneurin demonstrated no discriminative properties for this differentiation (AUROC: 0.643, 95% CI: 0.457 – 0.828, p=0.162).
Discussion
Our study aimed to investigate the potential of secretoneurin as a diagnostic biomarker for heart failure. The findings demonstrated that secretoneurin levels were significantly elevated in patients with heart failure compared to those without heart failure. This result suggests that secretoneurin is associated with heart failure, potentially revealing its prospective utility in diagnostic strategies.
This study adds to the emerging body of research that suggests secretoneurin’s role in cardiovascular pathophysiology. It is known that the granin family of proteins, of which secretoneurin is a member, plays an important role in cardiac pathophysiology [13]. Based on the literature review, several studies have highlighted the role of secretoneurin in cardiovascular pathophysiology, particularly in heart failure. In a comprehensive review by Watanabe, 2021, it was noted that secretoneurin, a member of the chromogranin-secretogranin (granin) family of proteins, is elevated in patients with heart failure compared to healthy controls [14]. This observation aligns with our study findings, where we observed significantly higher secretoneurin levels in heart failure patients compared to those without heart failure.
Our findings build upon this knowledge, providing further evidence for the involvement of secretoneurin in heart failure. Yet, the intricacies of secretoneurin’s role in the heart and its potential as a therapeutic tool warrant further investigation.
Moreover, Watanabe reported that high levels of secretoneurin are associated with an increased risk of mortality in patients with heart failure, aortic stenosis, or those undergoing various cardiac surgeries [14]. This suggests that secretoneurin may not only serve as a diagnostic biomarker but could also potentially be used as a prognostic marker in heart failure. However, our study did not investigate the prognostic utility of secretoneurin, and this could be an interesting avenue for future research.
Additionally, we examined the diagnostic potential of established heart failure biomarkers, hs-cTnT and NT-proBNP. Our findings were consistent with existing knowledge that these biomarkers are elevated in heart failure patients [15,16]. Our study further emphasized their diagnostic value by revealing their excellent and acceptable discriminative properties, respectively, in distinguishing heart failure patients from those without heart failure.
The ROC analysis performed in our study provided further insights into the diagnostic utility of these biomarkers. Despite a significant difference in secretoneurin levels between the two groups, secretoneurin did not display discernable discriminative properties. This indicates that although secretoneurin might be elevated in heart failure patients, it might not be sufficient on its own to distinguish heart failure from other conditions.
However, one noteworthy observation from this study is the comparable levels of secretoneurin in patients with heart failure, irrespective of gender and age demographics. This consistency across demographics indicates secretoneurin’s potential utility as a supplemental biomarker in a comprehensive diagnostic approach, as it appears to be unaffected by demographic factors that can typically influence biomarker levels.
Moreover, it is essential to acknowledge the complex pathophysiology of heart failure, with multiple overlapping factors contributing to the disease state. Heart failure is often associated with other illnesses, such as sepsis and ischemic heart disease, which may also influence secretoneurin levels [17,18]. This dual influence could potentially impact the discriminative properties of secretoneurin and may explain the results observed in this study. Further research is necessary to parse out these influences and provide more definitive insight into the role of secretoneurin in diagnosing heart failure.
Lastly, considering the findings of this study, it is intriguing to speculate about the future research directions in this domain. While secretoneurin may not have proven to be an effective standalone biomarker for diagnosing heart failure in this study, its elevated levels in heart failure patients could possibly indicate a more nuanced role in the pathophysiology of the disease. Further exploration of this role could lead to a more comprehensive understanding of heart failure and potentially pave the way for more advanced diagnostic strategies.
In conclusion, the present study provides valuable insights into the potential role of secretoneurin as a diagnostic biomarker in heart failure. Although it has not demonstrated robust diagnostic performance of NT-proBNP or hs-cTnT, secretoneurin still holds potential as an additional tool to be used in conjunction with existing biomarkers. Future research should delve deeper into understanding the intricate dynamics between secretoneurin, heart failure, and overlapping medical conditions to fully ascertain the clinical utility of secretoneurin in diagnosing heart failure.
Limitations
The study’s limitations should be carefully considered. Although a statistically significant difference in secretoneurin levels between the groups was observed, the wide 95% confidence interval associated with the AUROC analysis introduces uncertainty regarding secretoneurin’s discriminative abilities. This wide confidence interval can be attributed to the study’s relatively small sample size, which limits the precision of the results. Additionally, the presence of a well-established biomarker, NT-proBNP, which has demonstrated good discriminatory performance for heart failure diagnosis, suggests that secretoneurin may not offer significant additional value as a stand-alone diagnostic tool. Further research with larger sample sizes is needed to provide more conclusive evidence regarding the discriminatory capabilities of secretoneurin compared to NT-proBNP.
Conclusion
In this study, secretoneurin demonstrated statistical significance as a diagnostic biomarker for heart failure, although it lacked the discriminative properties of established biomarkers like NT-proBNP and hs-cTnT. Therefore, while secretoneurin may not serve as a standalone biomarker, its potential utility as an additional tool in a comprehensive diagnostic approach necessitates further exploration.
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
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3. Miró Ò, Gil V. Accurate predictions in the emergency department will lead to improvements in patient outcomes: about the urgency to apply this concept to patients with dyspnoea and acute heart failure. Eur J Emerg Med2019;26(6):390-1.
4. Khan S, Rasool ST. Current Use of Cardiac Biomarkers in Various Heart Conditions. Endocr Metab Immune Disord Drug Targets. 2021;21(6):980-93.
5. Everett BM, Ridker PM. Biomarkers for Cardiovascular Screening: Progress or Passé? Clin Chem. 2017;63(1):248-51.
6. Garg P, Morris P, Fazlanie AL, Vijayan S, Dancso B, Dastidar AG, et al. Cardiac biomarkers of acute coronary syndrome: from history to high-sensitivity cardiac troponin. Intern Emerg Med. 2017;12(2):147-55.
7. Ottesen AH, Christensen G, Omland T, Røsjø H. Glycosylated Chromogranin A: Potential Role in the Pathogenesis of Heart Failure. Curr Heart Fail Rep. 2017;14(6):478-88.
8. Røsjø H, Stridsberg M, Florholmen G, Stensløkken K-O, Ottesen AH, Sjaastad I, et al. Secretogranin II; a protein increased in the myocardium and circulation in heart failure with cardioprotective properties. PLoS One. 2012;7(5):e37401.
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10. Theurl M, Schgoer W, Albrecht-Schgoer K, Lener D, Wolf D, Wolf M, et al. Secretoneurin gene therapy improves hind limb and cardiac ischaemia in Apo E−/− mice without influencing systemic atherosclerosis. Cardiovasc Res. 2015;105(1):96-106.
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13. Troger J, Theurl M, Kirchmair R, Pasqua T, Tota B, Angelone T, et al. Granin-derived peptides. Progress in Neurobiology. 2017;154:37-61.
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Tahir Talat Yurttaş, Ali Cankut Tatliparmak, Sarper Yilmaz, Asım Bedri Erdem, Özgür Dikme, Özlem Dikme. Evaluating the Diagnostic Efficacy of Secretoneurin in Identifying Heart Failure Among Dyspneic Patients in the Emergency Department. Ann Clin Anal Med 2023;14(11):1025-1028
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Comparison of anxiety and patient satisfaction before and after elective hysterectomy under general or spinal anesthesia: A questionnaire study
Mustafa Levent Cetın 1, Ali Akdogan 2, Davut Dohman 2
1 Department of Anesthesiology and Critical Care, Bursa City Training and Research Hospital, Bursa, 2 Department of Anesthesiology and Critical Care, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey
DOI: 10.4328/ACAM.21787 Received: 2023-06-09 Accepted: 2023-07-31 Published Online: 2023-08-08 Printed: 2023-11-01 Ann Clin Anal Med 2023;14(11):1029-1033
Corresponding Author: Ali Akdogan, Department of Anesthesiology and Intensive Care, Faculty of Medicine, Karadeniz Technical University, 61080, Trabzon, Turkey. E-mail: draliakdogan@yahoo.com P: +90 462 377 58 98 F: +90 462 325 53 98 Corresponding Author ORCID ID: https://orcid.org/0000-0001-7592-3844
This study was approved by the Ethics Committee of Karadeniz Technical University (Date: 2010-10-21, No: 2010/56)
Aim: One of the most important purposes of preoperative assessment is to reduce anxiety. Anxiety has a negative effect on anesthesia, operation and post-operative healing. It was aimed to this study find out the causes of anxiety related to anesthesia, measure preoperative anxiety levels, and determine the relationship between anxiety and patient satisfaction in elective hysterectomy procedures.
Material and Methods: After obtaining informed consent, 101 volunteer patients aged 18-65 years who were going to undergo elective hysterectomy surgery were included in the study. Patients were asked demographic variables, the first three causes of anxiety related to anesthesia, to respond to State-Trait Anxiety Inventory [STAI] I and II tests and complete QoR-40 test.
Results: While preoperative STAI I values were higher than STAI II, postoperative STAI I values were found to be decreased. It was seen that the patients’ anxiety level was too high during the preoperative period. It was found that the causes of preoperative anxiety related to anesthesia were oversleeping after surgery, post-operative pain, nausea and vomiting. No relationship between preoperative anxiety and postoperative patient satisfaction was found.
Discussion: In this study, it was observed that being older, having given birth before, being single, and increased anxiety in patients who underwent spinal anesthesia. In addition, it was found that there was no significant change in anxiety level according to education level, number of children, occupation, and history of surgery.
Keywords: Anxiety, Hysterectomy, Patient Satisfaction, Anesthesia
Introduction
Preoperative evaluation includes taking the patient’s history, laboratory investigations, and anesthesia risk assessment. It aims to inform the patient about the upcoming procedure and relieve anxiety with pharmacological and non-pharmacological methods [1].
Anxiety that changes both psychological and physiological status, has a negative effect on operation, anesthesia and postoperative recovery. Listening to the patient’s anxieties strengthens the ability to cope with anxiety. There are too many aims of preoperative preparation. One of the most important is to reduce anxiety [2,3].
In this study, it was aimed to find out the causes of anxiety related to the anesthesia, measure pre- and post-operative anxiety levels and to determine the relationship between anxiety and patient satisfaction in elective hysterectomy procedures.
Material and Methods
After obtaining ethical approval and informed consent [2010/56-21.10.2010] 101 voluntary patients who were to undergo elective hysterectomy operation, aged 18 to 65 years were included and randomized in the study regardless of the educational status.
Pre-anesthetic examinations of all patients were performed before the operation, and patients who met the criteria were given verbal information about the study and their written and verbal informed consent was obtained. The questionnaire forms were filled out by literate patients on their own, while the the forms were read to illiterate patients by the researcher one by one in an understandable way, given a sufficient period of time and marked according to the patient’s response. Patients who had psychological disorders and any medical problem that might have limited evaluation were excluded from the study.
Patients were visited pre and postoperatively. Age, educational status, marital status, number of children, occupational status, history of surgery, type of anesthesia and demographic information about comorbidities took part in the first chapter.
Twelve questions were given that included concerns about anesthesia and it was asked to record the first common 3 causes of anxiety related to anesthesia in the second chapter. Patients were asked to respond to the STAI I and STAI II tests, which measured state and trait anxiety in the third chapter. They were asked to fill QoR-40 test consisting of 40 questions, which measured the quality of postoperative recovery in the fourth chapter.
Patients were asked to fill out the demographic data form, consisting of anxiety causes and STAI I and II in the preoperative period and QoR-40 ve STAI I in the postoperative period.
STAI measured state and trait anxiety levels. Higher and lower scores indicated greater and lower scores of anxiety, respectively. Patient’s anxiety was considered by the values from State- Trait Anxiety Inventory as 0-19 no anxiety, 20-39 low anxiety, 40-59 moderate anxiety, 60-79 high anxiety, 80 and above panic and very high anxiety.
QoR-40 [Quality of Recovery Score- 40]
A 5-point Likert-type scale was to measure the quality of postoperative recovery. Minimum of 40, maximum of 200 scores could be given. No special education was needed to apply the questionnaire. An important advantage was that the questionnaire could be completed quickly and by the patients themselves.
Statistical Analysis
All statistical analysis in our study were done with SPSS for Windows 11.0 Turkish package software. Anova analysis method was used in pre and postoperative STAI evaluation and T test, which is a descriptive statistical method, was used in the analysis of the causes of anxiety.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
The overall preoperative and postoperative evaluations of the 101 patients who were included in the study are shown in Table 1. Patients’ ages differ from 35 to 65, with a mean age of 49,71±8,86.
STAI-I values in the preoperative period were between 19-76; STAI-II values were between 20-80. Preoperative mean STAI-I values were 43,50±13,53, mean values of STAI-II in the same period were 40,30±9,65. STAI-I values in the postoperative period were between 20 and 52. Postoperative mean STAI-I values were 28,07±6,25 (Figure 1).
Preoperative and postoperative state-trait anxiety inventory [STAI-I] scores and the comparisons according to the general evaluation of the patients who were included in the study are summarized in Table 2.
STAI-I values decreased significantly in both groups under the age of 50 and 50 years old and older in the postoperative period to 27,75 and 28,48 respectively [p<0,05] (Table 2). The patients were divided into 2 groups according to the type of anesthesia: general and regional (spinal). The preoperative and postoperative mean STAI-I scores of 58 patients operated under general anesthesia were 40,28 and 26,31 respectively; the preoperative and postoperative mean STAI-I scores of 43 patients operated under spinal anesthesia were 47,86 and 30,44 respectively and this decrease was found to be significant (Table 2).
According to the marital status, the preoperative mean STAI-I score of 88 married patients included in the study was 42.78, decreasing to 28.19 in the postoperative period (Table 2). The preoperative mean STAI-I score of 13 single and widow patients in the study was calculated as 48.38, and the postoperative mean STAI-I score was 27.23. The decrease in STAI scores was significant in both groups [p<0,05] (Table 2).
According to the history of the operation, the patients were evaluated in 2 groups. The preoperative and postoperative mean STAI-I score of patients without any history of operation was 43,82 decreasing to 28,61 in the postoperative period (Table 2). The preoperative mean STAI-I score of patients with a history of operation was 43,18, which decreased to 27,52 in the postoperative period (Table 2). When comparing between the preoperative and postoperative periods of anxiety, this decrease in anxiety seems to be significant, which means high anxiety in the preoperative period [p<0,05] (Table 2).
The most common causes of preoperative anxiety in patients were the inability to wake up after surgery [51.5%], ‘Postoperative pain’ [31.7%], ‘nausea-vomiting’ [23.8%], Staying in Intensive Care Unit [14.9%] and awakening during surgery [9.9%] (Figure 2).
Patient satisfaction scores are shown in Table 3. According to the Patient Satisfaction Scale, which includes values ranging from 40 to 200, patients’ satisfaction scores range between 166,07 and 173,74. While the least satisfaction was observed in the Spinal anesthesia group [166,07] and the highest satisfaction was observed in the ASA I group [173,74]. The single/widow group appears to be the group with the most anxiety with the highest mean STAI-I value, but ranks third in the mean satisfaction score. In contrast to these findings, while the preoperative mean STAI-I score in the spinal anesthesia group was the second highest, the mean satisfaction score in the same group was the lowest.
Discussion
After evaluation of the socio-demographic characteristics of the patients in this study, it was found that patients’ mean age was 49,71±8,68 years, 64 patients [63,4%] were elementary school graduates, 88 patients [87,1%] were married, 92 [91,1%] patients had children and 91 patients [90,1%] were housewives. Given these findings, we can say that the sample included patients of childbearing age, literate and married with children.
Patients were evaluated and prepared during preoperative visits. Many studies have measured levels of anxiety during visits [4,5,6]. Arellano et al. for the aim of determining the right timing of the visit measured patients’ anxiety one week, a day before and just before the operation and they could not find any significant difference between them [7]. Lichtor et al. and Badner et al. measured the level of anxiety in the afternoon the day before the operation and just before the operation; while Lichtor et al. found a 70 % correlation between them, Badner et al. found a 73% correlation [8,9]. In our study, we measured the level of anxiety one day before the surgery.
Norris and Baird was reported 60% anxiety in 352 patients of 500 gynecologic patients [10]. Domar et al. reported that the mean anxiety score according to the STAI scale was 45 in 523 patients, 57% of whom were gynecologic [11]. In our study, we found the mean STAI-I score of 43,50 that was is in line with levels of anxiety in the previous studies.
There are conflicting results in the literature about the relationship between age and preoperative anxiety levels. Previous studies have reported lower preoperative levels of anxiety in older patients [12,13]. Shevde and Panagopoulos reported that the level of anxiety in elderly patients was lower [13]. Ramsay reported that the anxiety rates were 61% in the 13-21 age group, 84% in the 22-41 group, 80% in the 42-60 group, 57% in the 62-82 group, and they concluded that high anxiety levels in middle age was due to too much responsibility to their own families [14]. Norris and Baird reported that anxiety rates of patients younger than 30 years old were higher but not statistically significant [10]. Many studies have reported that age does not affect anxiety levels [4,11,15]. In the study by Jennings and Muhlenkamp, age effect could not be shown [16]. In our study, it was found that anxiety scores were higher in the group of patients younger than 50 years old [45,93] compared to the group older than 50 years old [40,36].
In many studies, levels of anxiety in women were higher than in men [11,17]. Fom an epidemiological point of view, the fact that depression and anxiety disorders are more common in females supports these findings. According to Badner et al., this difference was due to the higher anxiety associated with separation from their families in women [9], but Shevde and Panagopoulos and Domar et al. have shown that women could express their anxiety more easily [11,13]. Only the female gender took part in our study, and the difference between women was observed.
Although some studies have reported that the level of anxiety increased with the increasing level of education in some studies, other studies have reported that education status did not affect the degree of anxiety in other studies [11,12]. Caumo et al. found that preoperative levels of anxiety were higher in people with more than 12 years of education [18]. In our study, altough the highest mean STAI score was in the elementary school graduates, there was no statistically significant difference between levels of education.
It is generally accepted that the level of anxiety of patients is higher in tumor surgery operations or operations with organ loss [19]. Norris and Baird reported that the rate of anxiety in gynecology patients was higher [10]. In some studies, it was reported that the type of operation did not affect the levels of anxiety [4,11]. Patients who would undergo hysterectomy operations with organ loss were included in our study.
Shevde and Panagopoulos reported that the causes of anxiety related to anesthesia were 45% inadequate knowledge of the anesthetist, 43% lack of experience of the anesthetist, 37% inability to wake up after surgery and 34% postoperative pain [13]. While Chew et al. reported the most common causes of anxiety as pain [39,4%] and inability to wake up after surgery [18,9%]; in another study it was reported that the most common causes of anxiety were waking up during surgery [51,8%], inability to wake up after surgery [43,3%] and postoperative pain [38%] [5,20].
In many studies, it was reported that the most common cause of anxiety was inability to wake up after surgery. In our study, the most common cause of anxiety were inability to wake up after surgery [51,5%], postoperative pain [31,7%] and postoperative nausea-vomiting [25,7%].
Some studies have shown that recovery was faster in patients with low preoperative anxiety [3]. Faster recovery can be considered as a factor of increasing patient satisfaction. In our study, while single/widow group had the highest anxiety levels, it was the third group in postoperative satisfaction. While the Spinal Anesthesia group had the second common in preoperative anxiety, the same group had the lowest mean satisfaction score. ASA-I groups’ preoperative anxiety level was the third highest, the satisfaction score was measured high again. While the general anesthesia group had the lowest anxiety score, the satisfaction score was measured as high. In our study, no relationship was established between preoperative anxiety levels and postoperative satisfaction levels.
It was reported that in adult patients, high preoperative anxiety significantly increased postoperative pain, the need for analgesic and sedative drugs. A study of 10811 patients by Myles et al. reported that there was a relationship between mild or severe pain and low patient satisfaction levels [21]. Dexter et al. reported that pain was related to low patient satisfaction levels [22]. In our study no significant result was reported in this direction.
Considering that the patients could not express their feelings near their accompanying people in the Anesthesiology outpatient clinic, patients were visited in their clinics just one day before the operation. During this visit, it was observed that the patients were relaxed after the dual conversation. It was stated by the patients during the postoperative visit that this preliminary interview with the patient created a feeling of familiarity with the operating room and a comfortable sleep at night, reducing fear of the operating room.
Previous studies have shown that patients had different levels of anxiety. Our study was planned according to this point of the previous studies. Other studies evaluated patients without gender distinction and found that anxiety was more common in woman than in man. We wanted to research anxiety only in women. Again, other studies have evaluated all types of operations. In our study, we used only hysterectomy operations with organ loss, which were most commonly predicted to increase anxiety. In this study, it was observed that being older, having given birth before, being single, and increased anxiety in patients who underwent spinal anesthesia. In addition, it was found that there was no significant change in anxiety level according to education level, number of children, occupation, and history of surgery.
Limitations
As all authors, we believe that, with a wider range and larger patient population, including different genders, different types of operations and levels of anxiety measurement at different times, more meaningful, reliable and beneficial results could be achieved.
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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7. Salzwedel C, Petersen C, Blanc I, Koch U, Goetz AE, Schuster M. The effect of detailed, video-assisted anesthesia risk education on patient anxiety and the duration of the preanesthetic interview: a randomized controlled trial. Anesth Analg. 2008;106(1):202-9,
8. Aalouane R, Rammouz I, Tahiri-Alaoui D, Elrhazi K, Boujraf S. Determining factors of anxiety in patients at the preoperative stage. Neurosciences (Riyadh). 2011;16(2):146-9.
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Download attachments: 10.4328.ACAM.21787
Mustafa Levent Cetın, Ali Akdogan, Davut Dohman. Comparison of anxiety and patient satisfaction before and after elective hysterectomy under general or spinal anesthesia: A questionnaire study. Ann Clin Anal Med 2023;14(11):1029-1033
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Is vitamın D level related to bilateral lateral epicondylitis?
Haluk Yaka 1, Cumali Yılmaz 2, Hasan Rüzgar 2, Tahsin Sami Çolak 2, Ahmet Fevzi Kekeç 2, Mustafa Özer 2
1 Department of Orthopaedics & Traumatology, Konya City Hospital, 2 Department of Orthopaedics and Traumatology, Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey
DOI: 10.4328/ACAM.21793 Received: 2023-06-15 Accepted: 2023-07-17 Published Online: 2023-07-22 Printed: 2023-11-01 Ann Clin Anal Med 2023;14(11):1034-1037
Corresponding Author: Haluk Yaka, Department of Orthopaedics and Traumatology, Konya City Hospital, 42020, Karatay, Konya, Turkey. E-mail: halukyakakonya@gmail.com P: +90 554 615 39 26 Corresponding Author ORCID ID: https://orcid.org/0000-0001-7461-7298
This study was approved by the Ethics Committee of Necmettin Erbakan University (Date: 2022-03-04, No: 2022/3672)
Aim: This study aimed to examine the relationship between unilateral lateral epicondylitis (ULE), bilateral lateral epicondylitis (BLE), and vitamin D levels.
Material and Methods: Between January 2016 and January 2021, 112 ULE patients (67 men, 45 women, mean age 45.55±10.75 years), 90 BLE patients (47 men, 43 women, mean age 44.93±9.76 years), and 134 patients determined as the control group (47 men, 43 women, mean age 44.93±9.76 years) were included in the study. The three groups were compared in terms of vitamin D levels.
Results: The mean vitamin D level was 24.87±8.45 ng/ml in the control group, 16.67±8.08 ng/ml in the ULE group, and 12.2±5.71ng/ml in the BLE group. There was a significant difference in vitamin D levels between the control and ULE group, the control and BLE group, and the ULE and BLE group (p<0.001, p<0.001, p=0.014, respectively).
Discussion: Vitamin D levels of patients with bilateral lateral epicondylitis were significantly lower than those with unilateral lateral epicondylitis. This study shows that low vitamin D may be one of the etiological factors of lateral epicondylitis and may cause bilateral lateral epicondylitis at lower values.
Keywords: Vitamin D, Lateral Epicondylitis, ECRB, Elbow Pain
Introduction
Lateral epicondylitis (LE) is a common musculoskeletal disorder with a prevalence of approximately 30% in tennis players and 1% in the general population [1]. The etiology of LE does not appear to be related to sex and ethnicity, and has not been clearly established. Still, it is assumed that the main etiological factors are repetitive overuse and structurally abnormal collagen production [2,3].
In over 95% of LE cases, the extensor carpi radialis brevis (ECRB) is affected [4]. In the study by Ando et al., they suggested that the attachment area of the ERCB tendon to the lateral epicondyle of the humerus is 13 times smaller than the attachment area of the extensor carpi radialis longus (ECRL) tendon; therefore, the ECRB tendon is more fragile [5]. Bunata et al., on the other hand, associated LE with friction between the ERCB tendon and the humeroradial joint [6].
Vitamin D has anti-proliferative, pro-differentiative, and pro-apoptotic functions and is produced in the skin with exposure to sunlight [7]. In the last decade, the role of vitamin D in balancing the health of the human body’s immune system, reproductive system, and musculoskeletal system has come to the fore [8]. In addition, vitamin D deficiency has been associated with diabetes mellitus, cancers, cardiovascular diseases, and cognitive disorders [8,9]. Additionally, experimental studies show that vitamin D protects bones, muscles, and tendons [10]. In the same study, it was also shown that there is a vitamin D receptor in tenocytes. A recent study showed that vitamin D levels in unilateral LE patients were significantly lower than in the control group [11].
In this study, we hypothesized that there may be a relationship between bilateral LE (BLE) and vitamin D levels. This study aimed to examine the relationship between BLE and vitamin D levels.
Material and Methods
This single-center, retrospective study was conducted between January 2016 and January 2021 in the Department of Orthopedics and Traumatology Necmettin Erbakan University Meram Faculty of Medicine. Among the 527 patients who applied to our clinic with lateral elbow pain, 112 ULE (67 men, 45 women, mean age 45.55±10.75 years, range:18-60) and 90 BLE (47 men, 43 women, mean age 44.93±9.76 years, range:18-60) patients who met the inclusion criteria were included in the study. Inclusion criteria were age 18-60 years and a diagnosis of LE based on history and physical examination. The point of maximum tenderness on examination is usually above the lateral epicondyle or 1-2 cm to its distal [12]. When the ERCB tendon is palpated, pain occurs over the tendon, increased with wrist extension and forearm pronation [12]. Additionally, there should be no numbness or tingling in the examined extremity [12]. Exclusion criteria were previous trauma, history of upper extremity surgery, arthrosis, endocrinological diseases related to calcium parathormone metabolism, malignancy, rheumatological diseases, infection, and kidney diseases. In the same period, out of 681 patients (70 men, 64 women, mean age 40.48±11.74 years, range: 18-60) who applied to our clinic due to minor soft tissue trauma and had their vitamin D levels checked, 134 patients with no upper extremity complaints, no history of fracture-dislocation, no muscle and tendon damage, no inflammatory and degenerative orthopedic disease, no history of long-term immobilization, or any specific tendinitis who met the study inclusion criteria were determined as control group.
There is no universally accepted classification of vitamin D deficiency and insufficiency. In our study, Vit D ≥ 30 ng/mL was considered adequate, 20-29.9 ng/mL insufficient, and less than 20 ng/mL deficient [9,13].
Statistical Methods
Statistical analysis was performed using the IBM SPSS version 22.0 software (IBM Corp., Armonk, NY, USA). Descriptive data were presented as mean ± standard deviation (SD), minimum and maximum (min-max), number, and frequency. Kruskal-Wallis, One-Way ANOVA, Mann-Whitney U, and t-tests were used to compare independent variables. A p-value of <0.05 was considered statistically significant. Post-hoc power calculations were performed using the G*Power software (version 3.1.9.4, Heinrich Heine University, Düsseldorf), taking alpha error as 0.05 with a two-tailed significance.
Ethical Approval
Ethical approval was obtained from the Necmettin Erbakan University Ethics Committee” (IRB number: 2022/3672).
Results
The demographic information of the patients is summarized in Table 1. When ULE, BLE, and control groups were compared in terms of age and sex, there was no significant difference (p=0.14, p=0.56, respectively). The mean vitamin D level was 24.87±8.45 ng/ml in the control group (range: 10.9-49.0), 16.67 ± 8.08 ng/ml in the ULE group (range: 8.3-39.6), and 12.2±5.71 ng/ml in the BLE group (range: 4.2-27.3) (Table 2). When the control group and ULE were compared, the vitamin D level of the ULE group was significantly lower than the control group (p<0.001) (power: 0.99, effect size d: 0.94). When the control group and BLE were compared, the vitamin D level of the BLE group was significantly lower than the control group (p<0.001) (power: 0.99 effect size d: 1.42). When ULE and BLE were compared, the vitamin D level of the BLE group was significantly lower than the ULE group (p=0.014) (power: 0.95 effect size d: 0.5) (Tables 2 and 3).
Discussion
The most important finding of this study is that the vitamin D levels of the patients with ULE and BLE were significantly lower than the control group, but the vitamin D levels were significantly lower in the patients with BLE compared to those with ULE. To our knowledge, this is the first study to examine BLE and ULE patient groups regarding vitamin D.
The main factor determining the structural mechanical properties of tendons is the amount and quality of type-1 collagen that forms the extracellular matrix [14]. The cells responsible for the synthesis of type-1 collagen are tenoblasts, while cells regulating type-1 collagen and other extracellular matrix-related proteins and type-1 collagen relationships and maintain their structural integrity are tenocytes [15]. In the experimental histological study conducted by Min et al., type-1 collagen gene expression decreased in tenocytes suppressed with dexamethasone, and returned to normal when exposed to 1-alpha hydroxylase and vitamin D. They showed that vitamin D has protective effects on tendons as well as bones and muscles in tenocyte cultures [10]. A significant relationship was previously established between ULE and low vitamin D [11]. The decrease in the protective effect of vitamin D in deficient patients may predispose to tendinopathy. In this study, the BLE group having significantly lower vitamin D levels than the ULE group supports that vitamin D has a protective effect on the tendons. It also indicates that vitamin D deficiency may be one of the factors involved in the etiology of lateral epicondylitis.
Vitamin D deficiency is a systemic problem, and may cause tendinitis in many regions, including the ECRB tendon. However, anatomical disadvantages that distinguish the ECRB tendon from other tendons and may cause tendinitis susceptibility have been reported. These are the ECRB tendon being longer than other tendons in the lateral elbow compartment, the smaller attachment site in the lateral humeral epicondyle than other tendons, and the friction between it and the humeroradial joint during elbow movements. However, none of these mechanical causes alone can explain the etiology of LE [5,6]. According to the data we obtained, vitamin D deficiency alone cannot explain the etiology of LE. However, vitamin D was significantly lower in the BLE group than in the ULE group, which supports that one of the multifactorial LE etiological factors may be vitamin D deficiency.
Park et al. investigated whether there is a relationship between LE and sex, dominant side, waist circumference, smoking, alcohol use, manual labor, diabetes mellitus, hypertension, hyperthyroidism, hypothyroidism, metabolic syndrome, ipsilateral rotator cuff rupture, ipsilateral carpal tunnel syndrome, cholesterol level, triglyceride level, LDL, HDL, dyslipidemia, hemoglobin A1c, and CRP in their study on 937 participants and 245 patients with LE in at least one elbow [16]. They found a significant relationship between LE and female sex, dominant side, manual labor, and ipsilateral rotator cuff rupture. Despite examining detailed parameters, no grouping of LE patients in terms of ULE or BLE has been made, and there was no vitamin D among the investigated parameters. While no significant difference was found regarding sex in our study, Park et al. significantly associated female sex with LE. In this respect, the two studies do not support each other. Although Park et al. provided a lot of useful information in their study, they did not compare BLE and ULE.
Limitation
Some limitations of this study are as follows: The exclusion criteria were wide to evaluate the effect of vitamin D on LE without being affected by other confounding factors, and therefore the small number of patients is a limitation of our study. Other limitations include not knowing the duration of the patient’s complaints and not including occupation as a variable.
Conclusion
Vitamin D levels of patients with bilateral lateral epicondylitis were significantly lower than those with unilateral lateral epicondylitis. This study shows that low vitamin D levels may be one of the etiological factors of lateral epicondylitis and may cause bilateral lateral epicondylitis at lower levels.
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. Korucu IH, Tokgoz S, Kucuksen S, Kir HH, Iyisoy MS. A Vicious Circle in Lateral Elbow Tendinopathy Mechanism and a Novel Exercise Method. Selcuk Medical Journal. 2021;37(4): 359-35.
2. Keijsers R, de Vos RJ, Kuijer PPF, van den Bekerom MP, van der Woude HJ, Eygendaal D. Tennis elbow. Shoulder Elbow. 2019;11(5):384-92.
3. Pitzer ME, Seidenberg PH, Bader DA. Elbow tendinopathy. Med Clin North Am. 2014;98(4):833-49.
4. Goyal T, Choudhury AK, Paul S, Sethy SS, Singh V, Yadav RK. Outcomes of Continued Intensive Conservative Treatment Versus Arthroscopic Extensor Carpi Radialis Brevis Release for Recalcitrant Lateral Epicondylitis: A Non-randomized Controlled Trial. Indian J Orthop. 2022;56(9):1578-86.
5. Ando R, Arai T, Beppu M, Hirata K, Takagi M. Anatomical study of arthroscopic surgery for lateral epicondylitis. Hand Surg. 2008;13(2):85-91.
6. Bunata RE, Brown DS, Capelo R. Anatomic factors related to the cause of tennis elbow. J Bone Joint Surg [Am]. 2007;89(9):1955-63.
7. İnce B, Yıldırım MEC, İsmayılzade M, Dadacı M. Vitamin D and Systemic Effects of Vitamin D Deficiency. Selcuk Medical Journal. 2018;34(2): 84-9.
8. Durrani, Abdul Baqi. Subclinical Vitamin D Deficiency and Non-Specific Musculoskeletal Symptoms. Selcuk Medical Journal. 2020; 36(4): 357-60.
9. Yıldırım Dİ, Marakoğlu K, Evaluation of the Relationship Between Vitamin D and Hba1c Levels in Diabetic Patients. Selcuk Medical Journal. 2019;35(1): 37-42.
10. Min K, Lee JM, Kim MJ, Jung SY, Kim K-S, Lee S, et al. Restoration of Cellular Proliferation and Characteristics of Human Tenocytes by Vitamin D. J Orthop Res. 2019;37(10):2241-8.
11. Yaka H, Başbuğ V, Tekin AA, Özer M. Evaluation of the relationship between lateral epicondylitis and vitamin D. Jt Dis Relat Surg. 2022;33(2):414-18.
12. Oehler N, Mussawy H, Schmidt T, Rolvien T, Barvencik F. Identification of vitamin D and other bone metabolism parameters as risk factors for primary bone marrow oedema syndrome. BMC Musculoskelet Disord. 2018;19(1):451.
13. Liu E, Meigs JB, Pittas AG, Economos CD, McKeown NM, Booth SL, et al. Predicted 25-hydroxyvitamin D score and incident type 2 diabetes in the Framingham Offspring Study. Am J Clin Nutr. 2010;91(6):1627-33.
14. Thankam FG, Dilisio MF, Gross RM, Agrawal DK. Collagen I: a kingpin for rotator cuff tendon pathology. Am J Transl Res. 2018;10(11):3291-309.
15. Quigley AS, Bancelin S, Deska-Gauthier D, Légaré F, Kreplak L, Veres SP. In tendons, differing physiological requirements lead to functionally distinct nanostructures. Sci Rep. 2018;8(1):4409.
16. Park HB, Gwark JY, Im JH, Na JB. Factors Associated With Lateral Epicondylitis of the Elbow. Orthop J Sports Med. 2021;9(5). DOI: 10.1177/23259671211007734.
Download attachments: 10.4328.ACAM.21793
Haluk Yaka, Cumali Yılmaz, Hasan Rüzgar, Tahsin Sami Çolak, Ahmet Fevzi Kekeç, Mustafa Özer. Is vitamın D level related to bilateral lateral epicondylitis? Ann Clin Anal Med 2023;14(11):1034-1037
Citations in Google Scholar: Google Scholar
A Scientometric analysis of resuscitative endovascular balloon occlusion of the aorta (reboa) articles: Where do we stand?
Serkan Günay, Ahmet Öztürk, Ali Kemal Erenler
Department of Emergency Medicine, Hitit University, Erol Olçok Education and Research Hospital, Çorum, Turkey
DOI: 10.4328/ACAM.21819 Received: 2023-07-12 Accepted: 2023-08-14 Published Online: 2023-08-18 Printed: 2023-11-01 Ann Clin Anal Med 2023;14(11):1038-1043
Corresponding Author: Serkan Günay, Department of Emergency Medicine, Hitit University, Erol Olçok Education and Research Hospital, 19200, Çorum, Turkey. E-mail: drsrkngny@gmail.com P: +90 530 401 26 16 Corresponding Author ORCID ID: https://orcid.org/0000-0002-8343-0916
Aim: The aim of this study is to reach the data related to resuscitative endovascular balloon occlusion of the aorta (REBOA) through the Web of Science database, to make a scientometrics analysis of the data and to guide the researchers.
Material and Methods: All articles related to REBOA were reviewed on the Web of Science database. Articles were ranked according to the top 10 most published countries. All articles were analyzed through the database. In addition, the top 20 journals in which the most articles were published were listed according to their publication numbers. All articles were analyzed according to article type and subject headings. Abstracts of the top 10 most cited articles were prepared.
Results: The country with the most publications on REBOA was the United States (US). When we examine the journals that publish the most REBOA articles, the Journal of Trauma and Acute Care Surgery ranks first with 130 publications. Most of the 419 articles were found to have been published in the original article type. It has been observed that the studies have mostly focused on the clinical use of REBOA.
Discussion: There is a need for more comprehensive studies on the use of REBOA and its complications.
Keywords: REBOA, Scientometric Analysis, Journals
Introduction
Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a method in which a balloon is sent to the aorta with the help of a catheter and inflated and distal blood flow is prevented [1]. Although the frequency of use has increased in recent years, it was first used in the 1950s [2]. It has been used as an alternative to clamping the aorta, especially in non-compressible torso hemorrhagic patients. REBOA reduces bleeding, similar to clamping of the aorta after thoracotomy, allowing resuscitation and control of bleeding [3]. In addition, it is a less invasive method compared to thoracotomy and increases myocardial and cerebral blood flow by decreasing distal blood flow, just like clamping the aorta [1]. Especially in the last 10 years, REBOA has been re-entered into clinical use and it has been observed that many studies have been published on the use of REBOA. These studies have been and continue to be carried out in many areas from the training of REBOA to its application methods, clinical use, and experimental animal studies. Although many studies have been conducted in this field, information about REBOA is still limited.
Scientometrics is a discipline that statistically and mathematically analyzes technological and scientific data [4,5]. It is also referred to as the science of science. It sheds light on the researchers’ awareness of gaps and knowledge gaps in a certain field and what subjects they should focus on [6]. In a literature search,, scientometric analyzes were carried out in many scientific subjects and were determined to provide direction to researchers.
The Web of Science (WoS) database is a platform that allows researchers to access scientific and statistical data on certain subjects. It allows researchers to access publications and data on certain topics. The increase in the use of REBOA in recent years has allowed studies on many different subjects. However, when we look at the literature, there is no detailed data about these studies. The aim of this study is to reach the data related to REBOA through the WoS database, to make scientometrics analysis of them and to guide the researchers. Thus, it is thought that researchers will contribute to the elimination of deficiencies in the literature by deciding on which subjects they will focus on, and they can focus on different issues related to the use of REBOA.
Material and Methods
On January 2, 2023, all articles related to “Resuscitative Endovascular Balloon Occlusion of Aorta” were found in the WoS database by typing the keyword REBOA. This platform enables researchers to access scientific and statistical information on a particular subject and acts as a standard database for citation analysis because it provides more detailed information compared to other medical databases [7]. All articles related to REBOA were reviewed on the WoS database. Articles are ranked according to the top 10 most published countries. The number of citations of the published articles, the number of citations per publication for each country and H-Indexes were analyzed through the database. In addition, the top 20 journals with the most published articles in the database were listed according to the number of publications. The total number of citations by journals and the number of citations per article were examined. The impact factor of the journals for 2021 was obtained from the journal websites. All articles published in the WoS database have been manually scanned through the WoS database. The titles, abstracts and full texts of the articles were examined. All articles were divided into topics such as the clinical use of REBOA, REBOA education, general clinical information about REBOA, prehospital use of REBOA, REBOA indications, REBOA-related animal experiments, REBOA complications, and REBOA administration and techniques. Subsequently, these articles were divided according to article types, namely: “Original Articles”, “Reviews”, “Proceeding Papers”, “Case Reports” and others. All reviewed articles were analyzed according to article type and subject headings.
In addition, the articles were listed according to the number of citations on the WoS database, and the top 10 most cited articles were examined in detail and their abstracts were prepared. The data were entered into the Microsoft© Excel Program and the results were given as numbers and percentages. Ethical approval is not required as no live subjects were included in the study and it is a meta-data analysis of published studies.
Results
When the keyword REBOA was typed into the WoS database, a total of 758 articles were obtained. Among these articles, articles with REBOA in the author’s name, repetitive articles, articles not related to REBOA, and publications whose full text or explanatory abstract could not be reached were excluded from the study and a total of 692 articles were examined. In total, 15 articles were written in German, 2 in French, 1 in Czech, and 1 in Spanish. The remaining 673 articles were written in English. When the articles were ranked according to the most published countries on the WoS database, it was determined that the top 3 countries with the most publications on REBOA were the United States (US) (62.71%), Japan (11.56%) and England (8.52%). It was found that there were 434 publications in total from the US, 80 publications from Japan and 59 publications from England. The articles published in the US received a total of 7045 citations, while the articles published in Japan and England received 1271 and 1820 citations, respectively. It has been observed that the country with the highest number of citations per publication is England with 30.85. Most publications on REBOA were published in 2021.
When we examine the journals that publish the most about REBOA, the Journal of Trauma and Acute Care Surgery (J Trauma Acute Care Surg) comes first with 130 publications. This is followed by the Journal of Endovascular Resuscitation and Trauma Management (J Endovasc Resusc Trauma Manag) (n=68) and Shock (n=34). The most cited journal is Journal of Trauma and Acute Care Surgery with 3734 citations. World Journal of Emergency Surgery (World J Emerg Surg) and European Journal of Trauma and Emergency Surgery (Eur J Trauma Emerg Surg) are followed by 451 and 418 citations. The most cited journal per publication was found to be the World Journal of Emergency Surgery with 34.69. Information about the top 20 journals and top 10 countries with the most publications is shown in Table 1.
The 692 articles in the WoS database were manually scanned one by one and separated according to article types and content.
It was determined that while most 419 articles were published in the original article type, they were followed by review (n=74) articles. It has been observed that the studies mostly focused on the clinical use of REBOA. While the most studied topic was related to clinical use with 323 publications, it was followed by publications on animal studies with 97 publications. Data related to the subject content and article types of the articles published on REBOA are shown in Table 2. In addition, the top 10 most cited articles on REBOA are summarized in Table 3.
Discussion
Although REBOA is a method that has become more popular and frequently used in recent years, the clinical use of REBOA dates back more than 50 years. When the literature is examined, Edwards W.D, et al. conduct studies on balloon occlusion of the aorta [2]. When the WoS database is examined, it is seen that studies on REBOA have been included in this database since 2011. When we examine the studies carried out since 2011, it is seen that more than half of the studies (62.71%) were extracted from the US, and these studies were mainly published between 2019-2021. In the light of these data, it is observed that the majority of the contributions to the literature on the REBOA method, whose effectiveness and use have increased in recent years, come from the US. It is seen that even Japan (11.56%), which ranks 2nd after the US, lags far behind the US. When we examine the journals in which studies on REBOA are published, it is seen that most publications are in the Journal of Trauma and Acute Care Surgery (n=130). Again, it is seen that the Journal of Trauma and Acute Care Surgery is in the 1st place in terms of the number of citations (n=3734) and in the 2nd place in the number of citations per publication (n=28.72). When we examine the top 10 most cited journals, it is known that 8 of them are also included in the Journal of Trauma and Acute Care Surgery. According to information obtained from the journal’s own website, the Journal of Trauma and Acute Care Surgery is a publication that includes articles related to the care of patients who are severely injured or in critical condition due to surgical diseases. It is thought that the subject areas of the journal, the impact factor and the frequency of publication may have been effective in the selection of this journal by the authors. When the studies on REBOA are compared with other journals, it was found to be the leading journal on REBOA and has made great contributions to the literature. Considering the number of publications (n=68) in the Journal of Endovascular Resuscitaion and Trauma Management, it is seen that it is in the 2nd place, while it is slightly behind in the number of citations (n=125) and the number of citations per publication (n=1.84). Although the World Journal of Emergency Surgery ranks 11th in terms of the number of publications (n=13), it is seen that it ranks second in the number of citations (n=451) and ranks first in the number of citations per publication (n=34.69). It is known that a high citation count is an important parameter that shows the effectiveness of an article [8]. Although the number of publications is low, the high number of citations is accepted as a criterion for publishing qualified publications.
If we look at the article type and content of the publications related to REBOA, it is seen that the publications related to clinical use (n=323) and Original Article type (n=419) are mostly published. Of the publications on the clinical use of REBOA, 171 were original articles. Again, 35 of the publications related to its clinical use were in the form of review articles, while 47 of them were case reports. Morrison JJ et al., in their review-type study examining case reports on the clinical use of REBOA in hemorrhagic shock patients, stated that the use of REBOA did not increase mortality, but larger studies were needed to reduce mortality [1]. In a study conducted by Moore LJ, et al. in the original article type, in which they compared resuscitative thoracotomy and REBOA, they showed that mortality was reduced in patients using REBOA [3]. When the studies on REBOA are examined, it is seen that studies on animal experiments (n=97) are in second place. This shows that although the first use of REBOA is very old, the experience with REBOA is not very sufficient yet and experimental studies are still continuing to a large extent. When the studies on the complications of REBOA are examined, it is seen that only 26 of them are studies in the original article type. The majority of the remaining studies consist of review Studies in the form of case reports and examination of the studies. There is still a need for more studies on REBOA complications.
When the studies on REBOA training were examined, it was determined that there were 26 studies in total. In a study, it was mentioned that REBOA simulations and information learned from previous experiences are vital to improve patient care [9]. There are still questions about who and how often REBOA training will be given. In a study by Park et al., they emphasized the importance of frequent training and mentioned that surgical trainees were more successful in applying REBOA. However, they did not mention a clear period of how often it will happen [10]. Large-scale studies are still needed on how often and to whom REBOA training will be given. When the studies on the prehospital use of REBOA are examined, it is seen that there are 19 studies in total, and 13 of them are original articles. When studies are examined, it has been shown that REBOA may be effective in prehospital use [11-13]. In a study by Lendrum R, et al., they showed that REBOA is an effective method for prehospital use in patients with pelvic trauma without external bleeding [14].
However, prospective studies with larger populations are needed because the studies are mostly small case groups and retrospective studies. In addition, studies have not been able to make a clear definition of which patients would be suitable for REBOA use in the pre-hospital setting.
Limitations
Our study also has some limitations. Due to the nature of scientometric studies, the results may differ according to the period in which it was conducted. In addition, the data used in this study are data obtained from the WoS database. Therefore, there may be numerical differences between the data made by manually scanning and the database data. Again, since the scans of the articles are done manually, there may be overlooked articles. However, since such losses are relatively small, they do not affect the results of the study.
Conclusion
In conclusion, REBOA is accepted as a method that has increased in popularity and use in recent years. However, there is still no clear information about the conditions under which REBOA will be used and its complications. In particular, when the literature is examined, it is seen that case reports and reviews about the complications of REBOA are predominant. Still, questions remain about how often and to whom REBOA training will be given. More comprehensive studies are needed on these issues. However, it is seen that REBOA will take more place in our lives in a very short time and will become an indispensable part of resuscitation, especially in hemorrhagic shock 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. 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. Morrison JJ, Galgon RE, Jansen JO, Cannon JW, Rasmussen TE, Eliason JL. A systematic review of the use of resuscitative endovascular balloon occlusion of the aorta in the management of hemorrhagic shock. J Trauma Acute Care Surg. 2016; 80(2): 324-34.
2. Edwards WS, Salter PP Jr, Carnaggio VA. Intraluminal aortic occlusion as a possible mechanism for controlling massive intra-abdominal hemorrhage. Surg Forum. 1953; 4:496-9.
3. Moore LJ, Brenner M, Kozar RA, Pasley J, Wade CE, Baraniuk MS, et al. Implementation of resuscitative endovascular balloon occlusion of the aorta as an alternative to resuscitative thoracotomy for noncompressible truncal hemorrhage. J Trauma Acute Care Surg. 2015; 79(4): 523-30.
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6. Erenler AK, Ay MO, Baydin A. A Scientometric Analysis of Highly Cited Publications and a Summary of Top 25 Articles Regarding Covid-19. International Journal of Medical and Health Sciences Research. 2021; 8(1):24-35.
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8. Long HL, Drown L, El Amin M. The Effect of Open Access on Scholarly and Societal Metrics of Impact in the ASHA Journals. J Speech Lang Hear Res. 2023; 66(6): 1948-57.
9. Burkard DJ, Thompson J, Dull M, Haverkamp J, Koestner A, Davis A, et al. Resuscitative Endovascular Balloon Occlusion of the Aorta Process Improvement: Examining a Novel Case Evaluation Tool and Standardized Simulations. J Trauma Nurs. 2020; 27(2):82-7.
10. Park C, Grant J, Garigipati P, Kuhlenschmidt K, Black G, Bhat S et al. Resuscitative endovascular balloon occlusion of the aorta: simulation improves performance but may require interval training to prevent skill degradation. Eur J Trauma Emerg Surg. 2022; 48(3):1955-9.
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12. de Schoutheete JC, Fourneau I, Waroquier F, De Cupere L, O’Connor M, Van Cleynenbreugel K, et al. Three cases of resuscitative endovascular balloon occlusion of the aorta (REBOA) in austere pre-hospital environment-technical and methodological aspects. World J Emerg Surg. 2018; 13:54.
13. Thabouillot O, Bertho K, Rozenberg E, Roche NC, Boddaert G, Jost D, et al. How many patients could benefit from REBOA in prehospital care? A retrospective study of patients rescued by the doctors of the Paris fire brigade. J R Army Med Corps. 2018; 164(4):267-70.
14. Lendrum R, Perkins Z, Chana M, Marsden M, Davenport R, Grier G, et al. Pre-hospital Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) for exsanguinating pelvic haemorrhage. Resuscitation. 2019; 135:6-13.
Download attachments: 10.4328.ACAM.21819
Serkan Günay, Ahmet Öztürk, Ali Kemal Erenler. Scientometric analysis of resuscitative endovascular balloon occlusion of the aorta (reboa) articles: Where do we stand? Ann Clin Anal Med 2023;14(11):1038-1043
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In vitro evaluation of the cytotoxic effects of alkasite restorative material on human dental pulp stem cells
Tugba Elgun 1, Belen Sırınoglu Capan 2, Canan Duman 3, Nazli Ece Gungor Orduerı 4
1 Department of Medical Biology, Faculty of Medicine, Biruni University, Istanbul, 2 Department of Pediatric Dentistry, Faculty of Dentistry, Istanbul University–Cerrahpaşa, Istanbul, 3 Department of Pediatric Dentistry, Faculty of Dentistry, Istanbul Atlas University, Istanbul, 4 Department of Histology and Embryology, Faculty of Medicine, Biruni University, Istanbul, Turkey
DOI: 10.4328/ACAM.21846 Received: 2023-08-05 Accepted: 2023-09-06 Published Online: 2023-09-12 Printed: 2023-11-01 Ann Clin Anal Med 2023;14(11):1044-1048
Corresponding Author: Tugba Elgun, Department of Medical Biology, Faculty of Medicine, Biruni University, Istanbul, Turkey. E-mail: telgun@biruni.edu.tr P: +90 505 316 37 63 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1311-6892
This study was approved by the Ethics Committee of Biruni University (Date: 2019-11-07, No: 2019/34-12)
Aim: The clinical suitability of restorative dental materials is determined by evaluating their biocompatibility, and physical and chemical properties. The present study examined the cytotoxic effects of three different dental restorative materials on human dental pulp stem cells (DPSCs).
Material and Methods: In this study, composite, high-viscosity glass ionomer cement (HVGIC), and an alkasite were used. In total, 12 samples of each material were prepared for cytotoxicity assays. Cytotoxic effects were determined by considering biomaterial releases. Cell viability and proliferation were observed and analyzed at intervals of 24 and 72 hours using both the methyl-thiazole-diphenyl-tetrazolium (MTT) and xCELLigence cytotoxicity assays. Data were calculated using the RTCA-DP integrated software of the xCELLigence system and the GraphPad Prism 9.1.1 program. Data from the proliferation experiments were statistically evaluated using the Two-way ANOVA test.
Results: Alkasite exhibited the highest cytotoxicity, whereas HVGIC and composite did not exhibit any significant difference compared with the control. There was no difference between the two time points in the cytotoxicity of composite and alkasite in the MTT assay. However, the cytotoxicity of HVGIC was higher at 72-hours than at 24-hours. Similar results were obtained with both assays. Although alkasite exhibited higher cytotoxicity than composite and HVGIC, all materials exerted slightly cytotoxic effects (60%–90% cell viability) on DPSCs.
Discussion: Considering its aesthetic, and mechanical properties, alkasite can be clinically preferred instead of other materials in cavities that are not close to the dental pulp.
Keywords: Alkasite, Composite, Glass Ionomer Cement, Cytotoxicity, Dental Pulp
Introduction
Restorative materials should exhibit good mechanical properties, biocompatibility, and fluoride-releasing ability [1]. Amalgam, composites, compomers, and glass ionomer cements represent some common dental materials used for the restoration of primary and permanent dentition [2]. Amalgam has been used most commonly for many years as it exhibits good, long-lasting biomechanical properties; however, the presence of mercury in its composition and its non-aesthetic properties have made it less popular among dental patients lately [3]. In contrast, first developed in 1962, composite resins meet the increasing aesthetic and masticatory needs of patients while also exhibiting good retention [4].
The popularity of fluoride-releasing dental materials has increased recently because of their role in caries prevention. In this regard, glass ionomer cements are considered particularly advantageous because they are biocompatible, release fluoride, and chemically bond to enamel and dentin [5]. However, they also have certain disadvantages, such as sensitivity to moisture and poor mechanical strength. Although resin- modified and HVGICs can minimize these disadvantages, further improvement is necessary [6].
Cention N (Ivoclar Vivadent, Liechtenstein) is a newly developed dental material and is classified as an “alkasite,” which has been defined as a subgroup of composite materials. Cention N is an aesthetic and highly resistant material, which is particularly suitable for the posterior region of oral cavity. The presence of alkaline fillers in its composition enables the release of fluoride, calcium, and hydroxyl ions that can prevent demineralization and enhance remineralization. Therefore, the manufacturer of Cention N states that it combines the best properties of amalgam and glass ionomer cement. Cention N is a urethane dimethacrylate (UDMA) based self-curing restorative material with optional additional light-curing [7].
In addition to the physical and chemical properties of restorative materials, their clinical suitability is determined by their biocompatibility the ability of a material to create an appropriate biological response around application [8]. It is crucial that restorative materials used in clinical practice do not cause systemic or local cytotoxicity in the oral mucosa, gingiva, and pulpal tissues adjacent to the material [9].
This study aimed to evaluate the cytotoxicity of a newly developed alkasite restorative material on DPSC using methyl-thiazole-diphenyl-tetrazolium (MTT) and xCELLigence assays and compare this with a composite and a high-viscosity glass ionomer cement (HVGIC) routinely used in the clinic. To the best of our knowledge, this is the first study to examine the cytotoxic effect of alkasite material on dental pulp stem cells. Our two hypotheses were that the cytotoxicity of alkasite is higher than that of HVGIC and like that of composite.
Material and Methods
This study was approved by the Ethics Committee of Biruni University (Date: 07-11-2019, No: 2019/34-12) and was conducted in accordance with the World Medical Association Declaration of Helsinki.
Dental materials tested in this study
This study examined the cytotoxic effects of a composite (Gradia Direct, GC Europe, Belgium), a HVGIC; Equia Forte, GC Europe, Belgium), and an alkasite restorative material (Cention N, Ivoclar Vivadent, Liechtenstein) on DPSC.
Preparation of samples
In total, 12 specimens of each material were prepared under sterile conditions in a laminar flow chamber (Heal Force, China) and placed into cylindrical Teflon molds (5.0 mm diameter × 2.0 mm height). Thereafter, the lower and upper surfaces of the materials were covered with transparent matrix tape to prevent the formation of an oxygen inhibition layer; the polymerization phase was initiated by placing the Teflon molds between two glass coverslips to remove excess material and prevent air bubble formation. The materials were cured or set in accordance with the manufacturers’ recommendations. An amalgamator device (GC Europe, Belgium) was used to mix materials in capsule form, and a light device (Elipar™ S10; 3M ESPE, St. Paul, MN, USA) was used to polymerize light-cured restorative materials. The biomaterials were sterilized using ultraviolet light for 30 minutes.
Cell culture and experimental design
Human DPSCs (CELPROGEN, 36086-01, USA) were supplied as a cell line and cultured in Dulbecco’s modified Eagle’s medium (DMEM; Sigma Aldrich, St. Louis, MO, USA) supplemented with 10% fetal bovine serum (FBS; Sigma Aldrich, St. Louis, MO, USA), 100 U / mL penicillin / streptomycin (Sigma Aldrich, St. Louis, MO, USA), 100 U / mL L-glutamine (Sigma Aldrich, St. Louis, MO, USA), and 100 U / mL sodium pyruvate at 37°C under 5% CO2 humidified air. Third passage DPSCs were detached using a 0.05% trypsin–EDTA solution (Sigma Aldrich, St. Louis, MO, USA) and a monolayer was cultured at a concentration of 5 × 105 in 25 cm flask containing DMEM medium.
A total of 12 samples of each material were divided into three subgroups containing four samples each. Freshly prepared samples were placed in 10 ml DMEM and incubated for 24 and 72 hours to obtain eluates.
Determination of cell viability using MTT assay
Cytotoxic effects of the three tested materials on cell viability and proliferation were evaluated using the MTT assay (Sigma Aldrich Inc., St. Louis, USA). MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) is a stable tetrazolium salt. The production of NAD(P)H in the glycolytic pathways of living cells can decrease and cause formation of formazan crystals, the concentration of which is directly proportional to the number of living cells at the end of the experiment [10].
In this study, 3 × 104 cells were grown, placed on 96-well plates, and incubated at 37°C for 24 hours. The next day, 100 µl of different concentrations of the medium in which the biomaterials were stored for 24 and 72 hours were applied to the 96-well plates. To allow examination of the effects of these substances on cell viability over time, 10 µl of MTT was added 24 hours after the application of the medium and left to incubate for 4 hours at 37°C in the dark. Thereafter, 100 μl of the solubilization solution was added to each well and the plate was kept in the incubator overnight. The absorbance (optical density) of the samples was measured using a spectrophotometer (ELISA reader) at 590 nm.
Proliferation and cytotoxicity assay of DPSCs using xCELLigence assay
The xCELLigence system (Roche Applied Science, and ACEA Biosciences) was used to assess the survival of DPSCs upon exposure to various dental materials over time. Physiologic changes in the cells were identified and measured by the electronic impedance of the sensor electrodes. This real-time monitoring system provides quantitative information on the biological status of cells, including cell number, viability, and morphology; the cell index system displays the relative changes in the electrical impedance.
By following the procedure, 200 μL of the cell suspensions were seeded into a 16-well E-plate (30,000 cells/well; well volume: 250 μL; base diameter of well: 5 mm) in a laminar flow cabinet, placed in the incubator at 37°C and 5% CO2, and monitored using the RTCA-DP system at 15-minute time intervals for up to 72 hours with or without dental materials. Control samples received only medium and, in accordance with the xCELLigence technical manual, at least three repetitions of each experimental condition were performed to facilitate statistical evaluation [10].
Statistical analysis
Data were calculated using the RTCA-DP integrated software of the xCELLigence system and the GraphPad Prism 9.1.1 (GraphPad Software, Inc) program. Data from the proliferation experiments were statistically evaluated using the two-way ANOVA test, and a p-value of <0.05 was considered statistically significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Alkasite treated DPSCs had low cell proliferation rates related to the MTT assay after 24 h
The MTT cytotoxicity assay was used to observe and analyze cell survival at 24 and 72 hours intervals. All restorative materials exhibited varying levels of cytotoxicity against DPSCs, and alkasite samples showed significantly lower cell proliferation after 24 hours than the HVGIC sample (p = 0.002). Although the alkasite and composite samples exhibited no significant changes in DPSC proliferation over time (24–72 hours), the HVGIC samples demonstrated a significant decrease (79.7%) in proliferation rates after 72 hours (p = 0.01) (Figure 1).
No statistically significant difference was observed between the materials and the control after 72 hours; however, all materials in this study exhibited numerical decreases in cell viability. Therefore, they were found to be slightly cytotoxic (Table 1).
XCELLigence assay results
The effects of the HVGIC, alkasite, and composite samples on DPSC cells were monitored for 72 hours using a real-time cytotoxicity analysis system. Cell index values increased from 0.23 before the application of HVGIC and composite samples to the DPSC cells to 0.51 24 hours after the application. In contrast, the cell index value after alkasite application was 0.35. The cell index value increased in the first hour after applying of the release medium of alkasite (24th hour); however, the cells reached a plateau after that (25th hour), and the cell viability decreased compared with the control.
Monitoring the viability of cells released from the HVGIC and composite samples and the applied medium for 72 hours using the xCELLigence system showed that the cell index values were similar to that of the control, with continuous cell growth and proliferation cessation being observed after a while. A significant decrease in DPSC proliferation was observed in the alkasite group after 24 and 72 hours compared with the control (p < 0.01), whereas a significant increase was detected in the HVGIC and composite groups after 24 hours compared with the alkasite group. Although no statistically significant difference was noted between the HVGIC and composite groups after 24 hours, the increase in proliferation observed in the HVGIC group compared with the control was statistically significant. Alkasite demonstrated the highest cytotoxicity on cell viability after 72 hours (Table 2).
No differences were observed in the cytotoxicity effects of alkasite restorative material on DPSCs, when comparing the two time points, whereas both HVGIC and composite exhibited a significant increase in cytotoxicity at 72 hours compared with 24-hour treatment of the materials.
Discussion
Dental materials, which have better mechanical and chemical properties, are gradually developed for more aesthetic and long-lasting restorations of decayed teeth. In addition to having good mechanical, chemical, and aesthetic properties, dental materials should also exhibit suitable biocompatibility as they can directly or indirectly affect the surrounding structures via the substances they release during and after setting. These leachable substances can migrate through the dentinal tubules and damage the dental pulp, highlighting the importance of understanding the cytotoxic effects of restorative dental materials in deep cavities [11-13]. The present study examined and compared the cytotoxicity of a newly developed alkasite material, HVGIC, and composite on DPSCs and found that all three materials exhibited slightly cytotoxic effects, although this was statistically significant only in the alkasite group.
The number of ions and residual monomers released from the material, its composition, and the concentration of filler particles play a role in its cytotoxicity [14]. The present study found no statistically significant differences in cytotoxicity among the control, HVGIC, and composite, although the alkasite material demonstrated significant cytotoxic effects. This may be attributed to the chemical composition of the material: in contrast to composites that released only monomers and HVGICs that released only ions, alkasites were capable of releasing both (particularly, UDMA and fluoride), which potentially increased their cytotoxicity. In addition, previous studies have found that the amount of residual monomer increases with higher filler content in resin-based materials, thus decreasing the cell proliferation [15-22]. The filler content of the alkasite restorative material (78.4%) was higher than that of the composite (73%) examined in this study, which might have resulted in greater cytotoxic effects. To the best of our knowledge, only a single previous study by Awad et al. [16] has investigated the effects of alkasites on human gingival fibroblast cells and found greater cytotoxicity than that of composites. The results of the present study were in accordance with this.
Da Silva et al. [23] have suggested that a material is considered nontoxic or slightly toxic if the cell viability exceeds 90% or ranges between 60%–90%, respectively. In accordance with this, all materials evaluated in the present study were considered slightly cytotoxic after 72 hours, and these findings agreed with those of previous studies [16-22].
An increase in cell proliferation was also observed in the HVGIC group after 24 hours, and this was in accordance with the finding of Ersahan et al. [13] who observed no cytotoxicity with HVGIC in their study. On the contrary, they reported an increase in cell proliferation, suggesting that the material used was biocompatible. This might be attributed to the small-particle glass-filler technology used, low-setting exothermic reaction, and rapid neutralization [19].
No significant differences between the two time points were observed in the alkasite group, which is a fluoride-releasing dual-cure material. This means that the setting reaction of alkasite begins when the powder and liquid are mixed and can be accelerated further with additional light-curing. The cytotoxic effects of fluoride-releasing materials can also be affected by the amount of fluoride released [16,20,21]. Egil [22] reported that the amount of fluoride released by alkasite was lower than that released by HVGIC. Therefore, both the shorter polymerization time and the less amount of ions released might be effective in maintaining the cytotoxicity of alkasite.
The xCELLigence assay performed in this study revealed that the cytotoxicity of the composite increased after 72 hours, which is in agreement with the findings of previous studies [23, 24]; this could be attributed to an increase in monomer release with degradation over time.
The present study used the MTT and xCELLigence assays to investigate the cytotoxic effects of restorative dental materials on human DPSCs. The MTT assay is considered one of the most reliable biocompatibility assays because of its rapid results and sensitivity, although the use of end-point qualitative measures of cell fitness is a major limitation [23,24]. To the best of our knowledge, very few studies to date have evaluated the cytotoxicity of dental materials using both assays and, although they yielded similar results in the present study, the findings of the xCELLigence assay were more accurate and detailed [25].
The cytotoxicity of alkasite material was higher than that of any of the other materials assessed in this study. Therefore, our first hypothesis was confirmed, and our second hypothesis was refuted. The formation of a partial barrier to protect the pulp in deep cavities with increased dentin permeability can reduce the cytotoxic potential of dental materials. In addition to the mechanical properties of dental materials, an understanding of its cytotoxic effects is essential to allow appropriate material selection and increase treatment success.
Conclusions
Alkasite demonstrated acceptable cytotoxicity on DPSCs after a 72-hour but was more cytotoxic than HVGIC and composite, which demonstrated similar cytotoxicity. The MTT and xCELLigence assays yielded similar results.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Funding: This work was supported by Research Fund of the Biruni University, Project Number: Biruni-BAP-2019-02-09. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Conflict of interest
The authors declare no conflict of interest.
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Download attachments: 10.4328.ACAM.21846
Tugba Elgun, Belen Sırınoglu Capan, Canan Duman, Nazli Ece Gungor Orduerı. In vitro evaluation of the cytotoxic effects of alkasite restorative material on human dental pulp stem cells. Ann Clin Anal Med 2023;14(11):1044-1048
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Confirmation of anatomical proximities in endoscopic sinus surgery with computer tomography: A cadaveric study
Rukiye Ozcelik Erdem 1, Mehmet Akif Dundar 2, Mitat Arıcıgil 2, Hamdi Arbag 2
1 Department of Otorhinolaryngology, Dr. Vefa Tanır Ilgın State Hospital, 2 Department of Otorhinolaryngology, Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey
DOI: 10.4328/ACAM.21997 Received: 2023-09-26 Accepted: 2023-10-28 Published Online: 2023-10-30 Printed: 2023-11-01 Ann Clin Anal Med 2023;14(11):1049-1053
Corresponding Author: Rukiye Ozcelik Erdem, Department of Otorhinolaryngology, Dr. Vefa Tanır Ilgın State Hospital, Konya, Turkey. E-mail: ozcelikrukiye@gmail.com P: +90 553 080 05 14 Corresponding Author ORCID ID: https://orcid.org/0000-0001-5087-4652
This study was approved by the Ethics Committee of Necmettin Erbakan University (Date: 2016-10-07, No: 2016/687)
Aim: The aim of this study was to investigate the confirmation of anatomical proximities between endoscopic sinus surgery with computer tomography.
Material and Methods: This study was done on 5 fresh frozen cadaver heads between May 2017 to June 2018. High-resolution computed tomography (HRCT) was taken before the operations. Firstly uncinectomy was done. Then all stages of functional endoscopic sinus surgery (FESS), which contains anterior-posterior ethmoidectomy, dissection of the sphenoid sinus and frontal recess, and maxillary sinusotomy were performed from anterior to posterior. Distances between each other landmarks and distances to the nasal vestibule were measured during the surgery. All measurements taken during dissection were measured on the coronal, axial, and sagittal section HRCT. Dissection data were compared with radiological data.
Results: As a result of comparing the radiological data and dissection data, there was no significant difference between the data obtained from the sagittal section and the dissection data. A significant difference (P=0.03) was found between the dissection and radiological evaluation in the coronal section except for the measurements of SO-UT (p=0.853) and MP-SA (p=0.972), and in the axial section except for the measurements of the SO-C (p=0.579) and MP-SA (p=1).
Discussion: Measurements obtained in the paranasal sinus CT can be used during FESS. While the data obtained in the sagittal section are suitable for the operation plan and can be used directly, the coronal and axial section are not.
Keywords: Endoscopic Surgical Procedure, Multidetector Computed Tomography, Nasal Sinuses
Introduction
Technological advances in the therapeutic and diagnostic field in the last three decades have changed the diagnosis and treatment methods in sinonasal and skull-based diseases. With the widespread use of the endoscope, the external approaches applied in the sinonasal region have been replaced by endoscopic methods. Since it is a minimally invasive method, its usage and popularity are increasing day by day.
Working in a narrow field in endoscopic nasal surgeries brings difficulties in the field of view. The fact that the paranasal sinuses are adjacent to vital structures such as the orbit, optic nerve, carotid artery, and skull base carries the risk of complications that may lead to significant morbidity and even mortality [1]. The way to minimize complications is to have a good knowledge of the anatomy of this region [2]. In addition, anatomical orientation and anatomical knowledge during surgery are also very important [3]. In the preoperative examination, endoscopic examination and imaging methods are very important. Anatomical evaluation and variations of the person should be carefully analyzed [4]. The most important guides during surgery are the patient’s radiological images and preoperative evaluations [5]. The most commonly used radiological method in the evaluation of the paranasal sinus region is computed tomography, which provides cross-sectional images [6, 7].
There are many studies that made some anatomical measurements from the radiological images of the paranasal sinuses [8-11]. In the same way, some anatomical measurements were made from cadaver dissections in the literature [12-15]. However, the studies that are comparing radiological data with dissection data are insufficient [16, 17]. In this study, we aimed to find out which section is suitable for the surgical plan by evaluating the measurements taken during the dissection for landmarks and their neighborhoods used in endoscopic sinus surgery in paranasal sinus computed tomography.
Material and Methods
This study was approved by the Ethics Committee of Necmettin Erbakan University (Date: 2016-10-07, No: 2016/687). Between May 2017 and June 2018, functional endoscopic sinus surgery was performed on a total of 10 nasal regions, bilaterally, on 5 fresh frozen cadaver heads in the anatomy laboratory. Before surgery, high-resolution computed tomography (HRCT) was performed on all cadavers with a multislice computed tomography device (SOMATOM Sensation 64 model Siemens). The images were taken with the head parallel to the orbitomeatal line and positioned on the occiput in accordance with the axial plane. Scanning limits were from the alveolar root to the frontal sinus roof. Sections were taken at 120 kilovoltages, 500 milliamperes/second and 0.6 mm thick. Coronal and sagittal sections were obtained with reconstruction.
Cadaver heads were prepared in a position suitable for the operation with a fixation device. For endoscopic sinus surgery, 0ᵒ, 30ᵒ (Youshi, China: 4.0 mm in diameter, 18 cm in length) and 45ᵒ (Karl Storz, Tuttlingen, Germany: 4.0 mm in diameter, 18 cm in length) telescopes were used. After the nasal cavity was cleaned with aspirator and forceps before surgery, the distances of important anatomical landmarks to the nasal vestibule (NV) and each other were measured. Endoscopic sinus surgery was first applied to the right and then left nasal cavity. Various anatomical landmarks were determined to be used in measurements. These anatomical landmarks are Nasal Vestibule (NV), Basal Lamella (BL), Sphenoid Ostium ( SO ), Sphenoid sinus anterior wall (SA), Posterior wall of sphenoid sinus ( SP ), Posterior Wall of Maxillary Sinus (MP), Choana (C), Upper turbinate (UT). The following measurements were made between the determined anatomical landmarks: BL – NV, SO – NV, SA – NV, SP – NV, MP – SA, SO – C, SO – UT.
Evaluation of High-Resolution Computed Tomography Images
The distances in the coronal and axial sections were measured by multiplying the number of slices by the slice thickness. The distance between the two structures in the sagittal section was measured directly. However, measurements between the anterior surface of the sphenoid sinus and the posterior wall of the maxillary sinus were made directly between two structures in all sections (Figure 1). Dissection and radiological measurements were statistically evaluated.
Results
Endoscopic sinus surgery procedures were performed on 10 nasal cavities of five fresh frozen cadavers. Demographic characteristics of cadavers are given in Table 1.
Dissection data and radiological data were compared, and the difference between them was statistically evaluated (Table 2).
Since the data obtained from the dissection and sagittal section CT images were measured in the same plane, we used the Wilcoxon signed-rank test in the analysis of the data. The Kruskal-Wallis test was used to compare dissection with the axial and coronal sections, and the Mann-Whitney U test with Bon Ferroni correction was used as the postok. The Mann-Whitney U test was used to compare the axial and sagittal sections. Logistic Regression analysis was used to make the estimation of the dissection data. P<0.05 was considered statistically significant.
No significant difference was observed between the data obtained from the sagittal section and dissection measurements. A significant difference (P=0.03) was found between the dissection and radiological evaluation in the coronal section except for the measurements of SO-UT (P=0.853) and MP-SA (P=0.972), and in the axial section except for the measurements of the SO-C (P=0.579) and MP-SA (P=1).
In the regression evaluation, the data obtained in the axial and coronal sections were considered significant with the R square value of 93.6% to determine the BL dissection measurement. ‘BL-NV = (axial section BL measurement*1.21) + (coronal section BL measurement* 0.65) – 6.96’ was found. To measure the SO distance, only data in the axial section were considered significant with the R square value of 95.6%. ‘SO-NV= 41.11+ ( SO-NV * 0.79 in axial section)’ was found. For SO-UT, a correlation was found with the sagittal section with an R square rate of 93%. It was ‘SO-UT=1.89 + (SO-UT * 0.893 in sagittal section)’. The distance of the SA was found to be related to the sagittal section, with an R square value of 90.7%.’SA-NV=3.2 + (SA-NV * 0.953 in sagittal section)’ was found. There was no correlation in the regression test for SP-NV, MP-SA, SO-C.
Discussion
Endoscopy is used in many areas from skull base surgery to simple sinus surgery, orbital decompression, dacryocystorhinostomy or ethmoid/sphenoethmoidal artery ligation [18]. With the development of surgical instruments and the use of angled endoscopes, this diversity continues to increase [19].
Understanding the surgical anatomy of the paranasal sinuses and knowing their anatomical variations can reduce complications in endoscopic nasal surgeries. This requires preoperative evaluation with paranasal sinus tomography [20]. The contribution of imaging methods and measurements to the operation is indisputable, especially in patients who have undergone surgery or whose anatomy is impaired due to pathologies.
Another way to reduce complications is to know the surgical anatomy and the landmarks used during surgery. In functional endoscopic sinus surgery, it is necessary to know the landmarks for anterior ethmoidectomy, maxillary antrostomy, posterior ethmoidectomy, sphenoidotomy and frontal recess.
The basal lamella is a landmark for posterior ethmoidectomy. The distance of the basal lamella to the nasal vestibule was 5.4 ± 0.2 cm. Dissection data and radiological data were almost the same in the sagittal section radiologically. There was no correlation between the axial and coronal sections and the dissection data. However, in the regression analysis, the dissection value was obtained from the axial and coronal sections.
The middle turbinate, superior turbinate, choana and septum are landmarks for the sphenoid sinus. The sphenoid sinus is placed at the posterior end of the middle turbinate. The ostium is located at the anteroinferior border of the superior turbinate and approximately 1-1.5 cm above the choana [20]. The anterior wall of the sphenoid sinus is 5–6 cm from the anterior nasal spine. In our study, we measured the distance between the anterior wall of the sphenoid sinus to nasal vestibule (6.6 cm ± 0.3), and the posterior wall (8 cm ± 0.2).
When comparing dissection measurements with radiological measurements, there was a significant difference in the coronal and axial sections. On the sagittal section, the data were fully compatible with each other. These values showed us that the most suitable image to be used to evaluate the sphenoid sinus is obtained from the sagittal sections.
According to the study by Gupta et al [21], the distances from the sphenoid ostium to the choana (21.21 ± 6.02 mm.), to the posteroinferior of the superior turbinate (8.03 ± 3.52 mm) and to the vestibule (55.1 ± 3.54 mm) were measured on cadavers. In our dissections, the mean distance from the sphenoid sinus ostium to the choana was 1.7 cm ± 0.1, to the anterior border of the superior turbinate: 1.8 cm ± 0.1, and to the nasal vestibule: 6.8 cm ± 0.09. In the comparison of radiological data and dissection data, there was no significant difference in the distance of the SO-NV only in the sagittal section (P=0.317). There were no significant differences in the sagittal and axial sections for the distance of the sphenoid ostium-choana, and in the sagittal and coronal sections for the distance of the SO-UT. In all measurements related to the sphenoid sinus, the sagittal section was the most compatible section. For SO, dissection data were obtained from the axial sections radiologically. The relationship of the SO with UT can be viewed in the coronal section, and its relationship with C can be viewed in the axial section.
Since the sphenoid sinus has gained importance in many fields, including neurosurgery, the search to find a reliable landmark for the sphenoid sinus is still ongoing. Recently, it has been tried to reveal its relationship with the maxillary sinus. In a study by Dedhia et al. [22], the distance of the posterior wall of the maxillary sinus to the sphenoid ostium was measured as 1.5 mm. However, this study was obtained in alive surgery and by calculating the distances of the sphenoid sinus ostium and the posterior wall of the maxillary sinus to the columella. In another study, the measurement was made with the anterior surface of the sphenoid sinus and it was 2-4 mm [23]. In our study, the measurement was made between the anterior surface of the sphenoid sinus and the posterior wall of the maxillary sinus. The average distance was anatomically and radiologically similar and was 8 ± 1 mm. We think that we obtained more reliable data as we directly measured the distances between the two structures in our dissections and in the radiological evaluation.
Limitation
Since the number of cadavers in this study is low and they are of American origin, the data obtained in this study cannot be used in patients. Since we operated on cadavers, it was easy to recognize and measure landmarks due to less bleeding. However, it may not be possible to perform the same measurements in alive surgery due to bleeding and limited access to the operating area. In the future, extensive studies can be conducted on races. The usability of the measurements can be evaluated by comparing the measurements taken in the alive surgery with the measurements taken from cadaver dissection.
Conclusion
In order to evaluate the basal lamella, sphenoid sinus, choana, superior concha, nasal vestibule and maxillary sinus, which are important landmarks used in endoscopic nasal surgery, the sagittal section is the most reliable and suitable section as accordance with the dissection data. Although coronal sections are frequently used in paranasal sinus CT nowadays, the data obtained from sagittal sections are more suitable with the operation plan.
Acknowledgment
Thanks to Scientific Research Project of Necmettin Erbakan University Funding for their financial support.
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: Scientific Research Project of Necmettin Erbakan University supported this research.
Conflict of Interest
The authors declare that there is no conflict of interest.
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3. Vaid S, Vaid N. Sinonasal Anatomy. Neuroimaging Clin N Am. 2022; 32(4): 713-34.
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5. Mistry S, Strachan D, Loney E. Improving paranasal sinus computed tomography reporting prior to functional endoscopic sinus surgery–an ENT-UK panel perspective. J Laryngol Otol. 2016; 130(10):962-6.
6. Öztekin HCŞY, Durmaz E, Özler A, Yavuz HE. Tıbbi Görüntüleme Yöntemleri ve Tarihi-Teknolojik Gelişimi (Medical Imaging Methods and Their Historical-Technological Development). Mev Med Sci 2021; 1(1):15.
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8. Pernas FG, Coughlin AM, Hughes SE, Riascos R, Maeso PA. A novel use of a landmark to avoid injury of the anterior ethmoidal artery during endoscopic sinus surgery. Am J Rhinol Allergy. 2011; 25(1):54-7.
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Rukiye Ozcelik Erdem, Mehmet Akif Dundar, Mitat Arıcıgil, Hamdi Arbag. Confirmation of anatomical proximities in endoscopic sinus surgery with computer tomography: A cadaveric study. Ann Clin Anal Med 2023;14(11):1049-1053
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Effectiveness of beta-blockers with neurocardiogenic syncope
Meltem Yiğit, Arif Ruhi Özyürek, Zülal Ülger, Ertürk Levent
Department of Child Health and Diseases, Faculty of Medicine, Ege University, Izmir, Turkey
DOI: 10.4328/ACAM.22003 Received: 2023-10-04 Accepted: 2023-10-30 Published Online: 2023-10-30 Printed: 2023-11-01 Ann Clin Anal Med 2023;14(11):1054-1058
Corresponding Author: Meltem Yiğit, Department of Child Health and Diseases, Faculty of Medicine, Ege University, Izmir, Turkey. E-mail: meltemdr2009@gmail.com P: +90 532 256 46 03 Corresponding Author ORCID ID: https://orcid.org/0009-0009-8568-3675
This study was approved by the Ethics Committee of Izmir Bakırçay University (Date: 2023-10-18, No: 1231/1211)
Aim: Syncope is a condition characterized by sudden and temporary loss of consciousness, accompanied by a loss of postural tone. In its pathophysiology, there can be a sudden drop in cerebral blood flow, alterations in the composition of the blood reaching the brain, or psychological causes. The aim of this study is to search the etiologies of syncope in children and evaluate the effectiveness of ß-blocker treatment in cases with neurocardiogenic syncope.
Material and Methods: The study included 51 patients admitted to our hospital with syncope complaints over a period of 18 months. Patients were evaluated by history, physical examination, laboratory tests, Electrocardiography (ECG), 24-hour holter monitoring, tilt test and EEG. Patients with a positive tilt test were divided into two subgroups. One group was given ß-blocker treatment, and the other group was given only recommendations.
Results: The tilt test was positive in 23 (45,09%) of 51 patients presenting with syncope complaints. Metoprolol was administered to 11(21,56%) of the patients. Metoprolol was used as a ß-blocker for 6 months. Conservative treatment was administered to 12 (23.52%) of them. The group not given ß-blockers was advised to take enough water and salt, not to stand for long periods of time, raise the head of the bed by 20°, and not to get up suddenly from the bed or from where they were sitting. When the syncope recurrence was questioned at the end of the 1-year follow-up after treatment or offers, no recurrence of syncope was observed in patients who received or did not receive treatment.
Discussion: The tilt test is the only noninvasive test used in the definitive diagnosis of neurocardiogenic syncope and should be performed in doubtful cases to clarify the diagnosis. In the treatment and follow-up of patients with vasovagal syncope, it should be taken into consideration that some precautions before drug therapy may be sufficient. These suggestions are not to stand for a long time, to ensure adequate water intake, not fasting, to raise the head of the bed 20 degrees, and not to get up suddenly from the bed or sitting position. There are no difference between the two groups in terms of recurrence of syncope. ß-blocker treatment has no effect on the recurrence of neurocardiogenic syncope.
Keywords: Tilt Test, Syncope, Neurocardiogenic Syncope, Electrocardiogram
Introduction
Syncope is a condition characterized by sudden and temporary loss of consciousness, accompanied by a loss of postural tone [1,2].
In its pathophysiology, there can be a sudden drop in cerebral blood flow, alterations in the composition of the blood reaching the brain, such as hypercatecholamine and hypersympathetic nerve function, excessive vasorelaxation or relatively low blood volume or psychological causes [4].
Syncope can occur due to non-cardiac o cardiac pathologies. Non-cardiac causes include neurocardiogenic syncope, reflex mechanisms, orthostatic hypotension, psychogenic factors, metabolic or neurological causes, migraine, anxiety, cerebrovascular diseases, certain medications, and hyperventilation [3]. Cardiac causes may involve arrhythmic and non-arrhythmic factors.
The most common cause of syncope is vasovagal, also known as neurocardiogenic syncope. It is associated with insufficient maintenance of circulatory system continuity or adequate vasomotor tone during conditions such as postural changes, physiological alterations, volume loss, and emotional stress.
Lower extremity venous pooling leads to a decrease in venous return to the heart, resulting in a mild drop in blood pressure. Sympathetic activity increases, leading to enhanced ventricular contraction and a reduction in the left ventricular cavity. Ventricular mechanoreceptors are stimulated and transmitted to the brainstem via unmyelinated C fibers. In the efferent response of this reflex, sympathetic suppression occurs. This leads to vasodilation, slowing of heart rate, and a decrease in blood pressure [7].
The tilt test is the only test that can be used in patients suspected of having neurocardiogenic syncope. Patients with a positive tilt test can exhibit three types of responses to the test. The patient should rest for approximately 15 minutes before the test. The tilt table should be capable of being raised up to 90 degrees and should have supports for the feet [14].
While the patient is lying in a supine position, heart rate and blood pressure are monitored at five-minute intervals. After 15 minutes, the table is tilted to either 60 or 80 degrees, and measurements of heart rate and blood pressure continue. The tilt test can also be provoked with medication. Medications such as nitroglycerin, adenosine, or nitroprusside, isoproterenol, edrophonium, and epinephrine can be used [9].
In the vasodepressor type, only blood pressure drops, in the mixed type, blood pressure and heart rate drop, and in the cardioinhibitory type, only heart rate drops [11,12].
Material and Methods
This study was conducted on 51 patients, aged between 8 and 17 years (mean age: 13.147 ± 2.39), who presented with complaints of syncope to our hospital (between August 2001 and February 2003) during18 months. Of the patients, 15 (29.4%) were male and 36 (70.6%) were female. Six patients (11.8%) presented with presyncope symptoms, while 26 (51%) had experienced a single syncopal episode, 13 (25.5%) had experienced 2 episodes, and 6 (11.8%) had experienced 3 or more syncopal episodes.
Detailed medical history was obtained from all patients, and physical examinations were performed. Complete blood count, blood glucose, blood calcium, and ion levels were evaluated for all patients. ECG was performed to investigate possible cardiac pathologies, and PR, QRS, QT, and corrected QT were calculated. All patients underwent echocardiography, 24-hour Holter monitoring, and EEG.
A simple tilt test was administered to all patients. The patient was kept in the tilted position for 30 minutes, completing the total test duration in 45 minutes. If syncope or presyncope occurred, the test was terminated and considered positive. Positive test results were defined as a 30% decrease in heart rate based on the recorded maximum heart rate, and a 20% decrease in blood pressure based on the detected highest blood pressure.
In the study, out of the 51 included patients, the tilt test was negative in 28 (54,91%), and positive in 23 (45,09%). Among the consecutively positive tilt test results, beta-blocker treatment was initiated in 11 (21,56 %) patients. Metoprolol was used as the beta-blocker. The subsequent 12 (23.52%) patients with positive tilts test did not receive any medical treatment but were provided with recommendations. These recommendations included avoiding prolonged standing, ensuring adequate water intake, not fasting for extended periods, elevating the head of the bed by 20 degrees, and avoiding sudden transitions from lying down or sitting. Prior to initiating medical treatment, epileptiform discharges were observed in one of the monitored cases during EEG, treatment was adjusted, and the case was excluded from the study.
The patients were evaluated twice with a 6-month interval and followed up for one year to inquire whether they experienced syncope or presyncope during this period. The statistical analysis was conducted using the SPSS for Windows release 6.1 software package. Chi-square, Kruskall-Wallis, Mann-Whitney U, Bonferroni test, and one-way analysis of variance tests were employed. A p-value of <0.05 was considered statistically significant.
This study was approved by the Ethics Committee of Izmir Bakırçay University (Date: 2023-10-18, No: 1231/1211).
Results
A total of 51 patients presenting with syncope complaints were initially included in the study. However, one patient was excluded due to the diagnosis of epilepsy, and another patient did not attend the study. Forty-nine patients were included in the study. The ages of the study group ranged from 8 to 17 years (mean age: 13.14 ± 2.39). Thirteen of the patients were male (27%), while 36 were female (73%). It was observed that the number of females was significantly higher than males (p<0.003) (Table 1).
In one case, Holter monitoring revealed ventricular premature beats at a rate of 12%. However, since there were no syncope or presyncope attacks during these premature beats, they were classified as benign premature beats.
The number of syncopal episodes varied among the groups, with a maximum of 2 in the tilt test negative group, 5 in the tilt test positive group receiving treatment, and 3 in the untreated group. There was a significant difference in the number of syncopal/presyncopal episodes among the three groups (p=0.008) (Table 2).
All three groups were evaluated in terms of hemoglobin, sodium, potassium, calcium, creatinine, and blood sugar levels, heart rate, PR interval on the EKG, and QRS interval on the EKG, and no significant differences were found in any of these parameters.
Echocardiography results did not reveal any pathological findings that could be the cause of syncope.
EEG results were evaluated; in the group with a negative tilt test, cortical irritability in the frontal region was observed in 1 patient, and in the untreated group, epileptic discharges were detected in 1 case. These patients were excluded from the study.
All patients underwent tilt testing. The tilt test was positive in 23 cases (45,09%). In 2 of these patients, presyncope occurred during the test, and in 2 others, syncope occurred, leading to the termination of the test. A vasodepressor-type response was observed in 14 patients (60%), while mixed-type response was observed in 9 patients (40%). No cardioinhibitory-type response was observed in any of the patients. When comparing the three groups, a significant difference was found in systolic blood pressure at 30 minutes, and systolic and diastolic blood pressure at 45 minutes between the group with negative tilt test and the groups with positive tilt test (p < 0.01) (Table 3). Beta-blocker treatment with metoprolol was administered to consecutive 11 (21,56%) patients with positive tilt tests for a period of 6 months. One patient was excluded from the follow-up due to non-compliance. The subsequent 12 (23,52%) patients with positive tilt tests did not receive treatment. In one of these patients, epileptiform discharges were observed in the EEG, and they were excluded from the study. The group without beta-blocker treatment was given advises.
At the end of the 1-year follow-up period after treatment or recommendations, when recurrence of syncope was queried, in the group with negative tilt tests, 2 patients experienced presyncope once, and 1 patient experienced syncope once. In both the treated and untreated groups, no recurrence of syncope was observed (p=0.596).
Discussion
Syncope is characterized by a sudden decrease in cerebral perfusion leading to a transient loss of consciousness accompanied by a loss of postural tone [1,2-12]. Up to 15 percent of children experience a syncopal episode prior to the end of adolescence [5].
This study provides valuable insights into determining the etiology of syncope in children and evaluating the effectiveness of ß-blocker treatment in cases of neurocardiogenic syncope.
The most common cause of syncope is neurocardiogenic syncop [6]. The etiology of syncope was found to be related to neurocardiogenic and psychogenic factors in 40%, central nervous system in 32%, cardiac in 8%, medication and metabolic factors in 7%, and in 13% of cases, no specific cause was identified [6]. In our study, epilepsy was identified as the cause in 1.9% of cases presenting with syncope, and neurocardiogenic syncope was determined in 41.17%. In 56.93% of cases, no specific cause was found. However, no pathology was detected in repeated physical examinations and investigations, and these patients were referred to the pediatric health and child psychiatry outpatient clinic for further follow-up.
The tilt test is the only test that can be used in patients suspected of having neurocardiogenic syncope. Its use is still recommended for the diagnosis of TLOC by both the American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) and the European Society of Cardiology (ESC) guidelines [11,12].
ECG may be useful in explaining the etiology if the cause of syncope is cardiac in origin. In our study, all ECG results were found to be normal and did not provide useful information in explaining the etiology. In some studies conducted, it has been observed that echocardiography does not provide additional clinical benefit in patients with normal ECG and no history of cardiovascular disease [10].
The role of 24-hour Holter monitoring in diagnosing syncope is debated. This is because the patient may not experience symptoms or have a syncope episode during the 24-hour period in which the Holter device is attached.
EEG studies conducted on patients presenting with syncope have shown that only 1% of patients had epileptiform abnormalities. In our study, epilepsy was detected in 1 patient (1.9%), and treatment was arranged accordingly.
In a study conducted by Pongiglione et al., they found a vasodepressor response in 12.5%, mixed type in 68.5%, and cardioinhibitory response in 19% of cases [13]. In our study, vasodepressor response was observed in 12 patients (52.2%), while mixed type response was seen in 9 patients (47.8%). No patient exhibited a cardioinhibitory response.
In a study by Alehan et al., involving 20 cases suspected of neurocardiogenic syncope in patients aged between 12 ± 2.5 years, all patients were given ß-blockers. At the end of an 18 ± 6 months follow-up period, no recurrence of symptoms was observed, and they stated that ß-blocker use significantly reduced the recurrence of syncope [8].
In the present study, we gave ß-blockers to 10 out of 21 cases suspected of neurocardiogenic syncope, and provided recommendations to the remaining 11 patients. After a 12-month follow-up, when we inquired about the recurrence of syncope or presyncope, we found that none of the patients experienced a recurrence of symptoms.
Conclusion
In our study, we found that the history of syncope was significantly more in girls compared to boys. This result was found to be statistically significant. Among the cases presenting with syncope, epilepsy was detected in 1,9%, while neurocardiogenic syncope was identified in 41.17%. In 56.93% of cases no specific cause could be determined.
None of the patients showed electrolyte imbalance as a cause of syncope. Similarly, none of the patients with syncope attacks were attributed to cardiac pathology.
Regarding the tilt test results, vasodepressor and mixed-type responses were observed in the patients, while cardioinhibitory type responses were not observed.
Eleven (21,56 %) patients with a positive tilt test were diagnosed with neurocardiogenic syncope and prescribed beta blockers, 12 (23.52%) patients were not given beta-blocker treatment and only recommendations were made. After a one-year follow-up period, none of the patients experienced a recurrence of syncope. This indicates that beta-blocker therapy may not be as crucial for neurocardiogenic syncope and that recommendations alone can be equally valuable as medication treatment. In every case of syncope, a detailed history should be taken and a careful physical examination should be performed. In all cases, a routine ECG should be obtained. Further examinations are required in the differential diagnosis of syncope due to neurological or cardiological causes.
The tilt test is the only noninvasive test used in the definitive diagnosis of neurocardiogenic syncope and should be performed in doubtful cases to clarify the diagnosis.
In the treatment and follow-up of patients with vasovagal syncope, it should be taken into consideration that some precautions before drug therapy may be sufficient. These suggestions include not standing for a long time, ensuring adequate water intake, not fasting, raising the head of the bed 20 degrees, and not getting up suddenly from the bed or sitting position. We concluded that the use of ß-blockers in the treatment of neurocardiogenic syncope is not more valuable than the recommendations.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and Human Rights Statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
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Download attachments: 10.4328.ACAM.22003
Meltem Yiğit, Arif Ruhi Özyürek, Zülal Ülger, Ertürk Levent. Effectiveness of beta-blockers with neurocardiogenic syncope. Ann Clin Anal Med 2023;14(11):1054-1058
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