Supplement 3 2021
Evaluation of Vacuum-assisted stereotactic biopsy for isolated BI-RADS 4 microcalcifications
Esra Ummuhan Mermi Yetis 1, Alev Ozturk Gunaldi 1, Mehmet Mahir Atasoy 1, Levent Celik 2
1 Department of Radiology, Maltepe University Faculty of Medicine, 2 Department of Radiology, Radiologica Imaging Center, İstanbul, Turkey
DOI: 10.4328/ACAM.20507 Received: 2021-01-27 Accepted: 2021-03-06 Published Online: 2021-03-18 Printed: 2021-08-15 Ann Clin Anal Med 2021;12(Suppl 3): S250-253
Corresponding Author: Esra Ummuhan Mermi Yetis, Department of Radiology, Maltepe University Faculty of Medicine 34844, Maltepe, Istanbul, Turkey. E-mail: mdesramermiyetis@gmail.com P: +90 364 219 30 00 F: +90 364 223 30 30 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6410-590X
Aim: The aim of this study was to evaluate the long-term results of vacuum-assisted stereotactic biopsy (VASB) for microcalcifications with isolated Breast Imaging Reporting and Data System (BI-RADS 4).
Material and Methods: Three hundred sixty-seven patients who underwent VASB due to microcalcifications between June 2011 and October 2017 were screened. VASB was performed in all patients using stereotaxy in the lateral decubitus position. VASB, surgical pathology results and long-term follow-up find- ings were evaluated. Statistical analysis was evaluated with mean values and underestimation rates.
Results: Among 76 patients and 78 microcalcifications, 20 were defined as ductal carcinoma in-situ (DCIS), two were defined as atypical lobular hyperplasia (ALH), one as atypical ductal hyperplasia (ADH) and 56 as benign. The two cases reported as ALH in VASB refused the operation and were followed up, and no progression was detected in their follow-up. The DCIS underestimation rate was 20% (4/20). The mean follow-up time was 55.46 months, and the mean follow-up time in benign lesions was 53.4 months. No conversion to malignancy was detected in any of the patients whose VASB results were found benign (false negative rate 0%).
Discussion: In our study, no conversion to malignancy was detected in the long-term follow-up results of patients with isolated BI-RADS 4 microcalcification and having benign VASB results (false negative rate 0%). This method eliminated the necessity of surgical excision in 71.7% (56/78) of the cases with isolated BI-RADS 4 microcalcification in our study. VASB may be the standard method for BI-RADS 4 microcalcifications.
Keywords: BI-RADS 4; Mammography; Microcalcification; VASB; DCIS
Introduction
The detection of non-palpable breast lesions has increased with the increase in the number of mammography screening. Microcalcifications are detected in approximately one- third of screening mammograms [1]. It has been reported that approximately 55% of non-palpable breast cancers are associated with calcifications; 55% of the suspicious lesions detected in mammography are isolated microcalcifications [2]. Approximately 80% of ductal carcinoma in situ (DCIS) can only be detected as microcalcification on mammography [3]. Suspected microcalcifications can be surgically removed after wire marking. However, in some studies, it was found that 76- 81% of patients who underwent surgical excision had benign pathology [4]. Noninvasive methods such as core biopsy have been increasingly preferred recently due to low cost and morbidity [5].
Vacuum-Assisted Breast Biopsy (VABB) is superior to breast core biopsy due to its advantages, such as the capacity to obtain larger volumes of the specimen, obtaining a greater number of microcalcifications, decreased low cancer prediction rates and reduced sampling error [6]. The needle size in VABB systems ranges from 7 gauge to 14 gauge [7]. Vacuum-assisted stereotactic biopsy (VASB) is increasingly used for the diagnosis of suspected microcalcifications. When performed by experienced radiologists, the false negative rate of the VASB procedure can be as low as 0.6% [8]. Suspected isolated microcalcifications can be sampled by stereotaxy. Breast Imaging Reporting and Data System (BI-RADS) 5 microcalcifications should undergo surgical excision in all cases with accompanying mass, and structural distortion. Surgical intervention can be avoided in most patients with the routine use of VASB before considering more invasive methods for BI- RADS 4 microcalcifications [9]. The purpose of this study is to evaluate the long-term results of VASB for isolated BI-RADS 4 microcalcifications that were previously observed in the middle term.
Material and Methods
Before each VASB, potential risks and benefits were explained in detail, and informed written consent was obtained from each patient. Ethics committee approval dated 29.07.2020 numbered 2020/900/64 was obtained.
Patient selection
Patients who underwent VASB between June 2011 and October 2017 were retrospectively screened using the picture archiving and communication system (PACS). A total of 373 microcalcifications were detected in 367 patients. Twenty-nine patients were excluded from the study because they had BI- RADS 5 microcalcifications, 19 patients were excluded because of the accompanying mass, and 44 patients were excluded because of additional findings such as asymmetric density and parenchymal distortion. One hundred ninety-nine patients without long-term follow-up were excluded from the study. A total of 76 patients and 78 microcalcifications were included in the study (Figure 1). Two patients had bilateral breast calcifications.
Each patient included in the study had an initial breast USG evaluation that did not show any abnormalities. Long-term follow-up was considered as over 30 months. Patients with regular follow-up for 30 months or more (30-102 months) were included in the study.
Evaluation of the images
Microcalcifications in the initial mammography were classified by two radiologists unanimously, both with more than 10 years of experience (over 1500 mammograms per year). Classification of microcalcifications was made according to the currently available American College of Radiology (ACR) “Breast Imaging Reporting and Data System (BI-RADS) 5th edition” criteria. The most recent BI-RADS lexicon has removed the BI-RADS 3 microcalcification group from the classification due to its wide range of malignancy rates [9, 10]. Lesions were classified as suspicious BI-RADS 4 (A, B, C) or BI-RADS 5 having a high risk of malignancy. For those who had previous mammography films, the decision was made based on interval evaluation. Patients with BI-RADS 5 microcalcifications were suggested to perform surgical biopsy or VASB, stating that the benign pathology result would not eliminate the need for surgical excision. However, VASB was performed for all patients with BI-RADS 4 microcalcifications.
Biopsy procedure
All VASB procedures were routinely performed on a lateral decubitus platform with a full- field digital mammography system (Amulet, Fujifilm, Tokyo, Japan) using a 10-gauge VACORA TM Breast Biopsy System (Bard Biopsy Systems, Tempe, Arizona, USA). All patients were placed in the lateral decubitus position. Patients were positioned so that a 5 x 5 cm biopsy window was suitable for the localization of the lesion, following the application of compression with ML projection. The target lesion was determined by scout image and two 15 ° stereotactic views. Local anesthesia was applied using 5 mL of 2% lidocaine just before the 10- gauge needle was placed in the center of the lesion. A second stereotactic image was taken to confirm the position of the needle. The same steps were repeated when more than one lesion was targeted. Eight biopsy specimens were routinely obtained and the procedure was completed when microcalcifications were detected in these specimens. In all patients, the target breast tissue was checked through the biopsy window before releasing compression; If the microcalcifications did not decrease, the procedure continued to take additional samples. If microcalcifications are still observed after eight biopsies, additional four specimens were taken and the procedure was terminated with a total of 12 specimens. As a result, it was ensured that all patients had microcalcifications in their biopsy specimens. Prior to completion of the procedure, a radiopaque marking clip was left in the biopsy cavity, and if all calcifications were removed, a final check was performed with a mammogram to verify the clip localization (Figure 2). Tissue samples were then placed in formol and sent to the pathology laboratory. Biopsy specimens were imaged with 25 kV and 10 mA expression factors using the same digital mammography at the end of the procedure. None of the patients required a repeat biopsy.
Follow-up
The surgical operation was suggested for all patients whose VASB pathology result was atypical and was considered as premalignant. Follow-up was recommended for those with benign pathology results. Long-term follow-up was accepted as 30 months or more. Follow-up mammograms, breast ultrasonography and breast MRI findings of the patients, if any, were evaluated. Based on follow-up data, histological underestimation or false negative result rate was evaluated. Statistical analysis
False negativity was accepted as the final pathological decision of the lesion with benign pathology by the VASB procedure as malignant/premalignant.
The false-negativity rate was calculated by dividing the number of false-negative lesions by the total number of VASBs. Histological underestimation was defined as the emergence of invasive carcinoma after surgical excision in cases with DCIS as a result of the biopsy and DCIS or invasive carcinoma in cases with atypia.
Underestimation rate was calculated by dividing the number of underestimated lesions by the total number of lesions with ADH or DCIS determined after VASB.
The data were recorded in a spreadsheet on the computer, and then simple descriptive statistics were made using appropriate software (Excel; Microsoft, Redmond, Washington, USA) for analysis.
Results
Seventy-eight microcalcifications were evaluated in a total of 76 patients (median age 52.7, range 40-83). The BI-RADS Category and pathology results of microcalcifications are shown in Table 1.
Among 78 microcalcifications in VASB, 20 were defined as DCIS, two of them were ALH, one of them was ADH, and 56 of them were benign. Operation was suggested for two ALH patients. The patients did not want the operation and wanted to be followed. No significant interval change was found during the follow-up. One patient diagnosed with ADH was operated on. In this patient, no malignancy was detected in the postoperative pathology (underestimation rate 0%). All cases with the result of DCIS were operated. In the postoperative pathology, an invasive component was observed in 4 patients, one case evaluated as DCIS in VASB was reported as LCIS postoperatively. No residual tumor was observed in any patient after the operation. There was no recurrence in their follow-up.
All patients with benign VASB results were followed, none of them converted to malignancy during the follow-up (false negative rate 0%).
Benign cases were in the BI-RADS Category 4A or 4B group. The DCIS underestimation rate was 20% (4/20). The underestimation rate for BI-RADS 4C lesions was 15% (3/20). The follow-up period was at least 31 months (31-102 months). The average follow-up time was 55.46 months. Six-month follow-up data were available for all benign lesions. There were no additional cases of malignancy after a mean follow-up of 53.4 months for benign lesions. According to the follow-up results, the false negativity rate was 0%.
Discussion
Recently, with the increasing use of mammography screening, the detection of non-palpable breast lesions and biopsy requirements have increased. Microcalcifications may be the only finding in early-stage non-palpable breast cancer [11]. Needle-localized surgical biopsy (MLSB), an excisional biopsy from the suspected lesion, is considered the gold standard. However, due to the scarring, high cost and morbidity of this method, non-invasive methods are increasingly used. Lesions detected on mammography alone require stereotactic guidance, and vacuum-assisted breast biopsy (VABB) is currently the preferred biopsy method for stereotactic biopsies [12]. VABB is a fast and effective biopsy technique that can be tolerated by patients, without major complications. VABB has sufficient sensitivity and specificity for diagnosis. VABB often allows complete removal of the mammographic lesion [12].
With the routine use of VASB for BI-RADS 4 microcalcifications, unnecessary surgical excision can be avoided in many patients. In our study, according to the long-term results, the false negativity rate was 0%, as in our study, where we evaluated the mid-term results. Additionally, an average underestimate rate for DCIS was acceptable. While no malignancy was detected in one of our ADH patients after the operation, two ALH patients did not accept the operation and wanted to be followed up with routine mammosonography and MRI. The number of patients with the atypical pathological diagnosis was not sufficient.
ADH underestimation rates in the range of 0% to 88% have been reported for stereotactic biopsy techniques [13, 14]. There is one ADH case in our study, and we have few cases to make a reliable interpretation. In the literature, underestimate rates for cancer and DCIS vary between 10% and 30% [15, 16]. The underestimate rate in our patients diagnosed with DCIS was 20% and was similar to the literature.
Our study showed that VASB can be used as a first-line diagnostic approach for isolated BI-RADS 4 microcalcifications. Patients with benign VASB results can be followed up safely. In our study, VASB eliminated the necessity of surgical excision in 71.7% of cases with isolated BI-RADS 4 microcalcification. Failure to detect sufficient calcification in specimen radiograms, failure to detect calcium crystals in histopathological analysis, radiological-histological incompatibility or their combination may be the causes of missed cancer cases. The false negative rate for malignancy was zero in our study. This may be due to the experience of our radiologists, confirmation of the presence of microcalcifications in all included sample radiograms, and radiological-histopathological teamwork [17]. The experience of the radiologist and ensuring the use of specimens containing micro calcification should be considered when establishing guidelines for the VASB procedure.
Excisional biopsy may reduce the chance of sentinel lymph node sampling if the lesion is malignant. After VASB, the biopsy site is intact and preserves the opportunity for sentinel lymph node sampling when necessary. In lesions that can only be detected on mammography, VASB can replace NLSB.
Acceptable false-negative rates of VASB have been reported by experienced radiologists [17]. Radiologists may experience difficulties during follow-up due to scarring and structural deterioration after surgical excision. VASB provides better cosmetic results compared to surgical procedures. VASB is a process with lower cost, less morbidity and takes a short time. In necessary cases, the radiopaque marking clip is also left, and the next operations can be easily planned if necessary.
The use of a lateral decubitus table for VASB has some advantages over prone table systems. Microcalcifications have a higher resolution and provide a high contrast image. It can be performed in the same unit as mammography. Easier access is provided for deep lesions close to the axilla.
There were some limitations in our study. The number of patients with atypia pathology was low, and some patients did not accept the operation and wanted to be followed. We have a small number of patients and we think that larger series with long-term regular follow-up will contribute significantly to the literature.
In conclusion, in our study, the need for surgical excision was eliminated in 71.7% of patients with isolated BI-RADS 4 microcalcifications. According to the long-term results, the false negative rate was 0%. The average underestimation rate for DCIS patients was 20%.
In the presence of experienced radiologists, VASB is a fast and effective method, does not cause major complications and it can be used as the first choice for isolated BI-RADS 4 microcalcifications.
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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Esra Ummuhan Mermi Yetis, Alev Ozturk Gunaldi, Mehmet Mahir Atasoy, Levent Celik. Evaluation of Vacuum-assisted stereotactic biopsy for isolated BI-RADS 4 microcalcifications. Ann Clin Anal Med 2021;12(Suppl 3): S250-253
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Field study for determining the effect of COVID-19 on healthcare workers
Nesibe Sultan Çınaroğlu 1, Kenan Öztorun 2, Mustafa Kaçmaz 3, Zeynep Yılmaz Öztorun 4
1 Department of Surgical Disease Nursing, Niğde Zübeyde Hanım Health School, 2 Department of Urology, Niğde Ömer Halisdemir University Faculty of Medicine, 3 Department of Anesthesiology, Niğde Ömer Halisdemir University Faculty of Medicine, 4 Department of Pediatrics, Niğde Ömer Halisdemir University Faculty of Medicine, Niğde, Turkey
DOI: 10.4328/ACAM.20512 Received: 2021-02-28 Accepted: 2021-04-30 Published Online: 2021-05-12 Printed: 2021-08-15 Ann Clin Anal Med 2021;12(Suppl 3): S254-258
Corresponding Author: Kenan Öztorun, İnönü Mah. Haşmetli Sk Hande Sitesi No:31 51200 Merkez/Niğde, Turkey. E-mail: kenanoztorun@gmail.com P: +90533 4392443 Corresponding Author ORCID ID: https://orcid.org/0000-0001-9994-3479
Aim: This study determines the anxiety levels of health workers by evaluating their anxiety status in the challenging process of the pandemic.
Material and Methods: One hundred forty health workers who studied at pandemic hospital were included in the study. The data were collected using the Pandemic Period Data Form (PPDF), and the State-Trait Anxiety Inventory (STAI), prepared for assessing anxiety levels of health workers in the face of the COVID-19 outbreak.
Results: In the study there was a significant difference between the health care workers working in intensive care units and those working in non-intensive care units in terms of age, gender, and presence of children.
We found that there was a significant difference in STAI state anxiety scores (p < .05) of health workers in terms of having children, and they had higher levels of state anxiety. On average, the health workers from intensive care units had higher levels of PPDF anxiety.
In this study, we detected that the COVID-19 anxiety levels of the health workers between the ages of 20 and 30 were higher compared with those aged 41 and above (p < .05).
Discussion: It was found that the pandemic process had a negative impact on health workers as their anxiety increased in this process. Elimination of the gaps related to application or information in the published guidelines can help health workers feel more safe.
Keywords: COVID-19; Health workers; Anxiety state; Anxiety
Introduction
The present novel Coronavirus (CoV) disease, also called a severe acute respiratory syndrome (SARS)-CoV-2 and coronavirus disease 2019 (COVID-19), is an emerging global health threat [1]. The COVID-19 epidemic started from Wuhan city of China at the end of December 2019 and since then spread rapidly to other countries [2]. On March 11, 2020, the World Health Organization (WHO) announced that COVID-19 is ‘a public health emergency of international concern [3].
Existing evidence suggests that COVID-19 is transmitted by close contact and droplets. Therefore, health workers who care for COVID-19 patients are considered to have a high risk of infection, and the protection of healthcare workers is among the top priorities [4].
As with many previous infectious disease outbreaks such as severe acute respiratory syndrome (SARS) and Ebola, healthcare workers are at the forefront of the risk of infection and death [5]. In the first study conducted on health workers in Wuhan after the COVID-19 outbreak first appeared, it was found that 71.3% of health teams suffered from mental disorders at a sub- threshold and light level, 22.4% at a moderate level, and 6.2% at a severe level. It was emphasized that access to mental health services was important for health personnel working during the outbreak to improve their physical health perceptions and to alleviate acute mental distress [6].
This study evaluates the level of anxiety of health personnel working in the hospital environment where COVID-19 is being diagnosed and treated.
Material and Methods
The study included 140 health professionals working at the emergency services, inpatient services and intensive care units of Niğde Ömer Halisdemir University (NOHU) Training and Research Hospital. The data were collected using the Information Form, designed for identifying characteristics of individuals, the Pandemic Period Data Form (PPDF), a questionnaire prepared to assess the anxiety of health workers in the face of the COVID-19 outbreak, and the State-Trait Anxiety Inventory (STAI) to measure state anxiety. The data were analyzed using the IBM SPSS Statistics (version 23). Before proceeding with the study, approval from the hospital where the study would be conducted was obtained. In addition, approvals from the Ministry of Health of Turkey (Application Approval Code: 2020-05-11T22_09_29) and the Ethics Committee of Niğde Ömer Halisdemir University (No. 86837521-050.99-E.23016) were received.
Information Form related to Characteristics of Individuals: It consists of questions about age, gender, marital status, title, frequency of visiting the family, working unit, and frequency of contact with COVID-19-positive patients.
Pandemic Period Data Form (PPDF) (Questionnaire to assess the anxiety state of health workers against the COVID-19 outbreak): The questions addressed to the health professionals working at the NOHU Training and Research Hospital were related to adequacy of the equipment and devices in the service, working hours at the hospital, sleep, shelter and nutrition arrangements, the belief that the process will end, perceiving each patient as positive for COVID-19, and the fear of the employees of infecting themselves, their patient, family, and loved ones and were scored as Never (1), Rarely (2), Sometimes (3), Usually (4), and Always (5).
State-Trait Anxiety Inventory (Spielberger CD. 1970, Oner N.1985): Directive: A number of expressions used by people to describe their own feelings are given. The participant reads each expression and marks the appropriate option from one of the parentheses on the right side of the expressions that defines how he/she feels at the moment. The participant marks the answers quickly without losing too much time. In this way, the state of anxiety is measured.
Data Analysis
In this study, independent group t-test, variance analysis, and correlation analysis techniques were used for data analysis. Before the data were analyzed, the assumptions of the analyses were examined. Analysis of the data was carried out with the SPSS (version 23) software package. The margin of error was considered .05.
Results
Face-to-face interviews were conducted with 140 health professionals who were on duty for COVID-19 at the NOHU Training and Research Hospital.
In terms of the gender distribution of the health workers, 87 were women (62.1%) and 53 were men (37.9%). There was no differences between the PPDF scores of the health workers in terms of gender (t(138) = .11, p > .05). In other words, the PPDF levels of male and female health workers were similar. In terms of gender, there was a difference in the state anxiety levels of the health workers (t(138) = -4.08, p < .05). On average, male health workers had higher state anxiety levels.
The number of health workers was 83 (59.3%) in non-intensive care units and 57 (40.7%) in intensive care units. It was determined that there was a difference in the PPDF scores of the health workers in terms of the unit in which they worked (t(138) = -2.23, p < .05). On average, the health workers in intensive care units had higher levels of PPDF anxiety.
There was no difference in the STAI state anxiety levels of the health workers in terms of the unit in which they worked (t(138) = -29, p > .05). In other words, the state anxiety levels of those who worked in intensive care units and other units were similar (Table 1).
The number of health workers having children was 96 (68.6%), and the number of those who had no children was 44 (31.4%). There was no difference in the PPDF scores of the health workers in terms of having children (t(138) = -1.67, p > .05). In other words, the COVID-19 anxiety levels of health workers with and without children were similar.
It was determined that there was a difference in the STAI state anxiety levels of the health workers in terms of having children (t(138) = 2.42, p < .05). On average, those who had children had higher levels of state anxiety (Table 2).
In terms of the age variable, the health workers were found to have differences in PPDF scores (F(2, 137) = 3.43, p < .05). As a result of the Scheffe test conducted to determine the source of this difference, it was found that the COVID-19 anxiety levels of the health workers between the ages of 20 and 30 were higher than those of the health workers aged 41 and above (Table 3). In terms of the variable of age, there was a difference in STAI state anxiety levels of the health workers (F(2, 137) = 3.36, p < .05). As a result of the Scheffe test conducted to determine the source of this difference, the state anxiety levels of the individuals aged 41 and above were found to be higher than those of the individuals in the 20-30 age groups.
Discussion
In determining the impact of COVID-19 on health workers, this study found that there was a significant difference between the health workers in terms of age, gender, presence of children, working in intensive care and non-intensive care services, and there was no significant difference in marital status and title. In this study, it was observed that the state anxiety levels in the pandemic process differed based on gender, and the state anxiety levels of male health workers were higher.
Concerns about the transmission of the virus, the safety of their fellow health workers and peers may lead to resentment, anxiety, insomnia, and stress. The need for frequent contact with patients in isolation units has exhausted health workers physically and psychologically and caused high stress levels and insomnia. Healthcare workers were more likely to have poor sleep quality [7]. During the COVID-19 outbreak, more than a third of health workers suffered from insomnia. The literature supports the results of this study. Stress, anxiety, and fear caused by the pandemic process by 55.1% caused disturbance of sleep.
Hospitals have turned into very stressful environments during the outbreak. The troubles related to materials, equipment supply, creation of clean spaces, and the obligation of the staff to work in two-layer protection and masks at high temperatures and negative pressures uninterruptedly have amplified stress [8]. The findings of this study are in line with the literature, and 62.8% of the participants stateed that it is difficult to work continuously with protective equipment and this challenge is a source of stress.
In particular, health workers working in certain units of hospitals are at greater risk of infection. Those working in emergency services, intensive care, and infectious disease services, as well as family physicians in primary care, are exposed to relatively high risks [9]. In this study, health workers who work in intensive care units had higher COVID-19 anxiety levels on average compared with those working in non-intensive care units. This is due to the fact that patient treatment is more intensive, the contact with the patient is closer in these units, and patients in intensive care units have higher virus loads.
In terms of state anxiety levels, there was no difference in the mean scores of health workers in intensive care and non-intensive care units, and health workers in the hospital generally had similar anxiety levels. The lack of difference in state anxiety levels can be explained by the fact that health workers had common levels of anxiety in their family and social lives, regardless of the unit in which they work.
In some studies, the mean state and trait anxiety scores of health workers aged 35 years and above were found to be slightly higher, and this was not statistically significant. There are studies that show that the state of anxiety increases with age, as well as studies reporting no difference [10]. In the study, it was observed that anxiety and depression levels in young and less experienced health workers increased [11]. In this study, COVID-19 anxiety levels of the health workers aged 20 to 30 were higher than those of the health workers aged 41 and above. The state anxiety levels of the individuals aged 41 and above were higher than those in the 20-30 age group. As the rates of marriage and having children increase with age, older health workers may experience additional concerns for their spouse and children, and this may lead to anxiety scores that are numerally higher but statistically not significant. Familiarity with and adaptation to the working environment, higher levels of knowledge and ability to use personal protective equipment, and professional experience in the follow-up and treatment of clinically severe patients may be reasons for lower levels of COVID-19 anxiety in the health workers aged 41 and above. Higher levels of state anxiety in older age groups may be caused by additional anxiety for family members.
Health care workers need to protect their health and provide adequate working conditions, e.g., supply of necessary and adequate medical protective equipment, the regulation of adequate rest and recovery programs for strengthening flexibility and psychological well-being [12]. The safety of health workers is a priority concern. Seeing the friends they work with intubated, the loss of patients they provide care for, the fear of infecting their families and loved ones can damage their sense of security. These problems were reported by health workers during the fight against the SARS [13,14]. The fear of being infected is higher in health workers than in the community. This fear stems from the fact that health professionals fear infecting their family members or close friends, rather than becoming infected themselves. It was found in various studies that health workers from China and Canada fighting SARS had high levels of fear and anxiety about infecting family members [15,16]. In this study, health professionals experienced an anxiety level of 51.5% for getting infected with the virus, but their anxiety level for infecting the family members and close friends was 72.1%. For these reasons, health workers prefer to stay away from their homes and family members for a long period of time, without physical contact with their spouses and children and contacting them generally by telephone. This, in turn, leads to a significant decrease in emotional and social support from the family. This was often experienced in previous outbreaks and in the current fight against COVD-19 [17]. When face-to-face communication is not safe, hearing their voices on the phone and trying to understand how they feel and how they look after each other may be helpful. Staying in touch with their loved ones will give healthcare workers strength when they try to cope with their fears. It is believed that these recommendations may have positive effects on reducing the level of anxiety of health workers.
Health workers from different countries who had experience working in outbreaks were asked about the factors they believed to be effective in working with sufficient motivation in future epidemics. Health workers listed ensuring personal safety, having adequate disease knowledge, and providing compensation support as priority motivation factors [13,18,19]. In this study, anxiety levels of health workers also increased because they perceived each patient as COVID-19-positive (50.7%) and also because of the lack of sufficient community sensitivity to the disease (71.5%). Questions related to nutrition during the pandemic, accommodation, reporting possible problems to upper units, increases or decreases in the number of health workers, and working at different units during this process revealed no anxiety associated with them. No accommodation problem emerged for the hospital where the study was conducted, since the hospital administration created alternative accommodation facilities in the early days of the outbreak. It was observed that certain problems that came to the agenda during normal working periods were postponed because of the pandemic period.
Conclusion
This study demonstrates that the pandemic process had a negative impact on health workers, as their anxiety states increased during this process. It was observed that health workers experienced intense anxiety, particularly due to increased risk of infection compared with other individuals in the community, and the risk of infecting their family members, their loved ones, their patients, and other people. This, in turn, increased their anxiety levels and caused them to work under intense psychological pressure, in addition to the challenges of their increased workload and prolonged working with personal protective equipment.
In accordance with these results, eliminating the gaps in the practices or information in published guidelines about the process can contribute positively to health workers feeling safer. Regulation of working hours in accordance with the conditions of pandemic period, follow-up and evaluation of employee efficiency and sleep patterns by the responsible units, and provision of professional support when necessary, can contribute to the reduction of the burden of the physical working conditions of health workers and the psychological problems they experience.
The proportion of COVID-19 patients detected in the region of our health facility to the total population is less than 1%. Compared with metropolitan cities and other countries, it can be said that this proportion is lower. However, despite this, it was seen that the problems and concerns experienced by our health workers were similar to those reported in the literature. The presence of unexplained points on disease and transmission routes, as well as uncertainties and inadequacies in treatment, have created similar restrictions and problems in work, family, and social life for health workers on a global scale, regardless of the ratio of positive patients.
Future studies with more participants may deal with anxiety experienced by health professionals and ways of coping with them in the pandemic 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.20512
Nesibe Sultan Çınaroğlu, Kenan Öztorun, Mustafa Kaçmaz, Zeynep Yılmaz Öztorun. Field study for determining the effect of COVID-19 on healthcare workers. Ann Clin Anal Med 2021;12(Suppl 3): S254-258
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Prevalence of pain in adult patients
Fadime Çınar 1, Fatma Eti Aslan 2, Hayat Yalın 2, Betül İlbey Koç 3, Dilay Hacıdursunoğlu Erbaş 3, Emine Özdemir Aslan 2
1 Department of Health Management, Sabahattin Zaim University Faculty of Health Sciences, 2 Department of Nursing, Bahçeşehir University Faculty of Health Sciences, 3 Department of Nursing, İstanbul Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital, İstanbul, Turkey
DOI: 10.4328/ACAM.20513 Received: 2021-01-31 Accepted: 2021-03-20 Published Online: 2021-03-31 Printed: 2021-08-15 Ann Clin Anal Med 2021;12(Suppl 3): S259-263
Corresponding Author: Fadime Çınar, Sabahattin Zaim University, Faculty of Health Sciences, Health Management,Istanbul, Turkey. E-mail: fadime.cinar@izu.edu.tr P: +90 212 692 88 06 Corresponding Author ORCID ID: https://orcid.org/0000-0002-9017-4105
Aim: This study aimed to determine the frequency and characteristics of pain in inpatients.
Material and Methods: This study was conducted as an analytical and cross-sectional type of time prevalence on 25-26-29-30 July 2019, including 127 pa- tients hospitalized in a public hospital in Istanbul. Data were collected through the Introductory Information Form, the Brief Pain Inventory (BPI), and the Re- vised American Pain Society Patient Results Questionnaire through face-to-face interviews. The mean, percentage distribution and standard deviation values were calculated using descriptive statistical methods. First of all, the Kolmogorov-Smirnov, Shapiro Wilk-W tests were performed and the normal distribution of the data was examined. According to these results, nonparametric tests were applied. The Mann-Whitney U test was used between two independent groups, the Kruskal-Wallis test and Spearman’s Correlation analysis were used between more than two independent groups.
Results: As a result of the analysis of the obtained data, the average age of the participants included in the study was 48.13 ± 16.88 years. In addition, it was found that maximum 37% (n = 47) were primary school graduates and 53.5% (n = 68) were women. It was determined that 44.9% (n = 57) of the participants preferred most digestive system and surgical diseases as medical diagnosis and treatment, and 59.8% (n = 76) preferred paracetamol as analgesic use. It was determined that 21.3% (n = 27) of the pain they experienced was a stinging type. It was found that the most pain was felt in the abdomen and pelvic region in 56.7% (n = 72). The Brief Pain Inventory total score average was 5.80 ± 1.85 and the pain prevalence was 76.37%.
Discussion: The prevalence of pain in adult patients in Turkey, according to the survey results, is quite high. Despite the high prevalence of pain, moderate pain intensity may be associated with ethnic and socioeconomic factors in the perception of pain. It is recommended that health professionals who play an important role in relieving or eliminating pain, increase their knowledge of pain, and coping with pain.
Keywords: Pain; Adults; Prevalence; Turkey
Introduction
Pain is a health problem that leads people to seek help from health professionals [1]. Epidemiological studies on pain examine how much of the society complaints of pain, and that pain occurs with age, gender, race, and social differences. Prevalence is a result that explains the frequency of pain in a certain period of time. Study results on prevalence differ greatly [2]. The difference may arise from the lack of an objective definition of pain, which is subjective, and the different meanings and interpretations attributed to pain by researchers and evaluators. However, despite the fact that the knowledge of health professionals about pain has increased with the developing technology, the reality of pain continues. Although the pain formation process is physiopathologically similar, the expression of pain is affected by the cultural situation, gender, pain-causing situation, and the meaning and importance given to pain by patients [3]. In this context, when the literature is examined, it is stated that 64-90% of cancer patients suffer from moderate pain [4], chronic pain is a major world problem [5,6], postoperative pain is one of the most important causes of acute pain. It is reported to be experienced by all patients who underwent surgery, albeit of varying severity [7-9]. Although the reality of pain is known, it is known that culture is also effective in pain reporting [3]. This is really the prevalence of pain in patients who were hospitalized in Turkey. What are their sociodemographic characteristics? Are their medical diagnoses effective in reporting pain? This study was conducted to find answers to questions.
Material and Methods
This study, which was conducted as an analytical and cross- sectional type of time prevalence, was carried out to determine the frequency and characteristics of pain in inpatients. This study helps fulfill the goal of the national pain strategy of producing more precise estimates of chronic pain and high- impact chronic pain. This study of findings could be used to target pain management interventions.
Research Population and Sample
Within the scope of the study, all patients who were hospitalized to the surgery and internal medicine clinics in a public hospital in Istanbul, where the data will be collected, on 25-26-29-30 July 2019, constituted the population. The present study aimed to reach all patients by not choosing the sample. However, 127 patients were included in the study, with a prevalence of four days, due to the admission of pediatric patients and their refusal to participate in the study. Patients over the age of 18 who were treated in the hospital for any reason and who volunteered to participate were included in the study.
Research Questions
i. What has been the pain intensity of the patients in the last 24 hours?
ii. What is the severity of pain according to the medical diagnosis of the patients?
iii. What is the pain severity according to the age groups of the patients?
iv. What is the pain intensity according to the pain characteristics of the patients?
Data Collection Tools
The data were collected by means of inventory and questionnaires that included questions evaluating the frequency and characteristics of the patients’ pain using the face-to-face interview method with patients who were hospitalized for any reason and met the sample selection criteria in the public hospital. In this study, the Introductory Information Form and Brief Pain Inventory were used
The Brief Pain Inventory (BPI): It is a short, easy-to-apply assessment tool that can be used to assess pain. This scale was developed by Cleeland and Ryan (1994). A Turkish validity and reliability study was developed by Dicle et al. (2012), and the Chronbach alpha coefficients ranged from 0.55 and to 0.91 [10]. The Brief Pain Inventory evaluates the severity of pain (4 questions), localization of pain, medical treatments for pain, and the effect of pain on daily functions (7 questions) and questions how much pain has decreased in the last 24 hours or last week. Patients are asked to rate their pain when it is most severe and least severe, and are scored from 0 to 10 during data collection, as well as their average pain over the previous 24 hours. According to this scoring, 0 means no pain, and 10 means the presence of very severe pain. Patients are also asked to individually assess how their pain interacts with general activity, mood, walking ability, normal working, relationships with other people, sleep, and enjoying life. In addition, patients are asked to estimate the percentage reduction of pain they will feel after pain treatment and place their pain areas on the human figure. In the evaluation of the worst pain in the Short Pain Inventory, “1-4 points” is defined as mild, “5-6 points” as moderate, and “7-10 points” as severe pain. Ethical Aspect of the Research
In the planning phase of the study, research permission was obtained from a foundation university scientific research and publication ethics board (ethical approval number: E.1585 / 2019) and the hospital administration.
Data Analysis
SPSS 25.0 was used. The mean, percentage distribution, and standard deviation values were calculated using descriptive statistical methods. The Kolmogorov-Smirnov test was used for normality. According to these results, the Mann-Whitney U, Kruskal-Wallis and Spearman correlation analyses were used.
Results
The average age of the participants was 48.13 ± 16.88 years, and the age range did not exceed 24.4% (n = 31) in the 30- 40 age group. The educational status of the participants was primary school in no more than 37% (n = 47) and 53.5% of the participants were women (n=68). Clinically, the majority of patients (66.9%) were surgical patients (n = 85). In terms of medical diagnosis and treatment, the most common digestive system and surgical diseases accounted for 44.9% (n = 57), analgesics from the paracetamol group were preferred by 59.8% (n = 76) as analgesics and, it was determined that 21.3 % (n = 27) were of the stinging type. It was found that the greatest pain was felt in the abdominal and pelvic region (56.7% (n = 72)). It was determined that 29.1% (n = 37) of cases, the duration of pain was between 72 hours and 29 days at most (Table 1).
The Brief Pain Inventory Total Average Score of the patients participating in the study was 5.80 ± 1.85. The mean score for the worst pain in the last 24 hours was 9.25 ± 1.59 and the mean pain score for the last 24 hours was 3.87 ± 2.45. The average pain score in the last 24 hours was 6.55 ± 2.17. The current average pain score was found to be 4.39 ± 3.17. The mean percentage of pain relief with pain treatment in the last 24 hours was determined to be 61.73 ± 33.83. It was determined that 87.2% (n = 105) answered in the affirmative that today’s pain is different from the usual pain (Table 2).
The data obtained on the presence of current pain with the Brief Pain Inventory of the patients were as follows: 23.62% (n = 30) did not have pain, and 76.37 % (n = 97) had pain. According to the results of the study, the prevalence of pain was 76.37 % (Figure 1).
The difference was not found statistically significant (p> 0.05) according to the average pain severity score of the patients in the Brief Pain Inventory Total Score average, according to the age, gender, education level and clinical variable of the hospitalization. A significant difference (p <0.05) was found according to the clinical variable of their hospitalization. It was determined that the difference was due to surgery clinics for the mildest pain in the last 24 hours (p <0.05) (Table 3).
One of the research questions, “What was the severity of pain according to the age groups of the patients?” was asked for the evaluation. According to this evaluation, the highest average of the participants for the worst pain in the last 24 hours was determined to be 9.555 points in the 19-29 age group. The highest average for the least pain in the last 24 hours was in the 19-29 age group with 4.444 points. The average score of average pain in the last 24 hours was 7.069 in the 41-51 age group, and 4,772 points in the 63 years and older group, with the highest mean score for current pain (Figure 2).
According to the medical diagnoses of the patients, in one of the research questions, the highest average of the patients for the worst pain was 9.83 points with the diagnosis of cardiovascular surgery diseases; the highest average for the least pain was 4.61 points with the diagnosis of the digestive system and surgical diseases. The average score for pain was 7.4, and the highest mean score for upper-lower extremity surgical diagnosis and current pain was 4.92 points with the diagnosis of the digestive system and surgical diseases (Figure 3).
In evaluating the characteristics of the pain and the severity of the pain of the participants, the participants scored 10 points for the worst pain, the most pressing pain type of the highest average, 5.75 points for the pain type with the highest average pain, and the average score of the average pain was 7.28. The highest average score for current pain was 6.16 points in the type of pain in the form of cramp.
Discussion
Studies on the prevalence of pain in adults in Turkey are insufficient. In the literature, it has been stated that the prevalence of pain in our country is between 64-93% [3,11]. Population-based estimates of chronic pain among U.S. adults range from 11% to 40% (Interagency Pain Research Coordinating Committee. National pain strategy: a comprehensive population health-level strategy for pain. Washington, DC: US Department of Health and Human Services, National Institutes of Health; 2016).
In this study, it was determined that the prevalence of pain in different body parts was 76.3%, and the total score average of the Brief Pain Inventory of 127 participants living in Istanbul with an average age of 48.1 years was found to be moderate. Although this result is supported by the literature, the high frequency of pain can be interpreted as an indicator that pain continues to be a social health problem.
The average age of the participants was 48.1 ± 16.8 years, and the age range did not exceed 30-40. It was found that the educational status of the participants was mostly primary school, and most of the participants were females. In most prevalence studies, it was reported that pain increases with female gender and with advanced age [12-15]. Von Koff et al. in their study reported that in those who were educated, the older the age and the higher the degree of pain [12]. The results of this study were not similar, and it is thought that these results may add a different perspective to the literature.
Participants’ Brief Pain Inventory (BPI) total mean score was moderate, the worst pain in the last 24 hours was severe, the mean of the least pain in the last 24 hours was determined to be mild. Kuru et al. (2011) found the mean pain score as 3.6 ± 1.8, and the mean score of the worst pain experienced in the last 24 hours as 4.4 ± 2.6 [3]. In the study in Spain, 40.4% of those suffering from chronic pain described mild pain, while 14.3% described very severe pain [15]. In our study, the values of the pain intensity score were found to be higher, although they were similar to other population-based studies.
According to our findings, it was found that there were most digestive system and surgical diseases as medical diagnosis and treatment. It was determined that the participants mostly preferred paracetamol group painkillers as analgesics, and the stinging type was the characteristic of the pain they experienced. It was determined that the body area with the most pain was the groin-pelvic region. Although the highest prevalence of pain was in the shoulder, when assessing its severity, in a study by Kuru et al. (2011), it was found that the most pain complaints were in the lumbar region. It was found that 33% of the individuals applied to non-steroid anti- inflammatory and/or analgesic drugs to reduce pain, and 1.2% underwent surgical intervention [3]. In a study investigating the prevalence of pain, it was reported that 96.7% of 91 patients with pain used medication for pain, and 67.8% used daily analgesics [16]. In the literature, it has been shown that chronic pain mostly originates from the lumbar region [17-21]. Studies investigating the prevalence of pain reported that patients used analgesic drugs for pain [3,16]. The results obtained in our study are thought to be similar to the literature.
Limitations of the Study
Among the main limitations of the study are that the sample in this study does not represent all inpatients, but only includes patients in a public hospital operating in Istanbul, and the design of the study is cross-sectional.
Conclusion and Recommendations
The prevalence of pain among adult patients in Turkey, according to the survey results, is quite high. In the current study, the high prevalence of pain and the moderate pain intensity can be due to ethnic and socioeconomic factors in the perception of pain. A multidisciplinary approach is required in evaluations made for the resolution of pain and the negativities it causes. It is necessary to use pain scales with proven validity and reliability, which do not cause different interpretations between patients, nurses, and physicians and give correct results in every use, and common pain control procedures should be established. It is recommended that health professionals, who play an important role in relieving or eliminating pain, increase their knowledge of pain, and how to manage.
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.20513
Fadime Çınar, Fatma Eti Aslan, Hayat Yalın, Betül İlbey Koç, Dilay Hacıdursunoğlu Erbaş, Emine Özdemir Aslan. Prevalence of pain in adult patients. Ann Clin Anal Med 2021;12(Suppl 3): S259-263
Citations in Google Scholar: Google Scholar
Circadian clock gene variants may affect circadian fluctuations of anaerobic performance
Tülin Atan 1, Şaban Ünver 1, Ayşe Feyda Nursal 2, Serbülent Yiğit 3, Akın Tekcan 4
1 University of Ondokuz Mayıs, Faculty of Sports Sciences, Samsun, 2 Department of Medical Genetics, University of Hitit, Faculty of Medicine, Çorum, 3 Department of Genetics, University of Ondokuz Mayıs, Faculty of Veterinary, Samsun, 4 Department of Medical Biology, University of Amasya, Faculty of Medicine, Amasya, Turkey
DOI: 10.4328/ACAM.20514 Received: 2021-01-31 Accepted: 2021-03-30 Published Online: 2021-04-12 Printed: 2021-08-15 Ann Clin Anal Med 2021;12(Suppl 3): S264-268
Corresponding Author: Tülin Atan, Ondokuz Mayıs University, Faculty of Sports Sciences Kurupelit Campus, Atakum/Samsun/Turkey. E-mail: takman@omu.edu.tr P: +90 505 483 40 48 Corresponding Author ORCID ID: https://orcid.org/0000-0001-5660-8910
Aim: Circadian rhythm (CR) may be followed by almost all biochemical and physiological processes that occur in the human body. Physical activities involving anaerobic fitness have displayed a clear CR. The aim of this study was to investigate genotype and allele frequencies of (PER3 VNTR, PER2 VNTR and TIM1) gene polymorphisms in athletes and control groups and the second aim was to examine the anaerobic performance according to the genotype distribution of male footballers.
Material and Methods: The study included 20 male footballers and 30 voluntary male controls. To examine anaerobic performance, the footballers performed three randomized 30-s Wingate anaerobic power tests (WAnT) in the morning, at noon and in the evening with minimal one-week recovery time between each testing day. Genomic DNA was isolated from the blood samples. Polymerase chain reaction-based and restriction fragment length polymorphism (PCR-RFLP) analysis was used to identify gene variants from DNA material. Also, the differences between the basic performance characteristics of the athletes and the genotype distribution of these variants were investigated according to the daytime.
Results: The allele and genotype distribution of these variants was not significantly different between male footballers and the control group. Peak power and average power in the morning increased in athletes carrying TIM1 G/G variant (p<0.001) than in athletes carrying G/C and CC variant. Also, the athletes carry- ing the TIM1 G/G variant had a higher minimum power in the morning and evening (p<0.001) than athletes carrying G/C and CC variant.
Discussion: This is the first study that evaluates variants of circadian rhythm genes and the anaerobic performance of elite Turkish athletes. Our results sug- gested that the TIM1 gene variant may affect circadian fluctuations in anaerobic performance. People who carry the G/G genotype from the TIM1 gene have a higher anaerobic power. To understand ethnic and environmental differences, further studies are needed in this field.
Keywords: Circadian rhythm; Anaerobic performance; Variant; PCR-RFLP
Introduction
The human genome project has been recently carried to investigate the effects of several genes on athletic performance. These studies showed the impact of the genetic features on athletic performance and also the components such as strength, agility, force, nerve-muscle coordination, and flexibility were found to affect the identification of the athletic performance among the athletes and that they were regarded as a criterion for encouraging athletes to do sport, which they tend to [1]. Biologic rhythms are the cyclic changes that regularly occur gradually, and cyclic rhythms that are related to the sunlight are called the circadian rhythms (CRs) [2]. In other words, cyclic physiological changes, which occur within 24 hours are called CRs. The relationship between CR and several behavioral and physiological functions was mentioned in early publications [3]. Extensive studies have been conducted on the effect of CRs on several physiological variables associated with athletic performance. The studies have reported the circadian variations of maximum aerobic power, blood pressure, heart rate, and central temperature during physical exercise [2]. The daytime effect of responses on short-term anaerobic exercise has also been studied, but there have been conflicting results. According to Melhim [4], and Hill and Smith [5], athletes had higher values of Wingate anaerobic test performance in the afternoon than in the morning. As stated by Souissi et al., [6] athletes significantly improved peak power, mean power, and maximal power from morning to afternoon during the Wingate and Force-Velocity tests.
There are several genes that control biological clock such as cryptochrome 1-2, clock (CRY1-2), period 1-3 (PER1-3), timeless (TIM), casein kinase 1 epsilon (CK1E), reverse strand of erb alpha (REV-ERBA), retinoic acid-related orphan receptor A (RORA)-, and brain and muscle aryl hydrocarbon receptor nuclear translocator-(ARNT)-like 1 (BMAL1).
The aim of this study was to evaluate the CR difference between male footballers and controls and to examine differences in the anaerobic performance of male footballers according to genotype distribution.
Material and Methods
The study was organized and conducted in accordance with Helsinki protocol. The ethical approval was taken from the Clinical Research Committee of Ondokuz Mayıs University, number 2017/794.
Study population
The study was conducted on 20 male footballers (age 23.58±3.27 years; body height 176.30±4.73 cm; weight 74.60±6.31 kg) who are trained at least four times a week. The control group (age 22.00±2.31 years; body height 173.20 ± 6.48 cm; weight 78.60±8.21 kg) consisted of 30 voluntary males studying at the university. All subjects in the study were not using any medication chronically. The controls were not engaged in physical activity regularly. Only the footballers performed the WAnT, and the control group did not. In this study, the genotypes of the athletes and the control group were compared. In addition, it was investigated whether the gene variants of the athletes had an effect on anaerobic performance. Therefore, WAnT was applied to athletes only.
Written informed consent was obtained from each participant before the blood sampling.
Wingate Anaerobic Test (WAnT)
To examine anaerobic performance, the footballers performed three randomized 30-s WAnT. The three testing days involved three randomized testing times with minimal one-week recovery time between each testing day (morning: 09:00h, noon: 14:00h, and evening: 19:00h). A bicycle ergometer and a bicycle-mounted computer assembly were used in the anaerobic performance of the athletes (Monark 894E, Varberg, Sweden). Before each test, the seat and handlebar adjustments were made to the subjects to provide the optimal cycling position, and WAnT was applied with the standard methods prescribed [7]. WAnT was applied for 30 seconds with a weight of 7.5% per subject’s body weight. The athletes warmed up by pedaling for 5 minutes at a speed of 60-70 (RPM) and sprinted for 5 seconds on the 3rd and 5th minutes of warm-up. The athletes rested until the pulse dropped to 100 beats/min before the test to relieve the fatigue that occurs after the warm-up. After the rest period, the test started, and the athletes pedaled at the highest speed for 30 seconds against the determined resistance. The subjects were verbally encouraged during the test. As a result of the test, the maximal anaerobic power, average powers, and minimum powers of the subjects were obtained. The Borg scale was used to determine the rate of perceived exertion (RPE) [8]. Genotyping
Genomic DNA was obtained from peripheral blood using a commercial DNA isolation kit. The isolated DNA was kept at -20°C until analysis. PER3 VNTR and PER2 VNTR variants were genotyped through polymerase chain reaction (PCR) analysis, as described previously [9-10]. Each 25-μL PCR reaction mixture contained 150 ng genomic DNA, 10 pM of each primer, 10x PCR mix buffer, 200 μM dNTP, and one unit of Taq DNA polymerase. After an initial step of 5 min at 95 °C, 33 cycles of amplification (45sat94°C,30sat60°C,45sat72°C)andafinalextension step of 12 min at 70 °C were performed. The amplified products were analyzed by 2 % agarose gel electrophoresis. The TIM1 G/C was genotyped through polymerase chain reaction and analysis restriction fragment length polymorphism (PCR- RFLP), as described previously [11]. The amplified products were analyzed by 2 % agarose gel electrophoresis. In order to validate the accuracy and reproducibility of this method, each PCR reaction included negative and positive controls for each genotype. Second PCR was performed to confirm samples which results are not clear.
Statistical analysis
Statistical analysis was performed using the Statistical Package Program for the Social Sciences (IBM SPSS, version 20) and the OpenEpi Info software package version 2.3.1 (www.openepi.com). Continuous data were given as mean±SD (standard deviation) and (min-max). Chi-square tests were used to evaluate the significance of differences between the two study groups in the allele frequency and genotype distribution. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated. A p-value p<0.05 was considered statistically significant. The nonparametric Mann-Whitney U test was used in the comparisons between baseline clinical and demographics features of groups. For comparison of the baseline characteristics of the athletes according to these genotypes, each variant was initially analyzed for each clinical variable using analysis of variance (ANOVA) and post-hoc tests. Bonferroni correction was performed on the post-hoc tests. According to the post-hoc tests, the significance level was 0.01.
Results
In this study, a total of 52 subjects, including 20 elite athletes and 30 controls, were genotyped for the PER3 VNTR, PER2 VNTR, and TIM1 G/C variant. The baseline demographic characteristics of the subjects are shown in Table 1.
The genotype and allele distribution of PER3 VNTR, PER2 VNTR, and TIM1 G/C variants in Turkish footballers versus controls are presented in Table 2. The allele and genotype distribution of these variants were not significantly different between the male footballers and the control group (p>0.05).
In Table 3, the comparisons are made between the clinical parameter averages of individuals with genotypes of each gene. It was found that the peak power and average power in the morning increased in athletes carrying TIM1 G/G variant (p<0.01, p<0.01 respectively) when comparing the TIM1 G/C and TIM1 C/C genotypes. Also, athletes carrying the TIM1 G/G variant had higher minimum power in the morning and evening (p<0.01). Other variables did not show statistically significant differences (p>0.01).
Discussion
The type of selected sport is affected by either genotype or chronotype, and it is not clear how much the chronotype is affected by the sporting environment. Since no study has been carried out on the circadian rhythm genes in Turkish athletes, we aimed to evaluate PER3 VNTR, PER2 VNTR, and TIM1 variants in footballers and the control group and we aimed to examine the anaerobic performance according to genotype distribution of male footballers. The results demonstrated no differences in allele and genotype distribution of CR genes (PER3 VNTR, PER2 VNTR and TIM1) between male footballers and the control group.
In this study, we examined the genotype distribution of these variants in 20 male football players. To compare the performance of circadian phenotypes, indicators such as peak power, average power, and minimum power were measured in the daytime (morning, noon and evening). Although the allele and genotype distributions of PER3 VNTR, PER2 VNTR, and TIM1 G/G variants were not different in the footballers compared to the controls, there was a significant difference between genotype distribution and anaerobic performance status in terms of daytimes. We found that the peak power and average power in the morning were higher in athletes carrying TIM1 G/G variants. Also, minimum power in the morning and evening increased in athletes carrying TIM1 G/G variant. This means that footballers who carry the G/G genotype from the TIM1 gene have better anaerobic power.
Several important factors affect CR in physical performance. The causes of these factors are both external or environmental changes and internal or physiological changes occurring during the day. It is often difficult to identify a single cause of performance fluctuations due to the effect of different physiological systems on performance fluctuations, which occur simultaneously. Reilly and Waterhouse identified three major determinants that affect a CR in sporting performance [12]. These functions include perceptual and cognitive performance, metabolic variables, several behavioral, cardiovascular, and neuromuscular variables, and sensory-motor resting levels. Several points of genetic variance among individuals have a combined effect leading to polygenic sports performance. Circadian phenotypes, such as a person’s diurnal preference for morning or evening activity patterns and chronotype, which is a person’s sleep-wake phenotype, influence peak performance at the individual level [13]. Physiological responses during exercise, such as oxygen uptake, blood lactate, heart rate, etc., are based on the intensity of exercise. Generally, there is a peak of athletic performance in the afternoon during which there is a peak of the fueling metabolic activity of physiological processes [14]. Athletes with a high evening or morning phenotype want to do better endurance activities [15], and strength training [16], near their circadian peak. According to Souissi et al. [17], and Bernard et al. [18] there was a significant circadian variation in maximal anaerobic power during Force Velocity and Wingate tests and Cycle and Multi-Jump tests. Contrary to these findings, Reilly and Down [19] reported that there was no circadian fluctuation of the anaerobic performance in the Wingate test. Variations of CR genes may cause differences among studies.
A family of genes, i.e., the PER genes, influences cellular growth and differentiation, as well as, the cell cycle [20]. The PER family includes PER1, PER2, and PER3. A promising gene candidate, which affects daytime mood is the PER3 clock gene. A heterodimer with the CRY protein being translocated into the nucleus is formed by the PER3 protein product, inhibiting the CLOCK-BMAL-mediated transcription. It takes almost 24 hours to complete this feedback loop. The timing of the circadian feedback loop could be changed ostensibly due to differences in the size of the PER3 protein, considering that the PER3 gene contains an 18 amino acid-long 4 and 5 repeat homolog [21]. The VNTR polymorphism in the PER3 gene is located on chromosome 1p36.23, which has two alleles of 4 or 5 tandem 54 bp repeats (coding for a region of 18 amino acids in exon 18). It has been regarded as a possible genetic factor for circadian phenotypes and chronotypes [22]. Behavioral rhythmicity is significantly affected by the PER2, which belongs to the PER family of genes [23]. The main expression of PER2 is found in the peripheral nervous systems and the central nervous system. There is an association between human SNPs in the PER2 gene and chronotypes, depression, and abnormal circadian parameters, also higher alcohol intake. There is a VNTR polymorphism in intron 3 of the PER2 gene. There are three members, including TIM-3, TIM-1, and TIM-4 in the TIM gene family, which is located on the human chromosome 5q23- 35, including TIM-3, TIM-1, and TIM-4, related to the immune dysfunction which finally induces various diseases, such as allergic diseases, chronic viral infections, autoimmune diseases, immune rejections, and even tumors [11]. According to the studies, which have been concluded in the past years, regulation of the immune responses and maintenance of the immune homeostasis can be mainly affected by TIM-1. According to the accumulating evidence, there is an association between immune dysfunction due to certain TIM1 polymorphisms and allergic reactions, chronic viral infections, autoimmune diseases, and immunologic rejections [24].
The PER2, NPAS2, CLOCK, and TIM genes polymorphisms are related to sleep timing [25], sleep disorders [26], and diurnal preference [27]. It has been shown that the individual sport athletes comprise unusually high morning-types proportions along with a higher prevalence of the PER3 VNTR allele related to morningness [28]. According to Konorozva et al., [28] there was a strong relationship between PER3 VNTR genotype and chronotype. The daytime during which athletes preferred to train was associated with their chronotype. According to their data, there are morning types of white males of European descent who took part in the endurance sports in South Africa. It was reported that there were more morning-types in the Super Rugby players than in the control group, more evening- types in the control group than in the Super Rugby player group. Still, there were no differences in allele frequencies or PER3 VNTR genotype [29].
However, there are a few limitations to the current case-control analysis. First, we focused on only three variants involved in the circadian rhythm pathway; other regulatory genes in this signaling pathway may also contribute to the mechanism. Second, due to the relatively small sample size, the frequencies of some homozygous variants may have reduced statistical power. Third, the samples studied were from the same geographic region and race.
Conclusion
The difference in sports performance between elite athletes is due to the genetic basis of individuals. CR affects many physiological events as well as sports performance. To the best of our knowledge, this is the first study evaluating variants of CR genes and anaerobic performance in Turkey. Those carrying the G/G genotype from this TIM1 gene have higher anaerobic power (peak power, average power and min power), especially in the morning. Again, carriers of the G/G genotype had a higher evening min power value than those carrying the G/C and C/C genotype. This means that carrying the G/G genotype from the TIM1 gene has better anaerobic power. Our results suggested that the TIM1 gene may affect circadian fluctuations in anaerobic performance. The genetic characterization of circadian fluctuations is still not entirely clear, and further studies are needed to clarify the effects of these variants in this pathway and their relationship to individual traits.
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.20514
Tülin Atan1, Şaban Ünver, Ayşe Feyda Nursal, Serbülent Yiğit, Akın Tekcan. Circadian clock gene variants may affect circadian fluctuations of anaerobic performance. Ann Clin Anal Med 2021;12(Suppl 3): S264-268
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Effect of COVID-19 pandemic on the treatment process and adherence to treatment of the patients receiving allergen-specific immunotherapy
Emel Atayık, Gokhan Aytekın
Department of Allergy and Clinical Immunology, University of Health Science, Konya City Hospital, Konya, Turkey
DOI: 10.4328/ACAM.20515 Received: 2021-02-01 Accepted: 2021-03-26 Published Online: 2021-04-08 Printed: 2021-08-15 Ann Clin Anal Med 2021;12(Suppl 3): S269-273
Corresponding Author: Emel Atayık, Department of Allergy and Clinical Immunology, University of Health Science, Konya City Hospital, Konya, Turkey. E-mail: emelakinci@yahoo.com P: +90 545 300 31 97 Corresponding Author ORCID ID: https://orcid.org/0000-0002-7011-7752
Aim: During the COVID-19 pandemic, the number of hospital admissions has significantly decreased, due to both the risk of transmission and the restrictions imposed. The most adversely affected ones are patients who need to admit to a hospital due to their chronic diseases, such as those receiving allergen im- munotherapy.
Material and Methods: Files of the patients who were administered subcutaneous immunotherapy (SCIT) regularly, were retrospectively reviewed. At first outpatient clinic visits during the period of so-called normalization process (June-July-August 2020), the patients were asked to fill a mini questionnaire and validated coronavirus anxiety questionnaire.
Results: A total of 151 patients receiving SCIT were included in the study. The most common government-related factors hindering outpatient clinic visits of the patients were travel restrictions (40.6%) and the most common patient-related factors were fear of contracting SARS-CoV-2 (39.7%). Overall adher- ence to treatment during the 3-month period from March to April-May 2020 was determined to be 54.3%. The duration of immunotherapy, increased allergic symptoms, the need for additional treatment and treatment switch in SCIT because of the pandemic were significantly higher in patients non-adherent to SCIT treatment compared to adherent ones (p: 0.031, p: 0.001, p: 0.001 and p: 0.001, respectively).
Discussion: Access to allergen immunotherapy, applicability, and maintenance of the immunotherapy should be a priority during the COVID-19 pandemic. Considering both patient-related and government-related factors in the administration of immunotherapy, the process of immunotherapy should be continued, minimizing the risk of SARS-CoV-2 transmission. Furthermore, patients’ worry and anxiety levels may be reduced with these measures and their adherence to treatment may be promoted.
Keywords: COVID-19; Allergen immunotherapy; Anxiety questionnaire
Introduction
The 2019 Coronavirus disease (COVID-19), which emerged in the People’s Republic of China in December 2019 and was declared as a pandemic by WHO (World Health Organization) on March 11, 2020 has affected the whole world, particularly in health, and in social, cultural and economic aspects [1-3]. During the pandemic, the number of hospital admissions due to reasons other than COVID-19 has significantly decreased, due to both the risk of transmission and measures taken and the restrictions imposed [4]. The most adversely affected ones, surely, are the patients who need to admit to the hospital due to their chronic diseases. Patients receiving allergen-specific immunotherapy (AIT) may also be included in this patient group [5-7]. AIT is the only disease-modifying treatment option in allergic asthma, allergic rhinitis (AR), seasonal allergic rhinitis (SAR) and venom allergy. There are two main routes of administration: Sublingual and subcutaneous immunotherapy (SCIT), which has been used for a longer period of time and with more experience. AIT is a treatment modality that continues at gradually increasing doses, for a long period of time, modifies T-cell-mediated immune responses and provides an improvement in symptoms and clinical course [8-10]. Patients receiving SCIT should be administered immunotherapy at regular intervals and the COVID-19 pandemic adversely affects access to treatment for this patient group that needs to be treatedt at 1-4-week intervals. In addition, during the pandemic, the risk of SARS-CoV-2 transmission to the patient or his/her family members and some measures taken including isolations like quarantine, international and intercity travel restrictions, additional restrictions and prohibitions for certain age groups increases fear, worry and anxiety in patients. Such a case may also adversely influence adherence to treatment in patients receiving SCIT [11-13]. Therefore, in this study, we aimed to investigate the effect of the SARS-CoV-2 pandemic on adherence to treatment of the patients receiving AIT due to allergic diseases in our clinic, to determine the reasons why patients are coming late/not coming for treatment and to reveal the effect of SARS-CoV-2 pandemic on the anxiety of this patient group.
Material and Methods
Files of the patients who admitted to the allergy outpatient clinic between June 2015 and March 1, 2020 and were administered SCIT regularly with diagnoses of AR, SAR, asthma, and venom allergy that were established in accordance with clinical history, skin prick tests, allergen-specific IgE results and international guidelines [14, 15] were retrospectively reviewed. Adult patients over the age of 18 were included in the study. Patients who did not regularly attend SCIT treatment between June 2015 and March 1, 2020, whose treatment was terminated due to SCIT for a sufficient time, and whose files did not have sufficient data, were excluded from the study. In addition, patients who were diagnosed with allergic diseases in our center and continued their SCIT follow-up in other centers were excluded from the study. Age, gender, education level, history of comorbid diseases, presence of individual atopy, type of IT received and frequency of administration of patients included in the study were obtained from their files. At first outpatient clinic visits during the so-called period of normalization process (June, July-August 2020), the patients were asked to fill out a mini questionnaire developed by us about the March-April-May period, when the first SARS-CoV-2 case in Turkey was identified and some restrictions were imposed due to risk of transmission. Patients who had been administered AIT regularly before the pandemic but did not come for outpatient clinic visits during this period were asked to fill out a mini questionnaire by phone calls. The patients who did not come to at least one outpatient clinic visit during March-April-May 2020 were considered not adherent to treatment. This mini questionnaire asked whether they admitted to the hospital for AIT during March-April-May 2020, and, if they came late or did not come, the reasons were investigated. Government-related reasons (curfew, intercity travel restriction, failure to get an outpatient clinic appointment, disability and pregnancy status etc.) and patient-related factors (fear of contracting the virus, fear of transmitting the virus to family members, availability of direct access to drugs during this period, not feeling the need for treatment, COVID-19 infection or COVID-19 quarantine etc.) were addressed. Each patient was asked to fill the validated coronavirus anxiety questionnaire [16]. In this questionnaire, patients were asked if he/she felt dizzy and dull or was about to faint when he/she read or heard the coronavirus news. Additionally, they were asked if he/she had problems with falling asleep or sleeping because he/she thought about coronavirus, and if he/she felt like having a stroke or petrified when he/she thought about coronavirus or was subject to these issues. Also, they were asked if he/she lost my appetite when he/she thought about coronavirus or was subject to these issues and if he/she had nausea or stomach discomfort when he/she thought about coronavirus or was subject to these issues. Patients were asked to answer these questions with the appropriate one of the “Always, Usually, Sometimes, Seldom and Never” options.
Additionally, the patients were investigated about whether they experienced an increase in allergic complaints and, if present, the types of complaints, the need for additional anti-allergic medication, admission to the emergency department, additional drug supplement in addition to on-going treatments and use of food or herbal supplements.
Statistical analysis was performed with the IBM SPSS Statistics Version 22 software package (New York, United States). Normally distributed parameters were presented as mean ± standard deviation, and data that is not have a normal distribution were expressed as median (interquartile range: minimum–maximum). Descriptive data were presented as frequencies and percentages and compared using the Chi- square test. Comparisons between baseline characteristics were performed using independent Student t-test, Mann- Whitney rank-sum, Fisher’s exact or Chi-square tests where appropriate.
The study was approved by the Turkish Republic Ministry of Health Scientific Research Platform. In addition, the ethics committee approval was obtained from Karatay University Ethics Committee (with a decision dated 17.07.2020 and numbered 2020/014). Informed consent was obtained from the participants of the study.
Results
A total of 151 patients receiving SCIT in our clinic were included in the study. The median age of the patients was 31 (15-71) years and 55.6% of the patients were female. Eighty- three patients (55%) were postgraduate and above. The mean duration of allergic diseases was 5 (1-35) years and the duration of immunotherapy was 20 (3-58) months. The most common government-related factors hindering outpatient clinic visits of the patients were travel restrictions (40.6% of the patients) and curfew (40.4% of the patients). The most common patient- related factors were fear of contracting SARS-CoV-2 (39.7%) and transmitting SARS-CoV-2 to family members (30.5%). Patient’s demographic data are represented in Table 1.
When adherence to treatment of the patients was evaluated, overall adherence to treatment during a 3-month period from March to April-May 2020 was determined to be 54.3%. On a monthly basis, adherence to treatment was observed to be lowest in April (in ascending order, 79.5% in March, 61.6% in April and 62.3% in May). During the pandemic, 50.3% of the patients receiving SCIT had an increase in allergic complaints. The most commonly reported allergic complaint was sneezing (%22.5). Furthermore, 45% of the patients receiving SCIT needed additional treatment for these symptoms. The most commonly used additional treatment was oral antihistamines (24.5%). The treatment switch was performed in 60 patients (39.7%) due to non-adherence to SCIT. In 28 patients (18.5%), immunotherapy was discontinued at the patient’s own request and/or physician’s suggestion, immunotherapy doses were reduced in 32 patients (21.2%). Three patients (2%) admitted to the emergency department with allergic complaints; 9.3% of the patients received additional treatments like herbal and vitamin supplements.
When the patients adherent and non-adherent to SCIT treatment were compared, no significant difference was determined between both groups in regard to age, gender, education level, duration of allergic diseases, type of immunotherapy administered, presence of an additional comorbid disease and admission to emergency department (p: 0.174, p: 0.234, p: 0.809, p: 0.078, p: 0.230, p: 0.118 and p: 0.664, respectively). However, the duration of immunotherapy, increased allergic symptoms, the need for an additional treatment and treatment switching in SCIT because of the pandemic were significantly higher in non-adherent to SCIT treatment patients compared to adherent ones (p: 0.031, p: 0.001, p: 0.001 and p: 0.001, respectively) (Table 2). There was a statistically significant difference between the patients adherent and non-adherent to SCIT in regard to their responses in the anxiety questionnaire (Table-3).
Discussion
In our study, the COVID-19 pandemic was determined to hinder the treatment process in patients receiving allergen immunotherapy, leading to an increase in allergic complaints and, hence, to the need for additional treatment and treatment switch in AIT. In addition, it was shown that it may lead to the impaired mental and psychological status of the patients. AIT is a treatment method, which has been used for a long period of time, providing symptomatic and clinical improvement by modifying Th2-induced immune responses against bee venom and aeroallergens [14]. It requires physician visits at long-term and regular intervals (4-6). There has been a global hindering of SCIT administrations during the COVID-19 pandemic. For allergy clinics, the guidelines offer several recommendations for patient follow-up and procedures to be performed. These recommendations include suspension of the vaccines in the build-up phase of AIT and prolongation of intervals between the shots in the maintenance phase [11-13]. Other recommendations include examining patients at regular intervals in the clinic, procurement of social distancing, injecting one patient at once and ventilating the room for immunotherapy for a certain period of time after each patient [6, 11-13, 17].
In our current study, the overall adherence to treatment of patients receiving AIT was determined to be reduced by half (54.3%). During the pandemic, patients’ adherence to treatment and physician-patient interaction have been significantly reduced in many clinics, with increased use of telemedicine [4, 17-20]. Ojetti et al. reported that admissions to the emergency department in February and March 2020 reduced by 37.6% compared to the same period in 2019 [20]. Although international guidelines recommend continuation to allergen immunotherapy during the COVID-19 pandemic, in a previous study from Turkey, it was reported that 21% of the allergists could not continue to SCIT as it should have been and that 31% of the allergists had to terminate immunotherapy in patients in the build-up phase [17, 21]. Some restrictions brought by the pandemic may have influenced patient’s adherence to treatment, and higher COVID-19 anxiety levels of the non-adherent to AIT patients compared to those adherent to treatment may also have led to avoidance of environments at high risk for COVID-19 and reduction in their adherence to treatment.
In our current study, the duration of immunotherapy was higher in patients adherent to AIT, compared to the patients nonadherent to AIT. This may be due to the fact that some patients who are aware of the need for at least 3 years of immunotherapy may consider the received immunotherapy sufficient, leading to hindering of the treatment. In a study from Spain, 6.5% of the patients receiving venom immunotherapy terminated the treatment at their own request and refused to restart immunotherapy [22].
An increase in the number of allergic complaints and, hence, the need for additional treatment in patients nonadherent to AIT may be related to nonadherence to AIT, as well as to pollen dispersal that increases during March-April-May 2020 when the study was interested in. The idea that steroids may increase the risk of SARS-CoV-2 transmission during the pandemic has led to a reduction in the use of intranasal steroids, although there are opposite recommendations, and this reduction, in turn, may have caused an increase in complaints of rhinitis [23]. Some restrictions like curfews may have led to an increase in complaints of rhinitis by causing the patients to spend more time at home and be exposed to domestic allergens for a longer period of time.
AIT is a treatment method that is administered at regular intervals with particular standard doses. When the treatment is suspended, the dose of AIT should be readjusted. Therefore, in our current study, it is unsurprising that patients nonadherent to AIT had a higher rate of treatment termination and switching. Martinez-Lourido et al. reported that 22.9% of the patients receiving venom immunotherapy had a delay in treatment and, thus, a dose adjustment was performed [22]. Ozturk et al. reported that 72% of allergists increased SCIT intervals in patients in the maintenance phase of SCIT, as well as terminated SCIT in approximately one-third of the patients in the build-up phase [17]. In our study, however, the rate of patients whose SCIT was terminated was 18%.
In conclusion, immunotherapy patients require treatment during the COVID-19 pandemic as well. Access to AIT, the applicability, and maintenance of the immunotherapy should be a priority during this period. Considering both patient- related and government-related factors in the administration of AIT, the process of AIT should be continued, minimizing the risk of SARS-CoV-2 transmission in accordance with the recommendations by the guidelines and science councils. Furthermore, these measures can reduce patients’ worry and anxiety and their adherence to treatment may be promoted.
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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Emel Atayık, Gokhan Aytekın. Effect of COVID-19 pandemic on the treatment process and adherence to treatment of the patients receiving allergen-specific immunotherapy. Ann Clin Anal Med 2021;12(Suppl 3): S269-273
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The relationship between the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio and tumor characteristics in patients with breast cancer
Şeref Dokcu, Mehmet Ali Çaparlar, Aydan Eroğlu
Department of Oncological Surgery, Ankara University Faculty of Medicine, Ankara, Turkey
DOI: 10.4328/ACAM.20518 Received: 2021-02-03 Accepted: 2021-03-12 Published Online: 2021-03-28 Printed: 2021-08-15 Ann Clin Anal Med 2021;12(Suppl 3): S274-277
Corresponding Author: Şeref Dokcu, Surgical oncology department, Ankara University Faculty of Medicine, Cebeci Research and Application Hospital, Balkiraz, Cebeci, No:6, 06620 Çankaya/Ankara,Turkey. E-mail: serefdokcu@hotmail.com P: +90 5334434333 Corresponding Author ORCID ID: https://orcid.org/0000-0003-1807-8108
Aim: Many studies nowadays increasingly enlighten the nature of relationship between cancer and inflammation. NLR and PLR are proinflammatory indicators that are related to many clinicopathological characteristics of many types of cancer. In this study, we aimed to find out the relationship between NLR and PLR values and tumor characteristics in patients with breast cancer that are operated with help of basic and inexpensive peripheral blood test results.
Material and Methods: A database of 94 female patients who were operated in the Department of Surgical Oncology of the Medical School of Ankara Uni- versity was studied. All blood sample tests, pathology reports, immunohistochemical staining results of the patients were retrospectively scanned. Patient demographics and pathological properties of tumor obtained from the database. The NLR and PLR values were taken from the peripheral blood cell count. Data were presented as average value±standart deviation(SD), and maximum-minimum values. Later data were analyzed.
Results: NLR values were significantly different accordingly to T stage of tumor ( =11.452; p=0.022). On the other hand, the PLR value did not show a significant differentiation according to tumor size ( =5.865; p=0.209). It has been seen that this differentiation is between T1 and T2; T1 and T3 statistically. (U= 251.000 p=0.003; U=54.000, p=0.021).
Discussion: The NLR value is significantly related to the tumor size. But further research is needed to see the clinical reflection and added value to the clinical practice of these results.
Keywords: Breast cancer; Neutrophil-Lymphocyte ratio (NLR); Platelet-Lymphocyte ratio (PLR)
Introduction
Nowadays, breast cancer is the most common cancer among women and the second most common reason for cancer- associated women deaths [1]. Despite significant progress in recent years, approximately 20% of patients with breast cancer experience distant metastasis or relapse within 5 years because of late diagnosis [2,3]. Therefore, some diagnostic biomarkers such as free-floating tumor cells in serum, DNA, miRNA, lncRNA, and exosome have been developed to screen and detect cancer in the early stages. However, their clinical use is still limited because of the uncertainty and high cost of these biomarkers [4]. Lately, PLR and NLR parameters, which are determined from peripheral venous blood tests, are closely related to poor prognosis, relapse, and mortality in solid tumors as prognostic indicators [5,2].
Even if their numbers are limited, similar studies have been carried out comparatively on breast cancer subtypes [6], in elderly patient groups [7] and in healthy control groups, and similar results were obtained [7]. It is now accepted that cancer dependent chronic inflammatory process is closely related to cancer development course.
It is increasingly accepted that as components of the systemic inflammatory response, lymphocytes, neutrophils, and platelets have an essential role in carcinogenesis and tumor progression [9, 10]. Many authors recommend inflammation- based scoring systems. However, clinical applications are not at a level that can be used in routine practice, and there is no consensus on optimal limit levels. The Glasgow prognostic score is an inflammation-based prognostic scoring like NLR and PLR obtained from peripheral blood-based inflammatory components [5,6]. Neutrophils are known to support the potential of circulating tumor cells to metastasize to distant organs by secreting circulating growth factors such as vascular endothelial growth factor (VEGF) and proteases [11].
Studies have shown that cytokines and chemokines produced by inflammatory cells and tumor cells can contribute to metastasis development [12 ]. As it can inhibit the immune system by suppressing cytotoxic T lymphocytes’ activities, the neutrophilic response is associated with poor prognosis [13]. Lymphocytes that infiltrate the tumor are related to a better response to cytotoxic treatment and a better prognosis in patients with breast cancer [14]. Lymphocytes usually increase apoptosis through the cytokine microenvironment that they provide. They symbolize the immune response in the fight against cancer [15]. It is found that neutrophile-lymphocyte ratio (NLR) is an independent factor for negative outcomes in many solid tumors, including breast cancer. Fortunately, the determination of NLR depends on a minimal invasive peripheral venous blood test, which is highly specific and sensitive for evaluating the tumor’s activity and its’ interaction with microcirculation. These tests can be obtained easily in all routine clinics, and they do not require additional costs.
As these parameters obtained from peripheral blood tests are cheap and easily accessible, their predictive value is important for clinicians. Studies like this, which are carried on with breast cancer patients, will help the clinicians diagnose, treat, and predict overall survival. In this study, we aimed to show the relationship between the NLR and PLR values obtained from the peripheral blood test results at the diagnosis and the characteristics of the tumor, and the clinical reflections of this relationship.
Material and Methods
In this study, the database of 94 patients with breast cancer who were operated at the Surgical Oncology Clinic was examined retrospectively. Included data were obtained from preoperative routine blood tests, postoperative follow-up, and pathology reports. In this study, newly diagnosed primary or metastatic breast cancer cases that did not use any medication that can affect hematological parameters were included.
Therefore patients who are using steroids have hematological diseases, they have previously been diagnosed with malignancies, had acute or chronic inflammation signs before the operation, have recently received a blood transfusion, and were diagnosed with autoimmune disease. Patients with missing data in the database were also excluded. Demographic features and laboratory values of the patients were retrospectively scanned through the records of the hospital’s medical database. Clinical characteristics including age, menopause status, diagnosis, TNM stage, pathological type, receptors (estrogen, progesterone, HER2) were gathered. Patients were staged according to the TNM staging system of the American Joint Committee on Cancer [16] (AJCC 8th edition, 2017). Recent preoperative neutrophile, platelet, and lymphocyte counts were obtained from medical blood test records. The absolute neutrophile number was divided by the total lymphocyte number to calculate the NLR, and the final platelet number was divided by the whole lymphocyte number to calculate the PLR.
When patients were admitted to the hospital, peripheral blood tests were done to prepare for surgery. Later, neutrophile, platelet, and lymphocyte counts were obtained through the medical database. Pathology reports and immunohistochemical staining results were analyzed to obtain tumor size, lymph nodes, estrogen, progesterone, HER2 receptors, and Ki-67 percentages.
All patients involved in this study were female. Demographic and clinicopathological features of the patients are shown in Table-1. Our study was approved by the Hospital Ethics Committee of the Ankara University, Medicine Faculty (Decision number: I10-625-20). Written informed consent was obtained from all participants.
Statistical Analysis
Data are presented as average value±standard deviation (SD), and max-min values. Parametric test assumptions were examined before performing the difference analysis. Normality was checked with the Shapiro-Wilk test skewness and kurtosis. The homogeneity of the variances was checked with Levene’s test. If the assumptions were satisfied, the difference analysis was performed using one-way analysis of variance (ANOVA); otherwise,, the Kruskal-Wallis test was used. Paired comparisons were made using the Mann-Whitney U test. Statistical analyses are done at a 95% confidence interval. A P -value of less than 0,05 is considered statistically significant.
Results
The characteristics of the patients participating in the study are shown in Tables 1 and 2.
According to the pathological diagnosis, the PLR values of the patients are not statistically significant; F (3,90) = 1.189 p> .05. Similarly, the patients’ NLR values were not statistically significant according to the pathological diagnosis (F (3,90) = 1.648 p> .05).
The NLR value showed statistically significant changes compared to T stage; (X2 = 11.452; p = 0.022). The PLR value did not show statistically significant change according to the tumor size (X2= 5.865; p = 0.209). This difference is between T1 and T2, Statistical T1, and T3 tumors (U = 251.000 p = 0.003; U = 54.000 p = 0.021). As a result, it is seen that the NLR value increases significantly as the tumor size increases.
The PLR and NLR values were not statistically different according to the pathological axillary lymph node involvement (F (1,92) = 0.656 p> .05; F (1,92 = 2.103 p> .05).
There was no statistically significant difference in PLR and NLR values according to the receptor status of the tumor estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor (HER2) (p>.05). Similarly, there was no statistically significant difference between menopausal status and PLR-NLR values (p>.05).-
Discussion
In this study, we examined the relationship between NLR and PLR values with tumor characteristics. Our study showed that the NLR value statistically differs according to tumor diameter (T stage). This differentiation was evident, especially in between T1 and T2; T1 and T3 tumor sizes. This finding was invalid for PLR values. Likewise, no significant findings were obtained when comparing PLR and NLR values with the clinical pathology of the tumor and the demographic characteristics of the patients.
Inflammation and cancer; platelets play an essential role in tumor growth by increasing angiogenesis through VEGF (vascular endothelial growth factor) in cancer progression [17]. There is a direct relationship between platelet count and VEGF levels. While angiogenesis may contribute to metastasis through thrombocytosis, some studies have found that most VEGF levels are due to neutrophils. Neutrophils may also support tumor growth and metastasis by releasing reactive oxygen radicals (ROS), nitric oxide (NO), and arginase [18]
In contrast, lymphocytes represent the host immune response against malignancy by inducing cancer cell death and inhibiting tumor cell proliferation and migration [2,11]. A positive relationship was found between tumor diameter and NLR value in our study. Besides, NRL is an indicator of impaired cell- mediated immunity associated with systemic inflammation [12]. This shows that the cytokine microenvironment provided by neutrophils contributes to tumor growth.
Consequently, the numerators of NLR and PLR values, neutrophile, and platelet counts are considered negative outcome determinants, and their denominator, lymphocyte count, is considered a positive predictor of outcome. At the same time, NLR and PLR values are determinants of breast cancer risk [8,2]
Koh et al. (2015), who considered the relationship of NLR values with clinical outcomes, showed that an increase of NLR value is related to increased T stage, younger age, and positive HER2 status in their study with 2059 breast cancer patients. This outcome is coherent with the outcomes of the study by Azab et al. (2013) conducted with patients with operated breast cancer. This finding is consistent with the findings of Azab et al. (Azab et al., 2013) in their study with operated breast cancer patients. The study was evaluating the prognostic significance of the NLR value in 437 breast cancer patients. Patients with high NLR values were older. They also had more lymph node involvement and metastasis rates [19]. However, they could not define a significant correlation with relapse. Dirican et al. showed that high NLR values are significantly related to the T stage of the tumor, axillary lymph node status, and distant metastasis status. The study correlated the NLR value with disease-free survival and overall survival at 6-year follow-up in approximately 1500 patients using a cut-off value of 4 for NLR [20].
On the other hand, Yersal et al. found no statistically significant difference with the distribution of NLR and PLR values in 255 breast cancer patients by lymphovascular invasion, tumor size, pathological lymph node involvement, and breast cancer subtypes. But they found that PLR values in patients with lymph node metastasis were higher than in others [21]. We could not find a significant relationship between breast cancer receptor type and NLR and PLR values. Breast cancer is divided into subgroups according to receptor types. Yersal et al. did not find a significant relationship between breast cancer subgroups and NLR and PLR values in their study on 255 breast cancer patients [21]. Yao et al. found that NLR value is an easily accessible and inexpensive preoperative prognostic indicator for triple-negative breast cancer (TNBC) [22]. Liu et al. found that high NLR values are related to decreased overall survival in HER2 (+) patients in the study on 318 triple-negative breast cancer (TNBC) patients [6].
Conclusion
In summary, these results show that inflammation components are important triggers of tumor growth. This is consistent with the ‘seed and soil’ nature of cancer growth, according to Proctor [23] .
The most significant limitation of our study is that it is observational and single-centered, and the comparison of clinicopathological features of the tumor requires a more extensive patient series. Before considering the clinical application of PLR and NLR values as cancer markers, further prospective research is needed. It must evaluate particular cut-off values and required optimal cut-off levels. NLR value has the potential of becoming an accurate prognostic indicator. Mechanisms underlying the high NLR value and response to anticancer treatment in breast cancer need further investigation. Clearer findings on NLR and its association with breast cancer prognosis will facilitate selecting patients who are more likely to benefit from medical and specific surgical approaches [24].
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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Şeref Dokcu, Mehmet Ali Çaparlar, Aydan Eroğlu. The relationship between the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio and tumor characteristics in patients with breast cancer. Ann Clin Anal Med 2021;12(Suppl 3): S274-277
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Constipation associated with Parkinson’s disease in Morocco. A report on the clinical experience in Morocco
Abderrahmane Achbani 1, Youssef Bouchriti 2, Mohamed Boukrim 3, Hasnaa Sine 4
1 Department of Biology, Laboratory of Cell Biology and Molecular Genetics, Faculty of Sciences, University Ibn Zohr, Agadir, 2 Department of Geology, Geoscience and Environment Team, Faculty of Science, University Ibn Zohr Agadir, 3 Laboratory of Biostatistics, Clinical Research and Epidemiology, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, 4 Medical Biology, Human and Experimental Pathology and Environment, Faculty of Medicine and Pharmacy of Rabat, MOHAMED V University of Rabat, Rabat, Morocco
DOI: 10.4328/ACAM.20523 Received: 2021-02-05 Accepted: 2021-04-18 Published Online: 2021-05-03 Printed: 2021-08-15 Ann Clin Anal Med 2021;12(Suppl 3): S278-281
Corresponding Author: Abderrahmane Achbani, Department of Biology, Faculty of Sciences, University Ibn Zohr, P.B 8106 Dakhla Agadir, Morocco. E-mail: abderrahmane.achbani@edu.uiz.ac.ma P: +212-528220957 F: +212-528220100 Corresponding Author ORCID ID: https://orcid.org/0000-0002-4262-2399
Aim: Constipation is the most frequent symptom of autonomic dysfunction in patients with Parkinson’s disease. The objective of this work is to study the prevalence and clinical features of constipation symptoms.
Material and Methods: A cross-sectional descriptive study was conducted on a selected cohort of 180 patients, previously diagnosed with PD.
Results: The frequency of constipation in patients with Parkinson’s disease was 69.4%, and 96 % of Parkinson’s disease patients had constipation before the onset of motor symptoms. Patients with Parkinson’s disease with constipation had significantly longer duration of the disease and more advanced stages of Hoehn and Yahr scales. We also found that the group of patients with Parkinson’s disease with constipation sign had less significant symptoms of bradykinesia compared to the non-constipation group.
Discussion: The improvement of the management of patients with Parkinson’s disease requires the integration of the search for non-motor signs during con- sultation and the validation of evaluation scales in Arabic.
Keywords: Parkinson’s Disease; Constipation; Premotor symptom; Hoehn and Yahr scale
Introduction
Parkinson’s disease (PD) is the most common neurodegenerative disorder after Alzheimer’s disease [1], affecting 1% of the population older than 60 years [2]. Clinically, most patients suffer from the motoric disorder, including bradykinesia, rest tremor, rigidity, and postural and gait impairment. However, a number of patients also suffer from non-motor disorders, including olfactory, cognitive impairment dysfunction, anxiety, depression, sleep disorders, autonomic disturbances, pain, fatigue, and dementia [3, 4]. In fact, both mood disorders and constipation have been shown to increase an individual’s risk for subsequently developing Parkinson’s disease[5]. They are associated with neuropathological lesions commencing in the dorsal vagus nucleus, in the bulb and in the anterior olfactive nucleus, and will progressively propagate in the overlying structures [6, 7].
Constipation remains the most common symptom of dysautonomic and gastrointestinal symptoms, reported by 70- 80 % of patients with Parkinson’s disease [8], may also appear many years before the onset of motor symptoms and, therefore, in combination with the other non-motor symptoms, can be a predictive marker. The accumulation of α-Synuclein and associated neurodegeneration in the enteric nervous system, characterized by increased intestinal permeability, oxidative stress and local inflammation, explain constipation in these patients [9]. Early screening for such symptoms may constitute an important approach for early pre-clinical diagnosis. This study was conducted to determine the prevalence of constipation symptoms in PD compared to patients with Parkinson’s disease without constipation and to evaluate the relationship between these pre-motor symptoms and the clinical features of PD.
Material and Methods
Patients and criteria of inclusion
This is a cross-sectional study on a cohort of 180 patients (males and females), previously diagnosed with Parkinson’s disease. Patients were recruited from both private and public neurology centers in the city of Agadir in South-western Morocco. All the selected patients gave their written consent, according to the recommendation of the Ethics Committees of the Faculty of Medicine and Pharmacy of Marrakech.
Data collection
The data were collected between January 2017 and July 2018 using a detailed clinical questionnaire filled up by the clinicians through an interview with the patients. In order to distribute individuals into a number of classes, a k-means clustering algorithm was used to define 2 age clusters of disease onset (early-onset Parkinson’s ≤ at age 50 and late-onset Parkinson’s > at age 50).
Statistical analysis
Data are presented as means ± standard deviation (SD) or percentage. Independent sample t-tests, non-parametric test and Variance test were used. Variations in the distribution of categorical data were evaluated using the Chi-square test or Fisher exact test. A p-value below 0.05 was considered statistically significant. Statistical correlation was performed using the IBM SPSS statistics 22 software
Results
Patients diagnosed with Parkinson’s disease were recruited both in private and public neurology services. The size of the sample reached 180 individuals, including 117 males (65%) patients and 63 females (35%). The mean age of the patients included in the cohort was estimated to be around 68.1 ±11.3 years old. The results showed that the age at the onset of the disease, in the sample ranged between 35 and 80 years old. The mean age at the onset of symptoms for male and female population was 60.3±9.78 years.
Clinical features of PD patients with constipation
Among the 180 participants in the current clinical investigation, 125 (69.4%) patients suffered from constipation. To compare the characteristics of patients with constipation, PD patients were divided into two groups: constipated group (constipation group) and non-constipated group (non-constipation group). The maincharacteristicsofthecohortinrelationtoconstipation are presented in Table 1. There was no significant difference in Body Mass Index, and gender between the two groups. The age of PD patients in the constipation group (69.4 ±11.5 years) was significantly older than that of PD patients in the non- constipation group (65.1 ±10.2 years) (P<0.01). The duration of the illness in the PD group with constipation (8.8±5.6 years) was significantly longer than in the PD group without constipation (5.8±5.1 years) (P<0.05).
This result showed that the initial symptom differed from that of the non-constipation group. There was a correlation between the constipation group and the severity of motor symptoms of PD. Indeed, the comparison between the two groups in relation to the initial symptom showed that the non-constipation group experienced more significant symptoms of bradykinesia compared to the constipation group.
The clinical profile of the patients differed slightly between the two groups. Both groups presented three disease phenotypes, however, the percentage of patients with a mixed phenotype in the constipation group (33.4%) was significantly lower than in the non-constipation group (46.7%). The mean daily dose of levodopa was similar in the constipation group (420.1±154.1 mg/d) compared with the non-constipation group (390.5±154 mg/d). However, this result remains insignificant. The severity of the Hoehn-Yahr Stage (p<0.05) was significantly different in both groups. The H-Y stages in the PD group with constipation (3.62±1.97) were significantly increased compared with the no- constipation group (2.95±1.08) (P = 0.01).
A cluster analysis with a two-cluster solution revealed two profiles. The early-onset Parkinson’s group had a mean age at the onset of 49.8 ±5.8 years, compared to the later onset group (mean age of onset = 66.1±5.1 years). In relation to the age at onset of Parkinson’s disease, patients with constipation were significantly older than PD without constipation.
Pre-motor constipation
Among the 125 patients with Parkinson’s disease, 120 cases (96%) had constipation before the appearance of motor symptoms. Pre-motor constipation appeared in over half of the patients with a delay of 2 to 10 years for a significant proportion (68. 33%). The average duration of onset of premotor constipation was 4.6 ± 3.1 years (Figure 1).
Discussion
In the present study, 69.4% of Parkinson’ s disease patients were ascertained to have subjective constipation, in agreement with other reports, in previous studies reporting that constipation affects 70-80% of Parkinson’s patients [10-12]. Our results also suggest that constipation in our population had an average of 4 or more years delay before the onset of motor symptoms, which was consistent with previous reports that showed that the prevalence of constipation as a pre-motor sign ranged from 28.19% to 87% depending on the type of the studied population and the constipation criteria [13, 14]. This finding indicates constipation as a prodromal symptom of PD. Early involvement of enteric neurons may explain the discovery that constipation is an early symptom of Parkinson’s disease [15].
In previous studies, constipation has been correlated with the time since diagnosis and the severity of Parkinson’s disease [16]. In this study, it was observed that the group of Parkinson’s patients with constipation had late-onset Parkinson’s disease. This confirmed previous findings that showed an influence of old age at the onset of Parkinson’s disease on the development of certain symptoms, including constipation [16]. Our results also showed that patients with constipation had significantly longer duration of disease and more advanced stages of the Hoehn and Yahr scale. Presumably, in patients with Parkinson’s disease who are more advanced in age and stage of onset, less activity and poorer gastrointestinal motility may cause constipation. This is also supported by our findings that constipated patients are older than non-constipated Parkinson’s patients. Considering the clinical pattern of PD, we found that the group of patients with Parkinson’s disease with a sign of constipation had less pronounced symptoms of bradykinesia compared to the non-constipation group. This result might be attributed to the fact that bradykinesia was the most handicapping symptom of Parkinson’s disease. This restricts the physical activity and mobilization of patients.
Previous studies have investigated the impact of dopaminergic treatment on autonomic symptoms, such as constipation, in patients with Parkinson’s disease [10, 11]. In contrast, in this study, the PD group with constipation received a daily dose of levodopa similar to the PD group without constipation, which is inconsistent with the results of other studies suggesting that autonomic symptom alterations were associated with dopaminergic treatment. This difference may be partially explained because dopaminergic treatment was not initially used to treat patients in our study.
In the literature, constipation has been treated only by a few research papers on Parkinson’s disease in Morocco, and to our knowledge, this investigation is the most important to focus on the subjective aspect of the problem. Our study has certain limitations. This is a historical clinical investigation of the onset of premotor symptoms, in which information about the chronology of constipation and other symptoms was collected through patient reminders. Therefore, the subjective bias of the responses could not be ignored and may partially influence the precision of our results.
In conclusion, these results underscore the importance of the clinical and systematic evaluation of constipation in patients with Parkinson’s disease. The diagnosis of constipation may allow clinicians to identify PD in their patients at an earlier stage, especially if it is associated with other pre-motor symptoms including sleep and olfactory disorders. The improvement of the management of Parkinson’s patients requires the integration of the search for non-motor signs during the consultation and the validation of evaluation scales in Arabic.
Acknowledgment
Our sincere thanks go to all the patients who took part in this 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: This work was funded by the Laboratory of Cell Biology and Molecular Genetics, Department of Biology, Faculty of sciences, Ibn Zohr University, Agadir, Morocco.
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. Tysnes OB, Storstein A. Epidemiology of Parkinson’s disease. J Neural Transm. 2017; 124(8):901-5.
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9. Nair AT, Ramachandran V, Joghee NM, Antony S, Ramalingam G. Gut microbiota dysfunction as reliable non-invasive early diagnostic biomarkers in the pathophysiology of Parkinson’s disease: a critical review. J Neurogastroenterol Motil. 2018; 24(1):30-42.
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15. Olanow CW, Stocchi F, Lang A. Parkinson’s disease: non-motor and non- dopaminergic features. Hoboken, New Jersey: John Wiley & Sons; 2011.
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Abderrahmane Achbani, Youssef Bouchriti, Mohamed Boukrim, Hasnaa Sine. Constipation associated with Parkinson’s disease in Morocco. A report on the clinical experience in Morocco. Ann Clin Anal Med 2021;12(Suppl 3): S278-281
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Vitamin D deficiency in individuals applying to physical therapy outpatient clinic
Nilufer Aygun Bilecik 1, Zeynep Kilic 2
1 Department of Physical Medicine and Rehabilitation, Adana City Hospital, Adana, 2 Department of Physical Medicine and Rehabilitation, Ankara City Hospital, Ankara, Turkey
DOI: 10.4328/ACAM.20524 Received: 2021-02-06 Accepted: 2021-04-01 Published Online: 2021-05-03 Printed: 2021-08-15 Ann Clin Anal Med 2021;12(Suppl 3): S282-285
Corresponding Author: Nilufer Aygun Bilecik, Department of Physical Medicine and Rehabilitation, Adana City Hospital, Adana, Turkey. E-mail: drnilaygun@gmail.com P: +905323562611 Corresponding Author ORCID ID: https://orcid.org/0000-0002-5113-2287
Aim: The aim of our study was to determine if there is vitamin D deficiency in adults who were examined in our hospital’s Physical Medicine and Rehabilita- tion outpatient clinic and whose 25-OH vitamin D level was measured in laboratory examination, and to determine the difference between 25-OH D3 levels according to age, gender and seasons.
Material and Methods: The levels of 25-OH vitamin D in patients who applied to our outpatient clinic between April 2018 and April 2019 were examined retrospectively.
Results: The mean 25-OH vitamin D level in the examined patients (n = 1110) was 17.1 (19.2 ± 12.6). 25-OH vitamin D levels were statistically significantly higher in men than in women. The Vitamin D value in the April-October period was found to be significantly higher (p <0.05) than in the November-March period.
Discussion: In our study, widespread vitamin D deficiency and insufficiency were found in patients who applied to our hospitals. Emphasizing that this situation can be seen at a high rate even in sunny regions such as Adana, we think that it will be appropriate to inform people about benefiting from sunlight enough, proper nutrition and vitamin D supplementation when necessary.
Keywords: 25-Hydroxy vitamin D; Vitamin D deficiency; Age; Gender
Introduction
Vitamin D has important effects on calcium homeostasis and bone metabolism in the body [1, 2]. While Vitamin D2 is produced by plants, the main source of vitamin D in humans is UVB radiation from sunlight. 80-90% of the daily vitamin D requirement is obtained from sunlight, and a very low amount is taken from foods and foods [3, 4]. For the positive effects of vitamin D to occur, adequate exposure to sunlight or the active form of vitamin D, which is the active form of 1,25-Dihydroxy D, must be kept at normal levels. While the half-life of 1,25 dihydroxy vitamin D, which is the active form of vitamin D, is 4-6 hours, the half-life of 25-OH D3 is approximately 2-3 weeks, so 25-OH D3 levels are generally measured in the body [5-7]. Subclinical vitamin D deficiency and insufficiency affect most men and women in all age groups in many geographical regions. This situation arises as a result of a diet poor in calcium, together with insufficient exposure to sunlight [8]. Despite the uncertainty about the ideal level of vitamin D, many studies accept vitamin D deficiency as a common problem, especially in winter, even in areas with plenty of sunshine [9, 10].
Vitamin D deficiency and insufficiency in Turkey pregnant women, babies, adults, and is one of the major health problems affecting the elderly. In this study, it was aimed to determine the frequency of vitamin D deficiency in individuals who applied to our physical therapy outpatient clinics and to investigate if there is a significant difference between 25-OH D3 levels considering age, gender and seasonal differences.
Material and Methods
25-OH vitamin D levels in patients admitted to our hospitals in Adana province between April 2018 and April 2019 were analyzed retrospectively. The data of the patients whose outpatient clinic records were examined and who had chronic renal failure, chronic liver disease and who had dialysis unit registration were not included in the study. 25-OH vitamin D levels were studied with Chromsystems (Chromsystems, Instruments and Chemicals, München-Germany) reagents and Agilent 1100 (Agilent Technologies, Germany) using HPLC (High Performance Liquid Chromatography) method. According to the manufacturer’s information, Intra-assay CV <5%, inter-assay CV <7%, Linearity: 2.5-250 ng/ml. The patients were grouped according to age and gender. The distribution of vitamin D levels by months was examined.
Statistical analysis
Statistical analysis was done using the SPSS 22.0 program. Mean, standard deviation, median, min-max, ratio and frequency values were used in the complementary statistics of the data. The distribution of variables was checked with the Kolmogorov- Smirnov test. The Kruskal-Wallis and Mann-Whitney U tests were used in the analysis of quantitative data. The Chi-square test was used in the analysis of qualitative data. P-values less than 0.05 were considered statistically significant.
Results
The research was conducted on 1110 patients; 881 of the patients were female (79.4%), 229 were male (20.6%). The mean age of the patients was 55 ± 15.3, and the mean 25-OH vitamin D level was 19.2 ± 12.6. Taking 20 ng/ml as the cut-off value, it was found that the rate of vitamin D deficiency was 61.7% and the rate of vitamin D insufficiency was 26.3% (Table 1).
The mean 25-OH D3 level in female patients was 19 ± 13.1, while the mean 25-OH vitamin D level in male patients was 20 ± 10.1. While 25-OH vitamin D levels in 58.5% of men were below 20 ng / dl, this rate was 62.5% in women. The difference between vitamin D levels in both sexes was not statistically significant.
The mean 25-OH vitamin D value in men was significantly higher than in women (p <0.05) (Figure 1). The 25-OH vitamin D value was significantly higher (p <0.05) in the April-October period compared to the November-March period (Figure 2). The average 25-OH vitamin D level was 20.8 ± 15.4 ng/ml in the 18-39 age group (n = 178), 18.7 ± 12.0 ng/ml in the 40-69 age group (n = 731), in patients aged 70 and over (n = 201) was found to be 19.5 ± 11.7 ng/ml. The 25-OH D3 level did not differ significantly (p > 0.05) according to age groups (Table 2).
Considering the relationship between 25-OH vitamin D level and the periods, 25-OH vitamin D levels of 30 ng/dl and above were found to be statistically significantly higher in women in the April-October period compared to the November-March period (p=0.001). No such relationship was found in men. The rate of patients with 25-OH vitamin D level <20 ng/ml in the November-March period was significantly higher (p=0.001) compared to the April-October period (Table 3). There was no significant difference in vitamin D levels between men and women by age groups (p = 0,749 and p = 0,394, significantly).
Discussion
25-OH Vitamin D has an important effect on calcium and bone metabolism. It increases the absorption of calcium and phosphate from the intestine and is an important factor in bone mineralization. Vitamin D deficiency causes secondary hyperparathyroidism, bone resorption and increases the risk of fracture formation. Severe vitamin D deficiency (25-OH vitamin D level <12.5 nmol/l or 5 ng/ml) causes rickets in children and bone mineralization defect that causes osteomalacia in adults. There are also publications showing that it is associated with cardiovascular diseases and type 2 diabetes [11, 12]. Vitamin D deficiency is common, especially among the elderly. 25-OH Vitamin D deficiency is common in Europe. However, seasonal changes have a significant effect on 25-OH Vitamin D levels because cholecalciferol is synthesized in the skin under the influence of ultraviolet (UV) light [13, 14]. Almost no 25-OH Vitamin D is synthesized between October and March in the United States and the northern parts of Canada and Northern Europe [15]. However, this is generally not the case in more southern countries [16]. Studies have found that vitamin D deficiency has a high prevalence not only in the risk group, but also in the Middle East and Asian countries [15]. Vitamin D levels also have been investigated in several studies conducted in Turkey [17-21]. In studies conducted in the last twenty years, Turkey, India, China, Saudi Arabia and Iran, even in a tropical climate and sunny countries such as high rates of vitamin D deficiency have been reported [15, 22]. In the study conducted by Ucar et al. in Turkey, when the cut-off value was taken as 20 ng/ml, 51.8% vitamin D deficiency and 20.7% vitamin D insufficiency were found in patients [21]. In our study, when 20 ng/ml was taken as the cut off value, 61.7% vitamin D deficiency and 26.3% vitamin D insufficiency were detected. In a French study, 25-OH vitamin D deficiency was found at a rate of 14% in the winter months in healthy adults [23]. In a study conducted by Levis et al., in South Florida, the importance of seasonal changes was emphasized by finding a statistically significant increase in 25-OH vitamin D concentrations of 13% in women and 14% in men during the summer period [24]. In the study conducted by Bozkurt et al., in Turkey, 25-OH vitamin D levels were found to be significantly lower in winter than in summer [18]. In our study, 25-OH D3 levels were found to be significantly lower in winter than in summer, in line with the literature. In our study, 25-OH vitamin D levels in men were significantly higher than in women (p <0.05). Similarly, in the study by Ono et al., 25-OH vitamin D levels in men were found to be statistically significantly higher than in women [25]. Many factors, such as cultural factors, geography, race, as well as personal characteristics affect vitamin D levels and may vary depending on the population in which studies are conducted [6, 22]. Although our study was conducted in a sunny region, a high level of vitamin D deficiency was detected. 25-OH vitamin D deficiency was found in more than half of the cases in the study performed by Kaya et al. on postmenopausal women in the Izmir region [26].
The reasons limiting our study are retrospective examination of the patients’ records, their body mass indexes and the duration of exposure to sunlight, and the unknown presence or absence of any chronic diseases.
Conclusion
In conclusion, a high rate of vitamin D deficiency and insufficiency was detected in patients who applied to our hospital in Antalya, and we think that it would be appropriate to supplement the person with vitamin D, bearing in mind that even in areas with abundant sunny and tropical climates, there may be high rates of 25-OH vitamin D deficiency. In addition, patient education about the importance of sunbathing and dietary content can also contribute to treatment.
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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20. Olmez D, Bober E, Buyukgebiz A, Cimrin D. The frequency of vitamin D insufficiency in healthy female adolescents. Acta Paediatr. 2006;95(10):1266-9.
21. Uçar F, Taşlıpınar M, Soydaş A, Özcan N. 25-OH vitamin D levels in patients admitted to Ankara Etlik ihtisas training and research hospital. Eur J Basic Med Sci. 2012;2(1):12-5.
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26. Kaya T, Ulutas Ö, Aslanca D, Karatepe AG, Günaydin R, Karaca B. Sağlıklı Postmenopozal Kadınlarda Serum 25 (0H) Vitamin-D Düzeyi ve Hiperparatiroidi (Serum 25 (0H) Vitamin-D Level and Hyperparathyroidism in Healthy Postmenopausal Women). J Romatizma/Rheumatism. 2007;22(1):20-3.
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Nilufer Aygun Bilecik, Zeynep Kilic. Vitamin D deficiency in individuals applying to physical therapy outpatient clinic. Ann Clin Anal Med 2021;12(Suppl 3): S282- 285
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Salivary gustin and hyperemesis gravidarum
Nermin Kosus 1, Aydin Kosus 1, Muzeyyen Uyanık 2
1 Department of Obstetrics and Gynecology, Self employed, Ankara, 2 Department of Obstetrics and Gynecology, Medicana Bursa Hospital, Bursa, Turkey
DOI: 10.4328/ACAM.20526 Received: 2021-02-08 Accepted: 2021-04-08 Published Online: 2021-04-21 Printed: 2021-08-15 Ann Clin Anal Med 2021;12(Suppl 3): S286-289
Corresponding Author: Muzeyyen Uyanık, Department of Obstetrics and Gynecology, Medicana Hospital, Bursa, Turkey. E-mail: drmuzeyyenuyanik@gmail.com P: +90 5438090882 Corresponding Author ORCID ID: https://orcid.org/0000-0002-2032-178X
Aim: Hyperemesis gravidarum (HG) is described as unexplained excessive nausea and vomiting during pregnancy. Gustin is a polypeptide hormone present in saliva. It is necessary for normal taste sensation. Inhibition of gustin release causes gustatory buds abnormalities. In this study, levels of salivary gustin were evaluated in pregnant women with HG.
Material and Methods: This prospective case-control study was conducted on 30 women with HG and 30 healthy pregnant women without symptoms of HG. Fasting saliva samples were taken from all subjects for measurement of salivary gustin levels, and the groups were compared with each other for gustin levels.
Results: Salivary gustin levels were slightly lower in the HG group than in the control group. But this difference did not reach statistical significance. Logistic regression analysis revealed that gustin level has a borderline significance in the prediction of HG. High gustin levels decreased HG development risk by 35.6%. Gustin level predicted 36.3% of HG cases in the ROC analysis, which was not statistically significant.
Discussion: Gustin does not play any role in the etiopathogenesis of hyperemesis gravidarum, but due to the excessive number of variables affecting appetite, the role of salivary gustin on the etiopathogenesis of HG must be studied in larger prospective studies, which will include a greater number of variables in this matter.
Keywords: Emesis; Saliva; Hormone; Pregnancy; Gustin; Carbonic anhydrase
Introduction
Hyperemesis gravidarum (HG) is described as unexplained excessive nausea and vomiting during pregnancy, which causes fluid and electrolyte imbalances, nutritional deficiency and weight loss. It occurs in about 0.5% to 2% of pregnant women and is the most common cause of admission to the hospital in early pregnancy [1-3].
Many etiopathogenic factors have been considered for HG, including endocrine-hormonal factors such as higher levels of hCG, progesterone, and thyroid hormones during early pregnancy, hepatic dysfunction, changes in lipid metabolism, upper gastrointestinal system dysmotility, and psychological factors. However, no specific causative factors have been established [4].
The mechanisms that drive the pregnancy-induced changes in appetite remain largely unknown. Many maternal metabolic adaptations occur during pregnancy. The mother has to establish a negative energy balance during 1st trimester to avoid intake of toxic compounds, and a positive energy balance during the rest of the pregnancy to ensure the growth of the fetus, as well as fetal and maternal wellbeing. Changes in taste sensation and taste threshold are parts of this adaptation and they might be responsible for HG.
Gustin is a 37 KD molecular weight polypeptide hormone present in saliva. It is released by the parotid glands in the human. It contains two zinc atoms. Gustin has six fractions, and fraction II is mostly found in the parotid saliva. Its structure was found to be similar to that of Carbonic anhydrase 6 (CA6) [5]. Gustin is necessary for the normal development of the tastebuds. Inhibition of gustin release causes gustatory buds abnormalities, and it was shown that gustin affects directly gustatory buds and olfactory epithelium, as a growth factor. Gustin is relatively absent in patients with hypogeusia [6]. Nowadays some peripheral hormones secreted from GIS and regulating appetite become popular. Since the salivary gustin hormone is important in taste sensation, its abnormal secretion might be involved in the etiopathogenesis of HG. In this study, we evaluated salivary gustin levels in pregnant women with HG.
Material and Methods
This prospective case-control study was conducted on 60 pregnant women in their first trimester of pregnancy. The women were selected from the outpatient clinic of Maternity Clinic and the in-patient wards of the Hospital of Obstetrics and Gynecology at Turgut Ozal University Hospital between July 2012 and October 2013. The patients were divided into two groups according to the presence of HG. Thirty women with HG and 30 healthy pregnant women without symptoms of HG were taken into the study. HG was defined as persistent nausea and vomiting associated with ketosis and weight loss > 5% of pre- pregnancy weight. Inclusion criteria were as follows: singleton pregnancy with a live embryo, healthy women without any medical disorders, age range between 18 and 35 years, weight within 20% of normal weight for height at the beginning of pregnancy, and gestation between 6-14 weeks. The exclusion criteria were as follows: pregnant smokers or drug users, cases with any systemic disease and/or psychological disorder that can cause vomiting, and multiple gestation. In addition, those women with uncertain dates or early pregnancy loss were also excluded from the study. Approval for this study was obtained from the Local Institutional Review Board of the Faculty of Medicine, Turgut Özal University (No: B-30 2 FTH 0 20 00 00- 2492, Date: Dec 12, 2011). Informed consent was obtained from all participants.
All relevant data, including demographic information (age, gravida, parity, body-mass index (BMI), obstetric history, gestational week) were collected for further analysis. The gestational age was calculated according to the modified Naegele’s rule. Last menstrual period-derived gestational age was compared with ultrasound-derived gestational age using CRL [7], and if there was a marked discrepancy of 2 weeks or more, the woman was excluded from the study.
Fasting venous blood and saliva samples in the morning were taken from all subjects. Serum TSH (μIU/mL) level was measured by electrochemiluminescence immunoassay (ECLIA); serum FT3 (pg/mL), serum FT4 (ng/dL); serum human chorionic gonadotrophins (serum hCG) were measured quantitatively by the Sandwich principle. Blood urea, serum creatinine, sodium, potassium, glucose, AST, ALT and complete blood count were also measured to detect the severity of emesis. In addition, ketones in a morning urine sample were measured with urine stripes. Saliva samples were collected after rinsing their mouths with water thoroughly. Immediately after collection, saliva samples were centrifuged for 15 min at 4.000 rpm to remove any particles or sediments. The human CA6 concentrations in the samples were measured in saliva using a sandwich enzyme-linked immunosorbent assay (ELISA) with a human CA-6 commercial kit (Cusabio Biotech Co., LTD, Wuhan, China) according to the manufacturer’s instructions. Absorbance values were calculated at 450 nm in an automatic ELISA reader. The concentrations were calculated by converting the optical density readings with a standard curve. All samples were calculated in a duplicate manner. Saliva CA-6 levels were determined as ng/ml. The detection range was between 0.63 ng/ml and 40 ng/ml. The intra-assay and inter-assay variations were 8% and 10%, respectively.
Statistical analysis: The Statistical Package Program for the Social Sciences (SPSS 15.0; SPSS Inc., Chicago, IL, USA) was used for statistical analysis. Groups were controlled in terms of conformity to normal distribution using graphical check and Shapiro Wilk test. Since the groups were distributed normally, the mean and SD parameters were used. The median (minimum-maximum) was used for groups that were not distributed normally. The independent samples t- test was used for comparison of groups that were distributed normally. The Mann-Whitney test was used to compare groups that were not distributed normally. The Spearman correlation test was used to find the correlation between demographic parameters and gustin levels. Logistic regression analysis was performed for the determination of parameters that can predict the development of HG. Receiver-operating characteristics (ROC) curve analysis was performed to determine the effect of gustin in the prediction of HG. A p-value of ≤ 0.05 was taken as significant.
Results
The study included 60 pregnant women in the first trimester of pregnancy. Thirty women with HG and 30 healthy pregnant women without any HG symptoms were included in the study. During the follow-up period, 6 women in the HG group and 14 women in the control group were lost. The remaining 24 women with HG and 16 healthy pregnant women were taken as a control group. The mean weight of the women was 66.9 ± 12.2 kg and 63.0 ± 11.9 kg at the beginning of the pregnancy and during the emesis period in the HG group, respectively. Groups were compared with each other in terms of age, gravida, parity, gestational age and BMI before and during pregnancy. There was no statistically significant difference between groups in terms of these demographic parameters except for pre- pregnancy BMI (Table 1). Prepregnancy BMI was significantly higher in the HG group than in the control group (p=0.031). The groups were compared with each other for salivary CA6 levels. CA6 levels were lower in the HG group than in the control group. We did not find a significant statistical difference between groups (p= 0.149) (Table 1).
Correlation analysis between gustin levels and demographic parameters revealed a strong positive correlation between CA6 level and gestational week (Rho=0.640, p=0.003) (Table 2). Logistic regression analysis was done to find the most effective parameter in the prediction of HG. The analysis revealed that the CA6 level has a borderline significance in the prediction of HG (p=0.058). It was found that high CA6 levels decreased HG development risk by 35.6% (Odds ratio=0.644) ( (Table 3).
The ROC analysis was performed to find the most effective parameter in the diagnosis of HG. The only use of CA6 level predicted 36.3% of HG cases. This was not statistically significant (AUC=0.363, p=0.148 (95%CI=0.182-0.543)) (Figure 1).
Discussion
Salivary fluid is an exocrine secretion consisting mostly of water and containing a variety of hormones, electrolytes, mucosal glycoproteins, enzymes and many other factors [8]. Nowadays, saliva is being used as an auxiliary diagnostic parameter. Sialometry and sialochemistry have been used to diagnose some diseases [9]. It is used for the determination of hormonal status in obstetrics and gynecology [10].
In this study, we want to use saliva for a different diagnostic purpose; in the prediction of HG. The test would be very simple, easy, non-invasive. It could also be used for the monitorization of HG and response to treatment. We found that salivary gustin has a limited value in the prediction of HG. Gustin levels predicted only 36.3% of HG patients.
Taste sensitivity is different among populations and may be one of the most important determinants influencing the food choice of the individual [11]. Gustin is a polypeptide hormone present in the saliva and is important in taste sensation. Abnormality in this salivary growth factor is considered responsible for the maintenance of taste bud function and the function of the olfactory epithelium. During pregnancy senses of smell and taste change, which may alter the eating habits of pregnancy. A change in sense of smell and taste may be caused by a change in gustin levels. In previous studies, it has been shown that decreased gustin in the nasal mucous is associated with abnormal olfactory function [5,6]. Inhibition of salivary gustin release is associated with gustatory buds abnormalities and changes in taste sensation, which is already present in pregnant women. In this study, although gustin levels were lower in HG cases, there was no significant difference between HG and control cases. Since the number of cases in this study is limited, larger series might give different results on the role of gustin in HG.
In normal physiology, the secretion of gut hormones, including salivary hormones, may change according to metabolic need and nutrition [12,13]. The pregnancy itself might alter salivary hormone secretion and composition. In the 1st trimester, there is a negative energy balance, which could be induced by pregnancy-associated hormonal changes in GIS secretion. It might be a protective mechanism for the fetus. This is the time, in which mother and fetus need no additional energy, but they must be protected from any harmful substance or deleterious agent to keep developing fetus safe. Thus, most prominent symptoms occur during the 1st trimester of pregnancy. After the 1st-trimester, organogenesis is completed and physiological mechanisms are activated to increase maternal appetite to ensure adequate energy consumption for the mother and for the fetus. In this study, we found that gustin levels showed a small decrease in HG patients, which was not statistically significant. Since gustin is necessary for the normal function of the taste buds in the tongue, women will not be able to comprehend the tastes, as it happens in its absence or insufficient secretion. This might change the appetite and interest of women in different foods. After 1st trimester, adaptation and/or desensitization might develop, after which the symptoms disappear.
HG is seen more frequently in women with undesired pregnancy [14,15]. Some gut hormones act as neurotransmitters within the central nervous system to control food intake [16,17]. Their levels might be dysregulated due to stress. The hypothalamus is a crucial region for integrating signals from central and peripheral pathways and plays a major role in appetite regulation [18,19]. Psychological stress (an unplanned pregnancy, marital problems or pregnancy itself) can affect hormone levels in CNS, starting an activation from the cortex to hypothalamus, to the brain stem ending in the cranial nerves innervating salivary glands, changing the composition of saliva.
There are some limitations of our study. The first is the number of cases. Although we planned 30 cases for each group, due to the high dropout rates, case and control groups were formed from 24 and 16 patients, respectively. The small sample size decreased the power of the study.
The other important limitation is that we did not measure gustin levels at different gestational ages. They could be measured and compared with each other at the 1st, 2nd and 3rd trimester to see their relationship with appetite changes as pregnancy progress.
Another deficiency of the study is that other salivary factors which may affect appetite were not measured. The most important of them is Zinc. Zinc is an essential trace element that contributes to the active center of approximately 300 enzymes [20]. It is necessary for the function of gustin [21]. Deficiency of zinc also produces symptoms similar to deficiency of gustin. Measurement of zinc and other cofactors might be useful in the enlightening saliva-HG relation.
Conclusion
Due to the excessive number of variables, including genetic and environmental factors affecting appetite, the role of salivary gustin in the etiopathogenesis of HG and weight changes during pregnancy must be studied in the prospective studies, which will include broader groups of patients and a greater number of variables in this matter. Further study with larger series is required to fully understand the multiple signals regulating appetite in pregnancy and to contribute more to clinical practice.
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.20526
Nermin Kosus, Aydin Kosus, Muzeyyen Uyanık. Salivary gustin and hyperemesis gravidarum. Ann Clin Anal Med 2021;12(Suppl 3): S286-289
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Association between housing characteristics and population health
Bouchriti Youssef 1, Kabbachi Belkacem 1, Achbani Abderrahmane 2, Elghazali Oumaima 3, Kharbach Ahmed 4, Ait Haddou Mohamed 1, Gougueni Hicham 1, Ezaidi Sarrah 1
1 Department of Earth Sciences, Geosciences and Environment Group, Faculty of Sciences, Ibn Zohr University, Agadir, 2 Department of Biology, Laboratory of Cell Biology and Molecular Genetics, Faculty of Sciences, Ibn Zohr University, Agadir, 3 Faculty of Letters and Human Sciences, Doctoral program: Language, Culture, and Society, Mohammed V University, Rabat, 4 Laboratory of Biostatistics, Clinical Research and Epidemiology (LBRCE), Faculty of Medicine and Pharmacy of Rabat, Mohammed V University of Rabat, Morocco
DOI: 10.4328/ACAM.20528 Received: 2021-02-07 Accepted: 2021-03-23 Published Online: 2021-04-06 Printed: 2021-08-15 Ann Clin Anal Med 2021;12(Suppl 3): S290-295
Corresponding Author: Youssef Bouchriti, Geosciences and Environment Group, Department of Earth Sciences, Faculty of Sciences, Ibn Zohr University, PO Box 8106 Dakhla Street, 80000, Agadir, Morocco. E-mail: bouchriti.y.ege@gmail.com P: +21269781490 Corresponding Author ORCID ID: https://orcid.org/0000-0002-8566-1451
Aim: Human health can be significantly influenced by both the internal and external environment of housing. The aim of the study is to measure the association between housing characteristics and some clinical manifestations in the population living in the city of Agadir, Morocco.
Material and Methods: This is a correlational study, which covered 26 streets divided into three sectors in five districts of Agadir city in southern Morocco. All persons in the study area who agreed to complete the questionnaire were recruited, excluding the foreign population and healthcare workers. The sample size was 73 houses occupied by 420 people. We have designed a questionnaire for data collection based on characteristics of the housing, outdoor environ- ment, clinical manifestations, and general maintenance and equipment. Four samples of household dust were analyzed using a Scanning Electron Microscope.
Results: The most important clinical manifestations experienced by the population were of a nervous, respiratory, ophthalmic and rhinolaryngological natures. They are explained principally by age, the number of hours spent in the house, the occupied floor, allergies and medical consultations. Living in sector C appears to be a risk factor (RR = 1.21 [CI95% 1.06 – 1.38], p < 0.05). There is a statistically significant association between the presence of dust in the home and clinical manifestations (RR = 1.20 [CI95% 1.05 – 1.37], p < 0.05). These disorders are also linked to the orientation of houses towards the Northeast (RR = 1.45 [CI95% 1.33 – 1.66], p < 0.05), dust extraction and ventilation. The composition of the household dust samples indicates a probable continental and marine source.
Discussion: These results suggest that the risk of developing health disorders is related to both the indoor and outdoor environment of the housing.
Keywords: Indoor pollution; Outdoor pollution; Health; Housing
Introduction
Housing quality can influence both behavior and lifestyles, and, subsequently the health of its occupants [1]. Several studies have shown statistical correlations that are not necessarily causal between public health and some housing characteristics [2-4].
The indoor and outdoor environment of housing can influence the health of the occupants [5]. Indeed, respiratory, cardiovascular and metabolic diseases are linked to living in houses near heavy road traffic [6, 7]. The risk of respiratory infections can be reduced by reducing humidity [8]. Globally, 1 in 4 of all deaths are due to an insalubrious environment (available at: https:// www.who.int/phe/news/e-News-82.pdf?ua=1).
According to WHO estimates in 2018, indoor and ambient air pollution is responsible for more than six million deaths each year (available at: https://apps.who.int/gb/ebwha/pdf_files/ WHA71/A71_10Add1-fr.pdf). This pollution is a risk factor for morbidity and mortality, as it is associated with several diseases such as stroke, heart attack, lung cancer and broncho pneumopathy. The estimated cost of air pollution for global health and well-being is very significant (available at: https:// openknowledge.worldbank.org/handle/10986/25013). Some of the measures to reduce the number of deaths include action on housing [9].
In Morocco, in 2017, indoor air pollution can be held responsible for about 1,350 deaths, nearly 90% of which are caused by ischemic heart disease, stroke or acute lower respiratory tract infections, with the youngest (under 5 years) and oldest (over 75 years) groups are most affected by indoor air pollution [10]. This estimate is based on the global burden of disease [10] and the proportion of deaths due to air pollution calculated using the concentration-response functions [11]. The cost of indoor air pollution amounts to 0.26% of Gross Domestic Product [12]. In Morocco, 92.4% of urban residents live in buildings that are considered old. These families occupy houses with 1-2 rooms (35.7%), 3-4 rooms (49.4%) and 5 rooms and more (14.9%) [10]. Documentation on health and housing in Morocco is scarce. Our objective was therefore to study the correlation between habitat characteristics and health of the population of the Agadir region (available at: https://www.hcp.ma/file/205145/).
Material and Methods
Type of study and population
A cross-sectional observational study was conducted, from March to May 2019, in 26 districts divided into three sectors, covering five districts in the Agadir prefecture. A non-probability sampling method was adopted, with houses selected using an accidental sampling technique. The study involved 73 houses hosting 420 people.
Procedure
The people were informed about the objective of the study and its procedure. A questionnaire was designed for data collection based on characteristics of the housing, outdoor environment, clinical manifestations and general maintenance and equipment.
The typology of clinical manifestations has been simplified to provide information on people’s health disorders.
Measurement of clinical manifestations
These manifestations were classified according nervous, respiratory, ophthalmic and rhinolaryngological disorders. Household dust sampling and analysis
Four samples of household dust were collected from houses located at the four cardinal points. They were analyzed using a Scanning Electron Microscope (SEM) at Ibn Zohr University in Agadir city.
Statistical analyses
The data were analyzed using Epi InfoTM version 7.2 software (available at: https://www.cdc.gov/epiinfo/index.html) and R version 3.5.2 software (available at: https://www.r-project.org/). We studied the association between the development of clinical manifestations and exposure to a few habitat factors. Statistical significance was established by a p < 0.05 value. Yates’ Chi2 test (x2) was used for the comparison between the categorical variables, in addition to the exact Fisher test if the expected value is < 5. The relative risk values (RR) and 95% confidence intervals (CI95%) were estimated with multi-variate analyses to investigate risk factors leading to clinical manifestations in residents. Global model significance was tested by Fischer (F). Measures of Durbin-Watson (dw), tolerance (T) and variance inflation factor (VIP) were adopted to test the predictor’s multicollinearity.
Results
The results of the study are presented according to the characteristics of 73 houses hosting 420 people, and the association between clinical manifestations with exposure factors. The processing of the questionnaire data is carried out by Epi InfoTM version 7.2.
Characteristics of the houses
The 73 houses studied were distributed in three sectors, covering five districts of the Agadir Ida Outanane prefecture. The number of individuals living in these houses was 420, giving an average of 6 people per house. The houses host a single family (72.6%), two families (19.2%) or more families (8.2%). The proportion of houses with only one side was 60.3%, that of two sides was 31.5%, that of 3 and 4 sides was 8.2%. It should be noted that about half (49.3%) of the houses did not have a courtyard. A proportion of 59.5% of the courtyards had a roof and their surface was less than 9 m2. Only 7 houses had a garden with a surface area of no more than 10 m2.
About half of the houses (47.9%) were built with two floors, with an average of 3 rooms per floor. The mean age of the dwellings was about 20 years. The average number of windows per house was 6. The mean size of the windows was 1.1 m2. Characteristics of the housing environment
The exterior cladding was made of cement (83.6%) or bare ground (15.1%). During the period of the study, development work was observed in 15.1% of the dwellings.
The traffic lanes in the surrounding area accounted for 30.1% of noisy cases. The proportion of houses with a heavy-traffic parking was 39.7%. Houses built near agricultural sites represented 26.0%, those near a polluting source 21.9%, the latter were mainly carpentry, marble and a wastewater treatment plant.
Homes with an open interior space represented only 15.1%, these spaces were generally located on the ground floor (36.3%), on the first floor (18.2%) or on the second floor (45.5%) Population profiles
During the study period, 420 people in the houses with a mean age of 28 years (95% CI = [26.774 – 29.950]). The age distribution was dispersed around the mean value (standard deviation = 16.552, range = 85 years, Min = 1, Max = 86), a quarter of the population was under 17 years, the median age was 24 years, and the 3⁄4 of the population was under 40 years of age. This distribution was asymmetric on the right (Pearson’s asymmetry coefficient = 0.6)
Association between clinical manifestations and some exposure factors and association between clinical manifestations and some characteristics of the housing
People with clinical manifestations represent 66.43%. Living in sector C appeared to be a risk factor (RR=1.21 [CI95% 1.06 – 1.38], p < 0.05). The results of the multi-varied analysis (Table 1) show that these clinical manifestations are associated with some housing characteristics such as the age of construction, the number of families living in the same house, the number of sides, the size of the windows and the presence of a yard. Indeed, these disorders are most common among people living in houses built more than 30 years ago (RR = 1.08 [95% CI 0.87 – 1.34]). Also, for people who live with multiple family members (RR = 1.18 [CI95% 0.97 – 1.43]), for people who live in four- sided houses (RR = 1.52 [CI95% 1.42 – 1.63), for people living in houses with windows less than 1 m2 (RR = 1.12 [CI95% 0.83 – 1.51]) and for people living in houses without courtyards (RR = 1.02[CI95% 0.89 – 1.16)
Association between clinical manifestations and some characteristics of the outdoor environment
The multi-varied analysis in Table 1 shows that clinical manifestations can also be explained by a few factors related to the outdoor environment of the home. Indeed, people who live near heavy road traffic are more exposed (RR = 1.10 [CI95% 0.96 – 1.27]).
The presence of a car park with heavy traffic had little effect ((RR = 1.00[CI95% 0.87 – 1.15]). On the other hand, habitat near an agricultural site appears to be a protective factor (RR = 0.64 [95% CI 0.45 – 0.91]).
Approximately one-quarter of the inhabitants lived near a polluting company (23.57%) (No exposure effect); there is a significant association between the vicinity of a marbling facility and clinical manifestations (RR = 1.40 [CI95% 1.23 – 1.59]).
The presence of a construction site inside the house is a risk factor (RR = 1.25[CI95% 0.83 – 1.45], p < 0.05). For exterior siding, bare flooring is a risk factor (RR = 1.23[CI95% 0.98 – 1.55]), also a grass siding (RR = 1.52 [CI95% 1.41 – 1.63]) Association between clinical manifestations and some characteristics of the occupants
People over 20 years of age and older are more exposed; the highest risk was observed in the age groups 70-75 (RR = 1.51 [CI95% 1.41 – 1.62]), 50 – 55 (RR = 1.33[CI95% 1.12 – 1.59]) and 55 – 60 (RR = 1.32 [CI95% 1.07 – 1.63]). The time spent indoors seems to be a risk factor, as the highest risks are observed for occupancy times of 16 to 20 hours (RR = 1.07 [CI95% 0.90 – 1.28]).
It can be noticed that people living on the ground floor or fourth floor are more exposed (RR = 1.06 [CI95% 0.89 – 1.25] and RR = 1.16 [CI95% 0.86 – 1.58], respectively) (Table 2)
Allergies to acarids, pesticides and dust are significant risk factors for the development of clinical manifestations.
Association between clinical manifestations and some features of housekeeping
A high accumulation of dust was reported in 43.6% of house occupants. This dust accumulates essentially on windows (42.4%), furniture (32.5%), walls (11.9%), roofs (8.6%), and other surfaces (4.6%), its texture is essentially fine (78.1%). There was a statistically significant association between the presence of dust in the home and clinical manifestations (RR = 1.20 [CI95% 1.05 – 1.37], p < 0.05). These manifestations were more observed if these dusts are finer (RR = 1.16 [CI95% 0.96 – 1.40])
The high dust condensation seasons are autumn (44.3%) and summer (41.4%). The windows of the dwellings were oriented on average according to 144.7° (between SE and S), the houses with a single façade (60.3%) were oriented on average according to 129.9° (between E and SE)
Multivariate analysis in Table 3 shows that clinical manifestations were most commonly perceived in autumn (RR = 1.07 [CI95% 0.93 – 1.22]) and spring (RR = 1.07 [CI95% 0.89 – 1.36]). These disorders are also linked to the Northeast orientation of the houses (RR = 1.45 [CI95% 1.33 – 1.66], p > 0.05), the lack of ventilation (RR = 1.12 [IC95% 0.96 – 1.32]), or hand vacuum (RR = 1.04[IC95% 0.72- 1,51]) or a central vacuum cleaner (RR = 1.05[IC95% 0.79- 1.39]), or kitchen hood (RR = 1.40[IC95% 1.00 – 1.97]), or mechanical ventilation in the bathroom (RR = 1.29 [IC95% 0.96 – 1.75])
Clinical manifestations are low if dust is removed daily (RR = 0.88 [CI95% 0.76 – 1.02]), and if the frequency of house cleaning exceeds three times per month (RR = 0.81 [CI95% 0.61 – 1.07]) Factor analysis of clinical manifestations
Figure 1 summarizes the most important clinical manifestations perceived by the population. We noticed disorders of the following types: eye, nose or throat irritation, weariness, wheeze and headache.
Clinical manifestations are principally explained by the following variables: age, number of hours spent in the home, occupied floor, allergies and medical consultations (significant model: F < 0.05, R = 0.536, t > t (sig), 0 < T < 1, dw = 1.194 and VIF < 4) Analysis of the correlation matrix between the group of variables from the clinical manifestations (headaches, nausea, sneezing, shortness of breath, irritation of the eyes, nose or throat, blurred vision, coughing and wheezing) showed a strong positive correlation (r = 0.597 to 0.987). The variable “ Weariness “ and “ Respiratory disorders “ were positively correlated and the correlation was significant (r = 0.839).
Principal component analysis indicates that ten types of clinical manifestations can be represented by two factors, which explain 93.1% of the variance. This representation is of better quality since the extraction index is between 0.818 and 0.989, the model thus designed was significant in its globality (Fischer’s F test = 749,169 with a significance rate < 5%), this model explains 99% of the variance (R2 adjusted = 0.990). The ten explicative variables contributed well to explaining the model (Student’s t-test > t of significance).
There was also a missing multi-collinearity between 8 variables (T < 1 and VIP < 4), two variables were in collinearity; these are “Irritation of the eyes, nose or throat” and “Blurred vision”. There was a negative correlation between clinical manifestations and the number of windows that can be opened (r = -0.275), the correlation was significant at the 5% level. Clinical manifestations were inversely proportional to the number of windows that can be opened, they can be explained by factors related to the internal characteristics of the home, i.e., the external environment had little influence on these clinical manifestations.
However, there is a link between clinical manifestations and 4 other variables “the number of windows that can be opened, the age of construction, the frequency of house cleaning and the size of the windows”. Indeed, the correlation was significantly positive (r from 0.599 to 0.869 and F < 0.05). The clinical manifestations can be explained by these four variables, the model thus designed is significant as a whole (F = 43.578 with a significance rate less than 5%), this model explains 70% of the variance (adjusted R2 = 0.7).
Three explanatory variables: “the age of construction, the frequency of house cleaning and the size of the windows” contribute well to explain the model (Student’s test t > t of significance).
On the contrary, the variable “the number of windows that can be opened” does not contribute to explain the model (since the Student’s t-test < t of significance) (significantly negative correlation). We also note that there was no multi-collinearity between the 4 explanatory variables (dw = 2,280, T < 1 and VIP < 10).
Results of household dust analysis by SEM
The composition of the four household dust samples shows that this dust is dominated by carbonates followed by silicates (evaporation phenomenon) indicating a probable double source: continental (Calcium) and marine (Potassium); result in accordance with the characterization of external dusts. The analysis also shows the presence of elements associated with rock constituents (Iron, Calcium, Potassium, Sulphur, Aluminium, Sodium and Silicon) and elements resulting from evaporation: Sodium, Magnesium, Phosphorus (phosphates), Sulphur (sulphates) and Potassium. However, the analysis detected traces of Phosphorus: a result that requires further research.
Discussion
The most important clinical manifestations reported by the population are nervous, respiratory, ophthalmic and rhinolaryngological. In our study, we were able to identify several risk factors for these manifestations in the Agadir population attributable to housing. First, some exposure factors related to housing properties such as location, age of housing, number of families living in the same house, number of sides, size of windows and presence of a yard. In a similar way, Turunen et al. (2017) showed that respiratory infection risk is related to the quality of housing [13]. Also, the results a study by Habib et al. (2009) showed a significant positive association between housing conditions and chronic illness [14].
We also demonstrate that the outdoor environment is a risk according to Dong et al. (2008) [15] and Weitzman et al. (2013) [16]; living near heavy traffic, or near a polluting manufacturing plant, the construction site inside the house and the nature of the exterior siding.
Furthermore, the highest risk is observed in elderly subjects, which can be explained by the length of time spent in the house. Similarly, people who live on the ground floor or fourth floor, or who have allergies to dust mites, pesticides and dust are more exposed.
Our study also suggests the possibility of a positive association with characteristics of general housekeeping, such as the presence of dust inside the house and the fine texture of this dust. Furthermore, the study results of Herrin et al. (2013) show that the combustion of biomass for cooking is the most important adverse health effect [17]. Condensation of this dust is more frequent in autumn and summer when road traffic is intense combined with climatic conditions such as high relative humidity, temperature and wind direction.
Clinical manifestations are more frequent in autumn and spring, according to a study by Fielder (1991) [18], that seems to be essentially due to climatic conditions, air pollution both outside and inside the home and the presence of allergens in the atmosphere.
Our study also showed a positive association with the orientation of the houses towards the northeast, ventilation and dust extraction, in accordance with Mesa-Frias et al. (2014) who showed that poor ventilation rates were associated with respiratory-related morbidities [19].The occurrence of clinical manifestations is low if dust is removed daily, and if the total monthly frequency of cleaning in the house exceeds three times. Our study has some limitations. By its very nature, we note the problem of the temporality of the association. Information bias is possible regarding the accuracy of information on clinical manifestations observed in the population at the time of the study.
In the absence of other similar studies in Morocco, it is considered that our results may be in concordance with other countries even if there is a difference in context.
However, other research proposals are suggested to develop our study further, including the characterization of indoor pollution and prospective studies to study the impact of indoor pollution on health.
Conclusion
The results of this study show that the association between the development of health disorders and the properties of the housing is significant. Exposure to contaminants from both the outdoor and indoor environment has an impact on the health of the population.
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.20528
Bouchriti Youssef, Kabbachi Belkacem, Achbani Abderrahmane, Elghazali Oumaima, Kharbach Ahmed, Ait Haddou Mohamed, Gougueni Hicham, Ezaidi Sarrah. Association between housing characteristics and population health. Ann Clin Anal Med 2021;12(Suppl 3): S290-295
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Tissue oxidant, antioxidant and TNF-alpha levels in ureteropelvic junction obstructions
Ilyas Yagmur 1, Fatih Firdolas 2, Necip Pirincci 2
1 Department of Urology, Viranşehir State Hospital, Şanliurfa, 2 Department of Urology, Faculty of Medicine, Fırat University, Elazığ, Turkey
DOI: 10.4328/ACAM.20530 Received: 2021-02-08 Accepted: 2021-04-05 Published Online: 2021-04-27 Printed: 2021-08-15 Ann Clin Anal Med 2021;12(Suppl 3): S296-300
Corresponding Author: Ilyas Yagmur, Department of Urology, Viranşehir State Hospital, Şanliurfa, Turkey. E-mail: ilyasyagmur@windowslive.com P: +90 537 065 7829 Corresponding Author ORCID ID: https://orcid.org/0000-0003-3163-6557
Aim: In this study, it was aimed to determine the role of some oxidant, antioxidant agents and tumor necrosis factor alpha (TNF-alpha) in the pathophysiology of ureteropelvic junction obstructions because of their effect on cell life, development and death.
Material and Methods: A total of 56 patients who applied to the Urology Clinic of Firat University Hospital between 2015-2018 were included in the study. The patients were divided into two groups: ‘patients’ and ‘controls’. In the ‘patients’ group, 30 patients with ureteropelvic junction obstruction were evaluated. In the ‘control’ group, 26 patients who were diagnosed with a kidney tumor or non-functional kidney were evaluated. TNF-alpha, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and malondialdehyde (MDA) levels were measured in the tissue samples taken from the uretero pelvic junction segments of the study groups.
Results: MDA and TNF-alpha levels were detected to be significantly higher in the patient group than in the control group. SOD, CAT and GPx enzyme levels were lower in the patient group than in the control group (p <0,05). In the Pearson correlation graph, TNF-alpha revealed a negative correlation with SOD, CAT and GPx and a positive correlation with MDA. Also, a negative correlation was detected between SOD and MDA.
Discussion: In our study, it was concluded that oxidative stress and antioxidant mechanisms may have a role in the pathophysiology of ureteropelvic junction obstructions. In this regard, antioxidants were thought to be useful in the prevention and treatment of ureteropelvic junction stenosis.
Keywords: Oxidant; Antioxidant; TNF-alpha; Ureteropelvic obstruction; MDA
Introduction
Ureteropelvic junction obstruction (UPJO) is defined as insufficient urine flow from the renal pelvis to the ureter as a result of functional or anatomical obstruction. Obstruction in the kidney and urinary system can lead to recurrent urinary tract infection (UTI) and permanent renal parenchymal damage if left untreated [1]. The most common cause of UPJO is the presence of aberrant or accessory lower pole vein. UPJO secondary to inflammation, neoplasms, kidney stones and cysts can be seen [2]. In the kidney with obstruction at the ureteropelvic junction (UPJ), a decrease in glomerular volume, an increase in tubular dilatation, glomerular sclerosis, and tubular atrophy and interstitial fibrosis occur [3].
The diagnosis of UPJO is made by evaluating the results of various imaging methods or tests together. Currently, most UPJOs are diagnosed with antenatal USG [1, 4]. The use of biochemical markers in UPJO is important because they are not invasive tests, can be detected with simple urine test, and their costs are low. Although many markers have been studied in clinical studies and animal studies until now, none of them have entered routine clinical use. This is due to the insufficient number of studies or a limited number of patients. In the current literature, there are several markers defined such as tumor growth factor beta-1 (TGF-β1), monocyte [1, 5, 6].
Free radicals are constantly formed in living things, but these molecules are regularly destroyed by the antioxidant defense system. There is a balance between the formation of free radicals and their destruction through the antioxidant system, which is called oxidative balance [7, 8]. The harmful effects of free radicals can be eliminated with substances known as antioxidants. Living cells contain numerous types of low molecular weight antioxidants (e.g. vitamins E and C, carotenoids, flavonoids, etc.) and larger molecular weight antioxidant enzymes, both of which serve to prevent or repair damage caused by free radicals [9]. The endogenous antioxidant defense system consists of enzymatic antioxidants such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (KAT), and nonenzymatic antioxidants with glutathione and bilirubin.
In studies conducted with experimental models, radical oxygen species (ROS) have been shown as the primary cause in the pathogenesis of ischemic, toxic and immunologically induced kidney damage. The occurrence of oxidative stress in the kidney tissue as a result of various factors leads to serious kidney disorders [10, 11]. In this study, it was aimed to determine the role of some oxidant, antioxidant and tumor necrosis factor- alpha (TNF-alpha) in the physiopathology of ureteropelvic junction obstruction because of their effects on cell life, development and death.
Material and Methods
This study was conducted after receiving approval from the Ethics Committee for Non-Invasive Clinical Research, Faculty of Medicine, Firat University (date 17.09.2019, meeting number 13, decision number 10). In this study, it was aimed to determine the role of some oxidant, antioxidant and TNF- alpha in UPJO pathogenesis. A total of 56 patients who applied to Firat University Hospital Urology Clinic between 2015-2018 and met the study criteria were included in our study. The patients were divided into two groups: “patients” and “controls”. Thirty patients who were diagnosed with unilateral UPJO and had undergone pyeloplasty were included in the patient group. The control group included 26 patients who were diagnosed with unilateral kidney tumor or non-functional kidney and who had undergone nephrectomy. UPJ tissue samples taken from the study groups were examined in the biochemistry laboratory. Fifty-six patients included in the study were analyzed retrospectively. Demographic characteristics of the patients, presence of additional renal anomalies, renal parenchymal thickness, scintigraphy and pathology results, blood biochemistry parameters, urine culture results, discharge time and complications information were compiled.
Patients with bilateral hydronephrosis and bilateral UPJO, posterior urethral valve, ureterovesical stenosis, external genitalia anomaly, urinary system stone disease, urinary system infection, neurogenic bladder and vesicoureteral reflux, urea and creatinine values were not included in the study. TNF-alpha, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels were measured in tissues taken from ureteropelvic junction segments of individuals who underwent pyeloplasty and nephrectomy. TNF-alpha levels were determined spectrophotometrically using the Enzyme-Linked Immuno Sorbent Assay (ELISA) method, malondialdehyde level, superoxide dismutase, catalase and glutathione peroxidase activities using appropriate manual methods [7, 12-15]. Statistical analysis
IBM SPSS Statistics Version 22.0 package program was used for statistical analysis of the data. Categorical measurements were summarized as numbers and percentages, and continuous measurements as mean and standard deviation (median and minimum – maximum where necessary). Whether continuous measurements provided the normal distribution assumption was tested with the Kolmogorov- Smirnov test. In the comparison of continuous measurements between the groups, if the assumptions were met, the T- test was used in independent groups, and the Mann- Whitney U test was used if the assumptions were not met. The statistical significance level in all tests was taken as p <0.05.
Results
In the patient group, 30 patients diagnosed with UPJO were examined. All of these patients had unilateral UPJO. Among these 30 patients, 17 (57%) were male and 13 (43%) were female. The youngest of the patients was 1 year old, while the oldest was 57 years old. Urea and creatinine values of the patient group were within normal limits. Urinary tract infection was excluded by sending a pre-op urine culture from these patients.
Sixteen patients in the patient group had UPJO on the right side (53%) and 14 on the left side (47%). Open pyeloplasty operation was performed in 15 (50%) of these 30 patients, and laparoscopic pyeloplasty operation was performed in 15 (50%) of them. The average length of stay of the patients was determined as 4 days. DJ stents were implanted in all patients during the operation, and the implanted stents were removed 1 month later.
There were 26 patients in our control group. These patients consisted of patients with a diagnosis of kidney tumor (n = 17) or with a non-functional kidney (NFK) (n = 9). Blood urea creatinine values of control group patients were within normal values. Urinary tract infection was ruled out by sending urine culture from these patients in the pre-op period. Sixteen (62%) patients in the control group were male and 10 (38%) were female. Simple nephrectomy was performed in 9 (35%) patients in the control group due to the diagnosis of non-functional kidney (NFK), and radical nephrectomy was performed in 17 (65%) with the diagnosis of renal cell cancer (RCC). Right nephrectomy was performed in 12 (46%) and left nephrectomy in 14 (54%) controls. While 18 (69%) of these 26 patients underwent laparoscopic nephrectomy, 8 (31%) underwent open nephrectomy.
In our study group of 56 patients in total, 28 (50%) had the related disease on the right side and 28 (50%) on the left side. While 33 (59%) of these 56 individuals underwent laparoscopic surgery, 23 (41%) of them underwent open surgery.
TNF-alpha, CAT, GPx, MDA and SOD levels were measured in the tissues taken from the UPJ segment of patients with and without UPJO. The comparison of the levels of TNF-alpha, MDA and antioxidant enzymes with each other is shown in Table 1. In the patient group with UPJO of MDA, the mean in the tissue was 5.33 ± 1.45, in the control group without UPJO it was 3.38 ± 876. The MDA level was found to be statistically significantly higher in the patient group compared to the control group (p <0.05). The mean of SOD in the tissue in the patient group with UPJO was 14.80 ± 4.31, in the control group without UPJO, the mean in the tissue was 28.03 ± 7.68. SOD level was found to be statistically significantly lower in the patient group than in the control group (p <0.05). In the patient group with UPJO of CAT, the average in the tissue was 5.51 ± 3.23, in the control group without UPJO it was 9.70 ± 5.92. The CAT level was found to be statistically significantly lower in the patient group compared to the control group (p <0.05). In the patient group with UPJO of GPx, the mean in the tissue was 240.46 ± 58.67, in the control group without UPJO it was 326.79 ± 125.98. The GPx level was found to be statistically significantly lower in the patient group than in the control group (p <0.05) (Table 1).
TNF-alpha in the patient group with UPJO had the smallest value of 9.14, the highest value as 126.64 and the mean value of 32.27, the lowest value in the tissue was 1.22 and the highest value was 35.43 and the average value was determined as 6.47 in the control group without UPJO. It was found that TNF-alpha was statistically significantly higher in the patient group compared to the control group (Table 2).
The correlation graph for the patient group with UPJO with each other and with the renal scintigraphy values of the patients is shown in Table 3. In particular, it was observed that the renal scintigraphy values of the patients were not correlated with any markers. It was found that MDA has a negative relationship with SOD (p <0.05). It was observed that while MDA value increased, SOD value decreased significantly. However, it was determined that MDA had a strong positive relationship with TNF-alpha (p <0.01). While MDA increased, it was observed that TNF-alpha also increased statistically. It was determined that SOD has a positive relationship with GPx, and GPx decreased while SOD decreased (p <0.001). SOD had a negative relationship with TNF-alpha, while SOD decreased, TNF-alpha increased (p <0.001).
It was observed that there was a negative correlation between glutathione peroxidase (GPx) and TNF-alpha levels, and while GPx decreased, TNF-alpha increased (p <0.01). It was determined that TNF-alpha correlated with all markers except scintigraphy results, whereas scintigraphy results did not correlate with any markers.
Discussion
Today, there is no diagnostic method that can be considered the gold standard in demonstrating UPJO. Diagnosis is usually made by repeated imaging methods such as diuretic scintigraphy and sequential ultrasonography (evaluation of kidney dimensions and anterior-posterior diameter of the kidney) [1]. Therefore, it was necessary to use new methods, especially non-invasive and specific markers, in the diagnosis, treatment and follow- up of patients with UPJO. Most of the studies in this field are studies with tissue, serum and urine samples to understand the underlying pathophysiology of obstruction. However, there are fewer studies on diagnosis, follow-up and treatment options. Although the results of many studies are meaningful and promising, the general opinion is that more comprehensive new studies are needed [1, 4].
Oxidative stress mechanisms and inflammation are thought to play an important role in the pathogenesis and progression of UPJO. There is a limited number of studies in the literature on the relationship between oxidative stress and UPJO. In a study published by Zhe-Ming Xu et al., the levels of thioredoxin, an antioxidant substance in the urine and serum of patients with UPJO were examined. Thioredoxin level was found to be higher in the patient group compared to the control group [14]. In a study conducted by Manucha et al., it was stated that oxidative stress increased twice in obstructive uropathic patients compared to normal individuals, whereas antioxidant levels such as SOD, CAT and GPx decreased [16]. In our study, it was found that oxidative stress increased and antioxidants decreased. However, in our correlation test, scintigraphy results could not detect a relationship between oxidant-antioxidant substance levels.
There are few studies in the literature on the role of TNF alpha in the pathogenesis of ureteropelvic stenosis. In a study conducted by Koca et al. on the histopathogenesis of intrinsic UPJO, they compared the tissue TNF-alpha and Tumor growth factor beta 3 (TGF ß3) levels in the UPJ of 36 patients with UPJO and 14 non-UPJO controls. TNF-alpha levels were found to be statistically significantly lower in the patient group (0.53 ± 0.84) compared to the control group (0.86 ± 0.36). In a study conducted by Shirazi et al., urinary TNF-alpha levels of a patient group of 31 children with UPJO and a control group of 33 children without UPJO were compared. In the study, the level of TNF-alpha in the urine of the patient group (80 ± 26.07) was found to be statistically significantly higher than the TNF-alpha levels of the control group (13.90 ± 5.3) [17]. When the studies conducted were examined, it was observed that Koca et al. have achieved results different from others. It was determined that Madsen and Shirazi achieved results parallel to the results of our study.
In our study, we aimed to investigate the role of oxidant- antioxidant mechanisms and TNF-alpha in the pathophysiology of ureteropelvic junction strictures, which have been associated with many diseases in recent years and have been the subject of intensive research. Our study is of particular importance since the studies in this area are not sufficient, and our study was conducted directly on human UPJ tissues. In the studies we conducted in a study population consisting of 56 individuals in total, it was determined that MDA was statistically significantly higher in the patient group compared to the control group (p <0.01). Manucha et al. [16], in their similar study, detected oxidative stress markers approximately twice as high in the patient group as compared to the control group and obtained results parallel to our study. Again, regarding urinary system cancers, Pirinççi et al. [13] in patients with kidney tumors, Geçit et al. [7], on the other hand, detected higher levels of MDA in patient tissues with bladder tumors compared to healthy normal tissues. These results support that MDA is mutagenic and carcinogenic.
In our study, SOD, CAT and GPx enzyme levels, which constitute the most important enzymatic defense system against oxidants, were found to be statistically significantly lower in the patient group compared to the control group (p <0.01). In the study by Manucha et al. [16], which was similar to our study in this area, SOD, CAT and GPx levels were found to be lower in the UPJO patient group compared to the healthy control group, and it is seen that the results of this study coincide with our study. When we compare our study with studies on other diseases related to the urinary system in this field, Pirinççi et al. [13] in patients with kidney tumors, Geçit et al. [7], on the other hand, found that SOD, CAT and GPx levels were lower than those of normal healthy tissues in their studies on patients with bladder tumor. It is observed that Murowski et al. also detected lower SOD levels in patients with oligoastenozoospermia [12]. Contrary to all these studies, it is seen that SOD, CAT and GPx levels were detected higher in kidney adenocarcinoma cells [15].
In our study, TNF-alpha levels were found to be statistically higher in the patient group compared to the control group. When we compared our study with similar studies on TNF- alpha in UPJOs, it was observed that Shirazi et al. [17] obtained results in the same direction as we did, while Madsen et al. [18] did not detect a significant change in TNF-alpha levels between the patient and control groups. Contrary to the results of our study in this area, it was observed that Koca et al. [19] detected lower TNF-alpha in tissues of patients with UPJO than healthy tissues.
Conclusion
In our study, it was concluded that oxidative stress and antioxidant mechanisms may play a role in the physiopathology of ureteropelvic junction strictures. Based on this, it is thought that antioxidants may be useful in the prevention and treatment of uretero-pelvic junction strictures. However, more comprehensive and more randomized studies are required in order to obtain more accurate and healthy 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.
References
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2. Dogan HT, Canda AE, Gok B, Oguz U, Gumustas S, Atmaca AF, et al. Is there a difference in the number of interstitial cells, neurons, presence of fibrosis and inflammation in ureteropelvic junction tissues of patients with ureteropelvic junction obstruction with and without crossing vessels? Turk J Urol. 2019;45(4):302-6.
3. Otero HJ, Calle-Toro JS, Maya CL, Darge K, Serai SD. DTI of the kidney in children: comparison between normal kidneys and those with ureteropelvic junction (UPJ) obstruction. MAGMA. 2020;33(1):63-71.
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5. Bartoli F, Penza R, Aceto G, Niglio F, D’Addato O, Pastore V, et al. Urinary epidermal growth factor, monocyte chemotactic protein-1, and beta2- microglobulin in children with ureteropelvic junction obstruction. J Pediatr Surg. 2011;46(3):530-6.
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7. Gecit I, Eryilmaz R, Kavak S, Meral I, Demir H, Pirincci N, et al. The Prolidase Activity, Oxidative Stress, and Nitric Oxide Levels of Bladder Tissues with or Without Tumor in Patients with Bladder Cancer. J Membr Biol. 2017;250(5):455- 9.
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Download attachments: 10.4328:ACAM.20530
Ilyas Yagmur, Fatih Firdolas, Necip Pirincci. Tissue oxidant, antioxidant and TNF-alpha levels in ureteropelvic junction obstructions. Ann Clin Anal Med 2021;12(Suppl 3): S296-300
Citations in Google Scholar: Google Scholar
Real-time 3D transesophageal echocardiography for the assessment of secundum atrial septal defects in children
Pelin Kosger 1, Ayse Sülü 1, Tugcem Akin 2, Hikmet Kiztanir 1, Birsen Ucar 1
1 Department of Pediatric Cardiology, Eskisehir Osmangazi University, Faculty of Medicine, 2 Pediatric Cardiology Clinic, Eskisehir State Hospital, Eskisehir, Turkey
DOI: 10.4328/ACAM.20533 Received: 2021-02-09 Accepted: 2021-04-01 Published Online: 2021-04-11 Printed: 2021-08-15 Ann Clin Anal Med 2021;12(Suppl 3): S301-305
Corresponding Author: Pelin Kosger, Eskisehir Osmangazi University, Faculty of Medicine, Department of Pediatric Cardiology, Eskisehir, Turkey. E-mail: pelinkosger@gmail.com P: +90 222 2392979 / 05054758304 Corresponding Author ORCID ID: https://orcid.org/0000-0002-3926-9002
Aim: The need for more than one cross-section in the imaging of the atrial septum with two-dimensional (2D) echocardiography creates a limitation in determining the morphology of atrial septal defects (ASD) and negatively affects the success of the percutaneous closure procedure. In this study, measure- ments of ASDs and surrounding rims obtained by 3D transesophageal echocardiography (TEE) were compared with 2D TEE and angiographic balloon sizing measurements.
Material and Methods: The study included 24 pediatric patients with the diagnosis of ASD who were scheduled for transcatheter defect closure. All patients underwent catheter-angiography following a detailed 2D TEE examination.
Results: The data of 17 patients with optimal 3D TEE images were analyzed offline in the Q-lab. The diameter of the defects and surrounding rims, which were measured with two- and three-dimensional TEE were similar (p> 0.05). There was a strong correlation between the two measurement techniques in terms of defect diameter (r = 0.896, p <0.001). While the diameter of the defect measured by the sizing balloon was greater than that measured by 2D TEE, it was similar to that measured by 3D TEE (p <0.001, p = 0.14, respectively). There was also a strong correlation between the defect diameter measured by 3D TEE and balloon sizing diameter (r = 0.844, p <0.001).
Discussion: The “en face” visualization of the atrial septum with 3D TEE provides adequate identification of the defect morphology and adjacent structures. Furthermore, reliable determination of the defect size by 3D imaging may lead to appropriate device selection without the requirement for invasive measure- ment techniques such as balloon sizing.
Keywords: ASD; Echocardiography; 3D TEE; Percutaneous closure
Introduction
Secundum atrial septal defects (ASDs) are located in the fossa ovale region and are the most common type of ASD that is suitable for closure with a transcatheter [1,2]. Although, transcatheter closure of atrial septal defects has many advantages over the surgical repair, such as the shorter hospital stay, lower risk of complications, and prevention of the morbidity and mortality that can be caused by open heart surgery, the decision of the treatment modality depends on the size, shape, and the surrounding structures [3,4]. A detailed examination of the defect morphology is also necessary to access the best match between the defect and the device in the percutaneous intervention. Thus, complications such as arrhythmia, device embolization, erosion, and obstruction of the adjacent structures can be prevented. The sizing balloon measurement for the determination of the device size is considered the gold standard technique in the percutaneouse closure of ASDs. However, balloon sizing can stretch the defect rims and cause the defect to be measured larger than its size, leading to complications such as rupture of the interatrial septum, balloon rupture, cerebral microembolization, and cardiac perforation [5]. Real-time three-dimensional (3D) echocardiography can provide optimal evaluation of the interatrial septum and adjacentstructures,thusthesufficientdetectionofthedefect size, shape, and count during the procedure may eliminate the necessity for balloon sizing and its complications. Therefore, 3D echocardiography, which was claimed to be superior to 2D examination, has gained importance in the management of patients with congenital septal defects, in both children and adults [6-9].
In this study, we aimed to define the advantages and limitations of 3D TEE examination over 2D in evaluating the size, shape, and rims of atrial septal defects, which were considered suitable for closure by transcatheter or surgically in children.
Material and Methods
The study included 24 pediatric patients with the diagnosis of secundum ASD who were scheduled for transcatheter closure in the Department of Pediatric Cardiology, Eskisehir Osmangazi University between February 2019 and May 2020. Transthoracic echocardiographic examination was performed using a 3 MHz probe with a Philips EPIQ CVx (Philips Medical Systems, Andover, USA). A Philips EPIQ CVx device and a TEE probe with X7-2T two- and three-dimensional imaging features were used in the TEE procedure. The total septum, anterosuperior and anteroinferior rims (aortic and atrioventricular valve rims), posterosuperior and posteroinferior rims (VCS and VCI rims), inferior and posterior rims (coronary sinus and pulmonary vein rims) and defect diameter were measured at 0, 30, 90 and 120 degrees with 2D TEE. Rim length was considered deficient if the length was < 5 mm. The Ethics Committee of Eskisehir Osmangazi University approved this study (Approval number: 2020-374). Each patient provided informed consent prior to participating in the study.
Evaluation of three-dimensional images
Prior to the catheter-angiography procedure, 3D TEE images were obtained via X plane and zoom modes [10]. The data were transferred to the Q-lab software (Philips, Best, The
Netherlands) for analysis. The en face images of the atrial septum were obtained with the cropping method. On en face images, the measurements were performed for defect diameter, rims, and adjacent structures using a multiview technique for required patients (Figure 1).
The percutaneous closure procedure of the ASDs
All interventional procedures were performed under general anesthesia. After placing a sheath into the right femoral vein, pressures were measured by performing diagnostic catheterization, blood samples were collected, and pulmonary (Qp) and systemic (Qs) flows were calculated. The patients were given 100 IU / kg of heparin (maximum dose of 5000 IU). Activated clotting time (ACT) was kept longer than 200 seconds. The balloon catheter was placed in the defect through a stiff wire inserted into the upper left pulmonary vein by advancing through the femoral vein. The sizing balloon was inflated until the shunt flow was completely cut under the guidance of 2D TEE. The balloon diameter was measured on simultaneous fluoroscopy. Considering the flexibility and dimensions of the adjacent rims, the device diameter was determined to be equal to or 2 mm larger than the balloon diameter. Then, the device was placed under the guidance of 2D TEE and left in the septum. Statistical analysis
Statistical analysis was performed using the Statistical Package for Social Sciences, version 15 (SPSS, Chicago, USA). The results of descriptive analyses were expressed as mean ± SD for numerical variables. The consistency of variables with normal distribution was assessed using the Shapiro–Wilk test. The groups were compared using Student’s t- test for continuous variables, and the Mann–Whitney U test was used for non-normally distributed variables. Comparisons between measurements were performed using paired t-tests and linear regression analysis. The correlation between the continuous variables was performed using the Pearson correlation coefficient. A p- value of less than 0.05 was considered statistically significant.
Results
The mean age of 24 patients (15 females, 9 males) was 6.01 ± 2.99 years (3-13.6 years). The mean ASD diameter of the patients measured by 2D TTE was 14.1 ± 4.59 mm (7 – 24 mm), the mean pulmonary artery pressure measured by catheter- angiography was 20.5 ± 3.51 mmHg, and the mean Qp / Qs ratio was 2.03 ± 0.21. The number of defects was single in 19 patients and multiple in 5 patients. There were additional cardiac anomalies in two patients, one with mild pulmonary stenosis and the other with mild aortic valve insufficiency. In the 16 procedures for transcatheter ASD closure, Amplatzer Septal Occluder was attempted in 8 patients and the Occlutech Flex II Septal Occluder device was attempted in 8 patients. The remaining 8 patients were referred to the surgery due to insufficient interatrial septum size and surrounding rims, especially the posteroinferior rims. The mean defect diameter in those 8 patients was larger than in patients who underwent percutaneous closure (p <0.001) (Table 1). No major complications were observed during the procedure and at the follow-up. In one patient, a minimal residual shunt persisted from the inferior end of the defect following the placement of the device. The shunt amount gradually decreased during 1 and 3 months of follow-up, and the residual defect disappeared after 6t- months.
Three-dimensional TEE could not be performed in seven patients due to a bodyweight of <20 kg. In the remaining 17 patients, the minimum and maximum defect diameters measured with 2D and 3D TEE were similar (p> 0.05). In addition, a strong correlation was reviled between the two measurement techniques in terms of defect diameter (r = 0.896, p <0.001). The dimensions of the aorta, vena cava inferior, and vena cava superior rims were similar in 11 patients in whom the rims adjacent to the defect could be measured optimally by both 2D and 3D TEE (p> 0.05) (Table 2).
Sizing balloon was not used in 8 patients who did not undergo percutaneous closure, since it was not required. In the remaining 16 patients, the defect diameter measured by sizing balloon was larger than the diameter measured by 2D TEE (13.99 ± 4.23 mm and 12.31 ± 4.17 mm, respectively, p <0.001), while it was similar with the 3D TEE (13.99 ± 4.23 mm and 13.02 ± 4.58 mm, p = 0.14, respectively) (Table 3). There was a strong correlation between sizing balloon and 3D TEE measurements, and the device size (r = 0.960, p <0.001; r = 0.844, p 0.001, r = 0.910, p 0.001; respectively). The defect diameter measured by 3D TEE and the device size were not correlated (r = 0.303, p = 0.314).
Discussion
Transcatheter closure of atrial septal defects in children is a safe and effective method, and the defect should be closed in symptomatic patients with findings of increased volume in the right heart chambers. The presence of pulmonary obstructive disease is a contraindication to defect closure. Therefore, the response to the vasoreactivity test may be a determinant for contraindication [11,12]. In the present cohort, in accordance with the volume overload, the right heart chambers were enlarged and the Qp / Qs ratios were >1.5. Although the pulmonary artery pressure was less than 2/3 of systemic arterial pressure, the response to the vasoreactive test was positive in one patient with 38 mmHg. In 8 of 24 patients, device closure could not be performed due to insufficient surrounding rims and/or total interatrial septum size. One of the indications for surgical closure of atrial septal defects is that the rims and/ or total interatrial septum is insufficient to place the device. It has been reported that this may be related to the larger size of surgically closed defects compared to percutaneously closed defects, and therefore, higher surgical morbidity [13]. In our study, the defect size was significantly larger in patients in whom transcatheter closure could not be performed, compared to those in whom transcatheter closure could be performed. While no intraoperative or postoperative major complication was observed in our patients whose defects were closed with the transcatheter technique, clinical findings that may be compatible with cerebral ischemia were observed in one of the patients who have undergone a surgical procedure. This was in line with the view that morbidity associated with surgical repair may be more serious compared to the transcatheter technique. Recent studies comparing 2D and 3D TEE in terms of appropriate detection of defect size have shown that 3D TEE may have some advantages. [14,15]. Jori et al. reported that 2D TEE measurements were insufficient compared to 3D TEE, especially in determining the size of atrial septal defects with a complex structure [14]. Comparing with 3D TEE images, Lodato et all. stated that the defect size can be measured smaller than its actual size in the long axis and larger than its actual size in the short axis using 2D TEE [15]. The mismatch between the measurements is mainly due to the form of the defect. Atrial septal defects often have different forms, and it can be misleading to determine the maximum size of non- round defects using two-dimensional measurements. In the present study, one of the reasons for the consistency between measurement methods might be that the defects’ forms were generally round, and the other one was that 2D measurements could be larger than normal due to the fact that they were performed in color mode.
It is well known that secundum ASDs show morphological variation [16]. Therefore, determining the shape, number, and surrounding rims of the defect is as important as the size of the defect for successful transcatheter closure [17]. Transesophageal echocardiography is a technique that is widely used for this purpose and has very successful results [18]. However, since two-dimensional evaluation requires different angles and multiple appropriate sections, it may cause difficulty in orientation and overlook of anatomical details [19]. Especially the evaluation of the posterior-inferior rims and some irregular defects may be insufficient. This may result in residual shunt or embolization of the device [20]. On 3D echocardiography, morphology, spatial relationships, and rims of the defect can be evaluated accurately with real-time “en-face” images [19,21]. The use of three-dimensional TEE can increase the success of the procedure by allowing the detection of irregular atrial septal defects that cannot be detected by a two-dimensional examination [22]. When the three-dimensional images of our patient, whose minimal residual shunt was persisted after the transcatheter insertion of the device, were examined, it was observed that the lesion expanded irregularly in the inferior part of the lesion. Therefore, it was thought that the device may not have been able to provide full closure. In the sixth month after the procedure, there was no need for placing a second device due to the disappearance of the shunt with the endothelialization process of the device. In our study, all percutaneous device placement procedures were performed under the guidance of 2D TEE, and 3D TEE images were evaluated offline. Therefore, the interventionist had no knowledge of 3D TEE measurements during the procedure. However, in this patient, examining the “en face” images during the procedure could contribute to a better understanding of the defect morphology and the selection of a more suitable device. Three-dimensional TEE is also very useful for evaluating the relationship of the device placed in the defect with adjacent structures such as the aorta, and the erosion that it may cause. The device can clearly determine the distance between the defect and the aorta prior to placement, and the degree of erosion that may occur after placement. It is known that insufficient anterosuperior rim increases the risk of device erosion in the aorta [23]. In our study, the distance between the aorta and the defect in 3D TEE measurements was greater than in 2D TEE measurements, although there was no statistically significant difference. There was no difference between 2D and 3D TEE measurements in terms of other surrounding rims. However, it was considered an important advantage that 3D TEE enables real-time and high-resolution imaging in the examination of the defect and surrounding structures, as in determining the spatial relationship between the aorta and the defect.
Although “sizing balloon” is an adopted technique for determining the exact diameter of the defect, inflating the balloon more than necessary may lead to estimation of the defect size more than its actual size.
Consequently, using an oversized device increases the risk of erosion. Sizing balloon may lead to the ruptures of the mobile and thin rims of the lesion, increasing the complications associated with the procedure. Therefore, recently, the closure of ASDs with alternative imaging techniques is increasingly preferred without using the “sizing balloon” technique [24]. The use of three-dimensional echocardiography, especially 3D TEE, can enable to determine the accurate defect diameter without the requirement for sizing balloons, thereby preventing possible complications. In our study, the mean defect diameter measured angiographically with “sizing balloon” was similar to 3D TEE measurements, and the positive correlation between the two measurements supports that 3D TEE is a reliable technique and an alternative to sizing balloon.
The main limitation of the present study is being a single-center study with a small number of patients. Multicenter studies comparing 3D TEE and 2D TEE will be more informative in evaluating ASD morphology. Three-dimensional TEE images were examined offline, not during the percutaneous closure. Therefore, studies including the percutaneous closure of ASDs by the guidance of 3D TEE can provide more information on the effectiveness and reliability of the imaging technique.
With real-time “en face” imaging provided by three-dimensional echocardiography technology, the complex morphology of ASDs and their relationship with adjacent structures can be clearly understood. In addition, device selection can be performed by accurately determining the defect size without the necessity to use invasive techniques that increase the procedure length and time of fluoroscopy such as “sizing balloon”. Therefore, 3D TEE, when used by experienced operators, is a useful and non- invasive imaging technique that can increase the success rate of percutaneous procedures along with decreasing complication rates.
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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Pelin Kosger, Ayse Sülü, Tugcem Akin, Hikmet Kiztanir, Birsen Ucar. Real-time 3D transesophageal echocardiography for the assessment of secundum atrial septal defects in children. Ann Clin Anal Med 2021;12(Suppl 3): S301-305
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Anesthesia management in pediatric patients with and without congenital anomaly: A retrospective study
Gamze Küçükosman 1, Bengü Gülhan Aydın 1, Necla Gülçek 1, Duygu Tatlı 2, Hilal Ayoglu 1
1 Department of Anesthesiology and Reanimation, Zonguldak Bülent Ecevit University Faculty of Medicine, 2 Department of Pediatric Surgery, Zonguldak Bülent Ecevit University, Faculty of Medicine, Zonguldak, Turkey
DOI: 10.4328/ACAM.20535 Received: 2021-02-11 Accepted: 2021-05-03 Published Online: 2021-05-12 Printed: 2021-08-15 Ann Clin Anal Med 2021;12(Suppl 3): S306-311
Corresponding Author: Gamze Küçükosman, Department of Anesthesiology and Reanimation, Faculty of Medicine, Bülent Ecevit University, Zonguldak, Turkey. E-mail: gamzebeu@gmail.com P: +90 532 566 25 71 F:+903722612768 Corresponding Author ORCID ID: https://orcid.org/0000-0001-5224-0258
Aim: In this study, we aimed to compare peroperative anesthesia management in pediatric patients with and without congenital anomaly.
Material and Methods: The records of patients aged 0-16 who were operated between 2012-2017 in the pediatric surgery clinic were retrospectively evalu- ated. The patients were divided into two groups with a congenital anomaly (Group I) and without an anomaly (Group II). The patients were evaluated in terms of demographic characteristics, ASA risk, current surgery, anesthesia induction method-technique, difficult mask ventilation, complications related to anesthe- sia, and 30-day mortality rates in the postoperative intensive care unit (ICU) were evaluated.
Results: The study included 102 patients. A statistically significant difference was found between the groups in terms of the type of surgery and ASA risk (p<0.05). It was determined that 77.6% of the patients in Group I had easy mask ventilation, and the frequency of minor complications associated with intra- operative anesthesia was 42.9% (p<0.05). It was determined that the number of patients taken to the postoperative ICU was higher in Group I (p<0.05). It was determined that 10 patients with anomaly died, and 30-day mortality in ICU was 59%.
Discussion: Complication of surgical procedures in patients with anomalies affects the anesthetic management of these patients in many ways. A detailed evaluation of these patients will increase the quality of life and comfort.
Keywords: Pediatric anesthesia; Congenital anomaly; Mortality
Introduction
Pediatric patients’ physiological, anatomical and pharmacological characteristics are different from adults and each other [1]. Anesthesia management of pediatric patients with congenital anomalies requires a multidisciplinary approach because of prolonged surgery, excessive loss of blood and the need for transfusion, airway problems such as difficult mask ventilation and intubation, etc. [2, 3]. There are many reports of complications related to anesthesia management in newborn, neonatal period patients [1, 4-13].
Recent technological developments in anesthesia and surgical applications and equipment cause us to encounter such patients in anesthesia applications. This study aims to evaluate perioperative anesthesia management of patients with and without congenital anomalies, operated on for various reasons in the pediatrics clinic of our hospital.
Material and Methods
Permission for this retrospective observational study was granted by the local ethics committee (Date:19/04/2017, Meeting No: 2017/08). The records of patients aged 0-16 years who were operated on by the same physician between January 2012 and April 2017 were evaluated. Patients over 16 y/o, premature, and intubated outside the operating room for multiple trauma were excluded. Data were obtained from the hospital automation database and anesthesia records. While all patients with anomalies were included in the study, patients without congenital anomalies who had the same age, gender, and weight distribution and match compatibility were randomly selected.
A total of 102 patients were divided into two groups as those with a congenital anomaly (Group I, n:49) and those without (Group II, n:53). The gender, age (0-28 days, 29 days-1 year, 1.1-3 years, 3.1-6 years, and 6.1-16 years), weight, American Society of Anesthesiologists (ASA) risk category, current surgery (thorax+gastrointestinal, urogenital, other [minor surgeries such as burn debridement, swallowing a foreign substance, tongue-tie, etc.]), previous surgery (yes/no), surgical procedure (urgent/elective), premedication method, anesthesia- surgery-recovery durations, anesthesia induction method (iv, inhalation, iv+inhalation), induction agent (propofol, ketamine, fentanyl, propofol+fentanyl), anesthesia technique (laryngeal mask airway [LMA], endotracheal intubation, mask ventilation, sedation), use of neuromuscular blocker (yes/no), difficult mask ventilation (easy/difficult), and regional anesthesia (RA) applications (yes/no) data were retrieved from archives.
The need for invasive monitoring, use of steroids, antiemetic, atropine, neostigmine and anesthesia-related complications (difficult airway (difficult mask, difficult intubation), cardiovascular instability, laryngo/bronchospasm, aspiration, other (minor complications: difficult vascular access, hypothermia, allergy, pain etc.) were recorded from intraoperative records. From postoperative records, analgesic methods (tramadol, parol, local infiltration), presence of nausea/vomiting, intubated/extubated status of the patients leaving the theatre, postoperative follow-up location (intensive care unit (ICU), service) and 30-day mortality rates in ICU were evaluated.
Statistical Analysis
The study sample was determined as 70 patients, with 95% confidence (1-α), 80.7% test power 1-β), and d=0.621 impact size.
The data were analyzed using SPSS v.23. Kolmogorov- Smirnov was used to test the normal distribution. The normally distributed data were tested using t-test and presented as mean ± standard deviation, others were tested using the Mann Whitney-U test and presented as median (min-max). A p-value <0.05 was determined to be significant.
Results
The mean age of the participants included in the study was 4±4.13 years, and their mean weight was 14239.98 ±13550.47 grams. There was no significant difference between the groups in terms of demographics or surgical procedures (p>0.05) (Table 1); 46.9% in Group I were in ASA-2 risk category, and 79.2% in Group II were in ASA-1 (p<0.001) (Table1). There was a significant difference between the groups in terms of surgical procedures; 42.9% of the patients underwent thorax + gastrointestinal surgery (anal-ileal atresia, tracheoesophageal fistula (TEF), appendectomy, ileus), and 62.3% underwent urogenital surgery (circumcision, hypospadias, undescended testicle, hydrocele, hernia) (p=0.006). A total of 59.2% in Group I had no previous surgery, and the same was true for 92.5% in Group II (p<0.001) (Table 1). None of the patients were premedicated or applied RA.
It was observed that of the patients with a congenital anomaly, 8 were diagnosed with Down Syndrome, 5 with VACTREL syndrome, 6 with other syndromes (Griscelli, Frajil-X, Jarcho- Levin, Wolf- Hirschhorn, Sotos and Prader-Willi Syndrome). The remaining 30 had only single anomalies or comorbid pathologies and had no genetic diagnoses.
There was a significant difference in terms of anesthesia- surgery-recovery durations. They were longer in patients with congenital anomalies (p<0.001).
All patients were monitored and heating blankets were used to prevent hypothermia. The iv method was frequently used when transferring patients from the service to the theatre after checking their vascular access safety and re-opened in problematic cases. There was no significant difference in terms of anesthesia method or iv analgesic agents (p>0.005), or in terms of anesthesia induction method or the agents (p>0.005) (Table 2). Sevoflurane was used to maintain general anesthesia and rocuronium was used as a neuromuscular blocker. While neuromuscular blockers were used in 61.2% of the patients in Group I, they were used in 34% in Group II (p=0.001) (Table 2). In Group I, 61.2% of the patients received endotracheal intubation, while LMA was used in 50.9% in Group II (p=0.002). While 77.6% in Group I had easy mask ventilation, this rate was 98.1% in Group II (p=0.001) (Table 2). A total of 16 patients in Group I experienced difficulty in the airway [mask ventilation (n:11), intubation (n:5)], the number was 1 in Group II (difficult mask ventilation). Two patients urgently operated in Group II had aspiration. Other intraoperative anesthesia-related complications were observed in 42.9% in Group I and 88.7% in Group II (p<0.001) (Table 2).
Table 3 presents the need for intraoperative invasive monitoring, distribution according to the use of steroid, antiemetic, atropine and neostigmine, postoperative analgesic management, presence of nausea/vomiting, conditions for leaving the surgery room, and postoperative follow-up location.
Patients with adequate spontaneous breathing and SpO2≥ 96% were extubated; others were transferred to ICU. In addition to the patients diagnosed with TEF + esophageal atresia (n:10) and ileus (n:3; patients with Down syndrome with dysmorphic facial features and not diagnosed genetically and without anomalies), and one patient with Griscelli syndrome was intubated and transferred to ICU due to laryngo/bronchospasm. In addition to intubated patients (n:14), three patients [TEF + esophageal atresia (n:2), colostomy closure (n:1, Down syndrome)] were also intubated and transferred to ICU. All 10 patients who lost their lives due to cardiac arrest on around the 14th day in the ICU were patients with anomalies. The 30-day mortality rate in ICU was 59%.
Discussion
It was determined that since the surgical interventions in patients with congenital anomalies are complicated, they were in higher ASA risk categories and had longer anesthesia- surgery-recovery periods. It was identified that these patients were frequently intubated, that they had more frequent complications related to difficult airway, and higher ICU transfers.
Preoperative evaluation is vital for safe anesthesia and a successful perioperative process. It should include the patient’s clinical history, complementary examinations and informing the patientandrelatives[1,14,15].Inthestudy,duringthephysical examination of the infants, anomalies, facial structure, nasal and oral aperture, and the structures of tongue, teeth, and neck that could affect airway management were carefully examined, and in cases of asymmetric face, mandibular hypoplasia, micrognathia, and tongue anomalies, additional consultations and examinations were requested.
Premedication with sedatives is usually not recommended for newborns and pediatric patients due to possible side effects [1, 14, 15]. In our clinical practices, premedication is not administered to pediatric patients, and parents are allowed to accompany the child until the induction stage.
ASA reports physical condition, age, urgent surgery, and underlying disorders as risk factors for post-op critical events in pediatrics [5-13]. It is common for pediatric anesthesiologists to add 1 to ASA risk for newborns and infants due to the increased perioperative critical event risk [7, 13]. ASA 1 and 2 patients constitute the majority of pediatric cases for us. In this study, most of the patients with anomalies were in an ASA-2 or a higher risk category. We believe that newborn and neonatal patients in a pediatric surgery clinic are at a higher risk because these surgeries are frequently performed due to emergencies. Monitoring of infants and children is the same as for adults, except for a few small modifications. Additional invasive monitoring might be required depending the disease and surgical procedure [1, 5, 15], this is also the case in our clinic. In the study, 26 patients with anomaly and 3 patients without anomaly were placed urinary catheter. The reasons were the duration-type of the surgery (frequently thorax + gastrointestinal and urogenital) and the need for monitoring in the ICU. The patients’ body temperatures were monitored non-invasively, blankets were used to eliminate intraoperative hypothermia, and iv fluids were administered post-heating. The pediatric group’s respiratory-tract anatomy and physiological properties differ from those of adults [1, 15]. With theimprovementsinthelastdecade,currentpediatricairway equipment is now competing with those for the adult population and expands the pediatric anesthesiologist’s toolkit for airway management [1, 15-17]. In our clinical practice, anesthesia is planned considering the features of the upcoming surgery, and the use of supraglottic airway devices for pediatric patients is common. In the study, endotracheal intubation (61.2%) and LMA (22.4%) were used depending on the type and duration of the surgery.
Acquired or congenital-pathology-related airway problems increase morbidity and mortality in pediatric patients [6-8, 10, 12, 13]. Murat et al. [7] investigated anesthesia applications and morbidity in 24,165 pediatric patients over a 30-month period and determined difficult intubation rate as 0.42% and difficult ventilation rate 0.15%. In this study, difficult mask ventilation was 11.8% (n:12) and difficult intubation was 4.9% (n:5) for all patients. While there was no difficult intubation in the patients without congenital anomaly, there was only one difficult mask ventilation.
Airway management in pediatric anesthesia is particularly important and requires knowledge and experience. To avoid problems, it is necessary to be prepared. Intubation must be performed by anesthesiologists experienced in difficult intubation, bronchoscopy, and tracheostomy [4]. Airway management in newborns and children with congenital anomalies is rather difficult. In fact, in such cases, lethal respiratory problems and intubation difficulty are quite common [18, 19]. In our clinic, other clinics’ pediatric operations are carried out by implementing standard applications. Intubation and monitoring are performed by senior anesthesiology assistants and anesthesiology specialists experienced in pediatric anesthesia using necessary equipment (including video laryngoscopy). In the study, difficult intubation resulting from comorbid craniofacial anomalies happened only in 5 patients (with Fragile-X, Wolf-Hirschorn, Sotos, Down syndrome and dysmorphic facial structure). They were intubated in repeated trials using video laryngoscope.
The literature suggests that the same induction sequence and agents used in adult patients can be employed and that depolarizing agents as neuromuscular should be used with care due to possible arrhythmia, hyperkalemia and malignant hyperthermia [1, 5, 15]. We determined that, while anesthesia induction was frequently done with propofol and propofol + fentanyl combination, as there was already an open vascular access, induction in patients with vascular-access problems was performed by iv + inhalation, after opening vascular access by using inhalation agent, and that rocuronium was preferred as neuromuscular agent. As the operations in the study were usually thorax+gastrointestinal system surgeries that last long and require postoperative monitoring, the use of endotracheal intubation was frequent with more neuromuscular blocker use. It is possible that steroid, atropine and neostigmine were used in larger amounts because endotracheal intubation was used more in these patients and there were more complications like laryngo/bronchospasm.
There is a growing interest in pain management in pediatric patients, especially with the use of RA techniques [20-23]. However, safe and effective regional examinations in pediatric patients with anomalies require experience because of restrictions in positioning and difficulty in cooperation [24]. In pediatric patients, parenteral ketorolac, morphine, fentanyl, meperidine can be used as a postoperative analgesic, and in the age group of 1-12 years, oral diclofenac and oral, rectal or iv acetaminophen can be used [1, 5, 15, 24]. It is quite uncommon for our clinic to use RA application in pediatric patients; IV acetaminophen is used frequently. Tramadol is preferred for children over 12 years of age. However, tramadol was also used in patients under 12 years of age when their pain was not relieved despite acetaminophen use and local infiltration.
The anesthesia complications in pediatrics are difficult airway, unscheduled extubations, hypoxemia/hypoventilation, laryngospasms, wheezing, aspiration, and cardiovascular events [4-13]. The incidence of these events (laryngospasm, bronchospasm, bronchial aspiration, and postanesthesia stridor) is even higher in pediatric patients with anomalies [3, 18, 19]. In the study of Edomwonyi et al. [5] with 270 children under 16 years of age, the intraoperative complication rate was 9.3%, and the postoperative complication rate 14.8%. They stated that intraoperative complications were frequently associated with cardiovascular and respiratory systems, while postoperative complications were often related to the cardiovascular system and were accompanied by pain, and the highest complication rate was in infants younger than 12 months and they were not related to ASA levels. Moreover, it was reported that anesthesia-related morbidity and mortality could be minimized or prevented through early diagnosis and fast management of any complication. In our study, which does not include postoperative anesthesia complications, we determined that complications related to intraoperative anesthesia were observed at higher rates in patients with anomalies. As for patients without anomalies, minor complications such as difficult vascular access, hypothermia, allergy, pain, etc. were observed at a high rate of 88.7%. The reason why these complications were at higher rates compared to the patients with anomalies could be that, since it is harder to open vascular access in patients with anomalies, this issue was better taken care of in the service and that, as these children were younger, more care was taken during their transfer to the surgery room in order to protect them from hypothermia and to minimize the pathologies that could result from their current conditions. Patients might leave the theatre intubated or with oxygen support. If patients with syndromes have no severe postoperative airway obstruction or are clinically stable, they can be extubated. Ensuring postoperative hemodynamic stability in major surgeries is the most important issue and due to the drain, urine outlet, oxygenation and the need for monitoring, they can be accepted to ICU [24]. In our study, 86.3% of the patients were extubated; 13 patients with anomalies (26.5%) and 1 patient without (1.9%) were transferred to the ICU as intubated, and 3 patients as extubated.
Pediatric perioperative mortality rates have increased over the past decade. These rates are higher in Brazil (9.8 per 10,000) and other developing countries (10.7-15.9 per 10,000), compared to developed countries (0.41-6.8 per 10,000), with the exception of Australia (13.4 per 10,000). The major risk factors are as follows: newborn or less than 1 year old, ASA-3 or higher, and undergoing emergency surgery, general anesthesia, or cardiac surgery. The main causes of mortality are airway problems and cardio-circulatory events [25]. Flick et al. [11] reported the overall perioperative mortality rate for children in the US as 6.8:10,000 anesthetics. In the study, the mortality rate associated with cardiac surgery was 115.5 per 10,000 anesthetics; It was 1.6 per 10,000 anesthetics for non-cardiac surgery. In our study, 10 of the 17 patients with anomalies in the ICU lost their lives. They were in the smaller age group, operated under general anesthesia, and had an ASA-2 status. The 30-day mortality rate in the ICU was quite high (59%). This study has some limitations. The first limitation is that this is a retrospective, single-center study and the results cannot be generalized. Secondly, all operations were performed by one surgeon, the number of patients with anomalies was relatively small, it was not possible to determine mortality factors. Thirdly, premedication applications in pediatric patients were not carried out in our center, and RA applications, including neuraxial anesthesia, were rare. Finally, surgical procedures included operations ranging from simple to complicated.
In conclusion, in pediatric patients with more challenging airway management, additional anatomic problems make it even more difficult. Relatively more complicated surgical interventions in pediatric patients with congenital anomalies require longer intubation of these patients and their follow-up in ICU. The researchers believe that since it would affect morbidity and mortality in pediatric patients with congenital anomalies, with ideal airway management, in addition to effective preoperative preparations, keeping difficult airway equipment available and efficient perioperative clinic management are important.
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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Gamze Küçükosman, Bengü Gülhan Aydın, Necla Gülçek, Duygu Tatlı, Hilal Ayoglu. Anesthesia management in pediatric patients with and without congenital anomaly: A retrospective study. Ann Clin Anal Med 2021;12(Suppl 3): S306-311
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Factors predicting outcome after surgeries for cervical spondylotic myelopathy: A prospective study in Egypt
Sonia Elbhrawy 1, Ashraf Abdo 1, Hesham ElSaghir 2, Yasmine A. Ashram 3, Jaidaa Mekky 1
1 Department of Neurology, 2 Department of Orthopedic Surgery and Traumatology, Spine Unit, 3 Department of Physiology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
DOI: 10.4328/ACAM.20537 Received: 2021-02-12 Accepted: 2021-04-12 Published Online: 2021-04-23 Printed: 2021-08-15 Ann Clin Anal Med 2021;12(Suppl 3): S312-317
Corresponding Author: Sonia Elbhrawy, Department of neurology, faculty of medicine, Alexandria University, Champlion St., El-Azareeta, Alexandria, Egypt. E-mail: soniaelbhrawy250@gmail.com / sonia.elbhrawi@alexmed.edu.eg P: +201025520675 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6446-722X
Aim: In this study, we aimed to study factors affecting the outcome after surgeries for cervical spondylotic myelopathy (CSM).
Material and Methods: A prospective study was conducted on 25 patients who had CSM surgeries at our institution. The assessment was done before the operation, at 1, 3, and 12 months after surgery using the Modified Japanese Orthopedic Association score (MJOA).
Results: Patients with age ≥ 65 years had significantly lower MJOA scores than younger patients at 1, 3, and 12 months (P=0.007*), (P=0.007*), and (P=0.035*) respectively. Patients with diabetes had significant lower scores at 3 months (p=0.021*), and 12 months (p=0.017*). The duration of symptoms was signifi- cantly correlated with the MJOA score at 3 and 12 months (P=0.035*), (P<0.001*), respectively. There was significant positive correlation between preoperative and postoperative MJOA scores at 1, 3, and 12 months (P<0.001*), (P=0.013*), and (P=0.009*), respectively. The number of operated segments during surgery correlated with the MJOA score at 1 month (p=0.001*), and 3 months (p=0.003*). Hospital admission days after surgery were significantly correlated with MO- JAs at 1, 3, and 12 months (P<0.001*), (P=0.001*), and (P=0.004*), respectively. Preoperative somatosensory evoked potential, MRI, and mean arterial pressure at the beginning of surgery had no significant association with outcome.
Discussion: Age, diabetes mellitus, duration of symptoms, severity of myelopathy, number of operated segments and duration of hospital stay after surgery are considered predictors of outcome after CSM surgeries. MRI, somatosensory evoked potentials tests, and mean arterial blood pressure at the start of surgery had no significant association with outcomes.
Keywords: Cervical spondylotic myelopathy; MJOA score; Outcome
Introduction
Cervical spondylotic myelopathy (CSM) is the most common cause of spinal cord impairment worldwide [1]. It causes sensory and motor dysfunction of the upper and lower limbs, also it causes gait and sphincter dysfunctions. Surgical decompression is the main treatment, especially in moderate to severe disease, which has been proved to be effective in relieving these symptoms [1,2]. However, the majority of the patients improved after surgery [2]. Some showed variability in the degree of improvement. The Modified Japanese Orthopedic Association score (MJOA), is one of the commonly used outcome measures in patients with CSM that improve after surgery.[3] The aim of our study was to investigate the clinical, radiological, neurophysiological and surgical factors affecting neurological recovery and functional outcome after surgical decompression for patients with cervical spondylotic myelopathy.
Material and Methods
Patients and methods
This prospective study was conducted on 25 patients with CSM who required surgical decompression at our institution. Patients included in the study had symptomatic cervical myelopathy with at least one clinical sign (e.g. gait abnormality, hyperreflexia of upper limbs and/or lower limbs, Hoffman’s reflex and Babinski sign), and evidence of cervical spinal cord compression on magnetic resonance imaging (MRI) [4]. Patients with traumatic compression, pathologic fractures, spinal cord tumors, inflammatory disorders of the spinal cord, and infections myelitis were excluded from the study.
Preoperative assessment
All patients underwent history taking, neurological examination, and magnetic response imaging study to assess the cervical spinal cord compression level. The MJOA was performed to evaluate the upper and lower limbs and sphincter functions, as well as the severity of CSM for each patient [3]. The score is an 18-point scale that contains upper limb motor function (5 points) and lower extremity motor function (7 points), sensory function (3 points) and sphincter function (3 points) [3]. A score of 18 reflects no neurological deficits, whereas a lower score indicates a greater degree of disability and functional impairment. Mild myelopathy is A score of ≥15 MJOA indicates mild myelopathy; a score between12-14 indicates moderate myelopathy, and severe myelopathy is indicated by an MJOA score of <12.[3]
Some patients already had Somatosensory evoked potentials (SSEPs) before surgery to assess tract affection, and we just analyzed the results of SSEPs. Abnormality of SSEP latency or amplitude due to cervical spinal cord lesion was defined as follows: SSEP median nerve abnormality: absent N20, P22 and/ or abnormal right-left amplitude ratio of N20 wave. SSEP tibial nerve abnormality: absent P40 wave and/or abnormal N22-P40 inter-peak latency and/or abnormal right- left amplitude ratio of P40 wave [5].
Surgical technique and Anesthesia
All surgeries were performed by an experienced senior spine surgeon using an intraoperative neuro-monitoring modality. The techniques used were either anterior cervical discectomy and fusion (ACDF) or posterior laminectomy with fusion. Total
Intravenous anesthesia (TIVA protocol) using propofol and fentanyl was used in all the patients with short-acting muscle relaxants used only during intubation.
Postoperative Outcome
The outcome was assessed using the MJOA score and neurological examination at 1 month, 3 months, and 12 months after surgery.
Statistical analysis
Descriptive data were described as mean ±SD or n (%), and the statistical analyses were performed using IBM SPSS software package version 20.0. (Armonk, NY: IBM Corp). The Mann- Whitney test and the Kruskal-Wallis test were used to test the significant difference between different parameters in the studied group regarding the MJOA score. The correlation was calculated using the Spearman coefficient.
Ethical considerations
Before enrollment in the study, consent was obtained from all recruited patients for the use of their anonymous data and for the surgical process. The Ethical Committee (EC) at Alexandria University Faculty of Medicine approved the study. The EC has had FWA since 2010 and operates according to the ICH GCP guidelines and applicable local and institutional regulations and guidelines.
Results
Twenty-five patients with CSM had cervical decompression surgeriesusingIONM.Thesewere19malesandsixfemales with a mean age of 54.24 ± 11.96 years. A detailed description of the preoperative clinical, radiological, SSEP and surgical findings of patients is depicted in Table 1. An example of one case is shown in Fgure 1. The association between these findings and outcome (MJOA score) was analyzed as follows:
1. Age and outcome: Patients aged ≥ 65 years had significantly lower MJOA score than patients with age <65 years at 1 month, 3 months, and 12 months follow up (P = 0.007*), (P = 0.007*), and (P = 0.035*), respectively. (Table 2).
2. Diabetes mellitus comorbidity: It was found that the group of patients with diabetes had significantly lower scores at 3 months (p = 0.021*), and 12 months (p = 0.017*). (Table 2).
3. Duration of symptoms: It was significantly correlated with postoperative MJOA score at 3 and 12 months follow- up (P = 0.035*), (P <0.001*), respectively (Table 3).
4. CSM severity (preoperative MJOA score): There was significant positive correlation between preoperative and postoperative MJOA score at 1 month, 3 months, and 12 months (P < 0.001*), (P = 0.013*), and (P = 0.009*), respectively (Table 3).
5. Number of compressed cord segments on MRI: There was no correlation between the number of compressed cord segments and postoperative MJOA score (Table 3).
6. Preoperative SSEP and outcome: Patients who had preoperative normal median nerve SSEP and posterior tibial nerve SSEP had a higher MJOA score than patients with abnormal median nerve SSEP at upper limbs and abnormal posterior tibial nerve SSEP, with no statistically significant difference (Table 2).
7. Other factors related to surgery: The number of operated decompressed segments during surgery correlated with the postoperative MJOA score at 1 month (p 0.001*), and 3 months (p 0.003*) (Table 3). Baseline Mean arterial pressure (MAP) at the beginning of surgery did not correlate significantly with postoperative MJOA score (Table.3). However, patients with MAP drop < 70 mmHg during surgery had lower MJOA scores than group without, but there was no significant difference. (Table 2). Hospital admission days after surgery correlated significantly with the mean MOJAs at 1, 3, and 12 months follow- up (P< 0.001*), (P 0.001*), and (P = 0.004*), respectively (Table 3).
Discussion
The extent of outcome improvements can be predicted using a number of preoperative variables in our study group. The MJOA score was used as the outcome parameters to evaluate the recovery outcome.
1. Age and outcome
In the presenting study, it has been found that patients aged ≥ 65 years had significantly lower MJOA scores than patients aged <65 years at 1 month, 3 months, and 12 months follow up. This indicates that age is one of the main predictors of the outcome after surgeries of cervical myelopathy. The explanations for this difference between age groups is that the elderly have age-related degenerative changes in motor neurons, synapses and corticospinal tract and posterior column in the spinal cord that are less tolerant to the stress of surgery [6], they may have other comorbidities that may affect tasks of the MJOA scale, such as hip and knee osteoarthritis, diabetic neuropathy or urinary incontinence [7], and may have sever degenerative pathology that may require more complex surgery [6]. Two studies use a similar cut-off value for age and reported that “elderly” patients (≥65 years) exhibited worse outcomes on the MJOA score compared with “younger” patients (<65 years) [8]. Other studies found that age was a significant predictor of postoperative MJOA [8,9]. In contrast, some studies reported an insignificant association between age and surgical outcome [10].
2. Diabetes Mellitus and outcome
Our results revealed that patients with diabetes had significantly lower MJOA scores at 3 months and 12 months. This indicates that DM is one of the predictors of surgical outcomes, especially long-term outcomes. This explained by the fact that diabetic patients may have abnormalities in their spinal cord, such as infarcts, demyelination, or atrophy of the posterior columns [11]. Furthermore, diabetes may induce a state of chronic inflammation and amplify the hypoxic conditions due to associated microvascular and macrovascular disease [12]. Complications associated with diabetes, especially peripheral neuropathy, may impair a patient’s postoperative neurologic recovery and functional improvement. This was supported by many reports, which showed a significant relationship between diabetes and outcomes [13]. Others failed to identify a relationship between diabetes and outcomes.[14]
3. Duration of symptoms and outcome
Duration of symptoms was significantly correlated with postoperative MJOA score. This means that the longer duration of symptoms before surgery, the less recovery after surgery. The rationale behind this finding is that patients with longer disease duration may experience irreversible damage of the spinal cord due to chronic compression, which results in ischemia, inflammation, and apoptosis of the neurons of the corticospinal tracts [15]. Furthermore, a longer duration of compression may amplify the ischemia-reperfusion injury that results from the restoration of tissue blood flow after long periods of ischemia [16]. Other studies reported the association between postoperative MJOA scores and duration of symptoms [17,18], while others reported that duration of symptoms was an insignificant predictor of outcome [10]. This discrepancy between studies was due to the variability and non-specificity of symptoms at the onset and the concomitant carpal tunnel syndrome or other peripheral neuropathy that confuses patients about the onset of myelopathy symptoms.
4. CSM severity and outcome
There was a significant positive correlation between preoperative and postoperative MJOA scores at 1 month, 3 months, and 12 months. This indicates that the less severe the myelopathy, the better the recovery after surgery. Similar to our results, many studies have reported a significant association between preoperative myelopathy severity and surgical outcomes [9,10]. This is also explained by the fact that the more severe myelopathy, the more ischemia of the cord and the more necrosis and apoptosis [15,16].
5. Preoperative SSEP and outcome
In the present study, patients with abnormal preoperative SSEP had lower postoperative MJOA scores than patients with normal SSEP, however, this was no statistically significant differences. This means that SSEP was not sensitive in detecting myelopathy and was not related to outcome in patients with CSM, similar findings supported by Kellar et al. [19]. That is because CSM with motor dysfunction is usually more frequent than CSM with isolated sensory dysfunction, and SSEP has no role in the diagnosis of motor fibers of corticospinal tracts [19]. On the other hand, Lyu et al [20] reported that SSEP abnormalities commonly reflect severe cord dysfunction and have been correlated with low surgical response.
6. MRI features and outcome
In the present study, all (100%) our patients had increased signal intensities on T2-weighted MRI, thus we tried to find a correlation between numbers of compressed cord segments and the postoperative MJOA score, however, we did not find any correlation between them. This was supported by a systematic review by Tetreault et al. [21], who found low-
level evidence that MRI factors related to cord properties are predictors of outcome. It was concluded that MRI features of the spinal cord before CSM surgery cannot accurately predict functional outcome after surgery and, hence further studies and alternative imaging approaches may be required.
7. Surgical factors and outcome
With regard to blood pressure during surgery, we use MAP <70 mmHg as the threshold below which blood pressure is needed to be increased [22] because cord hypoperfusion due to hypotension increases the risk of neurologic deficits in spinal surgeries, and unfortunately, is common in patients with spinal cord injury [23]. In the presenting study, patients with MAP drop <70 mmHg during surgery had less MOJA scores at 1, 3, 12 months follow-up than in the group without MAP drop, however, the difference was not statistically significant. Also, it has been found that baseline MAP at the beginning of surgery was not significantly correlated with the outcome score. This may be due to the optimal ranges of MAP monitored during surgery remain unknown or controversial, also in the present study, blood pressure was immediately therapeutically raised above 70 mmHg, and it has been found that not only the average of MAP, but also the duration of hypotension be more important in spinal cord injury recovery [22].
The number of surgically decompressed segments was significantly correlated with the MJOA score, which means that multilevel decompression surgery had less recovery after surgery. This was explained by the fact that the number of operated segments represents more compressed cord, more severe myelopathy, more complex surgery, and more postoperative complication like dysphagia, wound infection rates, neck pain, postoperative narcotic usage [24]. Also, multilevel decompression surgery had increased soft tissue dissection and retraction needed for exposure, as well as the increased time and manipulation, which may be a direct causes of increased morbidity [24].
The number of days of hospital stay after surgery correlated significantly with the postoperative MJOA scale and recovery rate at 1, 3, and 12 months follow-up. This means that the longer hospital stay after surgery, the lesser improvement in outcome, as it is a reflection of the extra time needed to control postoperative pain or infection [25].
Conclusion
Age, diabetes mellitus, duration of symptoms, severity of myelopathy, number of operated segments and duration of hospital stay after surgery are considered predictors of functional outcome and have a significant association with outcome. With respect to the number of compressed cord segments on MRI, somatosensory evoked potentials tests, we have failed to identify a significant association with outcomes. Finally, patients with MAP <70 mmHg during surgery had less functional improvements than patients without, however, that was not statistically significant.
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. Harrop JS, Naroji S, Maltenfort M, Anderson DG, Albert T, Ratliff JK, et al. Cervical myelopathy: a clinical and radiographic evaluation and correlation to cervical spondylotic myelopathy. Spine. 2010;35(6):620-4
5. American Clinical Neurophysiology Society ACN. Guideline 9D: guidelines on short-latency somatosensory evoked potentials. J Clin Neurophysiol Off Publ Am Electroencephalogr Soc. 2006;23(2):168–79.
6. Terao SI, Sobue G, Hashizume Y, Li M, Inagaki T, Mitsuma T. Age-related changes in human spinal ventral horn cells with special reference to the loss of small neurons in the intermediate zone: a quantitative analysis. Acta Neuropathol. 1996;92(2):109-14.
7. Machino M, Yukawa Y, Hida T, Ito K, Nakashima H, Kanbara S, et al. Can elderly patients recover adequately after laminoplasty? A comparative study of 520 patients with cervical spondylotic myelopathy. Spine. 2012;37(8):667-71.
8. Nakashima H, Tetreault LA, Nagoshi N, Nouri A, Kopjar B, Arnold PM, et al. Does age affect surgical outcomes in patients with degenerative cervical myelopathy? Results from the prospective multicenter AOSpine International study on 479 patients. J Neurol Neurosurg Psychiatry. 2016;87(7):734-40.
9. Tetreault L, Wilson JR, Kotter MR, Nouri A, Cote P, Kopjar B, et al. Predicting the minimum clinically important difference in patients undergoing surgery for the treatment of degenerative cervical myelopathy. Neurosurg Focus. 2016;40(6):E14.
10. Karpova A, Arun R, Davis AM, Kulkarni AV, Massicotte EM, Mikulis DJ, et al. Predictors of surgical outcome in cervical spondylotic myelopathy. Spine. 2013;38(5):392-400.
11. Machino M, Yukawa Y, Ito K, Inoue T, Kobayakawa A, Matsumoto T, et al. Impact of diabetes on the outcomes of cervical laminoplasty: a prospective cohort study of more than 500 patients with cervical spondylotic myelopathy. Spine. 2014;39(3):220-7.
12. Arinzon Z, Adunsky A, Fidelman Z, Gepstein R. Outcomes of decompression surgery for lumbar spinal stenosis in elderly diabetic patients. Eur Spine J. 2004;13(1):32-7.
13. Kusin DJ, Ahn UM, Ahn NU. The influence of diabetes on surgical outcomes in cervical myelopathy. Spine. 2016;41(18):1436-40.
14. Oichi T, Oshima Y, Taniguchi Y, Matsubayashi Y, Chikuda H, Takeshita K, et al. Cervical anterolisthesis: a predictor of poor neurological outcomes in cervical spondylotic myelopathy patients after cervical laminoplasty. Spine. 2016;41(8):E467-73
15. Karadimas SK, Gatzounis G, Fehlings MG. Pathobiology of cervical spondylotic myelopathy. Eur Spine J. 2015;24(2):132-8.
16. Karadimas SK, Laliberte AM, Tetreault L, Chung YS, Arnold P, Foltz WD, et al. Riluzole blocks perioperative ischemia-reperfusion injury and enhances postdecompression outcomes in cervical spondylotic myelopathy. Sci Transl Med. 2015;7(316):316ra194.
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Sonia Elbhrawy, Ashraf Abdo, Hesham ElSaghir, Yasmine A. Ashram, Jaidaa Mekky. Factors predicting outcome after surgeries for cervical spondylotic myelopathy: A prospective study in Egypt. Ann Clin Anal Med 2021;12(Suppl 3): S312-317
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Is panoramic radiograph really safe in the posterior mandibular region for dental implant placement?
Suheyb Bilge 1, Umut Demetoglu 2
1 Department of Oral and Maxillofacial Surgery, Erciyes University Faculty of Dentistry, Melikgazi, Kayseri, 2 Department of Oral and Maxillofacial Surgery, Adnan Menderes University Faculty of Dentistry, Aydın, Turkey
DOI: 10.4328/ACAM.20685 Received: 2021-05-10 Accepted: 2021-07-24 Published Online: 2021-08-13 Printed: 2021-08-15 Ann Clin Anal Med 2021;12(Suppl 3): S318-322
Corresponding Author: Suheyb Bilge, Department of Oral and Maxillofacial Surgery, Erciyes University, Faculty of Dentistry, Kayseri, Turkey. E-mail: suheybbilge@hotmail.com P: +90 530 211 23 49 Corresponding Author ORCID ID: https://orcid.org/0000-0001-9282-7344
Aim: The aim of the study was to investigate the probable planning differences in the vertical bone measurements required for dental implant application between panoramic radiographs and the cone-beam computed tomography (CBCT) images due to the posterior mandible lingual concavities.
Material and Methods: Using a retrospective study design, the authors enrolled a cohort of patients who underwent dental implant surgery. The implant plat- forms placed based on the panoramic image were simultaneously examined in the coronal sections of the CBCT images in the same section. The sizes of the implants placed perpendicularly to the horizontal axis in the alveolar bones with an undercut were remeasured through careful examination of the undercut anatomy.
Results: A total of 202 regions in the posterior mandible were analyzed in 101 patients (47 males and 54 females). The incidence of an undercut in the posterior edentulous areas of the lower jaw was 27.72% in the first molar region and 60.39% in the second molar region (P<0.001). Implants placed in coronal sections based on CBCT images in both regions were shorter than dental implant platforms placed based on panoramic images in the same section, and this difference was statistically significant in the second molar region (PFM: 0.142, PSM<0.001).
Discussion: According to the present study, when the second molar region could not be examined preoperatively via CBCT, the clinician should use a shorter implant than planned based on panoramic radiography to reduce the risk of lingual bone perforation.
Keywords: Dental implants; Lingual concavity; CBCT; Posterior mandibula; Submandibular fossa
Introduction
Implant treatment has become an indispensable method in treating edentulous areas. Implant surgery enables the patient to regain function and esthetics through successful osseointegration [1]. The bone structure in which the implant is placed is an important factor that affects osseointegration. Therefore, it is important to evaluate the bone structure in 3 dimensions. Bone examination, palpation of the bone ridge, and precise evaluation of the bone size and morphology in the implant region are necessary for preoperative planning of mandibular implant placement [2–4]. Moreover, the size of the selected implant depends on the height and width of the available bone and the location of the mandibular canal. The concavity of the mandibular canal and submandibular fossa in the posterior region may lead to potential complications by restricting the available bone [2]. The submandibular fossa is a concavity on the medial surface of the mandible inferior to the mylohyoid line and contains the submandibular gland. The sublingual gland is also located in the sublingual fossa. This fossa is a shallow concavity on the medial surface of the mandible on both sides of the mental spin and above the mylohyoid line. Submandibular and sublingual fossae should be palpated before osteotomy [5]. However, it is difficult and time-consuming for the surgeon to check the angle of the ridge during implant placement. Although various anatomical regions can be analyzed using osteometry, diagnostic castings, etc., to evaluate the alveolar ridge, these techniques are not as effective in certain areas of the posterior mandible since the myeloid muscle prevents the correct evaluation of this area [1]. Mandibular posterior lingual concavity (LC) is a prevalent clinical finding, and the risk of perforation is high, particularly when the fossa is too deep [6,7]. Bone perforations are mainly observed in the posterior region, including the inferior alveolar nerve and the submandibular fossa. The posterior region is a high-risk area during implant placement owing to the risk of injuring the neurovascular bundle and perforating the lingual cortex. Perforation of the lingual cortex can lead to both implant failure and arterial trauma with hematoma [8]. For this reason, the morphology and size of the submandibular fossa constitute the data that should be reviewed in the preoperative evaluation. Periapical and panoramic radiographs can be used to evaluate the edentulous areas in the posterior mandible. On the other hand, these are particularly inadequate in showing the relevant anatomy in the buccolingual or horizontal dimensions (that is, to visualize thickness). Possible measurements in the posterior mandibular region, especially on panoramic radiographs, provides information about the vertical length of the alveolar bone. However, the actual height of the implant may differ in some cases because the aforementioned LC cannot be determined in panoramic radiographs. In addition, cone-beam computed tomography allows for better visualization of the anatomy and morphology of the surgical field. Such diagnostic imaging provides the clinician to better understand intraoral anatomical structures [9,10].
The disadvantages are the additional costs required for CBCT and exposing the patient to more radiation than is needed for panoramic radiographs, although the radiation amount to which the patient is exposed has decreased recently. In the present study, primary aims were to evaluate the differences inusingpanoramicradiographyandCBCTimagestodetermine the vertical size of the implant in the 1st and 2nd molar regions of the edentulous mandible and to research the necessity of CBCT applications to evaluate the size of the implant in this region. The second aim of the present study was to evaluate the frequency of submandibular concavity in patients in the 1st and 2nd molar regions.
Material and Methods
Study Design
Using a retrospective study design, the authors enrolled a cohort of patients with CBCT scans who underwent dental implant surgery with local anesthesia. Partially or completely lower edentulous patients who were admitted to Adnan Menderes University, Faculty of Dentistry, Department of Oral and Maxillofacial Surgery between January 2017 and January 2019 participated in this study. The study protocol was approved by the Adnan Menderes University Human Research Ethics Committee. In the present study, 1098 CBCT images were evaluated. The study included healthy patients of both sexes aged over 18 years with lower posterior edentulous areas. Patients under 18 years of age were excluded from the study. Patients without preoperative records or CBCT images and patients with less than 3.5 mm alveolar bone thickness on the coronal side and vertical bone height less than 6 mm according to the inferior alveolar nerve to the coronal side were also excluded from the study. Demographic measures were age and sex. Anatomical parameters were measured using preoperative CBCT with NewTom 5G Cone Beam 3D Imaging, Verona, Italy. Dental volumetric computed tomography scans were obtained with a 0.25-mm slice thickness. All scanning procedures were performed using a standard exposure and patient positioning protocol.
DICOM files of dynamic volume computed tomography images were imported into NNT Viewer software (NewTom, Verona, Italy). Panoramic images and CBCT coronal sections were created from the same DICOM data. The mandibular posterior edentulous areas were carefully detected and drawn on the cross-sectional images after the segmentation procedure. The presence of LC in the lower regions of the first and second molars of the enrolled patients was determined according to the method in the study by Hsun-Liang Chan et al. in 2010 [6]. LC was evaluated in the posterior mandibular region on the basis of the shape of the alveolar ridge of the mandibular bone 2mmabovethemandibularcanal.Firstandsecondlowermolar regions were specified. Based on the panoramic images, the implant platform was placed in a coronal-apical direction with respect to the alveolar crest, perpendicular to the horizontal axis, and 2 mm in the coronal direction from the mandibular canal (Figure 1a, 2a). In the present study, the same implant platform design was used in both panoramic and coronal section views. The implant platforms placed based on the panoramic image were simultaneously examined on the coronal sections of the CBCT images in the same section (Figure 1b, 2b). The size of the implant platforms placed perpendicularly to the horizontal axis in the alveolar bones with LC was remeasured by carefully examining the undercut anatomy (Figure 3a, 3b). All morphological assessments were conducted, and measurements were repeated three times by the same clinician.
Statistical analysis
Data normality was assessed using histograms, q-q plots and the Shapiro-Wilk test. Variance homogeneity was examined using Levene’s test. To compare the differences among groups, two independent samples (Wilcoxon test) were applied for quantitative data. Pearson’s chi-square analysis was used to compare categorical data. Data are expressed as means ± standard deviations or as frequencies (percentages). Coefficient of variation (CV) and intraclass correlation coefficient (ICC) were used for intraexaminer reliability. CVs ranged between 3.7% and 4.4%, while ICCs ranged between 0.96 and 0.97, showing excellent agreement. Analyses were conducted using TURCOSA (Turcosa Analytics Ltd. Co., Turkey). A p-value less than 0.05 was considered statistically significant.
Results
The study included 101 patients who met the inclusion criteria. A total of 202 regions in the posterior mandibula were analyzed in 101 patients (47 males and 54 females) enrolled in this study. The average age of the patients included in the study was 53.8 years. In the radiographic images, first molar and second molar regions were evaluated separately with 101 implant platforms. The incidence of an undercut in the posterior edentulous areas of the lower jaw was 27.72% in the first molar region and 60.39% in the second molar region. There were no significant differences in the edentulous mandible in terms of the posterior lingual undercut by age or sex (Page: 0.088, Psex: 0.115). The undercut frequency in the second molar region was found to be significantly higher than the undercut frequency in the first molar region (P<0.001) (Table 1).
It was revealed that the implant platforms placed in coronal sections based on CBCT images in both regions were shorter than dental implant platforms placed based on panoramic images in the same section, and this difference was statistically significant in the second molar region (PFM: 0.142, PSM< 0.001) (Table 2).
Discussion
Today, dental implants have become the most popular treatment method in cases of tooth loss and are widely used. Therefore, accurate clinical and radiographic evaluations are very important for preventing complications, increasing the success rate, and boosting patient satisfaction. The size of the bone and the location of the anatomical structures where the implant will be placed can be assessed using 2D radiographs such as panoramic or periapical radiographs. In addition, a cross-sectional examination of the anatomical location where the implant will be placed is also very important [11], since
it enables the angle, width and height of the implant to be determined more accurately.
The oral surgeon should know the size and shape of the jawbone in order to select the appropriate implant size and prevent complications. To prevent lingual or buccal bone perforation during drilling, the implant should be placed according to the shape of the jaw bone [3]. One of the areas that may challenge the clinician during drilling or where the anatomy cannot be seen is the mandibular posterior region. The submandibular fossa in this region leads to a concave bone margin in the lingual side of the alveolar bone, and this causes undesired bone perforations during drilling. In a study conducted in 2011, the perforation rate of the lingual cortex (LCP) was reported as 7% in the second premolar teeth, 9% in the first molar teeth, and 31% in the second molar teeth during the placement of an implant with a diameter of 4 mm [2].
Froum et al. [2] and Chan et al. [6] researched the risk of LCP in implant treatment in the posterior mandibular region. Both used CBCT, computed tomography (CT), and software allowing for virtual placement of the implants with a diameter of 4-5 mm of different lengths (depending on the height of the alveolar crest). These authors concluded that the risk of bone perforation during implant surgery was higher in patients with an apparent LC. Froum et al. [2] suggested computed tomography before the operation to assess the risk of alveolar inferior nerve injury and LCP for immediate implant placement in the posterior mandible to evaluate other options, such as a delayed protocol.
In the lower posterior region, LCP can lead to various complications. The position of the lingual nerve should also be taken into consideration for implant placement in the posterior mandible. The lingual nerve is a branch of the posterior body of the mandibular nerve, delivered in the infratemporal fossa, close to the lingual direction of the mandible in the third molar region [12]. Due to the changing course of the lingual nerve, LCP can lead to nerve dysfunction during the placement of the implant.
If LCP is left undetected and an implant is placed, then the implant can be lost or cause permanent inflammation or infection. This can potentially cause the spread of infection and significant problems. Because of the location of the LC, infection in this area can easily spread to the parapharyngeal and retropharyngeal cavities, which can cause more serious complications such as mediastinitis, pulmonary embolism or upper airway obstruction and internal jugular vein thrombosis [12].
In the literature, various classifications of lingual ridge types have been suggested. Chan et al. [5] classified the ridge types as P (parallel), C (thickening towards the apical) and U (LC). Watanabe et al. [3] classified the types as A (LC), B (parallel) and C (thickening towards the apical). In his study, Magat observed type P as the most common ridge (37.4%), followed by type U (LC) ridges (32.5%) and type C ridges (30.1%). The reported prevalence of type U ridges in the literature varies between 36-66% [6,11,13]. Watanabe et al. [3] evaluated the lower posterior LC in a Japanese population in 2010. Based on their study, they reported that approximately 36% to 39% of all patients had LC. In addition, Chan et al. evaluated multiple CBCT scans for the presence of LC in the lower posterior region [6]. Their results demonstrated that 66% of subjects presented posterior mandibular LC. These studies are consistent with the results of the present study, suggesting that 60% of the posterior mandibles exhibit LC. The probability of a concavity rises posteriorly in the jaw. Nickenig et al. [13] revealed that the prevalence of LC was higher in the second molar region. In accordance with the literature, mandibular LC was found to be significantly higher in the 2nd molar region than in the 1st molar region in the current study. In the current study, the presence of concavity in the lingual area was separately evaluated in the 1st and 2nd molar regions. Also, the type U bone incidence, which clinically concerns the clinician, was investigated; although it was seen in both regions, this incidence was observed to increase gradually in the 2nd molar region. Unlike other studies in the literature, the current study investigated the accuracy of planning the vertical length of the implant using panoramic films due to the presence of LC.
Panoramic radiography can be considered as a primary evaluation to obtain information about bone height and, to some extent, to acquire information about the horizontal distances [14]. However, panoramic radiographs provide information only in two dimensions and have various disadvantages, such as distortion and magnifications, which provide incorrect information [3,14]. In the current study, although LC was observed by 27% of the cases in the 1st molar region on panoramic radiographs, no significant difference could be detected between the planned implant length using the panoramic radiograph and the planned implant lengths using the CBCT image; the measurements complied with each other. However, it was observed that the bone LC increased in the 2nd molar region, and the planned implant lengths using CBCT were shorter than the implant lengths that could be placed using panoramic radiography during the planning stage; a significant difference was found. This shows that clinicians need to pay more attention to bone concavities in the 2nd molar region, and when required, CBCT should be applied preoperatively. On the other hand, some authors, such as Kalpidis and Konstantinidis, suggest that routine preoperative CT or CBCT screening is not necessary [15]. Alternatively, implant treatment planning and careful preoperative palpation of the lingual mandibular surface in the posterior mandible during surgery can facilitate sufficient reflection of the lingual mucoperiosteal flap and complete viewing of the lingual cortex [6,15]. As mentioned previously, differences in implant length between the two imaging methods may not always result in LCP. Weaknesses of the study include the limited study example and the lack of evaluation of the effects of angled implant placement. Experienced clinicians who do not evaluate the morphology of the region using CBCT preoperatively can understand that the drill is approaching the lingual border during the surgery, the implant length can be placed shorter than planned, or the implant can be placed in the buccal lingual direction to avoid concavity.
Conclusion
The present study reviewed the differences when planning the length of the implant for the mandibular posterior region using panoramic radiography and CBCT imaging. Panoramic radiographs gave results compatible with CBCT in the 1st molar region. However, although there was no significant difference, there were a low number of cases where the implant length differed. In the 2nd molar region, significant differences were observed between panoramic radiography and CBCT measurements, and bone concavities were observed more frequently in this region. Our study included 101 patients and derived some statistical results using the data acquired from these patients. Nevertheless, each patient should be evaluated alone. If CBCT imaging is not the preferred technique of choice, the clinician should always consider the possibility of reaching the lingual cortical border before the planned drill length and change the planning strategy (implant length or implant angle) in these regions during the surgery.
Our study was retrospective and evaluated the clinical significance of the presence of concavity in this region using the measurements from the images, as well as the differences in panoramic radiographs and CBCT images. This retrospective radiographic study can be used as a model for prospective studies that examine lingual concavities in a larger population. In addition, prospective studies can be planned to evaluate the relationship between the angular differences of placed implants and the frequency of LCP.
Acknowledgment
The authors thank Dr. Ahmet Ozturk, a statistician of the University Erciyes, Institute of Health Sciences, Department of Biostatistics for reviewing and confirming all the statistical analyses and 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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3. Watanabe H, Abdul MM, Kurabayashi T, Aoki H. Mandible size and morphology determined with CT on a premise of dental implant operation. Surg Radiol Anat. 2010; 32(4):343–9.
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The effect of anesthesia method on the distribution of leukocyte elements and neutrophil/lymphocyte ratio in elective cesareane sections
Selda Songur Dağlı 1, Recai Dağlı 2
1 Department of Obstetrics and Gynecology, 2 Department of Anaesthesiology and Reanimation, Kirsehir Ahi Evran University Faculty of Medicine, Kirsehir, Turkey
DOI: 10.4328/ACAM.20696 Received: 2021-06-04 Accepted: 2021-07-13 Published Online: 2021-07-30 Printed: 2021-08-15 Ann Clin Anal Med 2021;12(Suppl 3): S323-327
Corresponding Author: Selda Songur Dağlı, Department of Obstetrics and Gynecology, Kirsehir Ahi Evran University Faculty of Medicine, Kirsehir, 40100, Turkey. E-mail: seldasongurdagli@hotmail.com P: +90 5423160625 Corresponding Author ORCID ID: https://orcid.org/0000-0003-4887-4818
Aim: In this study, we aimed to investigate whether the anesthesia method in cesarean sections (CS) affects the distribution of leukocyte elements and the neutrophil/lymphocyte ratio (NLR).
Material and Methods: In our retrospective study, 99 patients with general anesthesia (GA) and 87 patients with spinal anesthesia (SA) with elective CS were included. Preoperative and postoperative 24th-hour blood samples were evaluated. The distribution of leukocyte elements and NLR were compared preopera- tively and postoperatively.
Results: The rate of neutrophils was 72.31% ± 6.25 preoperatively and 82.46 ± 4.96% postoperatively. This change was statistically significant (p = 0.00). There was no significant difference between the two groups in neutrophils, lymphocytes, monocytes, basophils, and NLRs in the postoperative period.
There was a significant difference in eosinophil distribution and eosinophil-lymphocyte ratio (ELR) between postoperative groups (p = 0.03, p = 0.04). In the postoperative period, the eosinophil rate was lower in the GA group.
Discussion: In CS anesthesia, there was no significant difference in leukocyte distribution and NLR rates between SA and GA in the postoperative period. Eo- sinophils and ELR were significantly different between the two groups.
Keywords: Anesthesia; Leukocyte; Neutrophil; Lymphocyte; Cesarean
Introduction
The neuroendocrine and immune systems are activated during trauma, surgery, ischemia, shock, infection, pregnancy. Acute changes occur in the white cell composition in the blood as a result of activation of the cellular and humoral immune system. Neutrophils, eosinophils, basophils increase, and lymphocytes decrease. In a study by Jilma et al., 4-6 hours after endotoxin, neutrophils increased by more than 300%, lymphocytes by 85% and monocytes by 96% reduced. The decrease in lymphocytes can last 2-7 days [1-3].
Neutrophilia and lymphopenia that develop in response to surgical or physiological stress are signs of a good prognosis. Neutrophil/lymphocyte ratio (NLR) has been defined as an indicator of physiological stress in recent years. These are easy, cheap and repeatable tests. It is predictive of post-diagnosis and pre-chemotherapy prognosis in cancer patients and is widely used in the clinic as a marker for systemic inflammation. In studies, patients with high NLR values have a better prognosis than those with low NLR values [4-7]. There are also studies for prognostic purposes in chronic diseases [8]. Recent literature has focused on creating community-based data and detecting thresholds to use NLR for prognostic purposes [9, 10].
There are many physiological changes during pregnancy and puerperium. In addition, when surgery and trauma caused by anesthesia are added along with a cesarean section (CS), the situation becomes even more complicated. There is an increase of more than 20 000/mm3 in the maternal white blood cell count during pregnancy and puerperium. These values are thought to be related to physiological stress during pregnancy [11, 12]. The effect of anesthesia on the immune system has been known for a long time [1]. The effects of anesthesia on surgical stress have been investigated. Today, studies examining the impact of CS anesthesia on NLR used for prognostic purposes are limited. We planned our research to provide data on this subject and to support the current literature.
In this study, we aim to investigate whether general (GA) and spinal (SA) anesthesia in cesarean affect NLR and the change in the distribution of leukocyte elements.
Material and Methods
Ethical approval for this study was obtained from the local Ethics Committee of Ahi Evran University Faculty of Medicine (no: 2019-02 / 20). It was planned in accordance with the Helsinki guidelines.
Research plan:
This is a retrospective study. The data were obtained by examining patient files.
Patient population:
CS patients were examined in Kırşehir Training and Research Hospital between 03.03.2019 and 03.01.2020.
Inclusion criteria were as follows: 37-41 weeks of gestation, pregnant women with elective CS by GA or SA.
Exclusion criteria were as follows: any blood disease, postpartum atony development, placenta ablation, placenta adherence anomalies, pregnancies below 37 weeks or over 41 weeks, preeclampsia, pregnant women with eclampsia, intrauterine exitus fetus, chorioamnionitis, known infections (such as upper or lower respiratory tract) pregnant women who had a blood transfusion before or after the operation.
During the research period, we examined 210 elective CS made by the same surgeon in the clinic. We excluded from the study because of four preeclampsia-eclampsia, eight pregnant women below 37 weeks of gestation, three detachments, three blood transfusions, one twin pregnancy, and five pregnant women with missing data in their files.
Blood sampling was done before the operation and at the 24th hour after the operation. Leukocyte distribution, NLR and eosinophil/lymphocyte ratio (ELR) in the blood were evaluated. The patients were divided into two groups as GA and SA, according to CS anesthesia. For standardization, the data of CS cases performed by the same surgeon, patients who had similar procedures during GA and SA were included in the study. Data of 99 patients in the GA group and 87 patients in the SA group were evaluated.
Standard GA application: 2-3 mg/kg propofol, 0.6 mg/kg rocuronium was induced. Afterwards, endotracheal intubation was applied, and the surgical procedure was started. It is maintained with 4 L/min 50% O2-air mixture until the baby is delivered, then 1 μg/kg of fentanyl citrate and 50% O2-N2O mixture.
Standard SA application: A subarachnoid block L3-L4 or L4-L5 vertebral levels are applied with a 26G spinal needle (Atroucan®, Brown, Germany) 10 mg of Heavy bupivacaine. The surgical procedure is started when sensory block is achieved at the T4- T6 level. During the surgical process, 2 L/min O2 is applied with a nasal mask.
Paracetamol-tramadol Hcl vials are used for postoperative analgesia in both groups according to the patient’s needs. Statistics
Statistical analysis was performed using the SPSS 21.0 Windows (SSPS Inc., Chicago, IL, USA) program. In descriptive statistics, mean ± standard deviation, median (IQR) values, categorical data were expressed as number (n) and percentage (%). The compatibility of numerical variables to normal distribution was evaluated using the Shapiro-Wilk test. Student t-test, Chi-square and Mann-Whitney U tests were used for statistical analysis. The results were evaluated at a 95% confidence interval, and those less than p < 0.05 were considered statistically significant.
Results
A total of 210 files were examined, but we analyzed data from 186 patients according to the inclusion and exclusion criteria. The demographic data of the patients and duration of the operation, 1st and 5th-minute APGAR scores are shown in Table 1, and the distribution of cesarean indications in Figure 1. There was no significant difference between the two groups in terms of maternal age, gestational week, body mass index (BMI), and duration of the operation. Apgar scores were significantly higher in the SA group at the 1st and 5th minutes compared to the GA group (p = 0.00, p = 0.00).
Preoperative hemoglobin value (g / dl) was 12.09 ± 0.15 in the GA group, 12.27 ± 0.14 in the SA group, p<0.40; 10.78 ± 1.55 in the postoperative GA group, 10.92 ± 1.27 in the SA group, p <0.48. Preoperative hematocrit value (%) was 36.74 ± 0.36 in the GA group, 36.97 ± 0.33 in the SA group, p <0.63; postoperative GA: 32.81 ± 4.11, SA: 33.08 ± 3.36, p <0.62.
Preoperative thrombocyte value (× 103) was 232.27 ± 69.57 in GA, 226.44 ± 61.44 in SA, p <0.54; Postoperative GA: 205.10 ± 60.12, SA: 190.52 ± 51.70, p <0.80. There was no significant difference in the hemoglobin, hematocrit, and platelet groups between the groups, preoperatively and postoperatively.
The preoperative neutrophil ratio in maternal blood was 72.31 ± 6.25%, while postoperative was 82.46 ± 4.96%. There was a significant difference between pre-and postoperative neutrophil ratios (p = 0.00).
Table 2 shows the distribution of preoperative and postoperative leukocyte elements in the GA and SA groups. Comparison of NLR and ELR according to the type of anesthesia is presented in Table 3.
Preoperative neutrophil (%) was 72.26 ± 6.39 GA, 72.37 ± 6.14 SA, p <0.90; lymphocyte (%) GA: 19.93 ± 6.01, SA: 19.77 ± 5.55, p <0.85; eosinophilia (%) GA: 0.70 ± 0.62, SA 0.86 ± 0.70, p <0.10; basophil (%)GA: 0.32 ± 0.14, SA: 0.34 ± 0.15, p <0.39; monocyte (%) GA: 6.52 ± 1.80, SA: 6.58 ± 1.76, p <0.39. In the postoperative period, no significant difference was found between the two groups in terms of neutrophil, lymphocyte, monocyte, basophil. Postoperative neutrophils (%) GA: 83.20 (81.87- 83.65), SA: 83.10 (80.95- 83.28), p <0.85; lymphocyte (%) GA: 10.30 (0.20-29.40), SA: 9.90 (4.60-40.30), p < 88; eosinophilia (%) GA: 0.20 (0.00-2.00), SA: 0.30 (0.00-2.00), p <0.01; basophil (%) GA: 0.20 (0.00-0.60), SA: 0.20 (0.00-1.40), p <0.10; monocyte (%) GA: 5.89 ± 1.76, SA: 6.11 ± 1.70, p <0.37. NLR in preoperative GA 3.7 (1.0-13.6), SA: 3.7 (1.4-17.1), p <0.37; postoperative GA 8.40 ± 3.05 in SA, 8.44 ± 3.26 SA, p <0.93. There was no statistically significant difference in NLR after surgery.
ELR in preoperative GA: 0.028 (0.0-0.6), SA: 0.034 (0.0-0.3), p<0.15; postoperative GA: 0.018 (0.0-0.5), SA: 0.028 (0.0-0.2), p<0.04.
When the postoperative GA and SA groups were compared, there was a statistically significant difference in eosinophil distribution and ELR. In the postoperative period, eosinophils decreased more in the GA group.
Discussion
Surgical stress activates inflammation factors. We compared the effects of GA and SA in the group with systemic physiological changes such as pregnancy. When inflammation is stimulated, lymphocyte decreases and leukocyte increases. The release of mediators (such as IL-6) released from lymphocytes increases. It was observed that the wound healing was better when the postoperative NLR was high. Postoperative infection was observed less frequently in these patients [13, 14]. Like NLR, ELR is used as a prognostic factor in inflammation [15, 16]. High ELR was considered a good prognosis.
In our study, it was observed that ELR was significantly lower in the GA group.
We found that neutrophil ratios significantly increased in all cesarean sections in patients who GA and SA in CS. Our findings are similar to the change in leukocyte elements during stress in other surgeries [4, 5].
In our study, when the NLR values were compared, we found no statistically significant difference between the groups. Erbaş et al. observed that NLR values were statistically significantly lower in the SA group than in the GA group [17]. However, in this study, there is no information about the standardization of the surgical procedure. In our study, the control blood value obtained at the 24th hour after CS performed by the same surgeon was examined. In a stuy by Erbaş et al., control evaluations were made according to the blood results two hours after the operation.
Doğan et al. compared patients who underwent elective surgery under general and epidural anesthesia. However, in this study, the type of operation and the gender of the patients are not standardized. In this study, they concluded that epidural anesthesia affected the leukocyte distribution less than general anesthesia [18]. Our study was conducted only on pregnant women. There was no significant difference in leukocyte distribution in patients treated with GA or SA.
Aldemir et al. in their study, comparing propofol (intravenous) and desflurane (inhaler) anesthesia, found that the NLR was lower in the propofol group than in the desflurane group. Propofol had a positive but transient effect on NLR [19]. Karagöz et al. showed that the NLR rate was not affected by the mode of cesarean section anesthesia. In this study, plateletcrit was recommended to predict the prognosis, and in our research, ELR was recommended [20].
Surhonne et al. found that in hernia surgery, NLR was higher in GA than in SA. Since our study included both pregnant women and only women with an average young age, it had a more specific group, which may be the reason for the difference [21]. Dermitzaki et al. compared interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) values in patients undergoing general and neuraxial anesthesia to evaluate the anti-inflammatory response. As a result of the study, there was no significant difference between the two groups. According to this research, IL-6 levels also increase in postoperative patients regardless of the anesthesia type [22]. In contrast, in the study by Zura et al., a significant increase in IL-6 levels was found in patients who underwent GA compared with patients who underwent SA [23]. There was no difference in NLR in our study between the two anesthesia, and ELR was significantly lower in GA.
Adıyeke et al. showed that APGAR values at 1 and 5 minutes in SA were higher than GA with spinal anesthesia in pregnant women with COVID-19. In our study, in accordance with the literature, Apgar scores were higher both at the 1st and 5th minute in the SA group [16, 24].
Limitations: Changes in leukocyte elements can be seen during the day, both due to the hormonal response whose level changes due to surgical stress and the diurnal rhythm. In addition, factors such as the change in personal analgesic need and the amount of analgesic administered, early feeding and early breastfeeding may cause changes in the anti-inflammatory response. Large-scale studies are required that take these factors into account.
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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Selda Songur Dağlı, Recai Dağlı. The effect of anesthesia method on the distribution of leukocyte elements and neutrophil/lymphocyte ratio in elective cesareane sections. Ann Clin Anal Med 2021;12(Suppl 3): S323-327
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Efficacy of balance training using biodex balance system on spatial and temporal gait parameters in patients with recurrent lateral ankle sprain
Hadeer G Maghraby 1, Abdel Rahman A Chabara 2, Reda K Abd Elrazik 3, Sara M Samir 4
1 Department of Physical Therapy for Musculoskeletal Disorders and its Surgery, Faculty of Physical Therapy, Modern University for Technology and Information, 2 Department of Physical Therapy for Musculoskeletal Disorders and its Surgery, Faculty of Physical Therapy, Cairo University, 3 Department of Physical Therapy for Musculoskeletal Disorders and its Surgery, Faculty of Physical Therapy, Benha University, 4 Department of Physical Therapy for Musculoskeletal Disorders and its Surgery, Faculty of Physical Therapy, Cairo University, Egypt
DOI: 10.4328/ACAM.20738 Received: 2021-06-08 Accepted: 2021-06-25 Published Online: 2021-08-06 Printed: 2021-08-15 Ann Clin Anal Med 2021;12(Suppl 3): S328-332
Corresponding Author: Hadeer G Maghraby, Demonstrator of Physical Therapy for Musculoskeletal Disorders and its Surgery, Faculty of Physical Therapy, Modern University for Technology and Information, 11865, Cairo, Egypt. E-mail: Hadeer.Gamal@pt.mti.edu.eg P: 01033594259 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6451-3794
Aim: Ankle sprains occur in athletes that stress the joint alignment and cause stress between the articular surfaces during weight-bearing.
The purpose of this study was to explore whether the addition of Biodex Balance System balance training to a recommended physical therapy exercise program may help patients with recurrent lateral ankle sprains improve their Spatial and Temporal Gait Parameters abnormalities.
Material and Methods: Fifty voluntary patients of both genders, diagnosed with chronic recurrent lateral ankle sprain, aged from 18 to 40 years. Patients were assigned into two equal groups of twenty-five patients: study group (A) who received Biodex Balance System added to the recommended physical therapy exercise program in the form of therapeutic exercises, and control group (B): the same recommended physical therapy exercise program like the group (A). Approximately 30 minutes per session, three times a week for 6 weeks was done for all exercise modes. The recommended physical therapy exercise program was performed three times a week for six weeks.
Results: There were statistically significantly higher results in step length, stride length, and single support time (p < 0.01) in the study group (A) in favor of the control group (B).
Discussion: In the treatment of patients with recurrent lateral ankle sprains, it was discovered that the inclusion of the Biodex balance system into the recom- mended physical therapy exercise program has a directional effect on improving spatiotemporal gait parameters, which are one of the major secondary effects of recurrent lateral ankle sprains.
Keywords: Biodex Balance; Training; Recurrent; Lateral Ankle; Sprain; Spatio-temporal Gait Parameters; Walkway System
Introduction
Both in clinical practice and in the sporting community, lateral ankle sprains are one of the various common problems of musculoskeletal injuries that require considerably more recovery time [1]. Twisting the foot in inversion and plantar flexion of the rear foot at the tibia during walking gait [2], cutting maneuvers during sports, or stepping off an uneven surface represents the most prominent causes of lateral ankle sprain [3].
The consequences of a lateral ankle sprain include damage to the lateral ankle ligaments and an impaired sensory pathway to the central nervous system. The most common initial consequences of the damage to lateral ligaments are anatomical structures Changes in joint loading and natural movement patterns result in reduced reach distance and shifts in the kinematics of the ankle joint [4]. A functional deficiency in postural stability is thought to occur in addition to anatomical changes associated with lateral ankle sprains [4].
After an ankle sprain, there is a deterioration of the mechanical and neurological properties of the joint, resulting in gait changes. The altered gait mechanics causes unnatural loads on the musculoskeletal system [3,5]. It’s necessary to consider the proper gait mechanics during rehabilitation for lateral sprains. Balance and gait are intertwined. Balance is a prerequisite for walking, and many gait disorders are in reality balance disorders [5].
One of the most common biomechanical changes in patients with lateral ankle sprain is increased inversion at the initial contact phase of gait, which is a contributing factor for chronic sprain and episodes of dysfunction, as a result of being closer to to the mechanism of injury [6].
During the midstance of gait, it was found that patients with recurrent lateral ankle sprain had a more inverted rear foot of the pivot leg (affected side) [7], lower values of gait velocity [8], step length, time in single support [8,9], and a more inverted rearfoot pre- and post- initial contact compared to healthy controls [9].
One of the most common repeatable and reproducible methods for recording barefoot plantar foot measurements and gait in children and adolescents is Walkway [10]. The walkway system pioneered a non-wearable device that is now considered the gold standard for accurately capturing kinetic, kinematic, and spatiotemporal gait characteristics [11,12].
As a result, the goal of this study was to compare the effects of balance training with the Biodex Balance System in combination with a recommended physical therapy exercise program on spatial and temporal gait parameters in patients with recurrent lateral ankle sprains.
Material and Methods
Study Design
A randomized controlled trial was conducted at the outpatient clinic of the Faculty of Physical Therapy, Modern University for Technology and Information over a period of three months. The study was carried out and approved by the Ethics Committee of the Faculty of Physical Therapy, Cairo University (P.T.RE/012/002887), and all participants signed an informed consent statement before starting the study after being informed about the study’s nature and purpose.
Participants
Fifty voluntary patients (forty males and ten females), aged from 18 to 40 years, whose BMI was 26 ± 2.94 kg/m2 were referred from orthopedists with chronic recurrent lateral ankle sprain. The inclusion criteria were as follows: 1- chronic unidirectional recurrent lateral ankle sprain (Grade II) [13]. 2- Written doctor’s recommendation for 2nd-degree LAS with chronic onset. 3- History of inversion trauma [14]. The exclusion criteria included the following (21): (1) Previous musculoskeletal damage or operation on the lower limb or the lumbar spine (2) Individuals who experienced a sprain of the medial or interosseous (syndesmotic) ankle ligaments, concomitant fracture, lower limb nerve damage [15].
The patients were randomized using the coin toss. Twenty-five patients (twenty males and five females) in the study group (A) received biodex balance training in the form of Maze Control Training, Random Control Training, and postural stability Training, in addition to the recommended physical therapy exercise program in the form of Therapeutic exercise. Twenty- five patients (twenty males and twenty females) made up the control group (B), received the same recommended physical therapy exercise program as group A.
Procedures
Assessments
Pre-and post-study assessment procedures were elicited by the same therapist for intrarater reliability.
WalkwayTM System Multi-Step Barefoot Analysis
Three Spatio-temporal parameters associated with gait parameters: (1) step length (m), (2) stride length (m), (3) single support time, were recorded by an instrumented walkway.
The patient’s gait was evaluated using the WalkwayTM System’s multi-step barefoot analysis, which records several sequential footsteps for foot function and gait analysis. Track and record different gait-recommended parameters in high-resolution formats and use specialized computer programs to aid data processing, leading to a more thorough and accurate analysis. This strategy imposes a limit on subjectivity. Figure (1). Interventions
Biodex Balance System TM SD
The biodex balance system is a reliable and valid device used to evaluate the participant’s static and dynamic balance stability on the unstable tilting platform. One unique feature is an attached LCD monitor that provides augmented visual feedback. The monitor provides information via a screen tracing, concerning the subject’s ability to balance on the platform as the subject tries to maintain the cursor in the middle of the screen grid. Unique training modes such as Maze Control Training (Improves sensory-motor control skills), Random Control Training (improves posture sway with varying movement levels), and LOS Training (improves postural dynamics) are used through Biodex Balance System TM SD – Static and Dynamic Balance system Training. (With 2.02 Software).
Each session lasted approximately 30 minutes. For six weeks, this session was repeated twice a week and was conducted for all exercise modes. To start with, the patients performed five minutes of warm-up exercises, which consisted of moderate- speed walking. For the first two sessions, the stability level of the platform was set to level plate stability 8. After that, every two sessions, the plate stability was reduced by one level. Each session included two repetitions of both of these exercise modes. In maze control training mode, the patient worked to follow the cursor inside these maze-like targets by following a repeatable pattern of motion on the screen. Random control training mode is suitable for motor control and vestibular training. In Random Control Training mode, tasks are displayed in random patterns, the Postural Stability Training mode is designed to emphasize particular movement patterns or techniques. The patient’s score is calculated using the target approach as the number of times the patient will hit the targets by leaning and changing their postural stanceduring the session [16] (Figure 2).
Recommended Physical Therapy Exercise Program
The greater muscle forces and more muscle groups are necessary to gain and maintain an upright posture during weight-bearing exercises. They also concluded that weight- bearing exercises had a greater effect on physical outcome measures because of their greater level of difficulty [17]. 1-Weight-bearing Exercise for Better Balance program Weight-bearing Exercises for Better Balance were performed three times a week for six weeks. Standing with a decreased base exercise to perform a warm-up exercise, graded reaching in standing, and walking practice. Between each trial, they did not rest, but a rest period of 10 seconds was given between each exercise [24].
2-The unilateral balance training program
A single-legged stance, wobbles board exercises, steamboats, anterior hop, quadrant hop, single-legged ball catch, toe touch down, and hops up and down were the components of the unilateral balance training program. Two times a week for six weeks, The program was performed. All exercises were done for the affected limb.
Statistical Analysis:
The mixed design MANOVA was performed to compare effects within and between groups on spatiotemporal gait parameters. For subsequent multiple comparisons, post-hoc tests using the Bonferroni correction were carried out. The level of significance for all statistical tests was set at p < 0.05. All statistical analyses were conducted using the statistical package for social studies (SPSS) version 25 for Windows (IBM SPSS, Chicago, IL, USA).
Results
General demographic data:
There was no significant difference between both groups in mean age, weight, height, and BMI (p < 0.05). Also, there was no significant difference in the distribution of sex and affected sides between groups (p < 0.05) (Table 1).
Effect of treatment on spatial-temporal gait parameters
Mixed MANOVA revealed that there was a significant interaction of treatment and time (F = 5.4, p = 0.001). There was a significant main effect of time (F = 123.21, p = 0.001). There was a significant main effect of treatment (F = 1.99, p = 0.04).
Table 2 showed descriptive statistics of spatial-temporal gait parameters and the significant level of comparison between groups, as well as a significant level of comparison between pre- and post-treatment in each group.
Between groups comparison:
There was a significant increase in step length, stride length, and single support time of group A compared with that of group B post- treatment (p < 0.01). (Table 2)
Discussion
The study group showed statistically significant higher results in step length, stride length, and single support time in comparison to the control group. These results are consistentwith a study investigating alterations in gait parameters and the effect of a a balanced 4-week comprehensive rehabilitation program. The measured step length, stride length, and single-leg stance test timings were significantly improved after 4 weeks of rehabilitation, which suggested that gait parameters are affected by recurrent lateral ankle sprain [20].
Treatments for ankle injuries include exercises to restore strength and gait mechanics. Gait is an especially important aspect of rehabilitation, as abnormal gait can have effects on other parts of the body further up the kinetic chain. Many of these treatments take time to see results and are therefore not ideal for a person who wants to return to their activity immediately [21].
The Biodex Balance System SD provides visual feedback on the position of the participant’s COP on a screen at eye level. Visual feedback balance training on an uneven surface has reduced ankle injury rates [22].
The improvement in the inverted foot position post- treatment in group (A) was consistentwith a researcher who used visual biofeedback, concluding that the pressure on the lateral aspect of the foot decreased. Reducing ankle inversion during walking could potentially lower the risk of subsequent lateral ankle sprains for individuals with recurrent LAS [23].
The use of immediate feedback is easier for the patient and leads to faster results. On the other hand, deviations from the center of gravity are worked better utilizing images. Technological devices, based on feedback, used by the different authors range from complex to basic. The complex group would include, for example, Biodex [24].
Future Directions
While this study sheds some light on the effect of balance training on gait, some questions remain unanswered. The underlying mechanisms that contribute to the changes shown in this research, such as enhanced proprioception, should be investigated further.
Further research is required about the effectiveness of various rehabilitation techniques on spatiotemporal parameters gait.
- Additionally, it is imperative to standardize efficient methods for rehabilitation of lateral ankle sprain aiming to prevent its recurrence in the community.
Limitations
Short rehabilitation time is a limitation; if the patients had a longer rehabilitation period, the treatment programs would have been more efficacious, and more evident results would have come out from this research.
Conclusion
Treatment based on feedback using innovative technology in patients with abnormal gait is mostly effective in improving gait parameters and, therefore, for the functional recovery of a patient.
Balance training using the biodex balance system (BBS) in combination with a recommended physical therapy exercise program may be helpful in the rehabilitation of patients with recurrent lateral ankle sprain.
Acknowledgment
The authors would like to express special thanks to Prof. Dr. Naguib Salem, Dean of the Faculty of Physical Therapy, MTI university, and Prof. Dr. Abd ElRahman Ali Chabara, Professor of Physical Therapy for Musculoskeletal Disorders and Surgery, Faculty of Physical Therapy, Cairo University for their support. The authors would like to express their gratitude to all participants committed to this study during this critical period.
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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3. Hertel J. Sensorimotor deficits with ankle sprains and chronic ankle instability. Clin Sports Med. 2008; 27(3):353-70.
4. Mettler A, Chinn L, Saliba SA, McKeon PO, Hertel J. Balance training and center-of-pressure location in participants with chronic ankle instability. J Athl Train. 2015; 50(4):343-9.
5. Riemann BL, Lephart SM. The sensorimotor system, part I: the physiologic basis of functional joint stability. J Athl Train. 2002; 37(1):71.
6. Miklovic TM, Donovan L, Protzuk OA, Kang MS, Feger MA. Acute lateral ankle sprain to chronic ankle instability: a pathway of dysfunction. Phys Sportsmed. 2018; 46(1):116-22.
7. Fraser JJ, Hart JM, Saliba SF, Park JS, Tumperi M, Hertel J. Multisegmented ankle-foot kinematics during gait initiation in ankle sprains and chronic ankle instability. Clin Biomech. 2019; 68:80-8.
8. Punt IM, Ziltener JL, Laidet M, Armand S, Allet L. Gait and physical impairments in patients with acute ankle sprains who did not receive physical therapy. PM R. 2015; 7(1):34-41.
9. Doherty C, Bleakley C, Hertel J, Caulfield B, Ryan J, Delahunt E. Lower extremity function during gait in participants with first time acute lateral ankle sprain compared to controls. Journal of Electromyography and Kinesiology. 2015;25(1):182-92.
10. Muro-De-La-Herran A, Garcia-Zapirain B, Mendez-Zorrilla A. Gait analysis methods: An overview of wearable and non-wearable systems, highlighting clinical applications. Sensors. 2014; 14(2):3362-94.
11. McDonough AL, Batavia M, Chen FC, Kwon S, Ziai J. The validity and reliability of the GAITRite system’s measurements: A preliminary evaluation. Arch Phys Med Rehabil. 2001; 82(3):419-25.
12. Kaminski TW, Hertel J, Amendola N, Docherty CL, Dolan MG, Hopkins JT, et al. National Athletic Trainers’ Association position statement: conservative management and prevention of ankle sprains in athletes. J Athl Train. 2013; 48(4):528-45.
13. Lazarou L, Kofotolis N, Pafis G, Kellis E. Effects of two proprioceptive training programs on ankle range of motion, pain, functional and balance performance in individuals with ankle sprain. J Back Musculoskelet Rehabil. 2018;31(3):437-46.
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Download attachments: 10.4328:ACAM.20738
Hadeer G Maghraby, Abdel Rahman A Chabara, Reda K Abd Elrazik, Sara M Samir. Efficacy of balance training using biodex balance system on spatial and temporal gait parameters in patients with recurrent lateral ankle sprain. Ann Clin Anal Med 2021;12(Suppl 3): S328-332
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Comparison of patients undergoing tracheostomy with and without fiberoptic bronchoscopy
Şule Batçık 1, Mustafa Süren 2, Mevlüt Çömlekçi 3, Melih Özdamar 4, Haluk Özdemir 5, Sibel Fadıllıoğlu 6, Tayfun Aldemir 7
1 Department of Anesthesia and Reanimation, Recep Tayyip Erdoğan University Faculty of Medicine, Rize, 2 Department of Anesthesia and Reanimation, Tokat Gaziosmanpaşa University Faculty of Medicine, Tokat, 3 Anesthesiology and Reanimation Clinic, Avcılar Murat Kölük Public Hospital, Istanbul, 4 Anesthesiology and Reanimation Clinic, Florance Nihgtingale Hospitals, Istanbul, 5 Anesthesiology and Reanimation Clinic, Marmara University Pendik Education and Research Hospital, Istanbul, 6 Anesthesiology and Reanimation Clinic (Retired), Bağcılar Education and Research Hospital, Istanbul, 7 Anesthesiology and Reanimation Clinic (Retired), University of Health and Science Kanuni Sultan Süleyman Research and Training Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.20749 Received: 2021-06-16 Accepted: 2021-07-07 Published Online: 2021-08-14 Printed: 2021-08-15 Ann Clin Anal Med 2021;12(Suppl 3): S333-337
Corresponding Author: Şule Batçık, Recep Tayyip Erdoğan University Faculty of Medicine, Department of Anesthesia and Reanimation İslampaşa Mah. Şehitler Cad., 53020, Rize, Turkey. E-mail: drsulebatcik@gmail.com P: +90 505.676.55.09 Corresponding Author ORCID ID: https://orcid.org/0000-0003-1110-6786
Aim: Fiberoptic bronchoscopy is increasingly being used during tracheostomy, especially in critically ill patients. In this study, we aimed to compare tracheos- tomy with and without fıberoptic bronchoscopy in terms of procedure time, blood gas values and complications.
Material and Methods: Sixty patients were randomly divided into two groups with 30 in each. Patients who underwent tracheostomy with fıberoptic bron- choscopy were included in Group 1, and without fıberoptic bronchoscopy in Group 2. Patients’ age, weight, body mass index, gender, height values, time of tracheostomy (time from skin incision to successful insertion of the cannula), complications, blood gas parameters, length of stay in the intensive care unit and complications were recorded.
Results: The two groups did not differ statistically in terms of demographic data, body mass index and Glascow coma score, length of stay in the intensive care unit, days of stay in the intensive care unit before percutaneous dilatational tracheostomy, status of the person who performed the procedure, complications, and blood gases values in both groups. Although rates of complications detected in Group 2 were not statistically significant. The increase in post tracheostomy oxygen saturation and PaO2 in Group 2 was statistically signifıcant. The duration of the procedure was longer with bronchoscopy.
Discussion: It was shown that fiberoptic bronchoscopy-assisted tracheostomy increased the duration of the procedure, but the complications were similar. Fiberoptic bronchoscopy-assisted tracheostomy can be used safely and effectively.
Keywords: Bronchoscopy; Intensive Care Unit; Tracheostomy
Introduction
Patients who need long-term mechanical ventilation due to chronic respiratory failure and who cannot be weaned from mechanical ventilation constitute approximately 10% of patients in intensive care units, and tracheostomy is a common procedure in these patients. [1]. Tracheostomy application increases comfort of the patient by providing a safer and manageable airway, earlier transition to enteral feeding, easier oral care and by decreasing the need for sedation. However, although tracheostomy has a long history, its indications, duration, techniques, cost and utility are still controversial [2]. In addition, tracheostomy has been associated with several complications, including stoma infection, pneumothorax, subcutaneous emphysema, tracheomalacia and tracheal stenosis [3].
Today, one of the most important questions is in which patients, when and through which techniques the tracheostomy will be performed. In a review published in 2018, it has been recommended that it would be beneficial to inspect the position of the tracheal tube and fiberoptic bronchoscopy can be used to avoid injury and stenosis, if necessary [2]. Some researchers have reported that fiberoptic bronchoscopy (FB) reduces the length of stay on mechanical ventilation, shortens the duration of hospital stay and the duration of intensive care, and if initiated early, causes less harm to the upper airways [4, 5]. Tracheostomy performed utilizing FB has been reported to have advantages, such as determining the incision site, avoiding accidental extubation, and detecting and managing complications (6). However, tracheostomy without FB has been proposed as an effective and safe method and to reduce healthcare costs (7).
This study’s objective was to compare patients undergoing FB- assisted tracheostomy and those undergoing tracheostomy without FB in terms of the time of the procedure, patients’ blood gas changes, and complications.
Material and Methods
This prospective randomized controlled study enrolled a total of 60 patients aged between 20-70 years, who were hospitalized in the reanimation unit of our hospital and underwent tracheostomy under elective conditions due to prolonged need for ventilatory support. The first patient was selected by lot and the other patients were sequentially allocated to the fiber optic group (Group 1) and the non-fiber optic group (Group 2). Enteral feeding of the patients was terminated 4 to 6 hours before the procedure. All tracheostomy procedures were performed electively at the intensive care beds by 2 inexperienced (at least 5 tracheostomies) under the supervision of the experienced physicians and 2 experienced (at least 50 tracheostomies) reanimation specialists.
Patients with infections at the site of tracheostomy, those with known or suspected intubation difficulties, patients with a history of neck surgery or anatomic disorders, those aged under 18 years old, patients with a PEEP value> 10 mmHg, bleeding diathesis and a platelet count <75000/dL were excluded from the study.
Patients’ age, gender, weight, height, BMI values, cause of admission to the intensive care unit, GCS score, time of tracheostomy (time from skin incision to successful insertion of the cannula), complications, blood gas parameters, length of stay in the intensive care unit and complications were recorded. Patients were routinely monitored with continuous ECG, arterial blood pressure, and pulse oximeter. Patients were administered IV fentanyl (2 mcg/Kg), propofol (2 mg/Kg), midazolam (2 mg) and vecuronium (0.1 mg/Kg) before the procedure as anesthetic management. Fifteen minutes before the procedure, oxygen concentration (FiO2) was increased to 100% during the procedure, and the patients were ventilated with Puritan Bennett 840 Ventilator System (Purital-Benneth Corporation, Overland Park, USA) assisted at control volume mode with tidal volume of 6-8 mL /Kg and respiratory rate set to normo-capnia. Tracheostomy Procedure
Tracheostomies were planned to be opened below the ring under the cricoid cartilage (between the 2nd and 3rd cartilages). The surgical site was cleaned with iodine solution, and covered sterile. In order to reduce bleeding, 2 mL 2% lidocaine with adrenaline (1:80000) was injected subcutaneously to the incision site. A 10-15 mm transverse incision was made from the tracheostomy site. A No. 140 cannulated needle was advanced at the midline through the tracheal rings towards posterior and caudal and the guidewire was left in the tracheal lumen. A lubricated small dilator was then slided over the guidewire to create a hole and the small dilator was withdrawn. The blue rhino dilator was pushed towards the tracheal lumen in the same way to create a hole large enough for the cannula to pass through.
In Group 1, the incision site on the trachea was determined utilizing the light of the bronchoscope with the Ciaglia Blue Rhino method, and the guidewire was confirmed to be within the trachea. In addition, the position of the cannula was also confirmed after the insertion. In Group 2, tracheostomy was opened with the Ciaglia Blue Rhino method without using bronchoscopy. In both groups, the heads of the tracheostomy tubes were inflated with air and both lungs were heard in order to confirm the success of the tracheostomy procedure.
Ethical Consideration
The local ethics committee of our hospital approved the study protocol prior to its initiation. The information about the aim of the study was given to the relatives of the patients, and written consent was obtained from the relatives of the patients who participated in the study. The study was conducted within the ethical principles of the Declaration of Helsinki.
Statistical Analysis
The data of this study were statistically evaluated using the SPSS for Windows (Statistical Package for Social Sciences, version 15.0) package software. Study parameters were evaluated using descriptive statistical methods (frequency, standard deviation, mean and percentage), as well as the Kolmogorov- Smirnov test to analyze the normality of the variables. For comparing the quantitative variables, an independent samples t-test was used for the comparison of parameters, which were normally distributed and the Mann-Whitney U test was used for the comparison of parameters, which were not normally distribution between the groups. For intra-group comparisons, paired samples t-test was used for parameters conforming to the normal distribution, and the Wilcoxon test was used for the parameters not conforming to normal distribution. For comparison of qualitative data, the Chi-square test was used. The p<0.05 values were considered statistically significant.
Results
This study included a total of 60 patients who underwent tracheostomy with or without FB under elective conditions due to prolonged mechanical ventilation. Patients’ average age was 56.6±20.2 (min-max: 20-70) years; 18 (30%) patients were female and 42 (70%) were male. The patients were separated into two groups as Group 1 and Group 2. Each group had 30 patients. There were no statistically significant differences between the groups in terms of gender and age. (p=0.573 and p=0.214, respectively). The demographic data of the groups are shown in Table 1.
The mean GCS was 6.0±2.9 in Group 1 and 6.0±3.1 in Group 2, and the difference was not statistically significant (p=0.999). The number of days on ventilation was 9.1±5.8 days in Group 1 and 7.3±5.9 in Group 2 with no statistically significant difference between them (p=0.081).
Tracheostomy procedure time was notably longer in Group 1 compared to Group 2 (p<0.001). However, no major difference was found between experienced and inexperienced practitioners in terms of the mean procedure time (p=0.739) (Table 2). Whereas no statistically notable difference was found between Group 1 and Group 2 in terms of SaO2 before and after the procedure (p=0.938 and p=0.760, respectively), the increase in SaO2 after tracheostomy was statistically significant (p=0.009). No statistically significant difference was found between the groups in terms of PaCO2 values before (p=0.283) and after (p=0.321) tracheostomy operations. In addition, there was no significant difference between the groups in themselves before and after the procedures (p>0.05). While no significant difference was found between Group 1 and Group 2 in terms of PaO2 values before and after tracheostomy procedures (p=0.363 and p=0.191, respectively), the increase occurred following tracheostomy in Group 2 was statistically significant (p=0.031). No statistically remarkable difference was found between the groups in terms of H2CO3 values before (p=0.367) and after (p=0.230) tracheostomy operations. In addition, there was no notable difference between the groups in themselves before and after the procedures (p>0.05). Again, no notable difference in pH values both between the groups and within the groups themselves before and after the procedures (for all p>0.05). Comparison of blood gas values before and after tracheostomy operations according to the groups is presented in Table 3.
The most common complication was minor bleeding in both groups, and it was observed in 10% of the patients in Group 1 and 30% of the patients in Group 2. No statistically notable difference was found between the groups in terms of complications (for all p>0.05). The distribution of complications according to the groups is shown in Figure 1. The mean duration of admission in the ICU was 28.8±20.2 days in Group 1 and 21.8±18.6 days in Group 2, and the difference was not statistically notable (p=0.088).
Discussion
Today, percutaneous dilatational tracheostomy (PDT) is increasingly used as an alternative to surgical tracheostomy. Fiberoptic bronchoscopy (FB) is the most commonly used technique for PDT [8]. In this study, we compared PDT applications with and without FB in terms of operational time, blood gas values and perioperative complications. In our study, no statistically notable difference was found between the two groups in terms of demographic and clinical data such as age, gender, BMI and GCS. Similarly, no significant difference was found between the FB and non-FB groups in the studies by Gadkaree et al. [9] and Maldonado et al. [10]. Again, in a study by Saritas et al., comparing FB and ultrasound guidance for PDT, no significant difference was reported in terms of the demographic data [6]. In this context, our findings are similar to those reported in the literature.
The duration of PDT operation is a major source of concern in critically ill patients. The addition of bronchoscopy to the procedure increases the cost [11]. The mean operational time was reported as 9.8±1.2 minutes by Shen et al. [12], 12.1±5.6 minutes by Tahal et al. [13] and 16.3±1.6 minutes by Ravi et al. [14] using flexible fiberoptic bronchoscopy. In our study, the mean procedure time was significantly longer with FB (13.4±4.9 minutes) compared to PDT without FB (8.1±6.1 minutes). Although the mean duration of operation with FB in our study was longer compared to non-FB procedures, it is consistent with the previously reported time range. We think that differences in the mentioned studies may result from the experience of the practitioners and the equipment used (e.g. flexible vs rigid bronchoscope etc.).
Bronchoscopy provides direct visualization, enabling education of those gaining experience in the insertion of tracheostomy. However, complication rates with bronchoscopy may also depend on the experience of the physicians [15]. In our study, the procedures were performed by experienced specialists or assistant doctors under the supervision of experienced specialists. Most of the cases, namely 25 cases (83.3%) in Group 1 and 24 cases (80%) in Group 2 were performed by the assistant doctors. Five (16.7%) procedures in Group 1 and 6 (20%) in Group 2 were carried out by experienced specialists. There was no notable difference between these two groups of physicians in terms of the parameters that we have studied. Hypoxemia during bronchoscopy is caused by various factors. The bronchoscope itself decreases the airway’s cross-section and restricts airflow [16]. Whereas, in our study, no notable difference was found between the FB and non-FB groups in terms of oxygen saturation. Moreover, no major difference existed before and after the procedure in our bronchoscopy group in terms of oxygen saturation. However, the increase in O2 saturation after the procedure was significant in the non- FB group (p=0.009). In a study by Hassanin et al., although O2 saturation decreased after sedation and during the procedure, there was no significant difference between the FB and surgical tracheostomy groups (p>0.05) [17].
Studies in the literature have reported concerns about unwanted side effects with bronchoscopy due to increased partial CO2 and partial O2 [18]. In the study by Hassanin et al., no notable difference was found between both groups in terms of PaCO2, while the increase in PaCO2 during tracheostomy in the FB group was significant [17]. In our study, no important difference was found between both groups in terms of PaCO2 both before and after the procedure. In addition, among other blood gas values, there was no significant difference between the groups in terms of PaO2 and pH values, both before and after the procedures (p>0.05). On the other hand, in a randomized controlled study by Eminoglu et al. comparing tracheostomy with FB and classical methods, there was a significant difference between PaO2 and pH values between 30 minutes before and 30 minutes after the operations, while pH values were noticeably lower in FB group following the procedure (p=0.01) [19]. We believe the differences between the studies might be attributed to several factors such as the techniques and equipment used and experience of the practitioners.
In general, complications caused by PDT procedures vary in a wide range from minor tissue damage to airway loss. Common complications include dysphonia, minor bleeding, surgical bleeding, posterior tracheal wall perforation, laryngotracheal stenosis and pneumothorax. In a study by Yaghoubi et al. on tracheostomy with fiberoptic bronchoscopy in 70 patients, subcutaneous emphysema, misplacement of the tube and mild hypoxia were seen only in one (1.4%) patient [7]. In the study by Gadkaree et al. comparing PDT operations with and without FB in 149 patients, no significant difference was found between the groups in terms of complications, and the authors concluded that the use of bronchoscopy would be beneficial [9]. Some studies have reported that although complications rates may be similar between tracheostomy procedures with and without FB, the risk of more serious and life-threatening complications may be higher when bronchoscopy is not used [11]. However, this was not confirmed in our study. In the present study, we most commonly encountered minor bleeding followed by hypoxia, subcutaneous emphysema, surgical bleeding and pneumothorax, although no notable difference was found between the groups in terms of the complications. Furthermore, the rate of minor complications was lower in the FB group compared to the non-FB group. We attributed this to the fact that the procedures performed by the inexperienced physicians were carried out under the supervision of the experienced specialists. In addition, major complications such as incorrect extubation, cuff rupture, esophageal perforation, tracheal stenosis, vocal cord paralysis and posterior wall damage were not observed in our study.
Study Limitations
The relatively small number of patients and the fact that the study was conducted in a single center are the main limitations of this study. In addition, late complications could not be evaluated. Finally, it was not possible to analyze the length of hospital stay and total costs of both techniques. On the other hand, the prospective and randomized controlled nature of the study is its main strength.
Conclusion
The most important result of this study is that the procedure time is longer when fiberoptic bronchoscopy is used. However, blood gas values and complications were similar between the groups. Therefore, we believe that FB can be used as a safe and effective alternative to classical surgical tracheostomy under elective conditions based on experience of the physician, patient’s preference and availability of technical equipment.
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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8. Decker S, Gottlieb J, Cruz DL, Müller CW, Wilhelmi M, Krettek C, et al. Percutaneous dilatational tracheostomy (PDT) in trauma patients: a safe procedure. Eur J Trauma Emerg Surg. 2016; 42(5):605-10.
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10. Álvarez-Maldonado P, Pérez-Rosales A, Núñez-Pérez Redondo C, Cueto- Robledo G, Navarro-Reynoso F, Cicero-Sabido R. Traqueostomía percutánea guiada por broncoscopia. Una técnica segura en cuidados intensivos [Bronchoscopy-guided percutaneous tracheostomy. A safe technique in intensive care]. Cir Cir. 2013; 81(2):93-7.
11. Díaz-Regañón G, Miñambres E, Ruiz A, González-Herrera S, Holanda-Peña M, López-Espadas F. Safety and complications of percutaneous tracheostomy in a cohort of 800 mixed ICU patients. Anaesthesia. 2008; 63(11):1198- 203.
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Şule Batçık, Mustafa Süren, Mevlüt Çömlekçi, Melih Özdamar, Haluk Özdemir, Sibel Fadıllıoğlu, Tayfun Aldemir. Comparison of patients undergoing tracheostomy with and without fiberoptic bronchoscopy. Ann Clin Anal Med 2021;12(Suppl 3): S333-337
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Effects of chronic diseases and polypharmacy on death anxiety
Burcu Korkut 1, Nergiz Sevinç 2
1 Family Doctor Specialist, Karabuk Provincial Health Directorate Community Health Center, 2 Department of Public Health, Karabuk University Faculty of Medicine, Karabuk, Turkey
DOI: 10.4328/ACAM.20750 Received: 2021-06-16 Accepted: 2021-07-25 Published Online: 2021-08-06 Printed: 2021-08-15 Ann Clin Anal Med 2021;12(Suppl 3): S338-342
Corresponding Author: Burcu Korkut, Family Doctor Specialist Karabuk Provincial Health Directorate Community Health Center, Karabuk, Turkey. E-mail: burcukorkut@karabuk.edu.tr P: +90 537 06316 27 Corresponding Author ORCID ID: https://orcid.org/0000-0003-4763-1902
Aim: Chronic diseases and polypharmacy are medical conditions that have negative effects on quality of life and mental state. The aim of this study is to inves- tigate the effects of chronic diseases and the use of multiple concurrent medications on death anxiety within the context of sociodemographic characteristics.
Material and Methods: This cross-sectional study included 324 individuals aged between 18-75 years who applied to Karabuk Community Health Center be- tween November 2020 and February 2021. Twelve questions were asked to evaluate the socio-demographic characteristics of the participants. Participants’ death anxiety levels were evaluated with the Turkish death anxiety scale consisting of 20 questions. The questionnaire and scale were applied to the partici- pants by face-to-face interview technique.
Results: The average age of the participants was 43.6±13.27 years. The average death anxiety scale score of the individuals was found to be 47.0±11.63. Individuals aged 51 and over, women with 2 or more children, those with hypertension and osteoporosis due to chronic diseases, and participants who use 4 or more drugs per day had significantly higher levels of death anxiety (p<0.05).
Discussion: The death anxiety scale score obtained as a result of this study was found to be moderate. Organizing training on death anxiety, which impairs the quality of life of individuals, may positively affect individuals and cause them to become attached to life. Making the necessary changes to healthy lifestyles, early detection of common diseases and taking precautions, and avoiding multiple drug treatments as much as possible may be beneficial in increasing the quality of life and reducing death anxiety.
Keywords: Chronic Disease; Death Anxiety Scale; Polypharmacy
Introduction
Chronic diseases are medical conditions caused by various physiopathological processes, develop gradually, and require long-term treatment and care [1]. Regarding terminology, chronic diseases are also defined as non-communicable diseases (NCD). NCDs are considered the most important health problem worldwide because they currently lead to disabilities and death. NCDs cause yearly 15 million deaths in the population between the ages of 30 and 70 years, and 71% of all deaths are caused by NCDs [2]. In 2018, the global evaluation of the causes and rates of death related to chronic diseases revealed that the first-ranked four causes were cardiovascular disorders (44%), cancers (9%), chronic respiratory diseases (9%), and diabetes mellitus (4%) (World Health Organization, Noncommunicable diseases country profiles 2018). In the mortality statistics published by the Turkish Statistics Institute (TURKSTAT) in 2019, the first three causes of death were cardiovascular diseases (38.4%), cancers (19.7%), and respiratory system diseases (12.5%) (available at: https://data.tuik.gov.tr/Bulten/ Index?p=Olum-ve-Olum-Nedeni-Istatistikleri-2019-33710). The rate of chronic diseases increases with age. Studies conducted in our country have shown that 70-90% of individuals aged 65 years or over had at least one chronic disease [3]. The increases in the rate of chronic diseases lead to a raised need for healthcare services and medication [4].
On the other hand, polypharmacy is usually a secondary finding in cases with more than one chronic disease and is defined as the simultaneous use of multiple and different drugs [5]. Although the definition of polypharmacy includes limitations like two, three, four, five, or more drugs, in the majority of the studies it is defined as the use of five or more drugs [6]. It is well known that polypharmacy causes drug-drug and drug-disease interactions and adverse drug reactions [7]. Furthermore, complicated treatment schemes containing multiple drugs decrease patient compliance. Studies conducted in this context have demonstrated that polypharmacy was an important problem in the treatment of individuals [6]. Anxiety and death anxiety are more common in individuals with drug- related adverse events and interactions, chronic disease, and/ or polypharmacy [8].
Death anxiety is an emotion, which is present from birth throughout the whole life, underlies all fears and plays an important role in the development of the structure of individuals’ character. It develops after the emergence of awareness of the loss of oneself and the world, the possibility of being nothing [9]. The thought of death and its impact on human life are unavoidable, and this unmeasurably emerging thought of death harms the individual’s psychology.
In this study, our objective was to investigate the relationship between chronic diseases, polypharmacy, and death anxiety within the context of socio-demographic characteristics. In this context, our goal was to include individuals aged 18 and above to evaluate the relationship between age and death anxiety and light the way for new studies with the obtained results.
Material and Methods
This cross-sectional study was conducted with 345 individuals between the ages of 18-75 who applied to the Community
Health Center (CHC) in Karabuk city center between November 2020-February 2021. The population of the study consisted of 345 people who applied to CHC for the first time for nutritional counseling, marriage counseling, smoking cessation outpatient services, and cancer screening within the specified date range, and all of them were included in the study without sampling. Participation in the study was voluntary, and the participants were first informed about the study and their written consent was obtained. The questionnaire was applied to 332 people who agreed to participate in the study through face-to-face interview technique. Eight participants were not included in the study because they filled the questionnaire incorrectly or incompletely, and the study was completed with 324 people. We received permission from the Ethics Committee for Non- invasive Clinical Research of XXX (No: E-77192459-050.99- 9595 Subject: 2020/382), and XXX (No: 98024045-604.01.02). This study was conducted according to the principles of the Helsinki Declaration. A questionnaire consisting of 32 items was used to evaluate the relationship between chronic diseases, polypharmacy, and death anxiety level within the context of socio-demographic characteristics. In the first section of the questionnaire, the participants answered 12 questions about socio-demographic characteristics, such as age, gender, marital and education status.
This study analyzed the age according to socio-demographic characteristics: as 18-25 years, 26-35 years, 36-45 years, 46 years and above. The number of children was stated as 1,2,3,4 and above. The educational status was classified as primary school, middle school, high school, university, graduate and doctorate. At the stage of comparing socio- demographic characteristics with the death anxiety scale score, ages were grouped as 18-30 years, 31-50 years, 51 years and above, while the numbers of children were classified as no children, 1, 2 and above.Educationalstatusweregroupedas12yearsandbelow and above 12 years. In many studies in the literature, the number of drugs used for the definition of polypharmacy differs from each other, and since the use of 4 or more drugs is considered as polypharmacy, therefore in our study, the classification was made as 1-3 drugs and 4 or more drugs.
The Death Anxiety Scale (DAS), which was used in the second section of the questionnaire, was developed by Templer (1970) and was adopted by Sarıkaya (2013) to the Turkish Version. This 5-point Likert scale consists of 20 questions (Şenol C. Anxiety and Fears Regarding Death in the Elderly Living in Institutions in Ankara Province. Master Thesis, 1989) [10]. Regarding the answer options, “never” was scored with zero, “seldomly” with one, “sometimes” with two, “often” with three, and “always” with four. The scale provides a total score between 0 and 80, and higher scores indicate higher death anxiety. The investigation of the mean, standard deviation, standard error values, and rate of the selection of the options showed that a score between 30 and 47 points at moderate death anxiety, a score between 48-64 at high, 65-80 at very high, 13-29 at low and 0-12 very low death anxiety.
The items numbered 1, 2, 5, 6, 7, 9, 10, 11, 17, and 20 were attributed to the factor “the uncertainty of death”; 4, 8, 12, 13, 14, 16 and 19 under “thought and witness of death”; 3, 15, and 18 under “suffering”. The validity and reliability analysis of the
Turkish version of the DAS was performed by Sarıkaya (2013), and the Cronbach’s Alpha value was found to be 0.95.
The data were evaluated in a computer environment using the SPSS 25.0 program. The compatibility of DAS scores with the normal distribution was tested with the Kolmogorov–Smirnov test. Quantitative data were presented as arithmetic mean, standard deviation, and percent distribution. An unpaired t-test and one-way ANOVA test were used to compare the SDL scores of the groups formed according to sociodemographic characteristics (Post-Hoc comparisons with Duncan test). The relationship between the state of having some chronic diseases and the mean score of SCA of the individuals participating in the research was analyzed with the unpaired t- test. P<0.05 values were considered significant in all analyses. In the study, Pearson’s chi-square test was used to evaluate the relationship between the age and number of children of the participants and the death anxiety scale score.
Results
Among the participants, 54.3% were females (n=176) and 45.7% males (n=148). The mean age was 43.62±13.27 years (min: 18; max: 75 years); 44.7% (n=145) of the participants were older than 45 years, 64.2% (n=208) were married, and 57.1% (n=185) were university graduates. The socio-demographic characteristics of the participants like age, gender, marital, and education status were summarized in Table 1.
The evaluation of the relationship between the scores of the Death Anxiety Scale and the socio-demographic characteristics is shown in Table 2.
The highest DAS score [50.13 (±12.04)] was in the age group of 51 and older. A statistically significant correlation was found between age and death anxiety (r=0.230, p=0.001). The death anxiety scale score was found to be statistically significantly higher in women than in men (p=0.000). The DAS score was also significantly higher in individuals who had two or more children [48.58 (±11.74)], and the correlation between the number of children and death anxiety was statistically significant (r= 0.205, p=0.003).
The statistical evaluation of the effects of chronic diseases and polypharmacy on death anxiety is summarized in Table 3.
The DAS score in hypertensive individuals was 48.91 (±11.79) (p=0.008). Patients with osteoporosis had a DAS score of 50.91 (±9.79), and death anxiety level was significantly higher in the osteoporotic participants (p=0.04). In the polypharmacy group, the DAS score was 49.30 (±11.13), so that the death anxiety was significantly higher in the individuals, who concurrently used 4 or more drugs (p=0.026).
Discussion
The increase in the prevalence of chronic diseases and polypharmacy is a result of the prolongation of the human lifespan, and it also increases the anxiety level caused by the death concept, which cannot be experienced. The death anxiety level is a psychological concept, which should be evaluated together with the physical health condition of the individuals. This study was conducted with individuals between the age of 18 and 75 years and it was found that the DAS score (50.13 ±12.04) was significantly higher in individuals aged 51 and older. Although most of the previous studies reported that the death anxiety level decreased with the increased age (Özen D. The Effect of Death Anxiety on Daily Life Functions of Elderly People Living in Nursing Homes. Unpublished Master Thesis, Istanbul, Halic University, 2008), a few studies showed that death anxiety increased with age [11]. A study evaluating death anxiety in 304 individuals aged 18 to 87 years found out that death anxiety was highest in the twenties, reached the second peak in females in fifties, and decreased after the seventies [12]. Some studies demonstrated that the mutual evaluation of age with other sociodemographic characteristics would provide more reliable results [11,12]. In our study, we determined that age is a parameter that increased death anxiety. We believe that this result depends on the peak of death anxiety in individuals aged 50 and older.
In our study, in which we also evaluated the effects of gender, the DAS score of women was significantly higher. Females constituted 54.3% of the participants, and their DAS score was 50.48 ±10.42 (Table 1). Madnawat and Kachawa (2007) and Depaola et al. (2008) found that death anxiety was high in females and increased with age [13,14]. The difference between females and males might depend on the cultural contrasts, females’ stronger ability to express their emotions and fears more easily, and males’ disability to express their anxieties and fears due to gender-related labels. Most of the studies reported high DAS score in females, which is consistent with our study [13,14].
Regarding the education status, we determined that this parameter did not affect the DAS scores. Aktürk and Şahin (2019) investigated the effects of education variables on death anxiety, continuous anxiety, and hopelessness levels and found that the education level had no effect on death anxiety level in academicians, bankers, and teachers, but it affected death anxiety in the nurse group [15]. In the same study, it was shown that the death anxiety score of the health vocational high school nursing graduates was significantly higher compared to nurses with associate and bachelor degrees. The investigators stated that this result depended on the low knowledge level of high school nursing graduates. In our study, 67.7% of the participants had more than 12 years of education and there was no significant difference in their DAS scores. This may depend on the diversity of the occupational groups, religious beliefs, and ethnic origins.
Considering marital status, 64.2% (n=208) of the participants were married, but however, no significant relationship was found between marital status and DAS score. According to the results of the study conducted by Erdoğdu and Özkan (2007), the death anxiety levels were higher in married participants [16]. This finding indicates that the increased DAS Scores in married individuals depend on a high sense of responsibility for children and partners. Although the majority of the studies reported a correlation between marital status and DAS score, it was found in our study that marital status had no significant effect on the DAS score. This finding may depend on the one- center design of our study, low educational level, and young age of the participants.
Considering chronic diseases, there was no significant correlation with DAS scores, although 89.2% (n=289) of our participants had chronic diseases. Likewise, Sayın-Kasar et al. (2016) found that the presence of chronic diseases did not always increase death anxiety [17]. Although Karahan and Hamarta (2019) determined increased DAS levels in patients with at least three chronic diseases, they reported also that particularly in elderly patients with multiple chronic diseases, death anxiety and anxiety deteriorated quality of life [3]. These conflicting results may be a result of the limitations related to the one-center design of the majority of the studies, an increase in the prevalence of chronic diseases along with the prolongation of human lifespan worldwide, and an increased acceptance of chronic diseases by the population.
Diabetes mellitus was present in 46% of participants (n=149), but there was no significant correlation between diabetes mellitus and DAS scores. Adakan et al. (2017) conducted a study on patients with type 2 diabetes mellitus (n=217) and a control group (n=100) [18]. They could not find a statistically significant difference between the groups for DAS scores of the participants. DM is a common chronic disease, which does not cause complications if regular and correct treatment is applied. Awareness and knowledge levels about DM are continuously being increased in the population with the help of the tools like social media and public service announcements. As a result of this, the death anxiety level was not affected by the presence or absence of diabetes mellitus.
Moreover, it was found that DAS scores in hypertensive individuals were significantly higher; 49.7% (n=161) of our participants were hypertensive and their DAS score was 48.91±11.79 (Table 3). Öztürk, Karakuş, and Tamam (2011) conducted a study on the elderly and determined that, as cardiovascular diseases are among the top causes of death, diseases like hypertension, which damage the vascular structure, remind patients of death and increase death-related worries and consequently increase significantly the death anxiety level in elderly with cardiac diseases and hypertension [19]. In our study, we determined that death anxiety increased in hypertensive patients, which was in line with the findings in the literature. This might depend on participants’ awareness that hypertension increases the incidence of relatively more dangerous diseases such as heart diseases, cerebral hemorrhage, and kidney failure.
In this cross-sectional study, it was also found that there was a statistically significant correlation between polypharmacy and DAS score. We determined polypharmacy in 31.8% of our participants and their DAS score was 49.30 (±11.13). Karahan and Hamarta (2019) included two groups in their study [3]. The first group consisted of 30 patients with at least three chronic diseases, and the second group of 30 individuals with no chronic disease. DAS scores were 62.03±17.2, and 17.05±5.31 in individuals with polypharmacy (n=30) and the control group (n=30), respectively. The difference was statistically significant. In this study, we noticed that the presence of chronic disease and multiple drug use are factors, which increase anxiety and death anxiety in elderly subjects. Besides, the increase in the number of drugs and the negative effects on the investigated health parameters indicated a frequently overlooked “polypharmacy”. Polypharmacy deteriorates prominently the quality of life. Particularly in elderly and single persons, death anxiety increases as a result of the worsened forgetfulness, which makes life relatively more difficult. In our study, it was found out that polypharmacy increased DAS scores being consistent with the findings in the literature.
Conclusion
In this one-center study with sample size, it was found that there was a statistically positive correlation between some sociodemographic characteristics like increased age, female gender, having 2 or more children, and death anxiety despite certain limitations of the study. In addition, we also determined a statistically positive correlation between hypertension, osteoporosis, and concurrent use of 4 or more drugs, and death anxiety. Healthcare professionals should be aware that patients diagnosed with chronic diseases and taking multiple medications, may experience changes in their emotional status and experience varying levels of anxiety. As chronic diseases and polypharmacy can increase the death anxiety level particularly in older female patients, sufficient information and psychological support should be provided at diagnosis and at the early stage of the disease to control the anxiety level. Besides, methods such as directing patients to social and physical activities, motivating them to start a hobby, and encouraging group activities can help to decrease death anxiety.
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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Latent ovarian stimulation in the management of infertile patients with hypogonadotropic hypogonadism
Mustafa Dogan Ozcil
Department of Gynecology and Obstetrics, Hatay Mustafa Kemal University, Tayfur Ata Sökmen Medicine Faculty, Hatay, Turkey
DOI: 10.4328/ACAM.20774 Received: 2021-07-06 Accepted: 2021-07-27 Published Online: 2021-08-06 Printed: 2021-08-15 Ann Clin Anal Med 2021;12(Suppl 3): S343-346
Corresponding Author: Mustafa Doğan Özçil, Hatay Mustafa Kemal University, Tayfur Ata Sökmen Medicine Faculty, Department of Gynecology and Obstetrics, 31060, Alahan-Antakya, Hatay, Turkey. E-mail: m.d.ozcil@hotmail.com P: +90 0326 2213317/ 229 10 00 GSM: +90 5323220266 F: +90 326 2455305 Corresponding Author ORCID ID: https://orcid.org/0000-0003-0819-6733
Aim: This study was designed to determine the effects of different treatment approaches on clinical pregnancy and live birth rates in patients with infertility due to hypogonadotropic hypogonadism (HH).
Material and Methods: The files of 31 patients with HH who applied with the complaint of infertility were retrospectively reviewed. Different infertility treat- ment protocols were applied to 21 of these cases, and the total number of cycles in which treatment was applied was recorded as 36. Of the 36 cycles, 22 were ovulation induction plus timed sexual intercourse, 3 were ovulation induction plus IUI, and the remaining 11 cycles were IVF/ICSI. Clinical pregnancy and live birth rates were determined as the primary outcome of our study.
Results: Twelve (33% of 36 cycles) of 21 patients conceived and 9 (25% of 36 cycles) had a live birth. When subgroup analysis was performed, pregnancy was detected in 9 cases (41%; 9/22) in the OI group, while 6 cases (27%; 6/22) had live births. In the IUI group, pregnancy was detected in 2 cases (66%; 2/3) and live birth in 2 cases (66%). In the IVF group, pregnancy was detected in only 1 case (9%), and live birth- in 1 case (9%; 1/11). Two out of 3 patients who received 75 IU / day latent ovarian stimulation with HMG for 3 months became pregnant.
Discussion: Latent ovarian induction with low doses of HMG in infertile patients with HH sensitizes developing follicles to exogenous gonadotropins and con- tributes to clinical pregnancy and live birth rates.
Keywords: Hypogonadotropic Hypogonadism; Infertility; Assisted Reproductive Technology; Latent Stimulation; Pregnancy
Introduction
Hypogonadotropic hypogonadism (HH) is classified as group 1 anovulation according to the World Health Organization (WHO) classification of female infertility [1]. It can also be called central hypogonadism or hypothalamic amenorrhea. In amenorrhea due to HH, either GnRH release is insufficient, or the pituitary is resistant to the GnRH effect [2]. In patients with HH, FSH, LH and estradiol levels are lower than normal [3]. Although estrogen/progesterone withdrawal bleeding is observed, progesterone withdrawal bleeding does not occur. In addition to primary or secondary amenorrhea, different clinical findings such as anosmia, osteopenia and short stature can be seen. The ovaries and uterus are smaller than expected due to estrogen deficiency secondary to FSH and LH deficiency. Serum AMH values may sometimes be low and sometimes close to normal. Secondary sex characteristics of those with a clinical picture of primary amenorrhea are generally not well developed. Its incidence is seen as 1/50000 in women and 1/10000 in men [2]. Approximately 5-10% of the patients presenting with anovulation complaints make up this group of patients. Genetic reasons have been blamed in the etiology and more than 20 genes have been described.
In patients with HH suffering from infertility are attempted to be treated with pulsatile GnRH treatment or the combined use of gonadotropic hormones such as FSH, LH and hCG. Assisted Reproductive Techniques (ART) are mostly used in infertile cases due to HH. Before ART, ovulation induction (OI) followed by timed sexual intercourse or intrauterine insemination (IUI) may be tried. In cases that do not respond to IUI treatment, one of the controlled ovarian hyperstimulation (COS) protocols is used [3-5]. There is no standard protocol applied in the treatment of infertility due to HH. While some authors suggest starting with high dose gonadotropin, such as 450 IU, some authors advocate the Step-down protocol [4]. This study was designed to determine the effects of different treatment approaches on clinical pregnancy and live birth rates in patients with infertility due to HH.
Material and Methods
This retrospective study was carried out following the approval of Mustafa Kemal University Tayfur Ata Sökmen Medical Faculty Ethics Committee (Prot no:2021/09/02- 01/07/2021). The files of patients with HH who applied to Mustafa Kemal University Tayfur Ata Sökmen Faculty of Medicine, Department of Obstetrics and Gynecology between 2013-2020 with the complaint of infertility were retrospectively reviewed. Screening of medical records revealed 31 cases meeting HH criteria. Different infertility treatment protocols were applied to 21 of these cases, and the total number of cycles in which treatment was applied was recorded as 36. The remaining 10 cases were not included in the evaluation because they did not receive any infertility treatment. Of the 36 cycles, 22 were ovulation induction plus timed sexual intercourse, 3 were ovulation induction plus IUI, and the remaining 11 cycles were IVF/ICSI.
Patients diagnosed with HH were selected among infertile cases and their demographic and hormonal characteristics were recorded. The treatment protocols applied to the patients, the drug doses used, and the duration of infertility were also recorded. Clinical pregnancy and live birth rates were determined as the primary outcome of our study. All participants underwent routine laboratory and radiological examination to diagnose the underlying factors of infertility. After 3-7 days of abstinence, a semen analysis was performed. Hysterosalpingography was performed in all participants. Basal hormone profiles of all cases were examined on the 2nd or 3rd day of menstruation, after hormone replacement therapy, and the diagnosis of HH was confirmed. Endometrial thicknesses in all cases diagnosed with HH were less than 5 mm, and while there was no progesterone withdrawal bleeding, estrogen or estrogen plus progesterone withdrawal bleeding occurred. Besides amenorrhea, decreased uterine and ovarian dimensions were interpreted as the absence of the trophic effect of estrogen. This study was conducted in accordance with the Declaration of Helsinki. Ethical approval was obtained from the local Ethics Committee. In additon to patients aged 18- 45 years with a BMI between 20-35 kg/m2 and without any systemic disease, those with FSH <2.5 mIU/mL, LH <2.5 mIU/ mL, endometrium thickness <4 mm, normal sperm analysis and HSG were included in the study. Estradiol value should be less than 60 pg/mL on the 2nd day of the cycle, and the values measured on the 3rd day were <80 pg/mL. Pituitary or adrenal tumor, endocrinological disorders were excluded from the study. COS protocol for IVF/ICSI
Cycloprogynova (Bayer Türk Kimya Sanayi. Ldt. Şti. İstanbul, Turkey) was started 3 months before starting COS in infertile patients scheduled for IVF/ICSI. The COS protocol was started on the 2nd or 3rd day of the cycle for the patients who had menstruation following the use of cycloprogynova for three months. No rFSH preparations were needed in any of the HH cases. They received daily human menopausal gonadotropin (HMG) preparation: Menogon (75 IU Ferring, Copenhagen, Denmark), or Merional (75 IU IBSA, Switzerland). In addition to the measurement of serum E2 values on the 4th and 5th days of HMG treatment, follicle dimension and endometrial thickness were measured by USG. While antagonist treatment was initiated in patients with a follicle diameter of 14 mm and in those with a sufficient estrogen elevation, the antagonist was not used in patients with low estrogen levels. When the mean diameter of two or three leading follicles reached 17 mm or more, hCG (Pregnyl amp 5000 IU 1×2, Organon, Oss, The Netherlands) or ovitrelle 250 microgram /0.5 ml was used to trigger ovulation.
In cases with ovulation induction, sexual intercourse was recommended 36 hours after hCG administration, while IUI was performed 36 hours after hCG in patients who underwent IUI. The oocyte pick-up was carried out in IVF/ICSI group following ovulation trigger, at least 35 and maximum 36 hours after administration. In the presence of a positive pregnancy test, luteal support was continued and USG was performed at the 4th week of the transfer and the presence of gestational sac and thus clinical pregnancy was confirmed. Clinical pregnancy rate is defined as the evidence of a gestational sac, confirmed by ultrasound examination. The live birth rate is defined as the delivery of a live fetus after 24 completed weeks of gestational age.
Statistical Analysis
Descriptive statistics were expressed as frequency, percentage, mean, and standard deviation. Categorical variables were analyzed using Pearson’s chi-square and Fischer’s exact tests. The normality of numeric variables was tested with the Kolmogorov -Smirnov test. One sample t- test was used to analyze numerical variables. All statistical analyses were performed using the SPSS (Statistical Package for the Social Sciences, SPSS Inc., Chicago, IL, USA) 21.0 package program. P<0.05 were considered statistically significant.
Results
The total number of infertile patients with hypogonadism who applied to our outpatient clinic was 31. Twenty-one patients received infertility treatment in our outpatient clinic, and 10 patients went to other centers for treatment after diagnosis. Twenty-one patients underwent 36 cycles of treatment. Twenty-two of them had timed intercourse, 3 had IUI, and the remaining 11 had IVF/ICSI. The mean age of the patients who were treated for infertility was 26.47 ± 5.22 years (OI: 26.07 ± 4.59; IUI: 28.00 ± 1.00; IVF: 27.29 ± 6.07). Two of our 21 patients were over the age of 35 and pregnancy could not be achieved. The remaining 19 patients were below 33 years of age. The mean duration of infertility was recorded as 5.37 ± 4.15 years for all patients. Mean basal FSH levels of the patients were 0.68 ± 0.72 mIU/mL, LH levels 0.37 ± 0.36 mIU/mL, and E2 levels were 28.89 ± 22.07 pg / mL. The mean daily HMG administered to the patients was calculated as 350.00 ± 101.50 IU. The mean induction time was recorded as 13.00 ± 3.86 days (OI: 13.05 ± 4.38; IUI: 10.33 ± 1.15; IVF: 13.64 ± 3.14). Mean total gonadotropin dose was 4222.27 + 1433.44 I.U (Table 1).
E2 levels on the day of hCG were 1845.32 ± 1092.32 pg/mL (OI: 1909.33 ± 1725.37; IUI: 1741.67 ± 38.19; IVF: 1866.90 ± 695.32). Endometrial thickness measured by USG on the same day was found to be 8.84 + 1.74 mm. Twelve (33% of cycles) of 21 patients conceived and 9 (25%) had a live birth. When subgroup analysis was performed, pregnancy was detected in 9 cases (41%) in the OI group, while 6 cases (27%) had live births. In the IUI group, pregnancy was detected in 2 cases (66%) and live birth in 2 cases (66%). In the IVF group, pregnancy was detected in only 1 case (9%), and live birth in 1 case (9%). During 36 cycles, IUMF was detected in 2 cases, spontaneous abortion in 1 case, and OHSS in 2 cases. One triplet pregnancy and one twin pregnancy occurred in our patients who conceived. When twin pregnancy was 21 weeks, two of the fetuses died (Table 1). After administration of HMG 75 IU/day for 3 months to 2 patients who could not get pregnant with IVF/ICSI, one of the patients became pregnant with IVF/ICSI and gave a live birth at term, the other patient became pregnant with twins with OI and timed intercourse and gave a twin live birth at 35 weeks. After HMG 75IU/day was administered for 3 months to 2 patients who did not respond to COS, IVF was performed, but pregnancy could not be achieved. Three of our patients, who could not conceive in the first cycle with OI and timed sexual intercourse, became pregnant with OI and timed sexual intercourse in the second cycle and gave live birth.
Discussion
HH is an uncommon but treatment-resistant cause of infertility. Although gonadotropins and pulsatile GnRH are used in its treatment, there is no standard treatment protocol. Increasing the sensitivity of follicles to HMG before treatment may increase the response to the COS protocol to be made. In this study, we discussed the effect of latent ovarian stimulation with HMG on clinical pregnancy and live birth rates. The demographic and clinical data of our patients with HH who participated in the study are shown in Table 1. We found the average age of the participants to be 26.47 ± 5.22. Eser et al. [4] found the mean age of HH patients to be 30.7, Kıyak et al. 27.8 [6] and Gustova et al. [5] stated that it was 33. We found the duration of infertility as 5.37 ± 4.15 years. Eser et al. estimated the duration of infertility in HH patients for 4.7 years [4]; Kumbak et al. reported it as 9.3 ± 6.1 years [7]. Our findings are consistent with the literature in terms of patient age and duration of infertility. Basal FSH and LH values of our patients were found to be 0.68 ± 0.72 mIU/mL and 0.37 ± 0.36 mIU/mL, respectively, in accordance with the literature. While Yılmaz et al. reported FSH values as 0.89 ± 0.73 mIU/mL [3], Eser et al. reported them as 1.1 mIU/mL [4]. The basal E2 value of our patients was 28.89 ± 22.07 pg/ml, which is similar to the literature data [6,8]. The participants’ average daily dose of HMG was 350 IU. Kumbak et al. (IVF) 325 IU [7], Ghaffari et al. 350 IU [8], Yılmaz et al reported it as 380 IU [3]. We recorded the average induction time as 13 days. Gustavo et al. reported this period as 13 days [5], Ghaffari et al. 13.8 days [8], Kumbak et al. reported it as 14 days [7]. We determined that the average total gonadotropin dose applied was 4222 units. Gustavo et al. stated this dose as 2700 IU, Kumbak et al. 4537 IU [7] and Yılmaz et al. reported it as 4741 IU [3]. Our E2 values, measured on the day of hCG and endometrial thickness measurements, were found to be similar to the literature data [3,4,6,7].
While 12 of the 21 patients participating in the study became pregnant (33 % of cycles), 9 patients (25%) had a live birth. In the timed sexual intercourse group, 9 patients (9/22, 41%) became pregnant, 6 of them (27%) gave live birth. In the IUI group, two out of 3 cases conceived, while both cases (66%) had live births. Only one case conceived in the IVF group (9%) and that patient had a live birth (9%). While the pregnancy rate in HH patients was reported as 12.2% by Kıyak et al. [6], it was noted as a 19.4% by Ghaffari et al [8]. Live birth rates were reported by different authors as 15.2%, 30% [3], 59.3 [7] and 69.2% [5]. As a result, pregnancy rates of all our cases are compatible with the literature. The high level of success in the timed sexual intercourse group may be due to the fact that our patients were young or unconsciously not did not undergo treatments that weaken their ovarian reserve. Our pregnancy success in IVF patients was 9%, and this rate is very low. When compared with the IUI group, patients in the IVF group are treatment-resistant and elderly patients.
As a complication, IUMF was detected in 2, abortion in 1, and OHSS in 2 cases. One of our pregnant patients had triplet pregnancy and one had twin pregnancy. Ulug et al. reported the rate of multiple pregnancy as 46.6% and the rate of abortion as 3.4% [1]. Ozcil reported the contribution of ART to twin pregnancies as 21%, and the fetal mortality rate as 20% in twin pregnancies with ART [9]. Gao et al reported abortion and multiple pregnancy in HH patients [10].
After the administration of HMG 75 IU/day for 3 months to 2 patients who could not get pregnant with IVF/ICSI, one of the patients became pregnant with IVF/ICSI, the other patient became pregnant with twins with OI and timed intercourse. After HMG 75 IU/day was given for 3 months to 2 patients who did not respond to COS, these patients responded to COS; IVF was performed. Three of our patients, who could not conceive in the first cycle with OI and timed sexual intercourse, became pregnant with OI and timed sexual intercourse in the second cycle.
Conclusion
Dormant primordial follicles under long-term HMG effect begin to grow into primary follicles and reach the preantral and antral stages, respectively [11]. This process takes approximately 72 days. Since there is no GnRH release in HH patients or the pituitary is insensitive to GnRH, FSH and LH release is either absent or insufficient. As a result, the follicles wait in the dormant phase and the follicles cannot reach further stage. Kumbak et al. stated that in order to create a follicular response to HMG, the silent ovaries should be activated first and the ovaries should be made sensitive to gonadotropes [7].
At least 72 days and 75 IU/day HMG priming may be required to complete this process and stimulate dormant follicles. At the end of this process, COS can be started by increasing the dose applied in accordance with the step-up protocol [12,13]. As a result, latent ovarian induction with low dose HMG in infertile patients with HH sensitizes follicles to gonadotropins. Applying COS to sensitized ovaries according to the step-up protocol will both increase the number of follicles and oocytes collected. Thus, latent ovarian stimulation can be considered capable of increasing pregnancy rates.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
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2. Hasdemir PS, Terzi H, Koltan S. O. Hipogonadotropik hipogonadizm olgularına yaklaşım: infertilite tedavisi ve uzun dönem yönetim. Kocaeli Tıp Dergisi. 2015; 4(1):13-18.
3. Yilmaz S, Ozgu-Erdinc AS, Yumusak O, Kahyaoglu S, Seckin B, Yilmaz N. The reproductive outcome of women with hypogonadotropic hypogonadism undergoing in vitro fertilization. Syst Biol Reprod Med. 2015; 61(4):228-32.
4. Eser A, Ergen EB. Hipogonadotropik Hipogonadizm Olgularında İnfertilite Tedavisi Sonuçları (Results of Infertility Treatment in Hypogonadotropic Hypogonadism Cases). Jinekoloji-Obstetrik ve Neonatoloji Tıp Dergisi/ Journal of Gynecology- Obstetrics and Neonatology Medicine. 2016; 13(4):160-3.
5. Cecchino GN, Canillas GM, Cruz M, García-Velasco JA. Impact of hypogonadotropic hypogonadism on ovarian reserve and response. J Assist Reprod Genet. 2019; 36(11):2379-84.
6. Kıyak H, Bulut B, Karacan T, Özyürek E, Gedikbaşı A, Api M. Management of ovulation induction and intrauterine insemination in infertile patients with hypogonadotropic hypogonadism. Journal of Gynecology Obstetrics and Human Reproduction. 2019; 48(10):833-8.
7. Kumbak B, Kahraman S. Women with hypogonadotropic hypogonadism: cycle characteristics and results of assisted reproductive techniques. Acta Obstet Gynecol Scand. 2006; 85(12):1453-7.
8. Ghaffari F, Arabipoor A, Lankarani NB, Etminan Z, Tehraninejad ES. Assisted reproductive technique outcomes in hypogonadotropic hypogonadism women. Ann Saudi Med. 2013; 33(3):235-40.
9. Özçil MD. İkiz Gebelikler ve Yardımcı Üreme Teknikleri ile Oluşan İkiz Gebeliklerin Feto-maternal Etkilerinin Karşılaştırılması (Comparison of Feto-maternal Effects of Twin Pregnancies Created by Assisted Reproductive Techniques and Twin Pregnancies). J Acad Res Med. 2021; 11(1):17-23.
10. Gao Y, Yu B, Mao J, Wang X, Nie M, Wu X. Assisted reproductive techniques with congenital hypogonadotropic hypogonadism patients: a systematic review and meta-analysis. BMC Endocr Disord. 2018; 18(1):85.
11. Öktem Ö, Urman B. Over hayat döngüsünü anlamak (Understanding the ovarian life cycle). Türk Jinekoloji ve Obstetrik Derneği Dergisi/ Journal of the Turkish Society of Gynecology and Obstetrics. 2011; 8(2):71-82.
12. Edgar DH, Whalley KM, Mills JA. Effects of high-dose and multiple-dose gonadotropin stimulation on mouse oocyte quality as assessed by preimplantation development following in vitro fertilization. J In Vitro Fert Embryo Transf. 1987; 4(5):273-6.
13. Sato F, Marrs RP. The effect of pregnant mare serum gonadotropin on mouse embryos fertilized in vivo or in vitro. J In Vitro Fert Embryo Transf. 1986; 3(6):353-7.
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Mustafa Dogan Ozcil. Latent ovarian stimulation in the management of infertile patients with hypogonadotropic hypogonadism. Ann Clin Anal Med 2021;12(Suppl 3): S343-346
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Intestinal endometriosis: Clinical reflections
Besim Haluk Bacanakgil 1, Emre Sinan Güngör 1, Işık Kaban 1, Gülşah İlhan 1, Serkan Sarı 2
1 Department of Obstetrics and Gynecology, İstanbul Training and Research Hospital, 2 Department of General Surgery, İstanbul Başakşehir Çam and Sakura State Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.20779 Received: 2021-07-10 Accepted: 2021-07-28 Published Online: 2021-08-15 Printed: 2021-08-15 Ann Clin Anal Med 2021;12(Suppl 3): S347-350
Corresponding Author: Işık Kaban, İstanbul Training and Research Hospital; Department of Obstetrics and Gynecology, Istanbul, Turkey. E-mail: drisikkaban81@gmail.com P: +90 5057946228 Corresponding Author ORCID ID: https://orcid.org/0000-0001-5134-0513
Aim: In this study aimed to analyze clinical, pathologic and radiological features of intestinal endometriosis in women and evaluate the recurrence and com- plications after surgery.
Material and Methods: Intestinal endometriosis was screened retrospectively in the histopathology reports of female patients who were operated in general surgery and gynecology-obstetrics clinics. Demographic characteristics of the patients, complaints at hospital admission, physical examination findings, laboratory and radiological imaging results were assessed. Surgical indications, surgical procedures, pathology results, follow-up period, complications and recurrence were documented and analyzed.
Results: The incidence of intestinal endometriosis (appendix, ileum, rectosigmoid) was 3.08%. Endometriosis was most common in the appendix (72%). The mean age of the patients was 41±9.9 years. The most common symptoms were lower abdominal pain (96%) and nausea (80%). Preoperative leukocytosis was present in 68% of the patients. Computed tomography (CT) was performed in 17 patients, and colonoscopy was performed in 2 patients. Among them, only 4 patients had findings suggestive of endometriosis (rectosigmoid localization). Surgical interventions applied to the patients were appendectomy, hysterectomy, ovarian cystectomy, terminal ileum resection and rectosigmoid low anterior resection. The most common condition was the coexistence of endometriosis and appendicitis. The mean follow-up period was 19.8 months. During this period, endometrioma developed in 2 cases and rectal bleeding in 1 case.
Discussion: According to our 15 years findings, intestinal endometriosis is most common in the appendix. Preoperative diagnosis is difficult as intestinal endo- metriosis may present with a variety of symptoms and conditions (acute/chronic). Most of our cases applied with urgent symptoms and findings. Symptoms were non-specific. The value of CT and colonoscopy in diagnosis is limited. Although it is not seen frequently, it should be considered, especially in cases with pelvic pain and lower abdominal discomfort, and the general surgeon and gynecologist should work together.
Keywords: Endometriosis; Intestine; Extragenital
Introduction
Endometriosis is an important health problem and is defined as the presence of endometrial-like tissue (glands and/or stroma) outside the uterine cavity [1]. Endometriosis affects 10-15% of women of reproductive age and 35–50% of women with pelvic pain or infertility and it is unusual in premenarcheal women and rare in postmenopausal women [2,3]. Endometriosis may present in multiple locations in the pelvis including, the uterus, ovary, pelvic peritoneum, urinary tract, rectum, colon, uterosacral ligaments, rectovaginal septum, vaginal wall, etc. It can also be seen in extra pelvic tissues and organs such as thr lungs and liver.
Intestinal endometriosis (IE) accounts for 3–37% of all endometriosis cases [4-6]. IE is usually asymptomatic and is found incidentally during surgery for other conditions. Rectal bleeding or dyschezia may occur if there are endometriotic implants in the lumen of the sigmoid or rectum, but these implants in the small intestine are often asymptomatic [4]. There may be nonspecific symptoms such as nausea, vomiting, diarrhea, constipation, abdominal pain and these symptoms mimic some intestinal disorders such as irritable bowel syndrome, Crohn’s disease, ulcerative colitis. The most common site of intestinal endometriosis is the rectosigmoid area (72%). This is followed by the rectovaginal septum (13%), the small intestine (7%), the cecum (3.6%), and the appendix (3%) [5]. Patients with intestinal endometriosis generally have lesions in multiple pelvic locations, so diagnosis is particularly difficult and it is not easy to locate the precise source of complaints. Although several radiologic techniques have been proposed for the diagnosis of IE, there is no gold standard. Transvaginal ultrasonography (TVUSG), computed tomography (CT), magnetic resonance imaging (MRI), or colonoscopy may be performed in the diagnosis of endometriosis.
The aim of this study was to analyze and evaluate the frequency, clinicopathological and radiological features of intestinal endometriosis in female patients undergoing abdominal surgery in a tertiary center, as well as to reveal postoperative recurrence and complications.
Material and Methods
The study was carried out in a tertiary center,
Istanbul Training and Research Hospital, from 2005 to 2019. This is a descriptive retrospective study. The diagnosis of endometriosis was scanned in the histopathology reports of female patients who underwent abdominal operations in general surgery and gynecology clinics. Among them, only intestinal ones were included in the study. The medical records of these cases were analyzed.
Demographic characteristics of the patients, complaints, physical examination findings, laboratory and radiological imaging results were assessed. Patient’s age,
surgical indications, surgical procedure, pathology results, follow-up period, complications and recurrence were documented. SPSS Statistics 26.0 program was used for statistical analysis. Mean, standard deviation, median, lowest, highest, frequency and ratio values were calculated for descriptive statistics of the data.
Results
Twenty-five of 812 cases were intestinal endometriosis cases (3.08%). Detailed characteristics of the cases are presented in Table 1.The mean age of the patients was 41±9.9 years. Except for the 74-year-old patient, the remaining patients were between 23 and 52 years old. This elderly patient had an acute abdomen, diameter of the appendix was 18 mm on tomography, laparoscopic appendectomy was performed, and in the histopathology of the appendix, there were acute appendicitis and endometriosis.
Two of our cases were nulliparous and the rest were multiparous. One of them was endometrioma plus terminal ileal endometriosis, and the other rectosigmoid was endometriosis. The most common symptoms were lower abdominal pain (96%) and nausea (80%). Peritoneal irritation findings were common. Preoperative leukocytosis was present in 68% of the patients. Computed tomography was performed in 17 patients. There were signs of appendicitis in 10 cases, and the mean appendix diameter was 11.4 mm. There were ileus findings in 3 patients, and wall thickening and compression and mass in the rectosigmoid in 2 patients.
Twenty of the 25 patients (80%) had an emergency diagnosis; 2/3 of the cases were operated with the diagnosis of acute appendicitis. Surgical interventions applied to the patients were appendectomy, hysterectomy, ovarian cystectomy, terminal ileum resection and rectosigmoid low anterior resection. The laparoscopic intervention was performed in 6 (24%) patients; 72% of the cases had endometriosis in the appendix, 16% in the rectosigmoid and 12% in the terminal ileum. In the same period, 3318 female patients underwent appendectomy, of which 18 patients had endometriosis in their appendectomy specimens (0.54%).
The cases were followed for an average of 19.8 months. During this period, endometrioma developed in 2 cases, and rectal bleeding in 1 case.
Discussion
Intestinal endometriosis is not a common entity, and its incidence has been reported in the literature as 3-37% [4-6]. Our rate was 3.08%. The most common location of extragenital endometriosis is the gastrointestinal tract [7], and the most common site affected within the gastrointestinal tract is the rectosigmoid junction, followed by the ileum, cecum and the appendix [8,9], respectively. On the contrary, in our cohort, endometriosis is most frequently located in the appendix (72%). Intestinal endometriosis can present with a variety of symptoms, making this diagnosis difficult. Although small endometriotic nodules on the serosal surface rarely cause symptoms, larger nodules may cause pain and a wide range of gastrointestinal symptoms, including diarrhea, constipation, rectal bleeding, abdominal bloating, and abdominal pain [10,11]. Since the presentation of IE can vary widely, it is difficult to make a diagnosis preoperatively. In our study, the most common symptom encountered in patients at admission was lower abdominal pain (96%). Besides that, there were only 4 cases of dysmenorrhea and 1 case of rectal bleeding, which could be considered relatively specific.
Intestinal endometriosis is difficult to diagnose before surgery because it mimics various bowel diseases [12]. Only 2 of our cases had a preoperative diagnosis associated with endometriosis. Most of our cases were patients with emergency diagnosis. The patients with intestinal endometriosis often have lesions in multiple pelvic locations, and since it is not easy to locate the precise source of complaints, imaging techniques are mandatory. CT and colonoscopy have limited value in the diagnosis, because the disease spreads inward from the serosa and in most cases, the mucosa remains unaffected. CT can reveal intestinal wall thickening in large lesions [12]. However, CT has a high diagnostic value in acute conditions (such as acute appendicitis, ileus). Acute disease was diagnosed in 15 of our 17 cases with tomography (88%). MRI is one of the most commonly used techniques for IE. The sensitivity and specificity of MRI in detecting pelvic endometriosis is about 90%. Only 2 of our cases had MR imaging. One of them was an endometrioma plus ileal mass, and the other was a rectosigmoid mass. TVUSG can detect the presence of pelvic endometriosis with high accuracy (sensitivity, 83%; specificity, 94%) and help predict the infiltration depth of nodules in the intestinal wall [12]. In our series, TVUSG was applied in 4 cases with gynecological indications and 1 case of rectosigmoid mass. MRI plus TVUSG is recommended for patients with IE [12].
Although colonoscopy is of little use in the diagnosis of intestinal endometriosis, because infiltration of the lesion into the mucosa is rare [13], the scarcity of mucosal involvement makes colonoscopy more useful in excluding other diagnoses rather than confirming the diagnosis of IE. Preoperative colonoscopy was performed in two of our cases, and these were cases with dysmenorrhea and rectal bleeding.
Surgical treatment of intestinal endometriosis remains controversial. In the presence of obstructive symptomsand acute situations, surgery is mandatory. However, in the absence of obstructionor acute situations, it remains unclear whether surgery should be performed. Surgical removal of intestinal endometriosis appears to be the most effective treatment in severely symptomatic patients. Several studies have demonstrated that surgical removal of all endometriotic lesions, including those in the bowel, is associated with a significant improvement in gastrointestinal symptoms and quality of life [7,14]. On the other hand, surgical treatment of intestinal endometriosis is associated with a significant rate of complications. A recent systematic review revealed a 6.3% rate of major complications following bowel endometriosis resection, including fistula, transient urinary retention and anastomotic leakage (2.7%, 3.5%, and 0.8% of cases, respectively) [15]. In our study, endometrioma developed in 2 cases after an average of 29 months after treatment, and rectal bleeding from the intestinal anastomosis site occurred in 1 case.
When surgery is required, several surgical approaches and techniques can be used. Surgical approach (laparoscopic, abdominal, vaginal, or combined) and surgical procedure (e.g. mucosal skinning, nodulectomy, full thickness disc resection, and segmental resection, bowel resection, transanal intussusception) are determined by the location and extent of endometriotic bowel lesions and by surgeons’ experience [5-9,14-16]. Although the indications for colorectal resection are limited, aggressive surgery improves quality of life [8,14]. The most common intestinal surgical procedures in our cases were appendectomy, rectosigmoid low anterior resection and terminal ileum resection, respectively. The cases undergoing bowel resection had severe wall infiltration and lumen narrowing. However, depending on the accompanying gynecological condition, interventions such as cystectomy and hysterectomy are also performed.
Bong et al reported recurrence and reoperation for pelvic endometriosis (bilateral salpingo-oophorectomy) in 1 patient 39 months after bowel surgery for intestinal endometriosis [12]. Several authors have previously reported that the recurrence risk increases if the lesions are not completely removed during the first surgery, and generally, recurrence occur at the same location [17,18]. Voiding difficulties and sexual dysfunction have also been reported after surgical treatment for rectal endometriosis [19]. Although some authors have reported complications related to anastomosis including rectovaginal fistula, anastomotic leakage, or pelvic abscess. Our patients did not experience such major complications. Postoperative follow-up revealed endometrioma in 2 (8%) of our patients, rectal superficial mucosal ulcer and bleeding in 1 (4%). Endometriomas were operated, and conservative treatment was applied for rectal bleeding.
In the present study, we aimed to reveal our 15-year clinical experience of intestinal endometriosis. Limitations of our study are retrospective analysis and the inability to access digital radiological images of some patients. Contrary to the literature, most of our cases were patients requiring emergency intervention. Again, unlike the literature, endometriosis was in the appendix. Preoperative diagnosis of IE can guide management. However, it is difficult to diagnose before surgery. Since IE is a relatively rarely seen entity, careful analysis of clinicoradiologic features will help diagnosis and treatment and follow-up strategies. Since genital endometriosis may also be present in cases of IE, the general surgeon and gynecological surgeon should work together, especially in patients in the reproductive period.
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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Besim Haluk Bacanakgil, Emre Sinan Güngör, Işık Kaban, Gülşah İlhan, Serkan Sarı. Intestinal endometriosis: Clinical reflections. Ann Clin Anal Med 2021;12(Suppl 3): S347-350
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Peripheral intravenous Ceftriaxone administration can cause upper extremity deep vein thrombosis in patients with heart failure
Adnan Yamanoglu 1, Zeynep Karakaya 1, Nalan Gokce Celebi Yamanoglu 2, Pınar Yeşim Akyol 1, Fatih Esad Topal 1
1 Department of Emergency Medicine, Izmir Katip Celebi University, Ataturk Training and Research Hospital, 2 Department of Emergency Medicine, Izmir Bozyaka Training and Research Hospital, Izmir, Turkey
DOI: 10.4328/ACAM.20509 Received: 2021-01-28 Accepted: 2021-03-10 Published Online: 2021-04-16 Printed: 2021-08-15 Ann Clin Anal Med 2021;12(Suppl 3): S351-353
Corresponding Author: Pınar Yeşim Akyol, Izmir Katip Celebi University, Ataturk Training and Research Hospital, Department of Emergency Medicine, Basın Sitesi, Izmir, 35360, Turkey. E-mail: yesimakyol@gmail.com P: +90 (232) 243 43 43 / +90 (232) 244 44 44 GSM: +90 505 357 29 41 F: +90 (232) 243 15 30 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2477-1443
Upper extremity deep vein thrombosis (UE-DVT) can result in pulmonary embolism in one in three patients and entails a high risk of mortality. UE-DVT has to date generally been linked to central venous catheter use and malignancy. Until today, there have been no previous reports of an increased risk of UE-DVT related to peripheral intravenous Ceftriaxone administration in patients with only heart failure (HF) as a risk factor.
We report a case of UE-DVT developing following iv administration of Ceftriaxone via a peripheral cannula with no provoking factor other than HF. This case showed us that Ceftriaxone administered via simple peripheral IV cannula can cause UE-DVT in cases with severe HF. Peripheral intravenous administration of Ceftriaxone may need to be avoided in patients with severe HF.
Keywords: Bedside ultrasound; Ceftriaxone; Heart failure; Intravascular thrombosis; Intravenous cannula
Introduction
Upper extremity deep vein thrombosis (UE-DVT) is a rare clinical entity, representing 1-4% of all deep vein thromboses (DVTs) [1]. In addition to local extremity discomfort, it entails a high risk of mortality as a cause of pulmonary embolism in one in three patients [2]. UE-DVT is classified into two groups. Primary UE-DVT occurs in association with idiopathic causes and anatomical variants, and is rare, with an annual incidence of 1-2/100.000 in the general population [1,3]. Secondary UE-DVT frequently occurs in association with one or more predisposing factors [3] and constitutes approximately 80-90% of all UE-DVT cases [4]. The most common predisposing factors for secondary UE-DVT are central venous cannulation and/or prothrombotic conditions, although kidney failure, history of DVT, history of trauma or surgery, heart failure (HF), and neurological diseases, which are predisposing factors for all DVTs, also constitute risk factors for UE-DVT [3].
Some medications are also known to be linked to UE-DVT [5]. However, we encountered no previous studies or case reports of an increased risk of DVT with Ceftriaxone use via the peripheral intravenous (IV) route in cases of HF.
We report a case of UE-DVT, which developed following Ceftriaxone administration via the peripheral IV route in a patient with no identified provoking factor for DVT other than HF. This case is reported since it involves a novel side-effect that may limit the use of Ceftriaxone via the peripheral route or else require particular care in patients with HF.
Case Report
A 56-year-old man presented to the emergency department (ED) due to pain and swelling in the right arm. He had only a history of coronary artery disease and subsequent HF. There was a history of chronic use of aspirin and ramipril + hydrochlorothiazide. There was no history of smoking, and no any other illegal substance or drug use. A detailed history revealed that the patient had presented to our hospital ED three days previously due to cough, fever and respiratory difficulty, and that pneumonia was diagnosed after tests. The patient was injected with 2 gr of Ceftriaxone in 150 cc of isotonic saline through a peripheral IV cannula in the right arm, and the patient was discharged with Ciprofloxacin group oral antibiotics. No other drug was administered through the same vascular access, and the cannula was removed during discharge. The patient again presented to ED with pain and redness in the right arm and with aggravated dyspnea. Extremity examination revealed a rash and edema beginning from the earlier cannula insertion site in the antecubital region of the right arm and extending toward the arm (Figure 1 a, b).
Bedside ultrasound for assessment of heart revealed a severely reduced left ventricular systolic function, biatrial dilatation and pleural effusion (Figure 2 a, b, c). Bedside ultrasound for vascular assessment of upper extremity revealed thrombophlebitis at the cephalic and basilic veins and UE-DVT at the subclavian, brachial and axillary veins (Figure 3). On thoracic CT angiography, there was no pulmonary embolism, while pneumonic infiltration and consolidation were determined in the upper lobe of the right lung, together with bilateral pleural effusion.
The patient was hospitalized. No Mycobacterium tuberculosis complex, Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, and Klebsiella pneumoniae growth was observed in sputum and blood cultures. Anti-HCV, Anti HIV, HBSAG, HIV Ag / Ab, and Anti HBc IgM values were negative. The patient’s homocysteine was within normal limits at 10.70 umol/L, Anti-ds DNA tested using IFT and EIA was negative, and anti-Beta2 glycoprotein 1 antibody IgM (1.23 U/ml) and IgG (4.32 U/ml) levels were negative. The lupus anticoagulant confirmatory test was negative, p-ANCA (1.36 U/ml), c-ANCA (0.32 U/ml), antinuclear antibody (FANA) (IFA), ACA IgM (1.84 GPL/ml) and IgG (2.7 GPL/ml) were negative, antithrombin, protein C and protein S levels were within normal ranges, and activate protein C was greater than 2.1. Since activated protein C resistance was not determined. A signed consent form was obtained from the patient.
Discussion
Genetic or acquired thrombophilic disorders leading to hypercoagulation are estimated to increase the risk of UE- DVT approximately 5-6-fold, although the mechanism by which hypercoagulable states contributes to DVT formation is still unclear [6]. Thrombophilic disorders include antithrombin III, protein C and protein S deficiency, Factor V Leiden and prothrombin gene G20210A polymorphism, antiphospholipid antibodies (lupus anticoagulant and anti-cardiolipins) [6]. The listed inherited thrombophilia disorders were subjected to laboratory tests, with the exception of Factor V Leiden, and the test results were negative for these. No need for genetic tests for Factor V Leiden was felt in the absence of activated protein C resistance and medical history.
Virchow’s triad is a widely recognized approach for explaining the risk of DVT formation. According to Virchow’s triad, in order for a clot to form on the vascular bed, either a flaw must be present in the vascular endothelium, or the blood flowing in the vascular bed must be impaired such as to cause thrombophlebitis, or stasis and pooling must be present in the region. Among these factors, impairment of the vascular endothelium and blood damage frequently appear in association with an acquired or genetic disease. However, stasis can also cause DVT even in healthy individuals without other risk factors following long journeys or major operations, particularly in the lower extremities, which are more affected by gravity. No inherited or acquired disease that might give rise to either endothelial damage or thrombophilia was determined in our patient, although HF capable of causing stasis was present. However, thrombosis would be expected to form primarily in the lower extremities that work against gravity in individuals with a disease such as heart failure that reduces blood flow in the entire body. In our case, thrombosis developed in the upper extremity following IV drug administration and occurred in a form following a vascular pattern, in other words, suggesting superficial thrombophlebitis. It subsequently spread, causing diffuse edema and pain in the proximal and medial aspects of the upper extremity. This also suggests that a DVT developed that proceeded from the superficial to the deep veins following a superficial thrombophlebitis. It is stated in the prospectus information that Ceftriaxone may cause <1% thrombophlebitis (available at: https://www.rxlist.com/rocephin-drug.htm#side_effects). In subsequent checks, macrolide group antibiotic was administered from the same vascular access from the other arm, and the vascular access was changed at 2-3 days intervals. The treatment continued in this manner, and no similar problem was observed.
Chemical agents reported in the etiology of UE-DVT include potassium chloride, diazepam, the antibiotics vancomycin and oxacillin, and a significant proportion of chemotherapeutic agents, and hypotonic (<250 mosm) and hypertonic (>350 mosm) solutions [5]. Even with these agents, DVT has frequently been reported in association with central catheters and malignancy, and in association with these drugs by the peripheral route, superficial thrombophlebitis has been more reported more than DVT [5].
Active infection can create a predisposition for thrombosis. This risk has previously been reported in association with infections growing in peripherally located central catheters [7]. The greatest association with thrombosis among systemic infections has been reported with cytomegalovirus infection, although underlying immunosuppression malignancy has been reported in the majority of those cases [8].
Ceftriaxone administered via simple peripheral IV cannula may result in UE-DVT in cases with severe HF with no other risk factor. Therefore, it may be necessary to avoid applying Ceftriaxone by the peripheral intravenous route in patients with severe heart failure.
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.
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
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2. Prandoni P, Polistena P, Bernardi E, Cogo A, Casara D, Verlato F, et al. Upper- extremity deep vein thrombosis: risk factors, diagnosis and complications. Arch Intern Med. 1997; 157(1):57- 62.
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4. Otten TR, Stein PD, Patel KC, Mustafa S, Silbergleit A. Thromboembolic disease involving the superior vena cava and brachiocephalic veins. Chest. 2003; 123(3):809-12.
5. Skillman, JJ. Superficial phlebitis: Inflammatory, infectious associated with deep vein thrombosis. In: Decision Making in Vascular Surgery, Cronenwett, JL, Rutherford, RB, editors. NY: WB Saunders; 2001.
6. Martinelli I, Battaglioli T, Bucciarelli P, Passamonti SM, Mannucci PM. Risk factors and recurrence rate of primary deep vein thrombosis of the upper extremities. Circulation. 2004; 110(5):566-70.
7. Thornburg CD, Smith PB, Smithwick ML, Cotton CM, Benjamin Jr DK. Association between thrombosis and bloodstream infection in neonates with peripherally inserted catheters. Thromb Res. 2008; 122( 6):782-5.
8. Justo D, Finn T, Atzmony L, Guy N, Stinvil A. Thrombosis associated with acute cytomegalovirus infection: A meta-analysis Eur J Intern Med. 2011;22(2):195-9.
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Adnan Yamanoglu, Zeynep Karakaya, Nalan Gokce Celebi Yamanoglu, Pınar Yeşim Akyol, Fatih Esad Topal. Peripheral intravenous Ceftriaxone administration can cause upper extremity deep vein thrombosis in patients with heart failure. Ann Clin Anal Med 2021;12(Suppl 3): S351-353
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Efficacy of manual lymph drainage in systemic sclerosis: A case report
Ayşenur Yılmaz 1, Bilge Başakcı Çalık 1, Elif Gür Kabul 1, Murat Taşçı 2, Veli Çobankara 3
1 Pamukkale University, School of Physical Therapy and Rehabilitation, Denizli, 2 Department of Rheumatology Abant İzzet Baysal University, Bolu, 3 Department of Rheumatology, Pamukkale University, Faculty of Medicine, Denizli, Turkey
DOI: 10.4328/ACAM.20516 Received: 2021-02-03 Accepted: 2021-03-18 Published Online: 2021-03-31 Printed: 2021-08-15 Ann Clin Anal Med 2021;12(Suppl 3): S354-358
Corresponding Author: Ayşenur Yılmaz, Pamukkale University, School of Physical Therapy and Rehabilitation, Denizli, Turkey. E-mail: fzt.aysenurgungor@gmail.com P: +90 258 296 42 46 GSM: +90 543 283 38 19 Corresponding Author ORCID ID: https://orcid.org/0000-0002-2357-0351
The aim of this case report was to evaluate the efficacy of manual lymph drainage (MLD) in a patient with Systemic Sclerosis in relation to pain, dyspnea, insomnia, edema, skin involvement, hand functions and quality of life . A 57-year-old patient with SSc who applied manual lymph drainage is presented in this case report. A Visual Analog Scale (VAS) was used to assess pain, dyspnea, edema and insomnia, volumetric measurements were taken of hand volume, the Hand Mobility in Scleroderma (HAMIS) test was applied for hand function, the Modified Rodnan Score (MRS) for skin involvement and the Short Form-36 (SF36) for Quality of Life. It has been observed that the application of MLD to systemic sclerosis patient has positive effects on skin involvement, edema, pain, dyspnea, insomnia, and quality of life. It is thought that it will be beneficial to add MLD application to the physiotherapy treatment program for patients with systemic sclerosis.
Keywords: Systemic sclerosis; Manual lymph drainage; Edema
Introduction
Systemic sclerosis (SSc) leads to restrictions because of the hardening of the skin, joint and muscle involvement. Problems on the hands show great variability depending on the stage of the disease. In the early stage, tissue edema is seen, especially on the fingers. Edema affects the face, extremities and trunk. Over time, fibrous tissue develops on the site of edema in the hands and fingers, and this reduces movement and functionality. This then restricts daily living activities and diminishes the quality of life [1,2].
Manual lymph drainage (MLD) is the application of light massage to the skin that increases smooth muscle contraction around the lymphatic vessels and thereby increases lymphatic flow and eliminates edema and excess amounts of interstitial fluid [3,4]. There is also an effect on the autonomic nervous system. Sympathetic responses are reduced and parasympathetic responses are increased. Decreased sympathetic system responses reduce the chronic inflammatory process [4].
MLD is used in patients with upper extremity edema, which has formed following breast cancer treatment. It is also used in the treatment of edema, which has formed for different reasons, and in a very broad spectrum of diseases and symptoms, such as venous and inflammatory edema (after trauma, infection, or surgery), Sudeck disease, scar treatment, rheumatoid diseases, headache and migraine [3].
The complex pathogenesis of edema in SSc includes microvascular changes, increasing sympathetic activity and inflammatory changes. In addition to the known microvascular changes in SSc, impaired lymphatic circulation in the upper extremities has been reported [5]. The presence of finger and hand edema in SSc can be considered to support the therapeutic approach of MLD. But there are not many studies on this subject in literature.
There are few studies in literature related to the effect of MLD on pain. It has been reported that pain is caused by the pressure of edema [2,3,6]. Therefore, knowledge of the changes in the patient’s perception of pain during and after the application of MLD in clinical applications would be of benefit in applying these practices with more awareness.
The Health Assessment Questionnaire (HAQ) is correlated with skin involvement, hand deformities, muscle strength and renal or cardiac impairment in SSc. In addition, respiratory problems are seen in SSc [2]. There are not many studies that examined the efficacy of MLD on respiratory problems [7]. The autonomic nervous system maintains homeostasis by the coordinated work of the sympathetic and parasympathetic systems. Parasympathetic system regulates the respiratory function, by providing a smooth muscle bronchoconstrictor effect. According to Vodder methods, MLD techniques can have effects on the autonomic nervous system. It can reduce sympathetic activity and indirectly increase the parasympathetic system. However, respiratory techniques are also used in MLD, Diaphragmatic breathing increases lymph flow and provides fluid flow in the body and repels edema [3,4,7].
Sleep quality decreases in patients with systemic sclerosis due to edema and pain. As a result, the quality of life will be affected in patients with systemic sclerosis due to pain, respiratory problems, edema, skin involvement and decreased hand functions [8]. This case report was planned to evaluate the efficacy of manual lymph drainage (MLD) applied to a patient with Systemic Sclerosis in relation to pain, dyspnea, insomnia, edema, skin involvement, hand functions and quality of life .
Case Report
The patient was 158 cm in height, weighed 82 kg, was a housewife and had no disease other than SSc. A 57-year old female with an 8-year history of SSC was followed up with a medical treatment in the Rheumatology Department of Pamukkale University Medical Faculty. Respiratory rate was 14/ min. The facial skin was taut, with limited lip movement and the facial features were unclear. Hands and fingers appeared to be swollen. The patient was in the edematous phase. There were no ulcers on the hands (Figure 1). The patient had no history of surgery and the family history revealed heart disease in her mother. The patient reported that she did not smoke or drink, and had recently experienced sleep problems and shortness of breath when walking and particularly when ascending stairs. She stated that the swelling and pain have increased, especially in the last month. The patient was admitted to the physiotherapy program with complaints of severe pain in the hands and feet that were restricting daily living activities. No change was made to the medical treatment while the physiotherapy program was applied. Informed consent for publication of the case was obtained from the patient. Evaluations and treatment of the patient were made by different physiotherapists. Before and after treatment, the patient was evaluated in respect of pain, dyspnoea, insomnia, and edema in the hand using a Visual Analog Scale (VAS) on a scale of 0-10 where 0 = the best status and 10 = the worst status [2].
Volumetric measurement to evaluate hand volume: the patient was instructed to place each hand separately into the water as far as the wrist, and the volume of the water displaced was calculated separately for each hand. The measurements were taken twice and the average was calculated for analysis. To prevent diurnal changes in edema, all the volumetric measurements were taken at the same time of day [1].
The Hand Mobility in Scleroderma (HAMIS) test is a valid and reliable tool for the evaluation of hand function in SSc and was applied to both hands for hand functional evaluation. The 9-item performance areas of the HAMIS test include holding and different movements in different dimensions, with tools and movements that are all related to a part of daily living activities. Each exercise is graded on a scale of 0-3, where 0 = normal function and 3= insufficient function. A maximum score of 27 can be obtained for each hand [2].
Quality of life was evaluated with the Short Form -36 (SF36). This is a 36- item scale, under separate subheadings, which is used to measure the functional status of an individual. The 8 sections of the scale are scored from 0 to 100. The subparameters evaluated in the scale are social competence, cognitive health status, physical capability, pain, emotional strength, energy/vitality, general health perception, and physical strength. Each subparameter is scored differently, with higher scores indicating an increased rate of development in the health status [7].
The Modified Rodnan Score (MRS) was used to evaluate skin involvement. The MRS is used in the follow-up of the course of the disease, with measurement of the skin by palpation. Scoring is applied as 0: normal skin, 1: mildly thickened skin, 2: moderately thickened skin (cannot be held), and 3: severely thickened skin (cannot be moved). The maximum score is 51, with higher scores indicating higher skin involvement. The first symptoms of skin changes in the early stage of the disease may not be evident, and in the late stage, the skin may be observed with an atrophic and hardened appearance [1].
The therapeutic exercises in the treatment program were applied with MLD using the Vodder technique. The program was applied as 15 sessions, 5 days a week for 3 weeks. The MLD technique was applied for 45 mins in each session. In all the sessions, the applications were started with the deep abdominal technique. First, MLD was applied to the neck region, after starting with effleurage, the swimming in the terminus technique was used. The lymph nodes in the neck were stimulated. Then MLD was applied to the trunk, which was drained in the first five days. In the following days, the axillary and inguinal lymph nodes were stimulated, then MLD was applied to the extremities [3-5]. In the working phase of MLD, a certain pressure is given, then it is moved on to the relaxation phase. These changes in pressure create a pump effect and lymph flow increases. The drainage is performed repeatedly and rhythmically [3,4].
Pre-treatment, the VAS scores of the patient were 7 for pain,10 for respiratory difficulty, 10 for insomnia, and 9 for edema felt in the hand during daily living activities, the MRS score was 22, volumetric measurements were 640.64 cm3 for the right hand and 677.6 cm3 for the left hand (Figure 1), the HAMIS score was 8 for the right hand and 5 for the left hand, and the SF36 subparameter scores were physical function 7.5, mental health 24.875, pain 0, emotional role 0, mental wellbeing 12, energy consumption 0, general health 20, and social function 25 points. Following treatment the evaluation results were VAS scores of 4 for pain, 8 for respiratory difficulty, 5 for insomnia, and 5 for edema felt in the hand during daily living activities, the MRS score was 14, volumetric measurements were 566.75 cm3 for the right hand and 542.08 cm3 for the left hand (Figure 2), the HAMIS score was 8 for the right hand and 5 for the left hand, and the SF36 subparameter scores were physical function 23.75, mental health 26.825, pain 25, emotional role 33.3, mental wellbeing 24, energy consumption 25, general health 35, and social function 87.5 points.
When the post-treatment results were compared with the pre- treatment values, there was an improvements of 3 for pain, 2 for respiratory difficulty, 5 for insomnia, and 4 for edema felt during daily living activities, according to the VAS points, an improvement of 8 points in MRS, volumetric measurements decreased by 73.92 cm3 in the right hand and by 135.52 cm3 in the left hand, and the HAMIS score did not change. An increase was observed in the SF36 subparameters.
Discussion
This case report was planned to evaluate the efficacy of manual lymph drainage applied to the scleroderma patient in the edematous phase on pain, dyspnea, insomnia, edema, hand functions and quality of life. As a result of this study demonstrated that MLD treatment applied to this SSC patient, positive improvements were obtained in skin involvement and edema in the hands, and this was seen to be reflected in the quality of life.
Difficulties in daily living activities occur because of conditions such as hardness in the hand, the presence of edema pain, reduced grip strength and slower hand movements that develop in connection with systemic sclerosis [1]. In patients with systemic sclerosis, quality of life is impaired due to pain, respiratory problems, edema and hand functions [8]. It was reported that MLD reduced edema in the upper extremities and increased quality of life in a patient with edema due to breast cancer [3]. Similar to the literature, there was a decrease in the edema volume in both hands. MLD stimulates the lymphatic vessels, and contributes to the movement of fluid in the lymphatic vessels and excretion of excess interstitial fluid. It also reduces sympathetic system activity and increases parasympathetic system activity, thus providing vasodilatation of the blood vessels and an improvement in circulation [4]. As a result, the edema is removed from the body through increased circulation.
Previous studies have shown that manual lymph drainage improves quality of life by reducing pain and edema in reflex sympathetic dystrophy, fibromyalgia and psoriatic arthritis. [3,6]. Self-perceived pain in the current patient was reduced following MLD, which was attributed to a decrease in the pressure created by edema, as the skin and subcutaneous nerve fibres are affected by the pressure of edema [4]. In the current patient, self-perceived sleep complaint in VAS was reduced. We think that the reduction in pain and edema also reduce sleep problems.
In addition, as a result of the treatment, the current patient reported a decrease in respiratory problems. Parasympathetic system regulates the respiratory function by providing a smooth muscle bronchoconstrictor effect. By increasing parasympathetic activity, the use of MLD has a positive effect on respiration [7].
It is important to use methods to reduce hand impairment and disability from the early stage of the disease. Because in SSc patients, the hand involvement leads to notable difficulties in daily living activities. It was also found that the quality of life was worsens to a greater extent in patients with skin involvement [8]. In the current patient, a decrease was determined in the MRS, and it is thought that the decreased area of skin involvement had a positive effect on the quality of life.
It was reported that MLD, added to the rehabilitation program, improved hand function and quality of life in SSc patients [2]. A decrease was observed in edema, skin involvement, pain and respiratory and sleep problems in the current patient. An increase was obtained in all the SF36 total point and subparameters. In patients with edema and lymphedema, the application of MLD has been shown to provide a reduction in extremity volume and pain and an increase in quality of life [3]. MLD improves quality of life for a variety of reasons. The pressure on the tissues is reduced and the lymphatic transport capacity is increased, which reduces the volume of the affected body part. In the same way that the reduced volume can reduce discomfort (pain, tension, weight), the functionality of the affected body area is increased. In addition to the effect on lymphatic vessels, blood flow in superficial arteries and collecting vessels increases and wound healing is accelerated. Moreover, MLD should be combined with exercise and skin care, which have a positive effect on the quality of life [1-4]. Quality of life is thought to have been positively affected because of the reduction in edema volume, skin involvement, pain, and respiratory and sleep problems.
They reported that the reduction was obtained in the HAMIS test in SSc patients. MLD with other treatments was applied in this study [2]. But in current patient, no change was determined in the HAMIS test. Combining manual lymph drainage with other treatments may increase its effectiveness. However, we think that our study is related to its short duration. Greater improvements could be obtained in the long term.
Previous studies on rehabilitation in SSc have included small patient samples and sometimes no control group. Although rehabilitation has been shown to be considerably effective in treatment, there is no evidence as yet that it can actually halt the disease [1,2]. High-quality randomized controlled studies with a longer follow-up are needed to prove the efficacy of MLD in SSc. However, large rehabilitation RCTs are difficult to conduct due to the SSc patients lack of information about the use and the efficacy of MLD and rehabilitation, the scarcity of physiotherapists specialized in MLD in evaluating and treating rheumatic patients, the difficulty of patients in accessing rehabilitation centers, and as patients are not in the edematous phase.
The effect of rehabilitation diminishes over time after treatment ends. Therefore, it should be emphasized that the treatment of SSc patients should be applied regularly and continuously. The limitations inherent in case studies are difficult to generalize as there is a single patient. The lack of objective evaluation of respiration before and after treatment can be considered a limitation of this study. In addition to our study is the short duration of treatment (3 weeks). After the treatment, how long the effect of the treatment continues was not followed. However, the observed result is consistent with the currently available literature.
In conclusion, the application of MLD treatment to a patient with scleroderma had positive effects on skin involvement, edema, pain, respiration, and quality of life. In SSc, MLD, when performed by experienced physiotherapists is safe and does not cause significant adverse effects for SSc patients. It will be beneficial to add MLD application to the physiotherapy treatment program in patients with systemic sclerosis. However, there is a need for further randomized, controlled studies to better reveal the efficacy of MLD in these patients.
Acknowledgment
The authors would like to thank the patient in this 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.
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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Ayşenur Yılmaz, Bilge Başakcı Çalık, Elif Gür Kabul, Murat Taşçı, Veli Çobankara. Efficacy of manual lymph drainage in systemic sclerosis: A case report. Ann Clin Anal Med 2021;12(Suppl 3): S354-358
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Giant Sister Mary Joseph nodule in gastric carcinoma
Ergin Erginöz 1, Ahmet N. Şanlı 1, Deniz E. Şanlı 2, Server S. Uludağ 1
1 Department of General Surgery, Istanbul University, Cerrahpasa School of Medicine, Istanbul, 2 Department of Radiology, Acibadem Kozyatagi Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.20525 Received: 2021-02-06 Accepted: 2021-03-28 Published Online: 2021-04-09 Printed: 2021-08-15 Ann Clin Anal Med 2021;12(Suppl 3): S359-361
Corresponding Author: Ergin Erginoz, General surgery resident, Istanbul University, Cerrahpasa School of Medicine. Cerrahpaşa street, No:34/E Fatih, Istanbul, Turkey. E-mail: eerginoz@ku.edu.tr P: +90 5368799771 Corresponding Author ORCID ID: https://orcid.org/0000-0002-8349-3298
Nodules in the periumbilical region are a rare finding as the differential diagnosis varies widely from umbilical hernia to malignant metastatic cancer. There- fore, any suspicious looking periumbilical nodules warrant further investigation of an underlying gastrointestinal or a genitourinary disease, as these usually indicate an advanced stage of malignancy. A Sister Mary Joseph (SMJ) nodule is one of these types of nodules that, once diagnosed, it must be promptly referred to the associated specialty to begin standard therapy for the patient. It is still unclear how these intra-abdominal malignancies spread towards the periumbilical region. Swift actions must be taken to make a diagnosis. In this case report, we present a 37-year-old male patient with a 15-cm Sister Mary Joseph nodule with an underlying gastric signet ring cell carcinoma.
Keywords: Sister Mary Joseph; Gastric carcinoma; Periumbilical nodule
Introduction
Sister Mary Joseph nodule was named after Sister Mary Joseph Dempsey, an assistant of Dr. Mayo at the Mayo Clinic, who observed that patients presenting to the clinic with a palpable nodule in the umbilical region usually presented with intra-abdominal malignancy [4]. The SMJ nodule is a palpable, cutaneous metastatic nodule that is malignant in nature originating from a tumor in the gastrointestinal tract [7]. These tumors often include adenocarcinomas of the gastrointestinal system (usually gastric, colon, and pancreas) and genitourinary tumors (ovarian and endometrial), carcinoid tumors, or undifferentiated tumors [1,2]. These nodules usually indicate advanced stage of the disease and are often associated with poor prognosis [6,7]. The pathophysiology remains unclear, but includes different routes towards the umbilical region. Some of the proposed hypotheses include hematogenous spread via branches of the external iliac artery and internal mammary artery, venous drainage including branches of the internal mammary vein and femoral vein, lymphatic drainage around the umbilical region, or via remnant structures such as the falciform ligament and the median umbilical ligament [3,5]. In the clinic, an SMJ nodule usually presents with an irregular lump in the periumbilical region varying from pink to brown color in appearance. The nodule may appear necrotic, vascular in nature, and hard in consistency. The size of the nodule is usually less than 2 cm, but it can reach to sizes up to 10 cm, as seen in this case report [3]. The differential diagnosis includes an umbilical hernia, SMJ nodule, neoplasm of the umbilicus, endometriosis of the umbilical region, melanoma, or a keloid [1,2]. Therefore, any nodule in the periumbilical region requires prompt referral to the corresponding secondary care centers.
Case Report
A 37-year-old male patient presented to our clinic with symptoms of fatigue, weight loss, and a periumbilical nodule. In physical examination, the patient was fully cooperated and appeared pale. The nodule in the periumbilical region was nearly 15 cm in size with irregular borders which was elevated above the umbilical region (Figure 1).
On palpation, the nodule was firm. Percussion and auscultation of the abdomen did not reveal any abnormality. The laboratory evaluation revealed anemia. Kidney and liver function tests were normal and electrolyte levels were within normal limits. Viral serology results were negative. The tumor markers included CA 19-9 849.80 U/ml (normally <39 U/ml), CEA 4.63 ng/ml (normal <6.5 ng/ml), AFP 16.03 ng/ml (normal <13 ng/ ml), PSA 0.60 ng/ml (normal <4 ng/ml). MRI of the abdomen revealed an umbilical protrusion (Figure 2).
CT of the abdomen also showed similar results with MRI. Whole body PET scan showed increased 18F-fluoro-2-deoxy-d-glucose (FDG) uptake along the greater curvature of the stomach and a linear FDG uptake along the distal esophagus near the gastro-esophageal junction (corresponding with esophagitis). Gastroscopy was performed and the biopsy of the greater curvature of the stomach was consistent with signet ring cell carcinoma of the stomach. Incisional biopsy of the periumbilical nodule was also consistent with a signet ring cell carcinoma infiltration.
Discussion
SMJ nodule usually presents with a periumbilical mass with varying morphological features such as pink to brown in color, and may include ulceration or vascularization. The pathophysiology of the SMJ nodule may involve the hematogenous, venous, lymphatic, or the remnant pathways, however, it is still unclear how intra-abdominal malignancy spreads through the periumbilical region [3,5]. To reach a definite conclusion, history of the patient, thorough physical examination, and proper imaging modalities are necessary. Once an SMJ nodule is diagnosed, the patient must be thoroughly examined to search for any underlying gastrointestinal or a genitourinary malignancy, since a SMJ nodule often indicates an advanced stage of malignancy. Therefore, any suspicious lesions should be biopsied and promptly referred to the associated specialty since, as presented in this case report, advanced stage of malignancy may be present in the patient.
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.
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Tso S, Brockley J, Recica H, Ilchyshyn A. Sister Mary Joseph’s nodule: an unusual but important physical finding characteristic of widespread internal malignancy. Br J Gen Pract. 2013;63(615):551-2.
2. Schoijet,I, Rojas A, Cortes C, Varela C. Sister Mary Joseph’s nodule: from the history to the images. A case-based literature review. Acta Gastroenterol Latinoam. 2018;48(2):82-9.
3. Gabriele R, Conte M, Egidi F, Borghese M. Umbilical metastases: current viewpoint. World J Surg Oncol. 2005;3(1):13.
4. Zhang K, Sankey C. The sister Mary Joseph nodule. J Gen Intern Med. 2015;30(5):689-90.
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6. Wronski M, Klucinski A, Krasnodebski IW. Sister Mary Joseph nodule: a tip of an iceberg. J Ultrasound Med. 2014;33(3):531-4.
7. Aljehani Y. An Unusual Cause for Sister Mary Joseph’s Nodule: A Case Report. Oman Med J. 2014;29(6):458-60.
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Ergin Erginöz, Ahmet N. Şanlı, Deniz E. Şanlı, Server S. Uludağ. Giant Sister Mary Joseph nodule in gastric carcinoma. Ann Clin Anal Med 2021;12(Suppl 3): S359- 361
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Intravenous thrombolytic treatment of a patient who had a stroke after COVID-19
Mustafa Cam, Ozgul Ocak
Department of Neurology, Canakkale Onsekiz Mart University, Canakkale, Turkey
DOI: 10.4328/ACAM.20527 Received: 2021-02-09 Accepted: 2021-04-05 Published Online: 2021-04-13 Printed: 2021-08-15 Ann Clin Anal Med 2021;12(Suppl 3): S362-364
Corresponding Author: Mustafa Cam, Canakkale Onsekiz Mart University Department of Neurology, Barbaros Street, Terzioglu Campus, Canakkale, Turkey. E-mail: mustafacam20@hotmail.com P: +90 5066493267 Corresponding Author ORCID ID: https://orcid.org/0000-0003-3116-203X
The infection, reported by the WHO as COVID-19, may occur with asymptomatic or mild symptoms, resulting in shock and even death. Stroke occupies an important place among the neurological complications of this disease. In the acute period, intravenous (IV) alteplase therapy is useful in patients suitable for the treatment.
This case report includes a 70-year-old patient with mild COVID findings, who had an early complication of stroke and who received a nearly complete benefit from thrombolytic therapy.
Stroke can occur in COVID patients at an early stage of the disease. IV thrombolytic therapy should be administered in appropriate patients during the period of acute stroke. As far as we know, the earliest application in our country was carried out in our hospital and was quite successful. After the treatment, the symptoms of COVID-19 also regressed and he was discharged on the 5th day of his hospitalization.
Keywords: Thrombolytic treatment; Stroke; COVID-19
Introduction
COVID-19 has caused millions of cases and hundreds of thousands of deaths all over the
world since December 2019. According to the World Health Organization (WHO), 5 months after the virus was defined as SARS CoV-2 due to its similarity to SARS CoV, the number of cases reached 6 million and the number of deaths reached 400 thousand. The incidence of acute stroke was detected in 5.7% of hospitalized patients due to COVID-19 [1]. No contraindications have been reported for iv alteplase given as treatment to COVID-19 patients who develop acute stroke [2].
Case Report
A 70-year-old female patient, who suddenly developed speech disorder with weakness and numbness on her left side, presented to the emergency room approximately 2 hours after the onset of her complaints. While speech was dysarthric in the patient’s neurological examination, the left nasolabial groove was obscure. The muscle strength of the left upper and lower limbs was 4/5. The brain CT was normal. Diffusion restriction zones located between the right caudate nucleus head and the lentiform nucleus, and the anterior part of the insular cortex were observed in diffusion brain MRI (Figure 1).
Fever was found in the examination performed in the emergency service. Respiratory system examination revealed a roughness in the breath sounds in left middle zone. Other system examinations were normal. In laboratory examinations, CRP: 5.7; Sedim: 58; WBC: 12000; LYM: 17; NEU was detected as 74%. In Torax CT, bronchiectasis enlargement in the medial segment of the right lung middle lobe and the left lung inferior lingular segment, as well as an increase in ground glass density was observed in both lungs (Figure 2). The patient, who was evaluated by the infectious diseases department, was diagnosed with COVID-19 and was started treatment.
The patient with an NIH score of 6 was given iv alteplase treatment. Neurological examination after thrombolytic therapy was evaluated as completely normal. When the control brain tomography taken 24 hours later was found to be normal, antiaggregant treatment was started. On the 5th day of his hospitalization, the patient whose symptoms of COVID-19 regressed and partial improvement was observed in the control thorax CT was discharged with the necessary recommendations.
Discussion
COVID-19 is considered a mutation of SARS (Severe Acute Respiratory Syndrome Virus) and MERS (Middle East Respiratory Syndrome Virus) [3]. The course of COVID-19 can progress from asymptomatic cases to complications such as severe acute respiratory disease and multiple organ failure, including acute heart and kidney damage, and eventually death may occur [4]. Coronaviruses are not primarily neurotropic viruses, and their primary target is the respiratory epithelium [1]. It is thought to cause thromboembolic events with both direct damage to the nervous system and high levels of inflammation, hypoxia, immobilization, and diffuse intravascular coagulation [5]. Increased inflammation activates the coagulation system by causing a cytokine storm, and diffuse intravascular coagulation due to thrombosis occurs in both venous and arterial systems [6]. CT scan of the chest typically reveals multiple ground-glass opacities, consolidation, and bilateral lung involvement [7]. This image was found to be compatible with the thorax CT images in our patient. Although the exact incidence is unknown, stroke is emerging as a complication of the COVID-19 pandemic. It should also be taken into account that patients may present only with a stroke clinic without classic symptoms such as fever, cough, and anorexia [8]. The clinic of our patient is also compatible with early COVID-19 findings. It should not be forgotten that a stroke is an emergency situation that needs to be taken fast in terms of diagnosis and treatment, even in the pandemic period. COVID-19 patients with acute stroke should be evaluated carefully and those who are suitable for treatment should be administered intravenous thrombolytic therapy or mechanical thrombectomy without delay, taking into account current guidelines [9]. Our case occurred with the emergence of COVID-19 cases in our country, and although there were reservations about the application of thrombolytic therapy, it was successfully applied. As far as we can examine, iv thrombolytic therapy has not been used in our country until then. This treatment is thought to be effective in regressing symptoms of COVID-19 infection.
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.
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Mao L, Wang M, Chen S, He Q, Chang J, Hong C, et al. Neurological manifestations of hospitalized patients with COVID-19 in Wuhan, China: a retrospective case series study. JAMA Neurol. 2020;77(6):683-90.
2. Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020 46(4):586-90.
3. Yeshun W, Xiaolin X, Zijun C, Jiahao D, Kenji H, Ling H, et al. Nervous system involvement after infection with COVID-19 and other coronaviruses. Brain Behav Immun. 2020;87:18-22.
4. Team NCPERE Vital surveillances: The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19)—China. China CDC Weekly. 2020 2(8):113–22.
5. Tu H, Tu S, Gao S, Shao A, Sheng J. The epidemiological and clinical features of COVID-19 and lessons from this global infectious public health event. J Infect. 2020;81(1):1-9.
6. Tveito K. Cytokine storms in COVID-19 cases? Tidsskr Nor Laegeforen. 2020;23:140
7. Shuchang Z, Yujin W, Tingting Z, Liming XCT. Features of Coronavirus Disease 2019 (COVID-19) (COVID-19) pneumonia in 62 Patients in Wuhan, China. American Journal of Roentgenology. 2020; 20:1–8.
8. Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic Manifestation of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. 2020; 77(6):683–90.
9. Qureshi AI, Abd-Allah F, Alsenani F, Aytac E, Borhani-Haghighi A, Ciccone A, et al. Management of acute ischemic stroke in patients with COVID-19 infection: Report of an international panel. Am J Emerg Med. 2020; 38(7):1548.e5–1548.e7.
Download attachments: 10.4328:ACAM.20527
Mustafa Cam, Ozgul Ocak. Intravenous thrombolytic treatment of a patient who had a stroke after COVID-19. Ann Clin Anal Med 2021;12(Suppl 3): S362-364
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