July 2021
Effect of COVID-19 pandemic on health perception, depression, anxiety and stress levels in Turkish society
Ruhusen Kutlu, Nur Demirbas
Department of Family Medicine, Meram Medical Faculty, Necmettin Erbakan University, Konya, Turkey
DOI: 10.4328/ACAM.20425 Received: 2020-12-03 Accepted: 2021-01-09 Published Online: 2021-02-12 Printed: 2021-07-01 Ann Clin Anal Med 2021;12(7):711-716
Corresponding Author: Ruhusen Kutlu, Department of Family Medicine, Meram Medical Faculty, Necmettin Erbakan University, 42080, Konya/Turkey. E-mail: ruhuse@yahoo.com P: +90 332 2236601 F: + 90 332 2236181 Corresponding Author ORCID ID: https://orcid.org/0000-0002-8502-0232
Aim: The purpose of this study was to evaluate the health perception, depression, anxiety and stress levels in Turkish society during the COVID-19 pandemic, and to examine the factors affecting.
Material and Methods: In this study, which was planned as a cross-sectional analytical study, individuals were reached through social media using the snow- ball sampling method. Health Perception Scale (HPS), Depression, Anxiety and Stress Scale (DASS), Perceived Stress Scale (PSS) was applied. The study was completed with 440 people.
Result: As the level of education increased, health perception scores also increased (p=0.049). There was a significant relationship between regular nutrition, exercise and self-devotion and perception of health (p<0.001, p<0.001, p=0.001). The total score of DASS was found to be statistically significantly higher in participants with COVID disease in the first degree (p=0.044). DASS depression subscale scores were statistically higher in singles than married. PSS levels were higher in the participants under the age of 40 (p=0.002), in women (p<0.001), in singles (p<0.001) and in those who did not have children (p<0.001).
Discussion: In this study, during the COVID-19 outbreak in the society, it was found that the participants had high levels of depression, anxiety and stress and low perception of health. Priority might therefore be attached to these in future psychiatric planning. Psychological interventions for prevention and treatment are necessary to reduce the psychological effects of the pandemic.
Keywords: COVID-19; Pandemic; Health perception; Depression; Anxiety; Stress
Introduction
The new coronavirus disease (COVID-19), which occurred in Wuhan, Hubei Province, China in December 2019, began to spread all over the world in early 2020. The COVID-19 outbreak was declared as a controllable pandemic by the World Health Organization (WHO) [1]. The disease continues to spread rapidly worldwide, with the first confirmed COVID-19 case reported on 11 March 2020 and the first deaths were announced on 17 March 2020 in Turkey. The Turkish government has taken various restriction measures, such as maintaining social distancing, travel bans for visitors from high-risk countries, the quarantine for citizens returning from these countries and closure of schools, shops and entertainment venues. This rapid increase in confirmed cases and deaths in the COVID-19 pandemic has created some psychological effects, such as stress, anxiety, and depression in both the medical staff and the general population.
The WHO has defined health as not only as the absence of illness and disability, but also as physical, mental and social well-being. This definition emphasizes that health is multi- dimensional, not one-dimensional, and addresses health with a holistic approach. The serious and fatal progressive diseases disrupt the balance of individuals, change a person’s plans for the future, the flow of daily life, and ultimately cause severe problems. These problems can range from disease adaptation efforts to clinical level mental disorders. Stress can negatively affect all aspects of human life, normal functions of individuals, and long-term exposure to stress also causes different health problems in people and negatively affects the quality of life [2]. While people are afraid that they and their relatives will be sick and die during this COVID-19 pandemic process, they also experience material and moral difficulties caused by the pandemic. In addition to fear of illness and death, staying under house arrest at the age of 65 and older, the closure of many workplaces, the social distance and other pandemic rules increase the depression and anxiety levels of the people and also affect the perceived stress level negatively [3].
The present study aimed to evaluate the stress state, anxiety and depression levels and health perceptions of the society trying to cope with this situation during the COVID-19 pandemic that is still ongoing in our country.
Material and Methods
Type, place and scopeof the research
In this study, which was planned as a cross-sectional analytical study, individuals were reached through the internet, social media and communication networks using the snowball sampling method. It was aimed to include 377 people with a 5% margin of error, a 95% confidence interval, and at least 420 people were planned in the study due to the possibility of missing survey questions and refusal to participate in the study. The study sample was composed of 440 adult participants. Ethical Permit for the Study
Ethical permission for the research was taken prior to the study from Necmettin Erbakan University Meram Faculty of Medicine, Department of Pharmaceuticals and Non-Medical Research Ethics Committee. (number 2020/2491). The study protocol was approved by the Turkish Ministry of Health,
General Directorate of Health Services (Approval Date/ Number: 03.05.2020/51_34). The participants were informed about the study and their written consent was obtained according to the principles of the Helsinki Declaration.
Data Collection Tools
The data were gathered online due to restrictions on face-to- face encounters with the participants because of the COVID-19 outbreak. After the approval of the ethics committee for the study was received, announcements were made with different social networks, the purpose of the study was explained and volunteers were asked to fill out a questionnaire at the given link. After applying the questionnaire form as a pilot for 10 individuals, problems with the comprehensibility and applicability of the questionnaire were corrected and this collected data were not used in the main study. The questionnaire created with Google forms was prepared anonymously and participants’ consent was requested. The first part of the four- part questionnaire included questions prepared for determining the socio-demographic characteristics of the participants, their daily lives and questions about the COVID-19 pandemic. The Health Perception Scale (HPS) was applied in the second part, the Depression, Anxiety and Stress Scale (DASS) in the third part, and the Perceived Stress Scale (PSS) in the fourth part. Sociodemographic Information Form
The questionnaire with information about the participant was prepared by the researchers by scanning the relevant literature. The form consists of 20 questions about the COVID-19 pandemic as well as questions regarding age, gender, marital status, education level, regular nutrition and physical activities. Health Perception Scale (HPS)
Health Perception Scale was developed in 2007 by Diamond et al. [4]. The scale consists of 15 items and it has 4 sub- dimensions: control center, precision, the importance of health and self-awareness. The answers are of the 5-point Likert type. Items 1, 5, 9, 10, 11 and 14 are positive, while items 2, 3, 4, 6, 7, 8, 12, 13 and 15 are negative. Turkish validity and reliability study of the test was done by Kadıoğlu and Yıldız [5].
Perceived Stress Scale (PSS)
The PSS scale was developed in 1983 by Cohen et al. [6]. The scale was used to measure the perceived stress level of the participants, the Turkish validity and reliability study of the test was done by Eskin [7]. The PSS scale consists of 14 items and is designed to measure how people perceive certain situations in their lives. The scale was prepared in a 5-point Likert type with 0: “Never” and 4: “Very often”. It has 2 sub-dimensions as ‘Insufficient Self-Efficacy Perception’ and ‘Stress / Disturbance Perception’. A high score obtained from the questionnaire indicates the excessive perception of stress.
Depression, Anxiety and Stress Scale (DASS)
This scale was developed by Lovibond, and the Turkish validity and reliability study of the test was done by Yıldırım [8,9]. The scale, which was previously made up of 42 items, has been shortened to 21 items, 7 of which measure depression, 7 measure anxiety, and 7 measure stress levels. In the scale directive, participants are asked to answer questions according to their situation over the past week. Depression Anxiety Stress Scale is a 4-point Likert-type scale and items are evaluated between 0 and 3 (0 = not suitable for me at all, 1 = suitable
for me, 2 = generally suitable for me, 3 = completely suitable for me). High scores on each of the depression, anxiety and stressdimensionsindicatethattheseproblemsarehighinan individual.
Statistical analysis
All the data obtained with the program were obtained through Google forms (available at: https://docs.google.com/forms/d/e/ 1FAIpQLScXA9G5vg5HqfmpUNbQRHSFLHbumgp4WgH6r_ H48dsZEg-X3w/viewform?usp=sf_link ) that were obtained in the study using internet and social media networks. Average, standard deviation values of numerical data were calculated. Compliance with normal distribution was evaluated with the Kolmogorov-Smirnov test. Those not in normal distribution were compared with appropriate statistical analyzes such as Kruskal-Wallis in binary groups and Mann-Whitney U in groups 3 and more. Reliability scoresfor each scale were calculated with Cronbach’s alpha. Pearson’s correlation analysis was used to determine the relationship between depression, anxiety and stress levels. Cronbach’s alpha coefficients of the scales and sub-dimensions used in the study were calculated. A p- value <0.05 was considered statistically significant.
Results
Among 440 people included in the study, 57.3% (n = 252) were female, 42.7% were male, and the average age was 40.58 ± 13.7 years; 69.5% (n=306) of the participants were married, 70.9% (n=312) have children, 37.5% (n=165) civil servants and 78.0% (n=343) were determined to be a university graduate, 72.3% (n=318) of the individuals did not have any chronic diseases, 76.8% (n=338) were eating regularly, only 14.3% (n=63) exercised for more than 150 minutes per week.
In the pandemic period, the mean total score of the individuals on the HPS was 51.15±6.4 (29-69) points. While the perception of health did not change with age, gender and marital status, a statistically significant relationship was found between education level and perception of health (p=0.049). As the education level increased, health perception scores also increased. There was a significant relationship between regular nutrition, exercise and self-devotion and perception of health (p<0.001, p<0.001, p=0.001, respectively) (Tables 1, 2).
The mean overall score of the study participants on the DASS scale was 15.5±12.1 (0-63) points, the score for the depression sub-dimension was 5.7±4.5 (0-21) points, the score for anxiety sub-dimension was 4.0±3.9 (0-21) points and the stress sub- dimension score was 5.9±4.4 (0-21). A significant relation was found between the total DASS score and gender (p=0.030). In particular, the stress subscale scores were statistically higher in women (6.2±4.3) than men (5.3±4.4). Similarly, a significant correlation was found between the total DASS score and marital status (p=0.020). Particularly, depression subscale scores were statistically higher in singles (6.9±4.9) than married (5.0±4.2). The total DASS scores were found to be higher in those who did not eat regularly and did not devote enough time for themselves. In this pandemic period, the total DASS score of the participants whose close relatives were infected with COVID 19 was statistically significantly higher (p=0.044). During this pandemic period, depression (10.6±5.5), anxiety (8.6±5.5) and stress (11.3±5.4) subscale scores were significantly higher in smokers than non-smokers (p<0.001) (Table 1,2).
The mean total PSS score of the participants was 24.3±7.4 (1-47). A statistically significant relationship was found between the total PSS score and age, gender, marital status and childbearing. The perceived stress levels were higher in the participants under the age of 40 (p=0.002), women (p<0.001), singles (p<0.001) and no children (p<0.001). Similarly, the perceived stress level was higher in those who did not eat regularly (p<0.001), who did not exercise regularly and adequately (p=0.001) and who did not take time (p<0.001).
In this period, individuals who smoked and increased the number of cigarettes smoked daily were found to have a higher DASS score (p<0.001) and PSS scores (p=0.001) (Tables 1, 2).
When the correlations between HPS, DASS, PSS and age were examined, there was a weak statistically significant correlation between DASS and PSS scores, and age and HPS (r=-0.123, p=0.010) (r=-0.222, p<0.001). There was a moderately significant positive correlation between DASS and PSS (r= 0.509, p<0.001) (Table 3). When a linear regression analysis was performed between the DASS total score and the PSS, 25.9% of the height in the total DASS was attributed to the total score received from the PSS (R2=0.259), (p<0.001) (Figure 1).
Discussion
Infectious disease outbreaks in recent years have had a significant impact not only on physical health, but also on the psychological well-being of communities. Severe acute respiratory syndrome (SARS) epidemic in 2002/2003, H1N1 influenza pandemic in 2009, Middle East respiratory syndrome (MERS) epidemic in 2012, and 2019 (COVID-19) pandemic has made history as important infectious diseases that affect all countries of the world today. Beyond medical risk, the pandemic has great psychological and social effects on society, and it is difficult to accurately predict their consequences [10,11]. In this study, which was carried out to better understand the psychological effect, anxiety, depression and stress levels of the COVID-19 outbreak in the society, it was found that the participants had high levels of depression, anxiety and stress and low perception of health.
Researches in China, the first country affected by the pandemic, show that the fear of unknown and uncertainty in COVID- 19 leads to the development of negative behaviors such as stress, anxiety, depression, somatization, and increased alcohol and tobacco consumption [12,13]. In a study conducted in the Turkish community during the COVID-19 outbreak, female gender, urban life, and a history of psychiatric disease were risk factors for anxiety, urban life was a risk factor for depression, female gender, having a comorbid disease and mental disease history were risk factors for the health perception [14].
The COVID-19 pandemic has caused a major global health crisis and has brought significant psychological burdens to individuals with large-scale behavioral changes [15]. Making the right decisions in relation to people’s health depends on the perception of the benefits of their choice for themselves and society [4]. Emotions often drive more perceptions of health than facts. Preserving health (primary prevention) through healthy lifestyle behaviors is an important step in establishing a healthy society. In the study presented, the level of health perception of individuals increased as the level of education increased. As the level of education increases, it is expected that people will have information about what they need to do to maintain their current health and raise it to a better level. However, a significant relation was found between regular nutrition, exercise and time spent on oneself, and health perception. Similarly, in studies conducted during the pandemic period, the perceived health status was low in those with low education level, low income level, and those without regular eating and physical activity habits [12,16].
In a study involving more than 50,000 people during the COVID-19 outbreak, one- third of the participants were shown to experience psychological distress [13]. Some researchers in China found that half of the population was psychologically affected by the epidemic in the first stage of the COVID-19 outbreak. They reported that when using DASS-21, there were 16.5% of moderate to severe depressive symptoms and 28.8% of moderate to severe anxiety symptoms [17].
Depression is basically a disease of unhappiness and disbelief, and people feel sad, pessimistic and reluctant. The self- confidence of the person with depression decreases, they are unable to gather their attention, forgetfulness, thoughtfulness, insomnia, and difficulties in making simple decisions [18]. In the presented study, depression and anxiety were found to be high in the female gender and singles. It can be predicted that stress, anxiety and depression levels will be higher after curfews because the restriction of individuals’ movements tends to produce or intensify such psychological problems.
In a study conducted on 976 people in Spain, they found that although psychological symptom levels were generally low, those with chronic diseases and young individuals reported more symptoms than the rest of the population [19]. Individuals with chronic diseases are expected to show higher levels of psychological symptoms because COVID-19 tends to be more severely in individuals with multiple comorbidities [17]. According to the age range, older adults are expected to be more psychologically vulnerable to pandemics, while younger adults are expected to protect themselves with an optimistic bias or high health perceptions [20].
Differently, in a study evaluating anxiety disorder, depressive symptoms and sleep quality, stress levels, anxiety and depression symptoms were reported to be significantly higher in young people than in the elderly [21]. In this study, the perceived stress level in young people, women and singles was high. Similarly, the perceived stress level increased in those who did not eat regularly, did not exercise regularly and those who could not spare time for themselves. Doing enough sports during the pandemic period will decrease depression and anxiety [14].
As a result of the study, it was observed that the presence of individuals with COVID-19 disease in their first-degree relative increased the levels of stress, depression and anxiety. Knowing that our loved ones have a potentially fatal disease and not seeing them due to isolation, avoiding physical contact can lead to psychological symptoms deficit [22,23]. As in the general population, psychological symptoms caused by the epidemic are observed in healthcare professionals during the pandemic period. In a study, the mental health status of approximately 1250 healthcare workers who treated patients with coronavirus pneumonia was examined, and depression was found in 50.4%, anxiety in 44.6% and insomnia in 34.0% of healthcare workers [24].
Consequently, measures taken during the pandemic (increasing handwashing, mask and physical distance) are global public health measures necessary to slow the spread of the virus. Efforts to develop medical treatments for COVID-19 patients continue at full speed. In addition, healthy individuals of the society who stay at home and comply with curfews or go out to work and are in contact with people are also psychologically affected during the pandemic period [16]. As seen at the end of the study, anxiety, depression and stress levels in society are increasing in this process, and health perceptions are affected negatively.
The media can increase negative feelings towards COVID-19 by reporting mixed and often bad results (for example, reporting the number of infected people and deaths). As negative emotions increase, it can be difficult to make the right decisions for health. While general measures are being taken for public health, there is a need to increase the trainings in order to raise public awareness of the subject and alleviate negative emotions, as well as suggestions of behavioral changes. Healthy eating, regular exercise and taking spare time for themselves will increase individuals’ perceptions of health, while reducing their anxiety, depression and stress levels. In addition, it is important to identify groups with low-risk perception to prevent the spread of the disease.
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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Comparison of antegrade locked intramedullary nails and retrograde expandable intramedullary nails in distal femur diaphysis fractures
Eyüp Şenocak 1, Naci Ezirmik 2, Ali Aydın 2
1 Department of Orthopaedic and Traumatology, Erzurum Region Education and Research Hospital, 2 Department of Orthopaedic and Traumatology, Atatürk University, Erzurum, Turkey
DOI: 10.4328/ACAM.20426 Received: 2020-12-03 Accepted: 2021-01-25 Published Online: 2021-02-08 Printed: 2021-07-01 Ann Clin Anal Med 2021;12(7):717-721
Corresponding Author: Eyüp Şenocak, Department of Orthopaedic and Traumatology, Erzurum Region Education and Research Hospital, Erzurum, Turkey. E-mail: dreyup55@yahoo.com P: +90 5073688183 Corresponding Author ORCID ID: https://orcid.org/0000-0002-9804-9309
Aim: In this study, we aimed to compare antegrade locked and retrograde expandable intramedullary nails, which are common methods in the treatment of distal femur diaphysis fractures.
Material and Methods: Twenty three femurs of 23 patients (12 males, 11 females) who underwent REN and 78 femurs of 71 patients (49 males, 22 females) who underwent ALN between January 2010 and December 2013 were included in the study. Functional outcomes were compared with HSS (Hospital for Special Surgery) and Neer scores for postoperative assesments at 24 and 48 week [1, 2].
Results: The mean duration of bone union was evaluated as 49.7 (range 21-140) weeks in patients with ALN and 32.9 (range 13-74) weeks as the mean dura- tion of bone union in the REN group.
In the ALN group with 71 patients, 50 patients had excellent and good functional results according to Neer evaluation and 47 patients according to HSS evalu- ation at 48th week. In the REN group for 23 patients, excellent and good results were obtained in 14 patients for the Neer evaluation and 16 patients for HSS evaluation at the 48th week. There was no significant difference between Neer and HSS functional evaluations at 24th and 48th week between the two groups (p> 0,5); it was seen that REN application in terms of union time was significantly better than ALN (p <0,5).
Discussion: ALN and REN applications are treatment options that can be used safely for distal femur fractures, and the REN option should be considered to have a significant positive effect on the duration of bone union for non-contraindicated situations.
Keywords: Distal femur; Antegrade locked nail; Retrograde expandable nail; HSS; Neer
Introduction
As a result of the rapid increase of industrial and traffic activities and personal arming, related accidents and gunshot injuries have become an important cause of general orthopedic trauma.
Fractures of the distal femur diaphysis have a relatively small proportion in the general trauma, it is considered important because of the complexity of surgical intervention in this anatomical region. Due to the high morbidity, prolonged hospitalization and postoperative complications due to plate-screw osteosynthesis, more biologic and less invasive intramedullary fixation options have become preferred. RENs have such advantages over ALNs due to being less invasive, requiring smaller incisions, causing less bleeding, and more comfortable for obesity. In addition, REN application is a good choice for distal femoral diaphysis fractures because of the need for less scopy.
However, REN application has potential disadvantages, such as causing arthritic changes in the knee, causing knee pain, and creating septic arthritis compared with ALN application.
REN and ALN applications both provide mechanically optimal load distribution and are ideal for fixation to allow early loading, as well as difficulties with distal locking in locked nails and doubts about the reliability of rotational stability in expandable nails especially in osteoporotic patients makes both of them technically problematic.
In this study, we aimed to compare ALN and REN within distal femoral diaphysis fractures that are not joint-related, and also, we aimed to determine which treatment and fixation method is more appropriate.
Material and Methods
Twenty-three femurs in 23 patients (12 males,11 females) who underwent REN, and 78 femurs in 71 patients (49 males, 22 females) who underwent ALN between January 2010 and December 2013 were evaluated retrospectively. The mean ages of REN patients and ALN patients were 38.59 (range 15-86) and 45.09 (range 15-88), respectively. Patients with an acute distal femur diaphysis fracture who had no knee joint deformity before the trauma, and had no walking problems were included. Patients with a periprosthetic fracture, patients with a pathological fracture, and children with open physis line were excluded from our study. The mean follow-up time in the ALN group was 28.4 (range 10-48) weeks, while in the REN group, 20.3 (range 12-32) weeks. The fracture pattern of the patients was evaluated according to the AO-OTA and Winquest-Hansen fracture classification. The demographic characteristics of the patients are shown in Table 1.
In our study, open fracture cases were evaluated in the emergency service, and debridements and tetanus prophylaxis were first performed under sedoanalgesia, and then debridement was re- made in the operating room pre-surgery.
In open fracture cases, allergic conditions were investigated, and prophylactic antibiothics with double (Penicillin G-Genta) or triple (Penicillin G-Gentamycin-Metronidazole) antibiotherapy was started in patients with dirty wounds, according to wound status.
As a general principle, unless there is a very serious soft-tissue defect, we plan to do surgery for our patients as soon as possible. In the patient group with ALN, the time to the surgery was 2.8 (range 0-16) days, and the REN group, 3.3 (range 0-14) days because of the relatively longer duration of fixation material supply. Cefazolin sodium (1 gram) was given prophylactically 1 hour before the operation, and the dose was repeated if the operation lasted longer than 2 hours.
All patients underwent surgery in the supine position over the radiolucent surgery table. Patients treated with ALN were locked with proximal and distal locking with an appropriate locked intramedullary nail by getting into the medulla from the trochanter major, or in cases where the fracture site was opened, the nail performing and reaming was done retrogradely from the fracture site to the trochanter major. Perop ALN application was shown in Figure 1.
In patients treated with REN, a 5 cm longitudinal incision was performed over the patellar tendon. The patellar tendon was cut longitudinally in the middle line and retracted. The posterior cruciate ligament was palpated and the attaching fascia of PCL on the femur was seen, and then the Kirschner wire was drilled into the femur medulla from 5 mm anterior of PCL, and the centralization of the AP and the lateral view were controlled with a scope. If the intramedullary centralization of the Kirschner wire was determined appropriately, the Kirschner wire was used as a guide for reaming the medulla. During all these procedures, patella articular cartilage was kept using deep retractors. The REN, which was expanded intramedullary with an appropriate length, was applied to the trochanter minor level. Perop REN application method is shown in Figures 2 and 3.
All patients received prophylaxis with lmwh (low molecule weight heparin) 0,4 cc single dose until mobilization and were given prophylactic antibiotherapy as cefazolin 1 gr 2*1 for 2 or 3 days post-op. The quadriceps exercises were started the postop first day, as much as the patient tolerated the pain. Mobilization was started on the 2nd postoperative day without weight-bearing with the crutch. The group of patients who underwent REN were allowed partial loading 3 to 6 weeks postop according to the state of the patient and the fracture pattern; The ALN group was allowed loading with fragmented fractures late term and non-fragmented fractures postop 2ndday. Full loading was allowed after the radiological callus formation in all patients. Patients’ postoperative follow-up was evaluated according to the duration of the bone union, early and late complications, and functional outcomes. Functional results were assessed and compared using the HSS and Neer scoring systems at 24th and 48th weeks postoperatively. Pain, function, range of motion of the knee joint, muscle strength, flexion deformity, and instability were assessed in the HSS score system and the results were classified as excellent, good, medium and bad. Pain, function, knee joint motion, working capacity, anatomic structure of the fracture site, and x-ray findings are evaluated using Neer’s score system, and results were classified as excellent, good, medium and bad.
Analysis of the data obtained as a result of the evaluations was performed using the “Statistical Package for Social Sciences” (SPSS 20) program. Student’s t-test was used when all numerical data were evaluated in two independent groups. When the histogram was used, the non-parametric variant of the Student’s t-test and the Mann-Whitney-U test were used for the data with no normal distribution. Pearson’s correlation test was used to evaluate the relationship between 2 numerical values.
Anova test was used for numerical data with more than 2 independent groups. However, the Kruskal-Wallis test, which is a non-parametric alternative to ANOVA, was used for non- normal distribution data. P<0.05 was considered statistically significant.
Results
All of these patients who underwent ALN and REN had bone union after surgery. Patients with ALN were followed for an average of 28.4 (range 10-48) months. The mean duration of union was 44.64 (range 21-140) weeks in these patients. The mean follow-up period was 20.4 (range 12-32) months for patients with REN. The mean duration of union was found about 32.9 (range 13-74) weeks in these patients. Compared to the ALN and REN patients according to the union duration; it was observed that the union time was significantly better in the REN group (p = 0,0002).
According to the HSS scoring at 48 weeks in the patient group with REN; 11 (47.8%) patients were excellent, 5 (21.7%) were good, 3 (13.04%) were moderate, and 4 (17.4%) patients were evaluated as poor. According to the Neer scoring, 8 (34.7%) patients were excellent, 6 (26.0%) patients were good, 5 (21.7%) patients were moderate, and 4 were evaluated as bad. According to the HSS scoring at 48 weeks in the patient group with ALN; 25 patients (35,2%) were excellent, 22 (31%) were good, 11 (15,5%) were moderate and 13 (18,3%) patients were evaluated as poor. According to the Neer scoring, 25 patients (35.2%) were excellent, 25 patients (35.2%) were good, 14 patients (19.7%) were moderate and 7 (9.8%) patients were evaluated as bad. No significant statistical difference was found except for the 48th week of the Neer evaluation of the patients who had REN in these evaluations.
Four patients who underwent ALN developed an antibiotic- responsive superficial infection. They all had proper antibotherapy, and implant removal was not required for these patients. Pseudoarthrosis developed in six patients, and one patient had nonunion. All six patients underwent pseudoarthrosis surgery and the nonunion patient underwent REN and iliac bone grafting after replacing the antegrade nail. After these operations, all of the patients had a bone union. In one patient, implant failure developed at the postoperative 5th month and the nail was replaced with a thicker one. A 66-year-old patient had a collum femoris fracture after union of the fracture line. The patient underwent implant removal and partial prosthesis. In one patient, a collum femoris fracture occurred during nail application. Treatment was adjusted by performing a long proximal femur nail.
Patellofemoral crepitation was detected in 13 patients (19.7%) who underwent REN, and in 1 patient who had ALN, and knee effusion occurred in 6 patients (26.0%) who underwent REN. Nothing was done to these patients and complaints disappeared spontanously.
No patient had varus, valgus deformity or rotation.
Discussion
In this study, we aimed to compare ALN and REN, which are common methods in the treatment of distal femur diaphysis fractures. In this case, we evaluated and compared the results of 71 patients who underwent ALN and 23 patients who underwent REN.
We found REN to be better than ALN for distal femur fractures in general. Duration of surgery, less bleeding, union time are significant advantages of retrograde nailing.
The previously reported mean age of patients was between 24 and 36 years. In a thesis study similar to ours, the reported mean age of patients was 45.9 years. In our series, the average age of 40.1 years was slightly higher than reported in the literature. Since our hospital is a university hospital, and the general patient age is higher than in state hospitals because of the increasing potential morbidity risk with age [3-6].
More active involvement of males in social and industrial life is responsible for the higher rates of distal diaphyseal femur fractures among men. While in the other studies, the ratio of male patients is between 61.2% and 88%; in our study, 65% of patients are males. Since there is no industrial potential in Erzurum that may cause more trauma to the male population, so there is not a big difference between males and females as in other studies cited below [3,5,6].
REN application offers several practical and theoretical advantages in the treatment of distal femoral fractures. It represents a rapid, practical, and less invasive approach with a reduced risk of bleeding that minimizes the soft tissue and periosteal dissection and that facilitates fusion by preserving the circulation at the fracture site. In our series, 71 of 94 patients (75.5%) with distal femoral fractures underwent ALN, and 23 (24.5%) patients underwent REN. The average volume of the perioperative bleeding and the average duration of surgery in patients undergoing ALN were 202 ml (range 100-420 ml) and 89.5 minutes (range 45-180 min), respectively, while the corresponding values in the REN group were 131.3 ml (range 50-300) and 66 (range 35-120) minutes, with a significant difference in favor of the REN group in terms of perioperative bleeding volume and duration of surgery (p<0.05) [7-18].
The union of femoral fractures is defined as the absence of pain in fracture line on physical examination, the demonstration of solid callus tissue on radiographs, and the ability of the patient to walk without symptoms and crutches. For femoral diaphysis fractures, the union process is considered normal if it is completed in less than 6 months, delayed if the union occurs without intervention between 6 and 9 months, and non-union if no callus is formed. The mean time to the union after fixation of the femoral diaphysis fractures by ALN was18 weeks in different two studies. In our patient group, patients treated with ALN were followed up for a mean duration of 28.4 months (range 10-48 months), with a mean union time of 49.7 weeks (range 21-140). Similarly, patients in the REN group were followed up for 20.3 months (range 12-32) on average, and their mean time to union was 32.9 weeks (range 13-74). Although significantly better union time was found in the REN group, the time to union was significantly longer in both of our study groups compared to previously reported studies because we accepted all the parameters we defined below to be completed as to say full bone union. In other studies they accepted only callus formation in radiographs as to say full bone union (p< 0.05) [15,20].
The Neer, Shelbourne, and the Hospital for Special Surgery (HSS) scoring systems are the most commonly used tests for assessing distal femoral fractures. Similarly, we also used the Neer and HSS scoring systems in our study. The reason for using two different evaluation systems is that one evaluation system may not be adequate for all patients. For example, while the Neer classification system appears to be inadequate for patients with ligament instability after distal femoral fractures, the HSS scoring system does not consider radiological findings, functional capacity, and the anatomical characteristics of the fracture site. The HSS and Neer classification systems are used at variable times during the course of management, and we believe that optimal standardization with regard to the duration of postoperative rehabilitation may allow clinicians to obtain more objective and Standard assessments. Contrastly with similar previous studies, we assessed the ALN and REN groups both separately and combined at 24 and 48 weeks using the Neer and HSS criteria. In a similar thesis study by Erkan Tan, MD, carried out in 2006, the mean Neer and HSS scores were 88.5 and 88.3, respectively, without the use of standardized timepoints [1,2,12].
In our study, the average Neer and HSS scores in the overall study population were 76.11 and 76.06 at the 24th week, and 79.47 and 79.33 at the 48th week, respectively. Another study found 88,5(range 67-100) and 88,3(range 69-100)Neer and HSS scores, respectively. According to the Neer score at 24 weeks for all patients, the outcomes were rated as excellent, good, moderate, and poor in 29 (30.8%), 27 (28.7%), 16 (17%), and 23 (24.4%), respectively. At 24 weeks according to HSS score, it was rated as excellent, good, moderate, and poor in 29 (30.8%), 31 (33%), 13 (13.8%), and 21 (22.3%), respectively. According to the Neer score at 48 weeks, excellent, good, moderate, and poor results were obtained in 33 (35.1%), 31 (33%), 19 (20.2%), and 11 (11.7%) patients, respectively. It was rated at 48 weeks according to HSS score as excellent, good, moderate, and poor in 36 (38.2%), 27 (28.7%), 14 (14.8%), and 17 (18%)patients, respectively. The mean Neer and HSS scores at 24 weeks in 71 patients undergoing ALN were 76.51 and 76.67, respectively; the same scores at 48 weeks were 80.45 and 79.67, respectively. The mean Neer and HSS scores at 24 weeks in 23 patients undergoing REN were 75.26 and 74.74, respectively; the same scores at 48 weeks were 77.39 and 78.61, respectively.
The difference in the number of cases between the ALN and REN groups is a limitation of our study. We compared a locked fixation system with an unlocked retrograde fixation system; that may be assessed as a limitation. Our retrograde locked case number was not enough to obtain a significant result for our study, so we did not include locked retrograde cases. Conclusion
According to our study we decided that the REN system is a better fixation system for distal femur fractures because of less bleeding, shorter surgery time and early bone union according to antegrade locked system nailing.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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2. Neer CS, Grantham AS, Shelton ML. Supracondylar fracture of the adult femur. J Bone Joint Surg. 1967; 49(4): 591-613.
3. Wiss DA, Fleming CH, Mata JM, Clark D. Comminuted and rotationally unstable frac-tures of the femur treated with an interlocking nail. Clin. Orthop. 1986; 232:35-47.
4. Thoresen O B, Alho A, Ekeland A. Interlocking intramedullary nailing in Femoral shaft fractures. J Bone Joınt Surgery. 1985; 67-A:1313–20.
5. Alho A, Stremese K, Ekeland A. Locked intramedullary nailing of femoral shaft fractu-res. J Trauma. 1991;31: 49-59.
6. Akbas A, Kunt M, Ünsaldı T, Bulut O. Eriskin femur cisim kırıklarının cerrahi tedavisi ve bu tedavide interlocking intramedüller çivilemenin yeri (Surgical treatment of adult femoral shaft fractures and interlocking intramedullary nailing in this treatment.). Acta Orthop Trau-matol Turc. 1994; 28: 161-7.
7. Bucholz RW, Brumback RJ. Fractures of the shaft of the femur. In: Rockwood C A Jr, Green DP, Bucholz RN, et al, editors. Rockwood and Green’s Fractures in Adults. 5th ed. Philadelphia: Lippincott Company; 1991. p. 1653–723.
8. Whittle AP. Fractures of the lower extremity. In: Canale ST, editors. Campbell’s opera-tive orthopaedics. 9th ed. St. Louis: Mosby-YearBook Inc; 1998. p. 2042- 179.
9. Papagiannopoulos G, Clement DA. Treatment of fractures of the distal third of the fe-mur. J Bone Joint Surg. 1987; 69:1:67-70.
10. Delong WG Jr, Bennett FS. The GSH supracondylar nail. Browner Bruce D, editors. Int-ramedullary Nailing. 2nd ed. Philadelphia: Williams and Wilkins Comp; 1996. p. 189-97.
11. Lucas ES. Seligson D, Henry SL. Intramedullary supracondylar nailing of femoral frac-tures. Clin Orthop. 1993;296:200-6.
12. Shelbourne KD, Brueckmann R. Rush-pin fixation of supracondylar and intercondylar fractures of the femur. J Bone Joint Surg. 1982; 64(2): 161-9.
13. Serin E. Sarıkaya M. Erişkin femur cisim kırıklarının tedavisinde plakla osteosentez ve int-ramedüller Küntscher çivileme sistemlerinin karşılaştırması (Comparison of plate osteosynt-hesis and intramedullary Küntscher nailing systems in the treatment of adult femoral shaft fractures). Acta Orthop. Trauma Turc.1998; 32: 307-14.
14. Arpacıoglu MÖ, Akmaz İ, Mahirogulları M, Kıral A, Rodop O. Erişkinlerdeki femur cisim kırıklarının kilitli intramedüller çivileme yöntemiyle tedavisi (Treatment of femoral shaft fractures in adults by locking intramedullary nailing). Acta Orthop Traumatol Turc. 2003;37(3): 203-12.
15. Ertürer E, Öztürk İ, Dirik Y, Uzun M, Aksoy B. Eriskinlerdeki femur cisim kırıklarında kilitli oymasız intramedüller çivi osteosentezinin radyografik ve fonksiyonel sonuçları (Non-radiographic and functional results of intramedullary locking nail osteosynthesis in femoral shaft fractures in adults). Acta Orthop Traumatol Turc. 2005; 39(5): 381-6.
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Eyüp Şenocak, Naci Ezirmik, Ali Aydın. Comparison of antegrade locked intramedullary nails and retrograde expandable intramedullary nails in distal femur diaphysis fractures. Ann Clin Anal Med 2021;12(7):717-721
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Oxidative stress in healthy individuals; circadian rhythm of thiol-disulfide balance
Kader Zeybek Aydogan 1, Nuray Yilmaz Cakmak 2, Bulent Yalcin 3
1 Departman of İnternal Medicine, Bor State Hospital, Nigde, 2 Departman of İnternal Medicine, Ankara City Hospital, Ankara, 3 Deparmant of Medical Oncology, Ankara Yildirim Beyazit University, Faculty of Medicine, Ankara, Turkey
DOI: 10.4328/ACAM.20430 Received: 2020-12-06 Accepted: 2021-01-05 Published Online: 2021-01-12 Printed: 2021-07-01 Ann Clin Anal Med 2021;12(7):722-725
Corresponding Author: Kader Zeybek Aydogan, Bor State Hospital, Departmant of İnternal Medicine, Bor 51710, Nigde, Turkey. E-mail: kzaydogan@gmail.com P: +90 544 483 4967 Corresponding Author ORCID ID: https://orcid.org/0000-0002-9331-9349
Aim: The dynamic thiol-disulfide balance plays a critical role in the healthy functioning of the organism. The most important role of this system is participation in the cell’s antioxidant defense. The hormone melatonin hormone has a circadian rhythm. It is not known whether the balance of thiol-disulfide shows secretion like melatonin throughout the day. This study examined the circadian rhythm of thiol-disulfide balance and variability with daily living activities in a healthy young population.
Material and Methods: Venous blood samples were taken every 2 hours from 8 healthy volunteers and the levels of melatonin, thiol disulfide and peripheral blood elements (lymphocytes and monocytes) were investigated. During the study, the daily activities of the volunteers were not restricted and the starvation- satiety variables were also studied.
Result: No significant time-dependent statistical change was observed in the 24-hour follow-up of native thiol, total thiol and disulfide levels, and measurements of blood lymphocyte and monocyte. The starvation and satiety levels were compared, and no significant difference was observed in thiol-disulfide balance.
Discussion: In this study, thiol-disulfide balance did not follow a circadian rhythm like melatonin, and was not affected by starvation and satiety.
Keywords: Thiol; Disulfide; Antioxidant; Oxidative stress; Melatonin; Circadian rhythm
Introduction
In the organism, under the influence of free radicals, various defense systems arise that protect from the harmful effects of these radicals. These are defense systems, protective mechanisms, recovery mechanisms, physical defense and antioxidant defense systems [1]. Antioxidants are substances that directly inactivate oxidants [2]. Thiols (RSH) are organic compounds containing a sulfhydryl group (-SH) and are a member of both enzymatic and non-enzymatic antioxidant system. The plasma thiol pool consists of albumin thiols, protein thiols, and less commonly, low molecular weight thiols [3]. Albumin with its high concentration in the circulation is the main component that carries protein-bound thiols [4]. As a result of the oxidation reaction of thiols (RSH), covalently bonded disulfide bonds (RSSR) are formed. As a result of the activation of antioxidant systems in a normally functioning organism, disulfide bonds are reduced back to thiol groups [5]. Thus, the dynamic thiol-disulfide balance is also preserved. The dynamic thiol- disulfide balance takes part in antioxidant defense of the cell, detoxification, signal transduction, apoptosis, regulation of enzymatic activities, transcription factors, and cellular signal transduction mechanisms [6, 7]. In addition, the dynamic thiol-disulfide balance is involved in the etiopathogenesis of many diseases. Examples of diseases in which abnormal thiol-disulfide balance is seen, are fibromyalgia, nephrotic syndrome, pneumonia [8, 9, 10].
Melatonin (MLT) is a hormone synthesized mainly by the pineal gland and released into the circulation [11]. Studies of melatonin, which main function is to regulate the circadian rhythm of the organism, have also shown its anti-inflammatory function [12, 13, 14]. The MLT oscillation shows a circadian rhythm. Synthesis and release that increase in darkness are suppressed with light and decrease to basal level [15]. Previous studies examining the balance between thiol-disulfide balance and circadian rhythm have used low molecular weight thiols (cysteine, glutathione) other than albumin [16, 17]. With a new method developed by Erel and Neşelioğlu in 2014, the dynamic thiol- disulfide balance depending on albumin can now be measured. In studies conducted with this newly developed automated method, plasma disulfide levels were found to be high in degenerative diseases and low in proliferative diseases [18].
Although the upper and lower limits reflecting normal values for healthy and young adult population were determined, variability during the day has not been investigated in previous studies. It is not known whether there will be a change in thiol- disulfide balance, especially during daily activities (eating, sleeping, miction and defecation). The aim of this study was to demonstrate the relationship between the circadian rhythm of thiol-disulfide balance, changes that may occur in the levels of daily living activities, and the MLT and peripheral blood elements in healthy young population.
Material and Methods
Study population
The study was conducted between February 1, 2016 and March 15, 2016 in the Internal Medicine Clinic of Ankara Ataturk Training and Research Hospital. A total of 5 females and 3 males aged between 26 and 36 years were included in the cross- sectional study. All parameters used in the study were studied specifically for the study group, and the study was initiated after obtaining the written consent from each volunteer participating in the study. Also, this study was approved by the local ethics committee of Ankara Atatürk Training and Research Hospital. The body mass index (BMI) of the study participants ranged from 20 to 25. The inclusion criteria for healthy sleeping volunteers were as follows: no cigarette smoking, no known chronic disease, no pregnancy status or suspected pregnancy, no psychiatric problem, no more than 1 cup of caffeine daily caffeine, no chronic drug use including oral contraceptive (OKS) and non-steroidal anti-inflammatory (NSAID). Those with active malignant disease or chronic illness, those with a BMI above 25, and those who refused to participate in the study were excluded.
Study Design
Venous blood samples were taken every 2 hours, starting at 08:00 in the morning (fasting) from each volunteer participating in the study, and the levels of thiol/disulfide, MLT and peripheral blood elements (lymphocytes and monocytes) were studied in the blood samples. Blood samples were taken at 08.00, 12.00, 16.00 to show fasting values and at 10.00, 14.00 and 18.00 to show satiety values. One night prior to enrolment in the study, volunteers’ meals were cut at 24.00 to standardize baseline fasting values. Each volunteer was provided with breakfast at 08.30, lunch at 12.30, dinner at 16.30, and snack at 21.00, according to the standard nutrition program. During the study, the volunteers were not restricted in their daily activities and were allowed to continue their basal activities. The volunteers’ blood samples were taken at 22.00, and then the eyelids were connected to sleep in a dark and silent room. At 24.00, 02.00, 04.00 and 06.00 blood samples were taken with heparinized vascular access; without interrupting the sleep cycles of the volunteers. After taking blood samples at 06.00, the volunteers were awakened and the study was terminated.
Biochemical Parameters
After the samples were centrifuged at 3600 rpm for 10 minutes in the biochemistry laboratory, the parameters of thiol disulfide in the blood were studied on the Roche Hitachi Cobas c501 automatic analyzer in the Biochemistry Laboratory of the Ankara Atatürk Training and Research Hospital using the automatic measurement method developed by Erel and Neselioglu. MLT samples were studied with an ELISA kit in Ankara Atatürk Training and Research Hospital Biochemistry Laboratory.
Statistical Analysis
The analysis of the data was made using the IBM SPSS Statistics 17.0 (IBM Corporation, Armonk, NY, USA) package program. Descriptive statistics were shown as mean, standard deviation, minimum and maximum for continuous numerical variables, and categorical variables as the number of cases and (%).The daily follow-up of the cases, it was investigated, using variance analysis in repeated measurements, whether there was a statistically significant change in melatonin, native thiol, total thiol, disulfide, lymphocyte and monocyte measurements performed at two-hour intervals. Using the Bonferroni corrected multiple comparison test, the follow-up times that showed
statistically significant differences between each other were determined. At p <0.05, the results were considered statistically significant.
Results
The characteristics of the research group
The demographic characteristics of 8 volunteers are shown in Table 1; 63% of the research population were female, 37% were male, and the mean age was 28.6 ± 3.6 years. The mean BMI of healthy volunteers with a body mass index range of 21.1-23.5 was 22.1 ± 1.1.
Changes in Plasma Melatonin measurements during the day
During follow-up, the average MLT values remained stable between 08:00 and 18:00, and the daily average minimum MLT value (885.92 ng / L) was recorded at 08:00. Average MLT measurements started to increase from 20:00 and reached its maximum value during the day (10601.39 ng / L) at 02:00. A decrease was observed in the average measurements after this time period, but the study ended at 06:00 without a decrease to the minimum value. The course of the average MLT values during the day is shown graphically in Figure 1.
Changes in Plasma Native and Total Thiol measurements during the day
During the 24-hour follow-up period, no significant time- dependent statistical changes were observed in the mean native and total thiol values of the cases. In the course of both native and total thiol levels, the maximum value was recorded at 10.00, and the minimum value was recorded at 02.00.
No statistically significant difference was observed between the levels of native and total thiols during fasting and satiety at 08:00, 10:00, 12:00, 14:00, 16:00 and 18:00 (p>0,05).
Changes in Plasma Disulfide measurements during the day During the 24-hour follow-up, no significant time-dependent statistical changes were observed in the mean disulfide values of the patients. No statistically significant difference was observed between the levels of native and total thiols during fasting and satiety at 08:00, 10:00, 12:00, 14:00, 16:00 and 18:00 (p>0,05).
Peripheral blood immune markers Lymphocyte and Monocyte measurements during the day
There was no statistically significant difference in blood lymphocyte and monocyte measurements during the 24-hour follow-up (p> 0.05). The mean blood lymphocyte and monocyte levels increased from 14:00 in the measurements following a constant course until 14:00, and the maximum level was reached at 22:00 for lymphocytes and at 00.00 for monocytes.
Discussion
Our study is the first study investigating the circadian rhythm of thiol/disulfide balance using this new method developed by Erel and Neşelioğlu. In addition, when the literature was reviewed, no study examining melatonin, peripheral blood lymphocyte, monocyte levels and activities of daily living and thiol/disulfide relationship was found.
Circadian rhythms control numerous activities, including the production and elimination of oxygen radicals, the activation and inhibition of the appropriate genes [19]. Antioxidant enzymes and low molecular weight antioxidants such as glutathione also have circadian rhythm and daily rhythmic changes as melatonin [20]. A study by Blanco et al. with 63 healthy volunteers demonstrated a circadian rhythm of the balance of glutathione and cysteine [17]. However, it is known that low molecular weight thiols such as glutathione and cysteine represent a small portion of the plasma thiol pool [21]. Albumin thiols are the main component carrying protein-bound thiols with their high concentration in the circulation [22].
In our study, no significant time-dependent statistical change was observed in the 24-hour follow-up of native thiol, total thiol and disulfide levels. We think that the circadian change may not have been observed due to the long half-life of albumin (21 days) and the fact that most of the thiol groups measured in our study originated from albumin.
One of the aims of our study was to examine the relationship between fasting and satiety and thiol disulfide. In our study, when the hunger and satiety levels after each 3 meals were compared, no significant difference was observed in thiol- disulfide balance, and this was attributed to the fact that albumin was not acutely affected by dietary changes during the day. In the study conducted by Blanco et al., a significant increase was observed in glutathione and cysteine levels after meals [17]. However, it should be kept in mind that these low molecular weight proteins represent a limited part of the plasma thiol pool.
As it is known, many laboratory parameters (such as blood glucose and lipid levels) are affected by the fasting state of the individual. These data are available; this new automated method is important in terms of showing that there will not be any limitation for hunger and satiety variables in the working schedule.
Melatonin levels in plasma regularly fluctuate during a 24-hour period. This circadian rhythm is controlled by the hypothalamus, and the main regulator of the rhythm is the light-dark cycle in the external environment [23]. In our study, similar results were obtained with the data supported in the literature. The MLT levels of healthy volunteers in our study followed a constant course between 08:00 and 18:00 and then increased from 20:00 and reached the daily maximum level at 02:00 at night. In our study, the circadian rhythms of peripheral blood lymphocyte and monocyte levels and the relationship with thiol- disulfide balance was also examined. The circadian rhythm of lymphocyte and monocyte levels followed a similar course as the results of the study by Sennels et al. [24]. These changes in peripheral blood lymphocyte and monocyte levels may be associated with an increase in cortisol and MLT levels. Conclusion
Our study is important in that it is the first study evaluating the circadian rhythm of thiol- disulfide balance. In conclusion, measurement of thiol-disulfide level with this new automated method should be used to monitor the degenerative and inflammatory picture, which is longer than the half-life of albumin and to show the presence of oxidative stress, without being affected by the hunger and satiety status of the individual. Our study has some limitations. The small number of volunteers participating in the study (n = 8) and its relationship with micturition defecation could not be examined. Newer and larger studies are needed to investigate the thiol-disulfide balance.
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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Kader Zeybek Aydogan, Nuray Yilmaz Cakmak , Bulent Yalcin. Oxidative stress in healthy individuals; circadian rhythm of thiol-disulfide balance. Ann Clin Anal Med 2021;12(7):722-725
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May red cell distribution width (RDW)/mean platelet volume (MPV) ratio be a diagnostic parameter in extrahepatic cholestasis due to biliary stones?
Eyup Sabri Seyhanli, Huseyin Avni Demir
Department of Emergency Medicine, University of Health Sciences, Mehmet Akif Inan Training and Research Hospital, Sanliurfa, Turkey
DOI: 10.4328/ACAM.20434 Received: 2020-12-08 Accepted: 2021-01-15 Published Online: 2021-01-26 Printed: 2021-07-01 Ann Clin Anal Med 2021;12(7):726-730
Corresponding Author: Eyup Sabri Seyhanli, University of Health Sciences, Mehmet Akif Inan Training and Research Hospital, Department of Emergency Medicine, Sanliurfa, Turkey. E-mail: eyyup-1976@windowslive.com P: +90 5068157998 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1800-1357
Aim: Establishing the diagnosis of extrahepatic cholestasis is highly challenging in emergency department conditions. It is necessary to find a fast and inex- pensive marker that will be diagnostic at the first stage. Therefore, in this study, we aimed to investigate the diagnostic values of RDW/MPV ratio and PMI values in EHC.
Material and Methods: The diagnosis of extrahepatic cholestasis was established in all patients using biochemical tests, abdominal ultrasound and MRCP. Patients’ WBC, Neutrophils (Neu), Lymphocytes (Lym), Monocytes (Mon), Red Blood Cell (RBC), Mean Corpuscular Volume (MCV), RDW, Platelet (PLT) and MPV values were evaluated. RDW/MPV, Lym/Mon, Neu/Mon and PLTxMPV (PMI) values were calculated.
Results: One hundred eighty patients who presented to our emergency department with abdominal pain were included as the patient group, and 106 patients who applied to our emergency department with dyspeptic complaints were included as the control group. Lymphocyte and monocyte counts were statistically significant between the two groups (p=0.02, p=0.05; respectively). RDW/MPV ratio was 1.54±0.33 in the patient group and 1.34±0.25 in the control group, and it was statistically significantly higher in the patient group (p=0.02). Serum ALT, AST, total and direct bilirubin and CRP values were significantly higher in the patient group (p<0,001). The mean hospitalization duration was 13.7 ± 6.3 days.
Discussion: We believe that RDW/MPV parameter to be studied in patients presenting to emergency departments with abdominal pain and jaundice can be helpful for the diagnosis of extrahepatic cholestasis due to biliary tract stones.
Keywords: Extrahepatic cholestasis; Biliary stones; Platelet mass; Red cells; Platelet volume
Introduction
Cholestasis is defined as the impairment of bile flow from hepatocytes into canaliculus and duodenum by mechanical obstruction, drugs, infection, autoimmune, metabolic, or genetic disorders [1,2]. The secretion of bile normally depends on the function of a number of membrane transport systems in hepatocytes and bile-duct epithelial cells (cholangiocytes), and on the structural and functional integrity of the bile-secretory apparatus [2,3]. Cholestasis is classified into two groups according to the localization of the obstruction as intrahepatic and extrahepatic, and it results from hepatocellular disease (intrahepatic) or abnormalities of biliary duct (extrahepatic) [1,4]. Extrahepatic cholestasis (EHC) is defined as the inability of a normal amount of inflow to the bile due to lesions or obstacles at the levels of choledoch or main hepatic duct. The main reasons of EHC include common biliary tract (CBD) stones, cholangiocarcinoma, ampullary carcinoma, pancreatic diseases (pancreatic head carcinoma, pseudotumoral chronic pancreatitis, pancreatic head pseudocysts), congenital malformations (cysts, Caroli disease), duodenal diverticula, ascariasis and hemobilia [5]. The diagnosis of EHC is established with physical examination, and the biochemical imbalance is supported by clinical symptoms and signs. These symptoms and signs include jaundice in the sclerae and skin, abdominal pain, nausea, pale stool and dark orange urine. As the clinical picture of cholestasis progresses, several complications may occur, such as cholangitis, sepsis, multiple organ failure, coagulopathy and renal failure, as well as cirrhosis may also be developed due to prolonged cholestasis. Cholestatic damage of the liver leads to hepatocellular necrosis and apoptosis, proliferation and stellate cell activation occur in the epithelial cells of the biliary tract, resulting in liver fibrosis [7,8].
Diagnosis of EHC is established through laboratory tests, hepatobiliary ultrasonography (US), computed tomography (CT), magnetic resonance cholangiography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP) [6].
In the emergency department, complete blood count, total bilirubin, direct bilirubin, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) that are helpful in showing liver damage, are primarily used for the diagnosis of cholestasis [9]. As far as is known, complete blood count parameters including hemoglobin, hematocrit, white blood cells (WBC) and platelets (PLT) are stated to be usually normal in cholestasis except for cholangitis attack [10].
In an emergency department, establishing the diagnosis of extrahepatic cholestasis is highly challenging. It is necessary to find a fast and inexpensive marker that will be diagnostic at the first stage. Within this context, complete blood count parameters have not been adequately reviewed in the literature. On the other hand, recently there have been many studies showing that levels of some parameters in complete blood change in different illness states in addition to biological functions [11-13].
It has been demonstrated that red cell distribution width (RDW), which is among complete blood count parameters and shows the change in red blood volume, may be a prognostic marker reflecting inflammatory status. The RDW level has been found to be associated with morbidity and mortality in the elderly [14,15]. RDW has been found to be significantly lower in patients with pregnancy-induced intrahepatic cholestasis that resembles EHC, but no correlation has been found between RDW and disease severity [11]. Platelets have been shown to be involved in the inflammation process besides their known hemostatic functions [16]. The mean platelet volume (MPV) is the best parameter showing platelet size and studies have reported changes in MPV value in diseases that progress with chronic inflammation including rheumatoid arthritis and ulcerative colitis [17]. The platelet mass index (PMI), which is formulated with “platelet count multiplied by MPV”, is a good marker of PLT functions and provides important information about the plaque- forming capacity. In addition, some studies have demonstrated that PMI is a better inflammatory marker than MPV [18,19].
Fewer tests that could be indicators of EHC will both save time and reduce costs. Therefore, the objective of this study was to investigate diagnostic benefit of RDW, MPV, PMI, Lymphocytes/ Monocytes (Lym/Mon) ratio and Neutrophils/Lymphocyte ratio (Neu/Lym=NLR), which are studied in almost all patients presenting to emergency departments, in patients with biliary tract stones induced extrahepatic cholestasis.
Material and Methods
Study Design
This study was conducted in the emergency and/or general surgery services of the Health Sciences University Mehmet Akif Inan Health Application and Research Center between January 2017 and June 2020 after receiving the approval from the Ethics committee. Patients with extreme obesity, hematologic disorders, those who were receiving chemotherapy, aspirin or drugs affecting platelet function, pregnant women, patients with a history of previous surgery for biliary tracts, those with chronic hepatic disease, advanced chronic obstructive pulmonary disease due to prominent pulmonary emphysema and patients with abnormal kidney function were excluded from the study. The patient group consisted of patients aged over 18 years who presented to the emergency department with complaints such as abdominal pain, nausea and jaundice, and who were diagnosed with extrahepatic cholestasis on physical examination, laboratory and imaging investigations and ERCP following hospitalization. The control group included patients aged over 18 years who presented to the emergency department with dyspeptic complaints, did not require hospitalization after investigations and treatments administered and who had no any diagnosed chronic disease/a history of receiving drugs. Complete blood count, biochemical parameters and imaging data studied at the time of presentation were retrospectively evaluated in both groups.
In order to evaluate the clinical status of patients, symptoms of obstructive cholestasis including jaundice, itching, the color of urine and stool were evaluated. Patients’ demographic data such as gender, age and complete blood count including WBC, Neu, Lym, Mon, red blood cell (RBC), Mean corpuscular volume (MCV), RDW, PLT, MPV were analyzed with an automated hematology analyzer (Sysmex Corporation Automated Analyzer XN-10, Chuo-ku, Kobe, Japan). RDW/MPV, Lym/Mon, Neu/Mon and PMI were calculated. C-reactive protein (CRP), ALT, AST, total and direct bilirubin, albumin, GGT, amylase, lipase and electrolytes were analyzed and recorded. The diagnosis of extrahepatic cholestasis was established in all patients using biochemical tests, abdominal ultrasound, MRCP. The diagnosis was confirmed with biochemical and imaging investigations in patients with extrahepatic cholestasis. Diagnostic and therapeutic ERCP was performed in all patients.
Ethical Considerations
All patients included in the study were informed in detail about the objectives of the study and gave verbal and written consent. Before the beginning of the study, the necessary ethics approval was received from the local ethics committee of our hospital on 15.06.2020 (Decision number: HRU/20.11.01) . This study was conducted in accordance with the ethical principles of the Declaration of Helsinki.
Statistical Analysis
Data obtained in this study were statistically analyzed using the SPSS version 22.0 (Statistical Package for Social Sciences. IBM Inc., Chicago, IL, USA) statistical package software. The normality of the data was analyzed with the Kolmogorov- Smirnov test. In a comparison of the variables between the groups, Student’s t-test was used for normally distributed variables and the Mann-Whitney U test for non-normally distributed variables. Numerical variables are expressed with mean±standard deviation, while categorical variables are expressed as frequency and percentage (%). P<0.05 values were considered statistically significant.
Results
The study included 180 patients diagnosed with extrahepatic cholestasis and 106 controls who presented to our emergency and/or general surgery departments with dyspeptic complaints. Among the patients, 57 (31.7%) were male and 123 (68.3%) were female; whereas among the control subjects, 35 (33.1%) were male and 71 (66.9%) were female. The mean age was 57.8±18.0 years in the patient group and 54.1±14.2 years in the control group. There was no statistically significant difference between the patient and control groups in terms of gender and age (p>0.05).
When blood analysis was compared between the patient and control group, the mean WBC value was found as 10.142±5.1 in the patient group and 9.7±3.1 in the control group (p=0.47). Neutrophil count was 7.7±5.0 in the patient group and 5.5±2.7 in the control group (p=0.37). Lymphocyte count was 1.7±0.71 in the patient group and 2.7±1.13 in the control group (p=0.05). Lymphocyte count was approximately statistically significant between the two groups. Monocyte count was 0.6±0.3 in the patient group and 0.7±0.22 in the control group. Monocyte count was statistically significantly lower in the patient group compared to the control group (p=0.02). The mean RBC value was 4.60±0.67 in the patient group and 4.90±0.65 in the control group (p=0.06). The mean MCV value was 87.0±8.69 in the patient group and 82.70±6.15 in the control group (p=0.65). The mean RDW value was 13.12±1.67 in the patient group and 13.32±1.58 in the controls (p=0.12). The mean PLT was 261.64±99.27 in the patient group and 275.19±71.34 in the control group (p=0.07). The mean MPV value was 8.84±1.84 in the patient and 10.13±1.26 in the control group (p=0.14). The RDW/MPV ratio was calculated as 1.54±0.33 in the patient group and 1.34±0.25 in the control group. The RDW/MPV ratio was statistically significantly higher in the patient group compared to the control group (p=0.02). The Lym/Mon ratio was 3.82±2.64 in the patient group and 4.24±1.76 in the control group(p=0.20).TheNeu/Lymratiowas6.81±9.08inthepatient group and 2.73±3.00 in the control group (p=0.68). PLTxMPV, which reflects PMI, was 2261.40±890.53 in the patient group and 2763.80±723.64 in the control group (p=0.66). Serum ALT, AST, total and direct bilirubin, and CRP values were significantly higher in the patient group (p=0,0). The mean hospitalization duration was 13.7 ± 6.3 days. Laboratory findings of the Patient and Control Groups are given in Table 1.
Discussion
Obstructive biliary stones are the leading benign cause in the etiology of extrahepatic cholestasis (EHC) (80%). The incidence of EHC with both benign and malignant causes increases with age. In this study, all patients had EHC related to biliary stones, and the mean age of the patients was 57.8±18.0 years, consistently with the literature [20]. The clinical condition of the patients is the first and most important parameter indicating the disease. The primary clinical symptoms of extrahepatic cholestasis are abdominal pain, jaundice of the skin and sclerae, dark urine, uncolored stool and itching. In adult extrahepatic (mechanical) obstruction, 40% of patients present with jaundice as the primary symptom [20]. In the current study, the patients were those who presented to the emergency department and the complaints of presentations were mostly mild-to-moderate abdominal pain (55%) and vomiting (25%).
Elevation in AST, ALT, total and direct bilirubin and GGT is seen as a result of the damage in the liver due to cholestasis. AST and ALT usually increase by 2-4 times compared to normal values, while GGT increases by 2-4 times, and ALP by up to 10 times of the normal values [21]. When the level of total bilirubin exceeds 2.5 mg/L, icterus is clinically seen and secondary biliary cirrhosis begins to develop at the bilirubin levels higher than 2-6 mg/L [10,21]. In our study, the total bilirubin value in the patient group was 3.88. In a study by Trifan et al., the mean total bilirubin value varied between 2.8 and 14.1 mg/dL before therapeutic ERCP, while this value returned to normal in the majority of the patients after endoscopic therapy [22]. In our study, all patients were referred to the gastroenterology and general surgery departments and were treated with endoscopic retrograde cholangiopancreatography (ERCP) method or surgical intervention.
As expected, in our study, AST, ALT, GGT, ALP, total and direct bilirubin levels were significantly higher in the patient group compared to the control group (p<0,001). However, these parameters may be related to the other diseases of the biliary duct, liver and pancreas. Therefore, the diagnosis of extrahepatic cholestasis can not be based only on clinical symptoms and signs. A marker indicating extrahepatic cholestasis has not yet been identified. There are various studies in the literature investigating complete blood count parameters in intrahepatic cholestasis, but we could find only one study examining complete blood count parameters in extrahepatic cholestasis [23]. Guducu et al. measured the levels of MPV and serum biliary acid as markers of fetal status in pregnant women with intrahepatic cholestasis, and could not find a correlation between MPV and any biochemical parameter [24]. Again, Yayla et al. studied WBC, MPV and Platelet/Lymphocyte ratio (PLR) as inflammatory markers in gestational intrahepatic cholestasis and found these parameters higher compared to the controls, while RDW was found to be significantly lower. In addition, they found that MPV was increased with disease severity [11]. Eroglu et al. found higher MPV values in the same patient group, while Neu/Lym ratio was also higher, and MPV predicted gestational intrahepatic cholestasis with 65% sensitivity and 59% specificity [25].
In order to evaluate extrahepatic cholestasis in a first-line health center with a complete blood count, Morsy et al. studied RDW, MPV, platelet distribution width (PDW), Platecrit (PCT), Neu/Lym ratio and PLR between patients with extrahepatic cholestasis of different etiologies, and could not find significant difference between the groups except for MPV and PDW that were significantly higher in the distal malignant group. The authors concluded that among complete blood count parameters RDW, MPV, PDW, PCT, Neu/Lym ratio and PLR were not helpful in understanding the etiology of extrahepatic cholestasis [23). In our study, no significant differences were found between the patient and control groups in terms of WBC, neutrophils, RBC, MCV, RDW, PLT, MPV, Lym/Mon ratio, Neu/Lym ratio and PMI, suggesting that these complete blood count parameters can not be useful in the diagnosis of extrahepatic cholestasis. In addition, PMI that is a good marker of PLT function was not significantly different compared to the control group, suggesting that platelet function of these patients might be not impaired during the first presentation and thus, there was no need for prophylactic antiplatelets. In our study, Lym, Mon and RDW/MPV values were significantly higher in the patient group compared to the control group. This result suggested that Lym and Mon functions might be more effective in the development of the clinical picture of cholestasis and associated formation of hepatic fibrosis.
The RDW/MPV parameter has never been studied in the literature so far, making us think that it may be useful for the diagnosis of EHC. However, since there is no study in the literature on this issue, we could not compare our results with other studies.
Study Limitations
This study has some limitations. First, the number of patients in the study was relatively small and the study was designed as a retrospective study. Secondly, the study was conducted in a single center. However, being the first study on this issue in the literature makes our strength aspect. We believe that our result will be guiding for future studies.
Conclusion
According to our results, we found that the RDW/MPV parameter was significantly higher in patients with extrahepatic cholestasis due to biliary stones. We consider that routine evaluation of this parameter in patients presenting to emergency departments with abdominal pain and jaundice can be helpful for the diagnosis of extrahepatic cholestasis due to biliary stones. This study is the first in the literature on this issue. However, our results should be supported by further multicenter studies containing a larger number of patients.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or 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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Eyup Sabri Seyhanli, Huseyin Avni Demir. May red cell distribution width (RDW)/ mean platelet volume (MPV) ratio be a diagnostic parameter in extrahepatic cholestasis due to biliary stones? Ann Clin Anal Med 2021;12(7):726-730
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Hypnosis: How effective is it in reducing perceptions of pain and fear of birth in pregnant women?
Soysal Çağanay
Department of Obstetrics and Gynecology, Dr. Sami Ulus Women’s and Children’s Health Teaching and Research Hospital, Ankara, Turkey
DOI: 10.4328/ACAM.20435 Received: 2020-12-11 Accepted: 2021-03-22 Published Online: 2021-06-24 Printed: 2021-07-01 Ann Clin Anal Med 2021;12(7):731-735
Corresponding Author: Soysal Çağanay, Dr. Sami Ulus Women’s and Children’s Health Teaching and Research Hospital, Department of Obstetrics and Gynecology, Alparslan Turkes Street, No:57, Bestepe, 06560, Ankara, Turkey. E-mail: cagnay@hotmail.com P: +90 5554869359 Corresponding Author ORCID ID: https://orcid.org/0000-0002-4381-6099
Aim: This study aimed to evaluate the effect of hypnosis on the perception of pain by decreasing the intensity and anxiety of pregnant women and reducing the fear of vaginal birth.
Material and Methods: A cross-sectional study was conducted with 75 pregnant women in the antenatal clinics of a tertiary hospital in Ankara, Turkey, from January 2018 to January 2019. Hypnosis was applied to pregnant women for five cycles on the days when they attended prenatal class for 5 weeks (1 cycle in one week). The Wijma Maternal Expectancy/Experience Questionnaire Version A was administered before and after hypnosis.
Results: A statistically significant difference was found between the total Wijma scores in the study group before and after hypnosis (p<0.05), indicating a significant decrease in the fear of childbirth and in the perception of labor pain after hypnosis.
Discussion: Considering the increasing cesarean section rates in Turkey and all over the world, with widespread hypnosis application to pregnant women, optional cesarean sections along with the fear of childbirth are expected to decrease. The potential anxiolytic and analgesic effects of clinical hypnosis for childbirth merit further larger prospective studies.
Keywords: Hypnosis; Labor pain; Anxiety; Fear of birth
Introduction
Cesarean section is one of the most common surgical interventions in the world [1]. Although the World Health Organization points out that ideal cesarean rates should be 10-15% of all births, the frequency of cesarean section is increasing worldwide [2,3].
One of the most important reasons for increasing cesarean rates is the fear of pain and vaginal delivery [4]. Due to fear of pain, pregnant women avoid vaginal delivery and require a cesarean section. Patients tend to perceive uterine contractions as pain because of their fears.
The human mind works differently as consciousness and subconsciousness. We control and continue our daily life with consciousness. The subconsciousness is like an endless warehouse and the manager of the nervous system, which works uncontrolled in the body. Instant and involuntary reactions are under the control of the subconsciousness. All the emotions we experience about the past are stored and affect our conscious behavior. Our fears, which prevent us from giving birth and make us suffer more at birth, are hidden in our subconsciousness. As everything we hear about childbirth is usually negative and stored as subconscious fears, pregnant women are already under the negative hypnosis of society. The first thing to do for a calm and comfortable birth is to remove these fears and negative emotions. Hypnosis is a method used as the key entry into the subconscious in alertness and awareness. Suggests helps to defeat the unnecessary and exaggerated fears in the subconscious mind and act in a healthier way. This is a technique that allows to get rid of fears, not to feel aches, and can be learned by anyone.
Hypnosis has been recognized by medical organizations (British and American Medical Associations) as an effective clinical tool that can be used by women in labor and may enhance feelings of self-confidence and well-being [5]. With hypnosis, it is possible to replace negative emotions and fears with positive expectations and give a more comfortable birth by gaining control over the pregnant woman’s body of the through positive thinking.
This study aimed to evaluate the effect of hypnosis on the perception of pain by decreasing the intensity and anxiety of pregnant women and reducing the fear of vaginal delivery.
Material and Methods
This cross-sectional study was conducted in the antenatal clinics of a tertiary hospital in Ankara, Turkey, from January 2018 to January 2019. Ninety-eight primigravida women between 24-36 weeks of pregnancy and 18-45 years of age were included in the study. Patients with chronic disease, pregnancy complications and a history of cesarean section were excluded. A total of 23 pregnant women were excluded because of developing pregnancy complications and due continued follow- up of pregnancy outside the province. The study was conducted with 75 pregnant women.
The Ethics Committee approved the study, and all individuals were informed about the study and informed written consent was obtained.
Pregnant women underwent hypnosis for five cycles on the days they came for prenatal classes for 5 weeks (1 cycle in one week). Each hypnosis session lasted 1 hour and was carried out for five weeks on the same day and hour. The hypnosis application was administered by the gynecologist who is authorized and certified by the Turkish Ministry of Health to apply hypnosis. During the session, suggestions (to perceive pain as a contraction, not as pain, and not feeling pain) were given to calm the pregnant women and to affirm their subconscious fears. The Wijma Maternal Expectancy/ Experience Questionnaire Version A (W-DEQ), which was found to be a valid and reliable tool to measure the fear of childbirth, was administered before and after the completion of hypnosis sessions (37th-40th gestational week). The effect of hypnosis on defeating the fear of labor and labor pain was evaluated. W-DEQ-Awas developed by Klaas and Barbro Wijma in 1998 based on the clinical experience of women’s fear of childbirth, which is a selfscale assessment instrument commonly used inmany studies [6-8]. It consists of 33 questions, with scores ranging from ‘not at all’ (0) to ‘extremely’ (5), giving a score between 0-165. A higher score indicates a more intense fear of childbirth. The answers to some of the questions that are positively formulated have to be reversed for the calculation of the women’s individual sum score [6]. According to the severity of fear, the fear of birth was evaluated in 4 groups; Fear of childbirth at a low (score≤37), moderate (score 38-65), severe (score 66-84), and clinical level (score≥85).
In W-DEQ, question 24 is related to birth pain. Pregnant women were asked to clarify the prediction of birth pain and were asked to score 5 points. Responses in the scale were numbered 0-5, 0 is expressed as “completely” and 5 as “none,” which means that 0 is extremely painful, 5 is no pain. This question is negatively charged and is calculated by turning in the opposite direction to adapt to the measurement. The reliability and validity study of the scale in Turkish was established by Korukcu et al. in 2012 and was found as reliable and valid means to measure the level of fear of childbirth among Turkish pregnants [9].
Pregnant women were placed in a quiet room to complete the questionnaire on their own, and the completed measures were checked by the researcher to ensure there were no obvious problems in their completion.
Statistical analyses were performed using SPSS software (Statistical Package for the Social Sciences, version 22; SPSS Inc., Chicago, IL). Continuous variables were presented as median (min-max), and categorical variables were presented as percentages (%). The suitability of the data for a normal distribution was determined by the Kolmogorov-Smirnov test. In the analysis of quantitative parametric data, the Anova test (Post Hoc Tukey’s test) and the non-parametric data,the Kruskal-Wallis test (Post Hoc Mann Whitney-U test) were used. Post-test changes of quantitative data were determined by the paired sample test, and the qualitative data by the Wilcoxon test. Spearman’s correlation coefficient was used in the analysis of nonnormally distributed quantitative variables. Statistical significance was considered at a two-tailed value of p<0.05.
Results
The mean age of the pregnant women was 26.33±3.45 years; 88.1% of the study group graduated from high school and upper; 97.3% received emotional or physical support from their
partners; 78.8% were primigravida. None of the 75 pregnant women had any previous experience with hypnosis.
A significant decrease was found in the fear of childbirth after hypnosis (Table 1). While there was a fear of birth at a clinical level in the majority of the study group before hypnosis, this ratio was found to change in favor of low fear at birth after hypnosis.
There was a statistically significant difference between total Wijma scores and thoughts of labor before and after hypnosis (Z=-7.520, p=0.000; Z=-7.673, p=0.000) (Table 2). Total Wijma scores were found as meaningfully lower, and thought of labor pain (negatively charged question) were found to be significantly higher after hypnosis, indicating a significant decrease in fear of birth and in the thought of labor pain.
It was observed that although patients had the thought that labor was painful, this idea was meaningfully changed after hypnosis. Twenty-seven patients (90.0%) who perceived birth as very painful and responded as 0-1 before (excessive pain) hypnosis were transferred to 2-3 group, and 34 patients (91.9%) who were in 2-3 group before hypnosis were shifted to 4-5 group (very little/painless group) (Table 3).
A significant relationship was found between fear of labor pain and fear of birth. Although total scores were higher in patients who thought the birth was painful both before and after hypnosis, a significant decrease was found both in the perception of labor pain and total scores (fear of birth) after hypnosis. The total score of the patients in group 0-1 (excessive pain) was 92.00±20.00, whereas in group 4-5 (little pain-painless), it was 64.88±6.89 before hypnosis (F=10.977, P<0.001), and the total score in group 2-3 (moderate pain) was 28.5±12.51, whereas in group 4-5, it was 21.89±7.96 (KW=59.396, P<0.001).
Discussion
Fear is a feeling of anxiety aroused by the thought of danger or the possibility of danger. In pregnant women who have fear of birth, the subconscious considers birth as a danger. In this study, we aimed to overcome the subconscious fear of vaginal delivery in pregnant women and to change the perception of pain felt by reducing fear and anxiety with hypnosis, and found that the thought about labor pain and labor anxiety, as well as fear of childbirth, significantly decreased with hypnosis applied to pregnant women.
One of the reasons for the increased cesarean rates is the fear of pain and vaginal delivery [4]. Studies indicate that fear of birth is a common phenomenon, severe in 6–10% of pregnant women, and an important reason for cesarean section [10]. Cakmak et al. (2014) found that the most common causes of cesarean section were fear of vaginal delivery and the thought that pain during cesarean section is less than in normal delivery [11]. Similarly, Jenabi et al. (2019) stated that fear of labor pain was found as the most important factor influencing women to choose cesarean section [12]. An interesting finding from the study by Akarsu and Mucuk (2014) was that although Turkish women believed that the ideal mode of delivery was vaginal, nearly half of them preferred cesarean delivery due to labor pain and fear [13].
Fear of pain is strongly associated with the fear of labor, and a previous negative childbirth experience or inadequate pain relief are the most common reasons for requesting a cesarean section. Consistent with the extant literature, in our study, we found that the thought of labor pain increased the fear of birth significantly. A significant decrease was found both in the perception of labor pain and fear of birth after hypnosis. About 40% of women who are afraid of childbirth also endorse a fear of unbearable pain during birth. Dehghani et al. (2014) investigated the relationship between fear of pain and preference of cesarean section and suggested that it is very important to pay attention to reducing not only fear of birth but also fear of pain in pregnant women [14]. Similarly, Geissbuehler and Eberhard (2002) examined the reasons of fear during childbirth and found that the most frequent reasons mentioned were fear for the child’s health and fear of pain [15]. Management of labor pain is an essential aspect of obstetric care and the major goal of intrapartum care. In recent years, many women have wanted to avoid pharmacological or invasive methods of pain relief during labor, and as a result, complementary methods like hypnosis have become increasingly popular. It has been proven that hypnotic techniques can be useful for a different kind of pain and have long been used for this purpose [16,17]. The term hypnosis first appeared in the 1840s and has been reported as an effective method of pain relief during childbirth in recent years [18]. Although parenteral opioids or epidural analgesia relieve pain during labor, they have also been associated with increased risks of adverse maternal effects, and their effects on the newborn are unclear [19]. Therefore, although there are still only a relatively small number of studies assessing the use of hypnosis for childbirth, in recent years, it has become increasingly popular as a means of labor pain management. A Cochrane review concluded that hypnosis might reduce the overall use of pharmacological analgesia during labor [18].
In our study group, it was observed that although patients thought labor was painful before hypnosis, this idea meaningfully changed after hypnosis. It can be clearly stated that altering patients’ perception of pain and anxiety can help reduce the severity of pain at birth they feel. In their study, Abbasi et al. trained 6 women to use self-hypnosis for labor in their study and stated that patients had experienced neither discomfort nor severe pain associated with delivery when they were hypnotized and tried to describe the effect of hypnosis on pain relief during labor and childbirth [20]. Similarly, Prasertcharoensuk and Thinkhamrop (2004) examined alternative and complementary therapies for pain management in labor, and found that women receiving hypnosis were more satisfied with their pain management in labor compared with controls [21]. Although the comparison of hypnosis with opioids or epidural anesthesia is not appropriate, as there is no known maternal or fetal side effect of hypnosis, it can easily be said that this is an important advantage. The Australian and New Zealand College of Anesthetists recommends considering non-pharmacological options before pharmacological options for pain management during pregnancy, as pain medications generally cross the placenta [22]. Neuro-imaging studies found that hypnosis reduced pain experienced from hot, noxious stimuli, and that the process was mediated by the anterior cingulate cortex [23]. Both effective and sensory aspects of pain perception were reduced when participants used hypnosis [23].
Psychosocial factors, including anxiety, fear, feelings of self- efficacy and social support have also been shown to have a relationship with women’s experiences of labor pain. When we evaluated fear of childbirth, we found that pregnant women had significantly lower fear of birth after hypnosis. Most studies show an association between hypnosis and a decrease in fear of childbirth [20,24]. Similar to our results, in a randomized controlled trial conducted by Werner et al. among 1222 healthy Danish nulliparous women, the tendency towards better childbirth experience was seen for the mode of delivery and lower levels of fear were seen in the self-hypnosis group [25]. When a woman learns to release the preconceptions, fears, and worries about birth that are widespread in our society, her experience of giving birth to her baby can be the most beautiful and empowering experience of her life. Mind and body working together can be a powerful and efficient combination.
As a result, the cross-sectional nature of this study, the small number of participants, its homogeneity are the limitations of this study in the interpretations of the results and in future. As the mothers could not be observed at birth, pain conditions and fears at birth were not detected. Despite these limitations, our work broadens the understanding of the effect of hypnosis on reducing the fear of pain and childbirth in pregnant women. Considering the increasing rates of cesarean section in Turkey and all over the world, with widespread hypnosis application to pregnant women, optional cesarean sections along with fear of childbirth are expected to decrease. The potential anxiolytic and analgesic effects of clinical hypnosis for childbirth merit further larger prospective studies.
Conclusion
The most common cause of increasing cesarean rates is fear of pain and vaginal delivery, which pushes the pregnant women to avoid vaginal delivery and demand cesarean section. We have demonstrated that hypnosis had a serious effect on reducing the severity of pain, anxiety and fear of childbirth. Taking into account the increased rates of cesarean sections in Turkey, the effect of hypnosis on reducing fear of childbirth should not be ignored and be emphasized on the use of a good alternative in increasing normal birth rates in our country and worldwide.
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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Soysal Çağanay. Hypnosis: How effective is it in reducing perceptions of pain and fear of birth in pregnant women? Ann Clin Anal Med 2021;12(7):731-735
Citations in Google Scholar: Google Scholar
Which dental implant surface is more effective in osteointegration: RBM surface versus SLA surface
Umut Demetoglu 1, Hakan Ocak 2, Timur Songur 3, Halis Ali Çolpak 4
1 Department of Oral and Maxillofacial Surgery, Adnan Menderes University, Faculty of Dentistry, Aydın, 2 Oral and Maxillofacial Surgeon, Dr.Ocak Private Clinic Kayseri, 3 Oral and Maxillofacial surgeon, Private Clinic, Ankara, 4 Department of Oral and Maxillofacial Surgery, Alanya Alaaddin Keykubat University, Faculty of Dentistry, Antalya, Turkey
DOI: 10.4328/ACAM.20436 Received: 2020-12-14 Accepted: 2021-01-27 Published Online: 2021-02-10 Printed: 2021-07-01 Ann Clin Anal Med 2021;12(7):736-739
Corresponding Author: Halis Ali Çolpak, Alanya Alaaddin Keykubat University, Faculty of Dentistry, Department of Oral and Maxillofacial Surgery, Antalya, Turkey. E-mail: halisalicolpak@gmail.com P: +90 5308752768 Corresponding Author ORCID ID: https://orcid.org/0000-0002-5958-0084
Aim: The surface characteristics of an implant direct the wound healing and are an important factor for osteointegration. There are very few studies evaluat- ing or comparing the clinical success of osteointegration of sandblasting with larger grit and acid etching (SLA) and rough surface as required by grit blasting (RBM) surfaces, which are important surface factors in selecting an implant. The aim of this study was to evaluate the osteointegration success in a total of 4793 implants in 2005 patients in SLA and RBM surface cylindrical implants of the same trademark and type.
Material and Methods: A total of 4793 implants and 2005 patients composed of 943 females and 1062 males were included in this study. Regions of implant applications were grouped into anterior and posterior parts of the mandible and anterior and posterior parts of the maxilla and evaluated with success rates.
Results: Among the implants, 1877 were RBM surface and the remaining 2675 had SLA surface. Seventy-four implants among the 1877 RBM surface implants failed (%96.06). The success rates were 94.75 % and 97.22%, maxilla and mandible, respectively. Among the 2675 SLA surface implants, 93 failed (%96.53). The success rates were 95.29% and 97.11% in maxilla and mandible, respectively.
Discussion: Recently, the studies have demonstrated increased bone and implant contact areas and a high degree of osteoconductive property when applied to surfaces in histological studies. In the presented study, RBM and SLA surface implants with the same trademark and same design were clinically compared, and no significant difference was found between them in terms of osteointegration success.
Keywords: Dental implant; Implant surface; Osteointegration
Introduction
Osteointegration was first defined by Brenemark et al. as fusion development between mature bone and implant without any soft tissue formation. Brenemark et al. also evaluated the factors affecting osteointegration in models in which they applied screw-type implants in canine mandibles and they reported that the depth of the implant in the bone and atraumatic procedures affected the osteointegration [1]. Nevertheless, Albrektsson et al. placed cylindrical implants in adult canine mandibles and evaluated the osteointegration microscopically. The results of the study revealed that osteointegration required a time period of 3 to 4 months [2]. Brenemark et al. in their electron microscopic study reported that structures in irregular layers were present between an implant and bone although they seem to be in contact with each other directly. They reported that the surface characteristics of an implant direct the wound healing and is an important factor for osteointegration. Bone growth has been observed to be more rapid and physical adhesion has been seen to be more successful in cases in which rough- surface dental implants were used [2,3]. Many studies have been performed with rough surface dental implants; osteoblast adherence has been seen to be much better in those implants and maturation and differentiation have been reported to be much faster in the cells adhered to the implant surface. At the same time, bone-implant contact in far greater rates and higher removal torque values have been seen in rough surface dental implants compared to machine- polished implants [2,3]. Among the implant surface types are hydroxyapatite coating [4], acid etching [5], blasting [6], sandblasting with larger grit and acid etching (SLA) [7].
The aim of the RBM technique is to provide a rough surface as required by grit blasting. Bioceramics used in the RBM technique decrease the possible biocompatibility issues by particle embedding on the implant surface of particle detachment [8]. SLA surface is made by sandblasting the implant surface by aluminum oxide (Al2o3) or titanium oxide (Tio2) particles and subsequently roughing this surface using hydrochloric acid or sulphuric acid [10]. Buser et al. reported higher removal torque values and more rapid osteointegration in SLA surface implants compared to implants with other surface properties [9].
SLA surface technique is a technique of surface roughing preferred by many implant manufacturers. Also, RBM is another technique that has recently been applied by implant manufacturers. Studies evaluating or comparing the clinical success of osteointegration of SLA and RBM surfaces which are important surface factors in selecting an implant are very few. The aim of this study was to evaluate the osteointegration success in a total 4793 implants in 2005 patients in SLA and RBM surface cylindrical implants of the same trademark and type (EBI Precision 1.8, KOREA ).
Material and Methods
The permission for the study was taken from the Local Ethics Committee, and it has been conducted in full accordance with the World Medical Association Declaration of Helsinki. A total of 4793 implants and 2005 patients composed of 943 females and 1062 males were included in this study. Regions of implant applications were grouped into anterior and posterior parts of the mandible and anterior and posterior parts of the maxilla and evaluated with success rates. Patients who smoked cigarettes had poor oral hygiene, uncontrolled diabetes, chronic renal and liver disease, and metabolic bone disorder and hemophilia and immunocompromising disease or had received radiotherapy to the head and neck region or antiblastic chemotherapy or implants placed with maxillary sinus lifting were excluded from the study. Criteria of the success of an implant were defined as stable implants at the end of a period of at least 2 months in the lower jaw and 3 months in the upper jaw, no sign of infection and observation of no marked radiolucent areas around the implants in periapical radiographs.
Results
A total of 2005 patients were included in this study. Among those, 943 were females and 1062 were males. A total of 4552 implants were applied in 2005 patients. Among the implants, 1877 were RBM surface and the remaining 2675 had SLA surface (Table 1). Seventy-four out of 1877 RBM surface implants failed (%96.06). The success rate was 94.75 % and 97.22%, maxilla and mandible, respectively. Among the 1877 implants, 215 were applied in the anterior maxilla and 12 (94.42%) failed. Thirty-two of the 623 implants applied in the posterior part of the maxilla failed (%94.87). Seven out of 180 (%96.12) and 23 out of 859 (%97.33) implants in the anterior mandible and posterior mandible, respectively failed (Table 2). Among the 2675 SLA surface implants, 93 failed (%96.53). The success rates were 95.29% and 97.11% in maxilla and mandible, respectively. Nineteen out of 290 implants applied in the anterior part of the maxilla failed (%93.45), while 30 out of 801 in the posterior maxilla failed (%96.26). In the anterior mandible, on the other hand, 19 out of 258 (%92.66) and 25 out of 1326 in the posterior mandible failed (%98.12) (Table 3).
Discussion
Continuous efforts such as the development of new surgical techniques, better bone graft materials, and improvement of implant design have been made in order to increase the implant success and decrease the healing time with the widespread use of implant application. It was reported in many studies that rough surface implants were more advantageous in bone healing compared to machine polished implants [7,8]. An increase in bone and implant contact area values is provided, since the contact area is increased in rough surfaces and this facilitates adhesion of osteoblasts to the implant surface and has positive effects on their proliferation [10,11].
Both acid etch [12] and media blasting [10] have demonstrated an increase in bone and implant contact areas and high degree osteoconductive property when applied to surfaces in histological studies. Cooper evaluated the effect of surface topography in dental implants on the surrounding bone and reported increased bone contact due to increased surface area and thus improved mechanical properties [13].
On the other hand, Davies pointed out the wetting capability of the surface in his hypothesis and reported that clot adherence around the implant provided a better osteointegration in rough surfaces [14].
Im et al. compared RBM and SLA surfaces in their study that was performed in the canine maxilla and reported good early stability values by periotest in implants with both surfaces. However, periotest performed in the 12th week resulted in higher stability values in RBM surfaces compared to SLA surfaces. No statistical difference was reported in torque values and bone and implant contact areas and bone area fraction occupied values between the groups. As a result, both SLA surface and RBM surface stability were demonstrated to be good and had good healing patterns compliant with the surrounding bone [15]. Also, higher bone and implant contact area values and osteoblastic activity have been observed in SLA surface and RBM surface implants compared to the machine treated implants in many previously published studies [12,16]. SLA, RBM and RBM acid etch surface implants were compared in a study by Coelho et al., and no difference was found in removal torque and implant bone interlocking values in spite of increased surface roughness of the SLA surface [17].
Buser et al. evaluated the association of bone and implant contact and tried implants with 6 different surfaces in the long bones of miniature minipigs. They found a direct proportion between increased surface areas and implant-bone contact. The highest bone implant contact area was found on the roughest surface at the end of the 6th month [18]. Wennerberg et al. compared two different blast surfaces and found that surface with increased roughness provided a better bone fixation and a serious rate of removal torque value, and increased implant contact area [19].
In a 5-year study performed using IMZ implants, the success rate of cylindrical implants roughened with titanium plasma was reported to be 95.8 % and 92.9% in mandible and maxilla, respectively [20]. Babbush and Shimura demonstrated a mean of 95.0% percent success rate in a 5-year clinical study with IMZ implants. The success rate was 96.0% in both partially and totally toothless patients and 92.0% and 99.0% in maxilla and mandible, respectively. The main factors positively affecting the success were reported to be the use of the longest and the widest diameter implants compatible with the clinical condition [21]. Some authors declerated that the widest and longest implants positively support primer stability and also osteontegration [22]. However, there are studies indicating that implant diameter and length have no effect on osteointegration [23]. Bischof et al. researched the factors related to osteointegration. They reported that the implant diameter, length, implant design do not influence the osteointegration, on the other hand, only the bone type of the jaws was found the primer factor for osteointegration [24].
The reported success rate of 95.3% that was achieved with SLA surface solid screw implants in the 5-year ITI follow-up report is similar to the implant success rate of the Branemark system [25]. Similarly, success rates of 94.36% and 97.22% were seen in maxilla and mandible, respectively, in RBM surface implants and 97.22% and 97.33% in mandible and maxilla, respectively, in the SLA surface implants in this present study. Both surfaces were found to be successful at similar rates and were found to be safe.
Conclusion
Consequently, RBM and SLA surface implants with the same trademark and same design were clinically compared, and no significant difference was found between them in terms of osteointegration success. Both RBM and SLA surfaces were found to be safely preferable with proper case selection, appropriate surgical technique, and patient motivation
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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Pregnancy outcomes after fetal reduction and selective termination: A retrospective study
Ali Acar 1, Sevcan Sarikaya 2, Fedi Ercan 3
1 Department of Obstetrics and Gynecology, Necmettin Erbakan University, Meram Faculty of Medicine, Konya, 2 Department of Obstetrics and Gynecology, Mardin Kızıltepe State Hospital, Mardin, 3 Department of Obstetrics and Gynecology, Konya City Hospital, Konya, Turkey
DOI: 10.4328/ACAM.20438 Received: 2020-12-15 Accepted: 2021-02-04 Published Online: 2021-02-19 Printed: 2021-07-01 Ann Clin Anal Med 2021;12(7):740-745
Corresponding Author: Sevcan Sarikaya, Mardin Kızıltepe State Hospital, Department of Obstetrics and Gynecology, Mardin, Turkey. E-mail: simsek_svcn_@hotmail.com P: +90 507 780 07 63 Corresponding Author ORCID ID: https://orcid.org/0000-0002-0922-4671
Aim: Fetal reduction (FR) and selective termination (ST) are the procedures applied for multiple pregnancies that positively change the gestational outcomes. Results regarding the reliability of these procedures are variable. In this study, pregnancy outcomes of FR and ST procedures and pregnancy loss rates related to the procedure were evaluated.
Material and Methods: A total of 228 women with multifetal pregnancies, who underwent FR and ST in the Department of Gynecology and Obstetrics of Nec- mettin Erbakan University, Meram Faculty of Medicine between January 2007 and June 2017, were analyzed.
Result: The mean gestational week in those with FR was 11.7 (±1.3). The mean gestational week in those with ST was 14.0 (±3.1). The gestational week for ST was significantly higher than the gestational week for FR (p<0.001). Out of a total of 132 pregnancies undergoing FR, there was a total pregnancy loss in one case (0.75%). There was no pregnancy loss in any of the pregnancies undergoing ST.
Discussion: With the increase in the number of fetuses, negative perinatal conditions such as preeclampsia, gestational diabetes, intrauterine growth retar- dation, postpartum hemorrhage and staying in the neonatal intensive care unit increase. In our study, it was observed that these risks were similar to the frequency in the general population in patients who underwent fetal reduction and selective termination.
The FR and ST procedures are successful methods to reduce fetal mortality and morbidity in the reduced numbers of fetuses, in conformity with ongoing pregnancies.
Keywords: Fetocid; Multifetal pregnancy; Pregnancy reduction; Selective termination
Introduction
In line with the recent increase in the use of assisted reproductive techniques, the incidence of multifetal pregnancies has increased [1]. There has been an increase in the twin pregnancy rate by 2.8% to 3.4% [2]. Upon the increase in the multifetal pregnancy rates, the incidence of complications, such as prematurity, congenital anomalies, fetal growth restriction, twin-to-twin transfusion syndrome and fetal death, has also increased [3]. In order to reduce these complications, it was first attempted to reduce the number of embryos transferred in the assisted reproductive therapies [4].
Fetal Reduction (FR) is used to decrease fetal complications in the antenatal period. FR and selective termination (ST) aim to reduce the incidence of adverse perinatal outcomes in multifetal pregnancy by reducing the number of fetuses. While FR is implemented between the 10th and 13th weeks of the gestation, ST can be performed in any week of gestation when a fetal anomaly is detected [5].
The conventional techniques used for FR and ST are only suitable for multichorionic pregnancies; mono-chorionic pregnancies require special techniques and have higher pregnancy loss rates [5].
ST is known to yield better obstetric results when used prior to the 15th week [6]. At the same time, FR is known to increase the miscarriage rates in multifetal pregnancies while reducing the preterm delivery rates [7]. The primary aim of the FR and ST procedures is to increase the number of healthy fetuses to be taken home.
In this study, the complications of the FR and ST procedures performed in multifetal pregnancies and the outcomes of ongoing pregnancies were evaluated.
Material and Methods
This study was a retrospective study performed in the Department of Gynecology and Obstetrics of Necmettin Erbakan University, Meram Faculty of Medicine between January 2007 and June 2017, were analyzed. This study is in compliance with the principles of the Helsinki Declaration, and the approval was obtained from the Ethics Committee of Necmettin Erbakan University, Meram Faculty of Medicine(2017/1012). A total of 228 women with multifetal pregnancies, who underwent FR and ST were included in this study. Seventy-two of these pregnant women who underwent FR and ST procedures were excluded for various reasons (delivery at a different center, the patients being inaccessible through file records, lack of data to be included in the study for accessible patients, unwillingness of the patients to take part in the study). The study included the remaining 156 patients. One hundred thirty-two of these patients underwent FR, while 24 underwent ST (Figure 1). The demographic data of the patients were retrospectively screened and included in the study form.
Informed consent was taken from the pregnant women scheduled to undergo FR and ST and from their spouses prior to the procedures. For the procedure, a GE Voluson 730 Pro ultrasound device was used. The procedure was always performed by the same operator (AA). The pregnant woman was placed in the supine position, and the abdomen was sterilized with an antiseptic solution (10% of polyvidone-iodine, Batticon®). The sac was selected that has the thickest nuchal translucency (NT) regardless of the fetal gender, and is the most accessible one with the use of a needle, and is located away from the cervix and is located closest to the uterine fundus [8]. Then, using a 22G spinal needle, 1% of potassium chloride was injected intracardially into the fetus to be transabdominally reduced. Fetal cardiac activity is checked following each injection of 1 cc (0.01 mEq/mL). Until the fetal cardiac activity ceases, one cc of KCI solution is administered. The procedure was terminated following the development of asystole. The fetus to be chosen in ST is the fetus with a fetal anomaly.
The weeks of gestation of all pregnant women undergoing FR and ST, as well as the fetal weight at the delivery, Apgar scores, neonatal intensive care requirements, early and late neonatal complications were analyzed. Moreover, the patients who underwent FR and ST procedures were asked a single question whether they regretted having done the procedure, and their answers were recorded in the form of “yes” or “no”. The two groups were compared in terms of the status of regret. Statistical analysis
The SPSS 18.0 software package was used for the statistical analysis of the data. The Kolmogorov-Smirnov test was used to determine whether the numerical measures met the normal distribution assumption. Categorical measures were shown as numbers and percentages, the data distributed homogeneously as mean ± standard deviation, and the data with non- homogeneous distribution as (median [minimum- maximum]). The Chi-Square test was used to compare the categorical measures between the groups. The independent t-test was used to analyze the homogeneously distributed data in the comparison of the numerical measures between the groups. The Kruskal-Wallis test was used to generally compare the non-normally distributed numerical measures between more than two groups. The statistical significance value was given as “p value” in all tests. A p-value of <0.05 was considered statistically significant.
Results
The mean maternal age at the time of delivery was 27.9 (±4.3) in all pregnancies with FR. There were no significant differences between age, pre-gestation weight, gravida and parity in the comparison of the FR and ST patients (Table 1). Among multifetal pregnancy patients who underwent FR, 58/132(44%) were the post-IVF ones, while this rate was 4/24 (16%) for the ST patients, and the cesarean section rate was significantly high in both groups (p<0.05) (Table 1). The mean gestational week in those with FR was 11.7 (±1.3). The mean gestational week in those with ST was 14.0 (±3.1). The gestational week for ST was significantly higher than the gestational week for FR (p<0.001).
Out of 132 patients undergoing FR, 20 were reduced to triplet pregnancy, 96 to twin pregnancies, and 16 to singleton pregnancies. Out of 24 patients undergoing 24, 23 were reduced to singleton pregnancy and 1 to twin pregnancy. One hundred seventeen (88.6%) of the patients undergoing FR had multi-chorionic/multi-amniotic multifetal pregnancies, while 15 pregnant women (11.4%) had dichorionic-triamniotic multifetal pregnancies. Fetuses with monochorionic placentation were selected for the reduction of the dichorionic-triamniotic triplet pregnancies, and triplet pregnancies were reduced to singleton pregnancy in this manner.
Among the pregnant women undergoing FR, 12/132 (9%) got pregnant spontaneously, 58/132 (44%) through assisted reproductive techniques, 32/132 (24%) through intrauterine insemination following the ovulation induction, and 30/132 (23%) through planned coitus following the ovulation induction. As a group, ovulation induction was the most common way to get pregnant in the pregnant women undergoing FR, (62/132, 47%). Among the pregnant women undergoing ST, 10/24 (42%) got pregnant spontaneously,4/24 (16%) through assisted reproductive techniques, 10/24 (42%) through intrauterine insemination following the ovulation indication.
Among the pregnancies undergoing FR, 4 (3%) were reduced from septuplet pregnancy, 4 (3%) from sextuplet pregnancy, 2 (1.5%) from quintuplet pregnancy, 32 (24%) from quadruplet pregnancy, and 54 (41%) from triplet pregnancy to twin pregnancy. Among the pregnancies reduced to triplet pregnancy, 10 (7.5%) were reduced from quadruplet pregnancy, 8 (6%) from quintuplet pregnancy, and 2 (1.5%) from septuplet pregnancy. The procedures were carried out in 2 different sessions at 7-day intervals in the pregnancies reduced from septuplet pregnancy to triplet and twin pregnancies. Fifteen (11.5%) of the pregnancies reduced to singleton pregnancy through FR were reduced from triplet pregnancy and 1 (1%) from twin pregnancy.
Only one (1/24, 4%) of the pregnancies undergoing ST was reduced from triplet pregnancy to twin pregnancy, while the remaining 23 (96%) were completely reduced from twin pregnancy to singleton pregnancy.
The pregnancies with FR were mostly reduced to twin pregnancy (96/132, 72.5%). The most frequent FR method used was the reduction from triplet pregnancy to twin pregnancy with 54 cases (41%).
The most common anomaly observed during ST was cystic hygroma (10/24, 41.6%). The total number of embryos reduced was 24 in a total of 24 cases undergoing ST.
Out of a total of 132 pregnancies undergoing FR, there was a total pregnancy loss in one case (0.75%). There was no pregnancy loss in any of the pregnancies undergoing ST.
When the patients undergoing FR were separately analyzed, it was found that the mean gestational week was 30.8 ± 3.7 weeks in the pregnant women reduced to triplet pregnancy, 35.4 ± 2.5 weeks in those reduced to a twin pregnancy, and 38.0 ± 0.8 weeks in those reduced to a singleton pregnancy. Except for one case, all pregnant women with ST were reduced from twin pregnancy to singleton pregnancy. The mean gestational week of 23 pregnant women reduced to singleton pregnancy was 37.8 ± 2.2 weeks. There was only one pregnant woman who was reduced to twin pregnancy. This pregnant woman delivered due to an early membrane rupture at 28 weeks of gestation. Furthermore, the pregnant women, who were reduced to triplet, twin and singleton pregnancies, were divided into three groups and compared among themselves. Accordingly, gestational week at the delivery, extremely early preterm deliveries (<32 weeks), preterm deliveries (37 weeks), infants with quite low weight of birth (1500 gr), infants with low weight of birth (2500 gr), 5th minute Apgar score lower than 7, GDM, preeclampsia, admission to NBIC unit, and perinatal mortality rates were significantly different (Table 2).
The results of the FR and ST cases reduced to singleton pregnancy are collectively summarized in Table 3. When the pregnancies that underwent FR-ST and reduced to a singleton pregnancy were compared, there were no significant differences between the two groups in terms of the gestational week, delivery before 37 weeks and before 32 weeks, birth weights lower than 2500 gr and 1500 gr, infants with a 5-minute APGAR score lower than 7, gestational diabetes, and preeclampsia (Table 3). Neither group had any infants lost in the neonatal period. Upon the comparison of both groups, it was seen that the pregnant women who underwent FR, 27/132 (%20,4) regretted it more compared to those who underwent ST, 1/24 (%4,1) and that this difference was statistically significant (p<0.05).
Discussion
The number of multifetal pregnancies has risen significantly as a consequence of the increase in advanced age pregnancies and the assisted reproductive techniques becoming widespread in recent years. The distinct increase in the incidence of multifetal pregnancies brings along negative perinatal outcomes [9]. Premature delivery, intrauterine growth restrictions, structural and chromosomal anomalies are the major causes of adverse perinatal results [10]. Perinatal results are getting dramatically worse particularly in multifetal pregnancies with 3 or more fetuses [11]. This situation, as a consequence, led to the idea of reducing such pregnancies to a lower number of multifetal pregnancies, which has been implemented since then.
In our study, 2/20 (10%) of the fetuses delivered through pregnancies treated with FR and reduced to triplet pregnancy were lost in the perinatal period, while 4/95 (4.2%) of those reduced to twin pregnancy were lost in the perinatal period.
These data demonstrate similar features with the multifetal pregnancies that occurred spontaneously and in the same numbers [12]. No loss was observed neither in the post- procedural period nor in the perinatal period in the FR and ST pregnancies that were reduced to a singleton pregnancy. There are quite varying numbers in the literature with regard to the methods of delivery of patients who underwent FR and ST [13, 14]. Among those undergoing FR in this study, 82.4% had cesarean section delivery, while 17.6% had a vaginal delivery. The high cesarean section rate is associated with the pregnancies being treatment-induced gestations, and therefore with social indications.
Multifetal pregnancy also increases the risk of gestational complications of the mother, including preeclampsia, postpartum hemorrhage and gestational diabetes [15]. This is directly associated with the rise in the number of fetuses of multifetal pregnancies. Upon the analysis of the pregnancies that were reduced to single fetuses through FR and ST in our study, it was seen that the prevalence of preeclampsia and GDM was at rates that were similar to the prevalence of the same in the general population (respectively 6.3% and 4.3% for preeclampsia; respectively 12.5% and 8.6% for GMD in the order of prevalence for FR and ST).
Despite being controversial, there are some opinions suggesting that FR can also be considered for twin pregnancies in the absence of medical or obstetric indications (e.g. Maternal heart disease, history of a preterm single delivery, cervical failure resulting in pregnancy loss) [16,17]. In this study, only one patient was reduced from twin pregnancy to singleton pregnancy through FR. This procedure was implemented due to maternal heart disease (history of heart transplantation).
The involuntary pregnancy loss was reported to be 5.4% in a monocenter series in which 1000 FR patients were analyzed [18]. The rate of loss was reported as 2.5% in those reduced from twin pregnancy to singleton pregnancy, and as 5% in those reduced from triplet pregnancy to singleton pregnancy. The pregnancy loss prior to week 24 in the post-ST period was reported as 4% in a single-center series consisting of 200 patients [19]. In a multicenter series, 402 cases were analyzed and this rate was found to be 7.5% [20]. Any complete pregnancy loss within 10 days in the post-procedure period is considered a procedure- induced pregnancy loss. Accordingly, out of 132 pregnancies in total that underwent FR in our series, one had a total pregnancy loss (0.75%). This was a pregnant woman who was reduced from septuplet pregnancy to twin pregnancy. No pregnancy loss occurred in any of the pregnancies that underwent ST. The fact that the rate of pregnancy loss in our study was much lower than the literature data can be explained by the fact that the procedures were conducted by the same operator at all times throughout the study. Much of the literature data consist of a review of the data from procedures conducted by multiple operators. Post-FR pregnancy results, including the rates of total pregnancy loss and prematurity, improve with increasing operator experience [18].
The multifetal pregnancies reduced to singleton pregnancy result in fewer preterm deliveries compared to the multifetal pregnancies reduced to twin pregnancy [21]. In our study, deliveries prior to week 37 in pregnancies with FR were observed in all pregnancies that were reduced to triplet pregnancy, in 62.1% of the pregnancies that were reduced to a twin pregnancy, and in 12.4% of the pregnancies that were reduced to a singleton pregnancy. Similarly, deliveries prior to 32 weeks in pregnancies with FR were observed in 45% of the pregnancies reduced to triplet pregnancy, in 15.7% of the pregnancies reduced to a twin pregnancy, and in 6.2% of the pregnancies reduced to a singleton pregnancy. These preterm delivery rates are similar to those in multifetal pregnancies and support the fact that the FR procedure does not constitute any additional risks for preterm delivery.
Alvarado et al. reported that the rate of pregnancy loss was 3.6% in 28 dichorionic pregnancies undergoing ST, and that the rate of delivery prior to week 34 was reduced by 11.8% [22]. Furthermore, in the literature, it is recommended that the ST procedure be performed in the advanced weeks rather than early. [23]. In our study, the preterm delivery prevalence in the FT patient group under 32 weeks was 45% in those reduced to triplet pregnancy, 15.2% in those reduced to a twin pregnancy, and 6.2% in those reduced to a singleton pregnancy. In the ST patient group, however, the prevalence of preterm delivery under 32 weeks was 4.3% in the patients that were reduced to a singleton pregnancy. These data are in concordance with the rates of preterm delivery reported in the literature.
Studies evaluating birth weights in pregnancies with FR and ST support the fact that birth weights in these pregnancies do not differ from spontaneous multifetal pregnancies in the same numbers [24]. When the FR and ST cases reduced to singleton pregnancies were compared, no significant differences could be observed in terms of birth weights under 2500 g and under 1500 g.
A large number of studies showed that the pregnancies with FR and ST, the Apgar score at the time of delivery and the requirement for admission to the NBIC unit were not different from the spontaneous multifetal pregnancies in the same numbers. Tse et al. analyzed the results of 52 triplet pregnancies and showed that the weight of birth increased in pregnant women with FR and that the newborn intensive care requirement reduced, while the preterm delivery rate reduced [25]. Among the fetuses delivered through pregnancies reduced from triplet pregnancy after FR and ST in our study, 90% were admitted to the NBIC unit, as well as 23% of the fetuses delivered through pregnancies reduced to a twin pregnancy, and 6.3% of the fetuses delivered through pregnancies reduced to a singleton pregnancy. Among the fetuses delivered through pregnancies reduced to singleton pregnancy after ST, 4.3% were admitted to the NBIC unit. Upon the comparison of the FR and ST cases reduced to a singleton pregnancy, no differences could be observed with regard to the prevalence of fetuses admitted to the NBIC unit (p=0.75). Out of 23 fetuses in total that were delivered through pregnancies reduced to singleton pregnancy after ST, one (4.3%) was admitted to the NBIC unit. No neonatal deaths occurred among these infants. These data are in concordance with the literature.
No studies were seen in the literature on what families that went through FR and ST felt about this decision they made. In our study, the patients were asked whether they regretted the procedure they went through. Among the mothers that
underwent FR, 20.4% answered “I regret it”, in addition to 4.1% of the mothers who underwent ST and gave the same answer. Upon the comparison of both groups, it was seen that the pregnant women who underwent FR regretted it more compared to those who underwent ST, and that this difference was statistically significant (p<0.05). This was probably caused by the termination of a fetus with fetal anomalies, which was the reason to have ST. On the contrary, the fact that a normal fetus is “seemingly” terminated in FR pregnancies explains why this rate is significantly high.
Conclusion
The FR and ST procedures are successful methods to reduce fetal mortality and morbidity in the reduced numbers of fetuses consistent with ongoing pregnancies.
Acknowledgment
We would like to express our sincere thanks and appreciation to Mrs. Nurcan Sağlam and Mrs. Naciye Öney, the responsible nurses of Necmettin Erbakan University, Meram Medical Faculty, Department of Obstetrics and Gynecology, Unit of Perinatology, for their rigorous and selfless acts in preparation and keeping records of the data.
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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Ali Acar, Sevcan Sarikaya, Fedi Ercan. Pregnancy outcomes after fetal reduction and selective termination: A retrospective study. Ann Clin Anal Med 2021;12(7):740-745
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A cross-sectional analysis of serum vitamin D and immunoglobulin E in allergic disorders
Farhan Khashim Al-Swailmi 1, Syed Imran Ali Shah 2, Ghassab Mohammad Al-Mazaideh 3, Mirza Zeeshan Sikandar 4
1 Department of Pharmacy Practice, University of Hafr Al-Batin, Hafar Al Batin, Saudi Arabia, 2 Department of Biochemistry, University of Hafr Al-Batin, Hafar Al Batin, Saudi Arabia, 3 Department of Pharmaceutical Chemistry, University of Hafr Al-Batin, Hafar Al Batin, Saudi Arabia, 4 Department of Biochemistry, Central Park Medical College, Lahore, Pakistan
DOI: 10.4328/ACAM.20439 Received: 2020-12-15 Accepted: 2021-01-14 Published Online: 2021-01-25 Printed: 2021-07-01 Ann Clin Anal Med 2021;12(7):746-750
Corresponding Author: Syed Imran Ali Shah, Department of Biochemistry, University of Hafr Al-Batin, Hafar Al Batin, Saudi Arabia. E-mail: simranali@uhb.edu.sa / s.shah10@alumni.imperial.ac.uk P: +966534510690 Corresponding Author ORCID ID: https://orcid.org/0000-0002-0833-0771
Aim: Allergic disorders constitute a major health problem in the modern world. Hypersensitivity to various allergens mediated by immunoglobulin E (IgE) forms the pathologic basis of allergies. The emerging role of vitamin D in immunity makes it a potential preventative and therapeutic agent against allergies. The present study explored the link between serum vitamin D and IgE levels in local patients with known allergies.
Material and Methods: Eighty subjects were recruited for this cross-sectional study and segregated into Group 1 (non-allergic control subjects, n=41)) and Group 2 (allergic subjects, n=39). Complete blood count (CBC), serum IgE and serum vitamin D with its associated biochemical markers, including parathyroid hormone (PTH), calcium and phosphate were determined for comparison between the two groups. Basic demographic data, medical history and sun exposure duration were also recorded.
Results: IgE levels (Group 1, 87.13 IU/L ± 57.66 vs. Group 2, 1542.54 IU/L ± 1239.79; p=0.000) and eosinophil count (Group 1, 2.80% ± 1.83 vs. Group 2, 4.61% ± 4.19; p=0.014) were significantly higher in patients with allergies. No difference was observed between the groups in serum vitamin D levels and other mark- ers. In patients with allergies, serum vitamin D was inversely related to serum IgE (r= -0.374, p= 0.019).
Discussion: High serum vitamin D is associated with low IgE levels in patients suffering from allergic conditions, suggesting a potential interplay between aller- gic mechanisms and vitamin D. Further studies are warranted to clarify the role of vitamin D in the pathogenesis and clinical management of allergic disorders.
Keywords: Allergy; Vitamin D; Immunity; Immunoglobulin E; Hypersensitivity
Introduction
Allergic conditions constitute a major worldwide cause of chronic disability in individuals of all age groups and have a tremendous negative health economic impact. Allergic disorders have a complex etiology, with an almost equal contribution of genetic susceptibility and exposure to environmental factors [1]. In the last few decades, the prevalence of allergic conditions such as asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis and food allergies has increased considerably [2-5]. With booming populations, growing urbanization and increasing westernization, South Asian countries have experienced a rise in allergic disorders due to a mix of environmental exposure and genetics due to high prevalence of consanguinity [6]. Immunoglobulin E (IgE) antibodies produced by the B-cells of the immune system lie at the heart of the hypersensitivity response seen in these allergic conditions. IgE, by binding to high-affinity IgE receptors present on the surface of basophils and mast cells, trigger degranulation and release of histamine and leukotrienes upon interaction with the allergens, which causes pronounced inflammatory responses leading to various allergic manifestations such as sneezing, bronchospasm, excessive nasal secretion, skin rashes along with itching, hyperemia, swelling and fever [7, 8].
Vitamin D is a fat-soluble vitamin obtained chiefly by dermal photobiogenesis that yields pro-vitamin D (cholecalciferol), which is subsequently activated into vitamin D (1,25- dihydroxy cholecalciferol) through hepatic and renal metabolic transformations [9]. Primarily involved in calcium homeostasis, recent evidence suggests a multifunctional activity of Vitamin D. It has been found to serve important roles in glucose metabolism, cardiovascular function, neuroprotection, endocrine control and immune regulation [10]. Vitamin D mediates immunity via a multitude of mechanisms including inhibition of the production of interleukins by T-cells and immunoglobulins by B-cells [11]. Vitamin D exerts immunomodulatory effects on allergen-induced hypersensitivity via activation of vitamin D receptor (VDR), which is expressed on B cells, T cells, regulatory T cells (Tregs), dendritic cells and macrophages [1]. Biochemical variations in vitamin D status alter the development and function of these immune cells, thereby modulating immune mediators like IgE and cytokines, and affecting the allergic response [12].
There are conflicting reports regarding the clinical role of vitamin D in allergic disorders, and loco-regional data are limited [6, 13, 14]. Vitamin D deficiency is quite common in the local population, and so are allergies. However, the existing data on the association between serum vitamin D and IgE levels are not clear [15]. The present study investigated the potential impact of vitamin D on IgE hypersensitivity in locally affected populace by ascertaining the correlation between serum vitamin D and IgE levels. Serum parathyroid hormone (PTH) levels were also determined due to its role in regulating vitamin D and mineral metabolism [16], along with serum calcium (Ca), serum phosphorus (P), complete blood count (CBC) and sun exposure for comparison with healthy non-allergic individuals.
Material and Methods
This analytical cross-sectional study was conducted from May 2020 to October 2020 in compliance with the ethical guidelines as outlined in the Helsinki Declaration. Study approval was granted by the Research Committee, College of Pharmacy, University of Hafr Al-Batin. Considering a 20% incidence of allergic disorders, a total of 80 subjects between the ages of 15 to 65 years were recruited from Lahore, Pakistan out of the target population of 1.2 million people based on a 90% confidence level and ±9.25% margin of error. Subjects taking multivitamin and/or nutritional supplements or steroids for any condition were excluded. Subjects with known history of bone disorders, autoimmune conditions, renal failure and/or hepatic diseases were also excluded. Written informed consent was obtained from each study participant prior to recruitment. The participants were grouped into two groups: Group 1 (n=41) comprised of healthy persons without any known allergy, while Group 2 (n=39) included patients having diagnosed allergy. Detailed medical history and demographic data were obtained from all subjects to ensure fulfillment of inclusion and exclusion criteria. Personal data were kept completely anonymous. Venous blood (5 ml) was drawn and centrifuged at 3000 revolutions/ minute for 10 minutes. Serum was separated and stored in aliquots at -20oC until analysis. Another 5 ml of blood was drawn in EDTA containing vacutainer tubes for complete blood count (CBC) including hemoglobin (Hb), hematocrit and blood cell counts using the Coulter counter technique for erythrocytes (red blood cells, RBC), platelets, total leukocytes (white blood cells; WBC) and differential counts for neutrophils, lymphocytes, monocytes and eosinophils. Quantitative determination of serum vitamin D (25-hydroxy cholecalciferol) concentration was done using an electrochemiluminescence binding assay (Elecsys® vitamin D total assay, Roche Diagnostics International Ltd., CH-6343 Rotkreuz, Switzerland) on a Cobas® e411 analyzer. Serum IgE levels were measured using a double-sandwich immunoassay for electro-chemiluminescent detection (Elecsys® IgE immunoassay, Roche Diagnostics International Ltd., CH- 6343 Rotkreuz, Switzerland) on Elecsys® immunoassay analyzer. Serum parathyroid hormone levels (PTH) were estimated using a sandwich electrochemiluminescence immunoassay (Elecsys® PTH, Roche Diagnostics International Ltd., CH-6343 Rotkreuz, Switzerland) on a Cobas® e411 immunoassay analyzer. Serum calcium and phosphorus were also measured. A validated questionnaire was used to calculate the average daily sun exposure, which took into consideration factors including the time of day and duration of exposure, occupation, clothing and head gear [17]. Subjects were then grouped as those having 1) daily sun exposure < 1 hour, 2) daily sun exposure between 1 -2 hours and 3) daily sun exposure > 2 hours.
Data were analyzed in an anonymized form using the Statistical Package for Social Sciences (SPSS), version 23. Descriptive data were presented as frequencies and percentages. Group mean differences were assessed using the independent sample t-test, and correlations were assessed using Pearson’s correlation.
Results
The participants were segregated into two groups: Group 1 (non-allergic healthy control subjects, n=41, mean age 44.37 ± 14.13 years) and Group 2 (allergic subjects, n=39, mean age 44.21 ± 15.30 years) with no age difference (p=0.961). Group 1 consisted of 24 males and 17 females, while Group 2 consisted of 33 males and 6 females. Within the allergic subjects (Group 2), 9 (23%) people had ocular allergies, 13 (35%) had respiratory allergies, 3 (8%) had a food allergy, 4 (10%) had a dermal allergy and 10 (26%) had combined features of ocular and respiratory allergies (Figure 1). Among the 80 study participants, 51 (63.75%) had an average sun exposure of less than one hour per day. Thirty-two (78.4%) subjects in Group 1 and 19 (48.71%) in Group 2 had average daily sun exposure of less than one hour. Seven (17.07%) subjects in Group 1 and 12 (30.76%) in Group 2 had sun exposure between 1 to 2 hours per day. Only 1 (2.43%) subject in Group 1 and 8 (20.51%) in Group 2 had daily sun exposure of over 2 hours.
Markedly high serum IgE levels were observed in allergic subjects compared to control subjects (Group 1, 87.13 IU/L ± 57.66 vs. Group 2, 1542.54 IU/L±1239.79; p=0.000)(Table 1). Significantly higher eosinophil count was seen in allergic subjects compared to control subjects (Group 1, 2.80%±1.83 vs. Group 2, 4.61%±4.19; p=0.014) (Table 2). No obvious difference was observed in any other parameter (Tables 1 and 2).
A weak positive correlation was observed between serum vitamin D and IgE levels in Group 1, though it barely reached the level of significance (r= +0.309, p= 0.049) (Table 3, Figure 2). A significant negative correlation was seen between serum vitamin D and IgE levels in Group 2 (r= -0.374, p= 0.019) (Table 3, Figure 3).
Discussion
The present study was carried out to assess serum IgE and vitamin D levels with other associated parameters in patients with allergies and to compare them with healthy non- allergic individuals. The results of the present study indicated considerably higher serum IgE levels and eosinophilia in persons with known allergies. No difference in circulating vitamin D levels was demonstrated between healthy non-allergic subjects and allergic subjects, suggesting that vitamin D status does not change in allergic conditions. However, serum vitamin D levels were found to be inversely correlated with serum IgE levels in allergic patients, reflecting the potential protective role of vitamin D against progression of allergy. Higher vitamin D levels in patients with allergic predisposition may have a role in mitigating the severity of the disease.
The present findings are in line with those reported in several other studies. In a study of patients with bronchial asthma, low vitamin D levels in the serum were associated with increased severity and poor disease control. Additionally, vitamin D levels were also shown to be associated with higher serum IgE levels and eosinophilia [5]. An observational case-control study by Dadaci et al. in patients with seasonal allergic conjunctivitis reported higher serum IgE levels [2]. A recent study by Ansari et al. showed significantly higher serum IgE levels in patients with allergic rhinitis [18]. Similarly, another study by Demir et al. on patients diagnosed with allergic rhinitis revealed higher serum IgE levels, and a significant negative correlation was reported between serum IgE and vitamin D levels in patients with allergic rhinitis [19]. A case-control study of young children with recurrent wheeze reported elevated serum IgE and eosinophil counts in patients compared with controls. An inverse correlation was also observed between serum vitamin D levels and disease severity [20].
Many preceding studies have shown serum vitamin D levels to be lower in patients with allergic conditions compared to age-matched non-allergic healthy individuals [2, 5, 18, 19, 21]. The findings from the current work did not demonstrate such a difference in serum vitamin D levels between allergic and healthy individuals, possibly because of the inclusion of multiple allergy groups, whereas the other studies targeted an exclusive allergic group including bronchial asthma, allergic conjunctivitis or allergic rhinitis. Moreover, several previous studies have shown sub-optimal vitamin D status in allergic as well as non- allergic groups but the mean vitamin D was optimal in our study population, including the allergic and non-allergic groups. In the present study, mean serum levels of other biochemical markers for skeletal health associated with vitamin D including PTH, calcium and phosphate were also within the normal range. Nevertheless, the existing data on circulating vitamin D levels in allergic patients compared to healthy subjects remain incongruous.
Our findings are in accordance with results from a study by Naghizadeh et al. in which no difference in serum vitamin D concentration was noted between allergic and non-allergic groups in a study of young adults [22]. The allergic group included patients diagnosed with allergic rhinitis, asthma and atopic dermatitis, which is similar to our mix of allergic patients. In line with our findings, serum IgE levels were also shown to be elevated in allergic groups compared to the non- allergic group [22]. A genetic study by Manousaki et al. found no association of allergic conditions or raised IgE levels with alleles typically associated with reduced serum vitamin D levels [23]. However, the observation did not exclude association of serum vitamin D levels with allergic disorders or elevated IgE levels. Moreover, the study was conducted on a specific white European population and was not powered enough for general applicability of the results [23].
The present data showed that a higher number of patients with allergies had longer estimated sun exposure compared to healthy controls. Comparison of vitamin D levels between groups based on the duration of sun exposure could not be performed due to the discrepant distribution of subjects in each group. The role of sun exposure in allergic conditions needs to be evaluated since endogenous vitamin D synthesis occurs under the influence of ultraviolet rays from the sun, and adequacy of dietary vitamin D intake and sun exposure have been shown to be associated with reduction in respiratory allergies [17, 24]. Conversely, long sun exposure has also been associated with exacerbation of allergic symptoms [25]. The present work is limited by its relatively small sample size and distribution, which did not allow comparisons between different allergic groups. Moreover, the present study design did not permit intervention with vitamin D supplementation in allergic patients and their follow-up. Large scale studies with randomization and subset analysis are needed to elicit concrete clinical evidence on the role of vitamin D in allergic conditions.
Conclusion
The present study has brought forth an inverse relationship between serum vitamin D and IgE levels in the local population affected by various forms of allergies. The generated data suggest that vitamin D has a potentially beneficial role in ameliorating IgE-mediated hypersensitivity in patients with allergies. Estimation of serum levels of vitamin D in patients diagnosed with allergies may be contemplated as part of their clinical management. The present findings indicate a possible therapeutic function for supplementation of vitamin D in allergic disorders, but comprehensive future studies are needed for further exploration of this aspect in order to derive meaningful conclusions.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: The authors extend their appreciation to the Deanship of Scientific Research, University of Hafr Al-Batin for funding this work through the research group project No. G-103-2020.
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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Farhan Khashim Al-Swailmi, Syed Imran Ali Shah, Ghassab Mohammad Al- Mazaideh, Mirza Zeeshan Sikandar. A cross-sectional analysis of serum vitamin D and immunoglobulin E in allergic disorders. Ann Clin Anal Med 2021;12(7):746- 750
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Determination of epiphyseal screw lengths in distal radial fractures: A computerized tomography analysis study
Levent Umur 1, Enes Sari 2
1 Department of Orthopaedics and Traumatology, Kadikoy Acibadem Hospital, Istanbul, Turkey, 2 Department of Orthopaedics and Traumatology, Near East University Hospital, Lefkosa, TRNC
DOI: 10.4328/ACAM.20440 Received: 2020-12-16 Accepted: 2021-01-31 Published Online: 2021-02-09 Printed: 2021-07-01 Ann Clin Anal Med 2021;12(7):751-755
Corresponding Author: Levent Umur, Department of Orthopaedics and Traumatology, Acibadem Kadikoy Hospital, Tekin Street, No:8 Istanbul, Turkey. E-mail: dr.flumur@gmail.com P: +90 5322017339 Corresponding Author ORCID ID: https://orcid.org/0000-0003-4961-4508
Aim: The aim of this computerized tomography study was to determine the optimal epiphyseal screw length using the diaphyseal screw length as a reference while performing volar plate osteosynthesis of the distal radius.
Material and Methods: Computerized tomography scans of 49 wrists (35 men and 14 women) were used for the measurements. The mean maximal length of one diaphyseal screw and four distal epiphyseal screws was measured and statistical analyses were performed.
Results: The results of this study revealed that the epiphyseal screw lengths were highly correlated with the diaphyseal screw length. Based on the data derived from measurements, we recommend using epiphyseal screw lengths of 14, 14, 16 and 14 mm for FU, NU, NR and FR screws, respectively, for 10 mm diaphyseal screws, 16, 16, 16 and 14 mm, respectively, for 12 mm diaphyseal screws, and 16, 18, 18 and 16mm, respectively, for 14 mm diaphyseal screws to achieve safe and secure fixation in volar plating of distal radial fractures.
Discussion: Using predetermined epiphyseal screw lengths in volar plating of distal radial fractures may decrease operation time, reduce intraoperative radia- tion exposure, and avoid the risk of intra-operative or postoperative extensor tendon injury.
Keywords: Radius distal fracture; Volar plate; Screw length; Prediction; Safe surgery
Introduction
The volar plate osteosynthesis is a popular treatment option for distal radial fractures. Volar plating of the distal radius may complicated with irritation and/or rupture of the extensor tendons. Drilling the dorsal cortex or the placement of excessively long epiphyseal screws may cause tendon complications [1]. Although most surgeons rely on the sensation of drilling the dorsal cortex and using depth measuring tools to determine epiphyseal screw lengths, comminution and fragmentation of the dorsal cortex may lead to errors. In addition, evaluation of the epiphyseal screws may be difficult on standard radiographic views due to the trapezoidal shape of the distal radius. Alternative intraoperative fluoroscopic images (skyline view, radial groove view or supinated view) were also defined to detect oversized screws with a sensitivity of 75-85% for 2 mm screw protrusions [2], but drilling depth cannot be determined with these methods [3]. Several authors have recommended the use of unicortical epiphyseal locking screws to avoid dorsal cortex penetration and extensor tendon injury [4, 5]. The unicortical screw length is suggested to be a minimum of 75% of the total thickness of the distal radius epiphysis to maintain reduction [6]. Intraoperative assessment of the screw length with fluoroscopy may not be adequate to avoid excessively long secrews. On the other hand, very short screws may cause a loss of reduction.
Recent studies have focused on predicting epiphyseal screw length in volar plating of distal radial fractures in effort to minimize extensor tendon complications. Ljungquist et al. recommended using the lunate depth as an estimate for the length of the longest screw when fixing distal radius fractures with volar plate techniques to avoid extensor tendon irritation and rupture [7]. Similarly, Letissier et al. conducted a radiological study in which computerized tomography scans of 40 patients were virtually plated. They concluded that the epiphyseal screw lengths were highly correlated with the diaphyseal screw length [8].
The aims of this computerized tomography study were as follows: 1. to evaluate a potential relationship between the length of the diaphyseal screw and the lengths of epiphyseal screws in volar plating of distal radial fractures, 2. to offer optimal screw lengths for safe and secure fixation for volar plating of distal radial fractures, 3. to ease the determination process of epiphyseal screw lengths without excessive fluoroscopic exposure for distal radius fractures.
Material and Methods
The shapes of commercially available plates are very similar by means of the positions for epiphyseal and diaphyseal screw holes [8]. Therefore, we conducted this CT analysis study to evaluate the measurements of the distal radius and to determine the screw length applicable to most of the volar plate designs.
Computed tomography (CT) scans of 84 patients from our institution’s imaging database from January 2016 to June 2019 were retrospectively evaluated. CT scans of skeletally mature patients without radius pathology were included. Patients younger than 18-years, patients with a radial fracture or anatomic abnormality, and scans with inadequate imaging of the distal radius were excluded. CT scans of 49 patients (35 men and 14 women) met our inclusion criteria and furtherly evaluated. All scans were performed using a CT scanner (Siemens Somatom Definition Flash, Munich, Germany) for the evaluation of patients with upper extremity trauma. The slice interval of these CT scans was 1 mm. CT images were evaluated using RadiAnt DICOM Viewer (version 4.6.5.18450). The determination of the epiphyseal and diaphyseal screw holes was as follows: the watershed line was defined as a line, which was drawn parallel to the radiocarpal joint and 4.5 mm proximally to the intersection of the distal radial articular surface and scapholunate joint in coronal and 3-D CT images. The watershed line then was divided into 4 equal quadrants, and the intersection points of these quadrants with the watershed line were marked to mimic 4 epiphyseal screw holes (far ulnar (FU), near ulnar (NU), near radial (NR) and far radial (FR)) in distal radius volar anatomic plate. Plate templates were not used since the screw lengths are not affected by the plate and all commercially available plates provide almost exact epiphyseal and diaphyseal screw locations. An imaginary diaphyseal screw hole (D) of distal radius volar anatomic plate was marked in radial shaft 4 cm proximal to the distal radial articular surface in coronal and 3-D CT images (Figure 1). The watershed line is demonstrated by a yellow line drawn 4.5 mm proximal to the radiocarpal articular surface in all images (a- f). The diaphyseal screw hole is demonstrated with a red dot marked 4 cm proximal to the radiocarpal articular joint (e-f). Epiphyseal screw holes are demonstrated with yellow dots (a. Far Ulnar, b. Far Radial, c. Near Ulnar, d. Near Radial). The projections of the epiphyseal and diaphyseal screw holes were marked also on horizontal and sagittal CT images. The epiphyseal and diaphyseal screw lengths were measured from the near to far cortex on CT images in the sagittal plane. In order to simulate volar plating operation, the epiphyseal screws were given 10 degrees angulation relative to the line, which is perpendicular to the longitudinal axis of the radius in sagittal images (a. Far Ulnar, b. Near Ulnar, c. Near Radial, d. Far Radial, e. Diaphyseal, Yellow line: Watershed line, Blue line: Sagittal plane, Green line: Axial Plane) (Figure 2).
Statistical Analysis
Descriptive parameters and linear regression analysis were used in the statistical evaluation of the data. The normality of the distribution of the study population was verified using the Kolmogorov-Smirnov test. A regression analysis was performed between the maximum lengths of the diaphyseal screw and the distal epiphyseal screw in each region (FU, NU, NR and FR). Statistical significance was set at p 0.05 with a confidence interval (CI) of 95% while evaluating the results. All analyses were performed using IBM SPSS Statistics 22.0.
Results
Linear regression analysis between the diaphyseal screw length and each of the epiphyseal screw length regions showed a linear correlation and resulted in 4 regression equations. The results were statistically significant (p<0.05) with a CI of 95%. The coefficients of correlation values (R) of FU, NU, NR and FR epiphyseal screws were 0.60, 0.59, 0.55 and 0.57, respectively, and the coefficients of determination values (R2) of FU, NU, NR and FR epiphyseal screws were 0.36, 0.34, respectively (Table 1). The maximum length screws of FU, NU, NR and FR were found as 17.4, 18.07, 18.96 and 16.66 mm for 10 mm diaphyseal screw, 18.98, 19.81, 20.28 and 17.96 mm for 12 mm diaphyseal screw, and 20.56, 21.55, 21.6 and 19.26 mm for 14 mm diaphyseal screw, respectively.
Discussion
The results of this CT analysis study revealed that there was a statistically significant correlation between the diaphyseal screw length and the epiphyseal screw lengths in volar plating of distal radial fractures. The regression analysis showed high coefficients of correlation values (R>0.5) for each epiphyseal screw region. In order to limit the risk of dorsal cortex penetration and achieve optimum strength for fixation, in the literature, it is shown that epiphyseal unicortical locking screws should be at least 75% in length to produce stability similar to bicortical fixation [9]. Therefore, in our study, epiphyseal screw measurements were recalculated and determined to be between 75% and 85% of maximum epiphyseal screw lengths and rounded down to commercially available screw sizes (Table 2). The results of this study suggest the use of epiphyseal screw lengths of 14, 14, 16 and 14 mm for FU, NU, NR and FR screws, respectively, for 10 mm diaphyseal screws, 16, 16, 16 and 14 mm, respectively, for 12 mm diaphyseal screws, and 16, 18, 18 and 16mm, respectively, for 14 mm diaphyseal screws.
The use of these predetermined lengths may help the surgeon avoid the risk of dorsal cortex penetration and therefore minimize the complication of extensor tendon injury. There are novel studies to prevent these complications, such as using intraoperative computed tomography-guided navigation systems, and all efforts of the researchers aimed at preventing dorsal and intraarticular penetration [10]. Compared to these techniques, the use of predetermined screw lengths may also reduce intraoperative radiation exposure through the use of fluoroscopic imaging. Extensor tendon injuries may also occur with over-drilling of the far cortex [11]. In extraarticular osteoporotic fractures, even if the dorsal cortex is intact, depth measuring and feeling of the dorsal cortex during drilling may be hard. Moreover, dorsal comminution of the distal radius displaces the extensor tendons more anteriorly from their original anatomic position and causes a higher risk for extensor tendon injury. Using predetermined sizes gives surgeons the advantage of using depth stop drill bits to avoid intraoperative tendon injuries by leaving the dorsal cortex intact.
Letissier et al. suggested to use 18, 18, 20, and 16 mm epiphyseal screws for FU, NU, NR and FR, respectively, for diaphysis screws shorter than 14 mm, and 20, 20, 22, and 18 mm epiphyseal screws for diaphysis screws of 14 mm or longer in their study of the virtual plating of distal radius [8]. In our study, every radius was evaluated and compared with its own diaphyseal screw length in our study. Therefore, it can be considered that no gender evaluation is needed for the same ethnicity. Conversely, using an equal length of the epiphyseal screw with a 10-mm-diaphysis and a 13.9-mm- diaphysis can cause dorsal cortex penetration or insufficient fixation problems. For this reason, we evaluated the diaphyseal lengths in 3 groups (10-11.9, 12-13.9, 14 and above). Yuen et al. reported that the mean FU, NU, NR and FR screw lengths were 20 mm, 20.8 mm, 19.6 mm and 15.4 mm, respectively, in their cadaveric study [12]. In our study, the measurements of the distal radial epiphysis thickness were in concordance with these previous studies. However, we suggest using screw lengths between 75% and 85% of bicortical measurements for safe (avoiding dorsal cortex penetration) and secure (avoiding secondary loss of reduction) fixation.
This study has some limitations. First of all, we conducted a CT analysis study to determine the epiphyseal screw lengths, not specific to any commercial plate design, but which may be applicable to most of the available plates. This may seem like a potential error, but we think that the measurements of the distal radius may be a valuable guide for surgeons, since the screw length measured cortex to cortex in locking plates, to avoid tendon complications while performing volar plate surgery. Previous studies have measured the length of the epiphyseal screws placed perpendicular to the plate [11]. In this study, measurements were made for screws with a fixed 10 degrees angulation. Screw angulation can be manipulated in several commercially available plates, thus may alter the epiphyseal screw lengths. Additionally, we designed our study to position epiphyseal screws 4.5 mm proximal to the radiocarpal joint line. More proximal placement of the volar plate may also alter screw lengths. Moreover, it should be kept in mind that ethnicity changes may result in different anatomic features, and therefore measurements may differ. This technique may not be practical for the surgeons preferring to apply the distal epiphyseal screws first as an aid for reduction. On the contrary, a predetermined screw length can be a helpful guide for safe screw placement and secure fixation.
Conclusion
We recommend to use epiphyseal screw lengths of 14, 14, 16 and 14 mm for FU, NU, NR and FR screws, respectively, for 10 mm diaphyseal screws, 16, 16, 16 and 14 mm, respectively, for 12 mm diaphyseal screws, and 16, 18, 18 and 16mm, respectively, for 14 mm diaphyseal screws to achieve safe and secure fixation in the volar plating of distal radial fractures. Using predetermined epiphyseal screw lengths in volar plating of distal radial fractures may avoid the risk of extensor tendon injury, decrease operation time and reduce intraoperative radiation exposure.
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
1. Dolce D, Goodwin D, Ludwig M, Edwards S. Intraoperative evaluation of dorsal screw prominence after polyaxial volar plate fixation of distal radius fractures utilizing the Hoya view: a cadaveric study. Hand. 2014;9(4):511-15.
2. Stoops TK, Santoni BG, Clark NM, Bauer AA, Shoji C, Schwartz-Fernandes F. Sensitivity and Specificity of Skyline and Carpal Shoot-Through Fluoroscopic Views of Volar Plate Fixation of the Distal Radius: A Cadaveric Investigation of Dorsal Cortex Screw Penetration. Hand. 2017;12(6):551-6.
3. Haug LC, Glodny B, Deml C, Attal R. A new radiological method to detect dorsally penetrating screws when using volar locking plates in distal radial fractures: The dorsal horizon view. Bone Joint J. 2013;95B(8):1101-5.
4. Dardas AZ, Goldfarb CA, Boyer MI, Osei DA, Dy CJ, Calfee RP. A Prospective Observational Assessment of Unicortical Distal Screw Placement During Volar Plate Fixation of Distal Radius Fractures. J Hand Surg Am. 2018;43(5):448-54.
5. Seki Y, Aoki T, Maehara H, Shirasawa S. Distal locking screw length for volar locking plate fixation of distal radius fractures: Postoperative stability of full- length unicortical versus shorter screws. Hand Surg Rehabil. 2019;38(1):28–33.
6. Wall LB, Brodt MD, Silva MJ, Boyer MI, Calfee RP. The effects of screw length on stability of simulated osteoporotic distal radius fractures fixed with volar locking plates. J Hand Surg Am. 2012;37(3):446-53.
7. Ljungquist KL, Agnew SP, Huang JI. Predicting a safe screw length for volar plate fixation of distal radius fractures: Lunate depth as a marker for distal radius depth. J Hand Surg Am. 2015;40(5):940-4.
8. Letissier H, Dardenne G, Stindel E, Borotikar B, Le Nen D, Kerfant N. Predicting epiphyseal screw length in anterior plating of distal radial fractures. J Hand Surg Eur. 2020;45(4):354-9.
9. Im JH, Lee JY. Pearls and Pitfalls of the Volar Locking Plating for Distal Radius Fractures. J Hand Surg Asian Pac Vol. 2016;21(2):125-32.
10. Kaneshiro Y, Hidaka N, Yano K, Kawabata A, Fukuda M, Sasaoka R, et al. Intraoperative computed tomography with an integrated navigation system versus freehand technique under fluoroscopy in the treatment of intra-articular distal radius fractures. J Plast Surg Hand Surg. 2019;53(5):255-9.
11. Synek A, Borgman L, Traxler H, Huf W, Euler E, Chavalier Y, et al. Using self-drilling screws in volar plate osteosynthesis for distal radius fractures: A feasibility study. BMC Musculoskelet Disord. 2016;17(1):1-7.
12. Yuen G, Yee DKH, Fang C, Lau TW, Leung F. Screw length in volar locking plate fixation for distal radial fractures. J Orthop Surg. 2015;23(2):164-7.
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Levent Umur, Enes Sari. Determination of epiphyseal screw lengths in distal radial fractures: A computerized tomography analysis study. Ann Clin Anal Med 2021;12(7):751-755
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Perceptions and attitudes of clinical year’s medical students towards assessment tools used in Northern Border University, Arar
Muhammad Ayub Jat
Department of Surgery, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia
DOI: 10.4328/ACAM.20442 Received: 2020-12-16 Accepted: 2021-01-17 Published Online: 2021-01-28 Printed: 2021-07-01 Ann Clin Anal Med 2021;12(7):756-759
Corresponding Author: Muhammad Ayub Jat, Assistant Professor Surgery, Department of Surgery, Faculty of Medicine ,Northern Border University, 1321, Arar, Saudi Arabia. E-mail: dr.ayubjat@yahoo.com P: +966535213066 Corresponding Author ORCID ID: https://orcid.org/0000-0001-7671-0314
Aim: In this study, we aimed to determine the perception and attitudes of clinical years’ medical students of 4th – 6th year toward the assessment tools used in the Faculty of Medicine, Northern Border University, Arar, Saudi Arabia.
Material and Methods: This cross-sectional study was conducted in the college of Medicine from September to November 2020. A multistage stratified random sample method was used to select 270 medical students of clinical year’s (4th -6th year). The respondents’ perceptions of the preferred type of traditional written examination multiple-choice questions (MCQs), short essay questions (SEQs) as good tools for assessing basic theoretical knowledge regarding the subject were determined. Student’s perceptions towards Objective Structured Clinical Examination (OSCE), Objective Structured Practical Examination (OSPE), problem- based learning (PBL) clinical short and long cases were also assessed. Furthermore, perceptions towards relatively recent non-traditional methods such as log book/assignments, open-book exam, and clinical presentations/seminars were also determined. A questionnaire will be provided for the degree of agreement assessment by 3- points Likert scale (1-Agree, 2- Neutral 3-disagree).
Results: This study included 270 medical students, of whom, 162 (60%) were females and 108 (40%) were males. About half (49%) of participants agreed that assessment methods are comprehensive, reflect what they were taught, and challenge them. Multiple-choice questions were the commonest (60%) preferred written assessment format. OSCE (56.6%) and OSPE (54.8%), as well as long and short clinical cases (52.6%), were considered good tools for assessing clini- cal competencies and skills. Students had good perceptions towards problem-based learning, log-book/assignments and clinical presentations. Male students preferred problem- based learning (PBL) more than female students.
Discussion: This study concludes that according to medical students of clinical year’s the most useful assessment tool for written examination was MCQs for assessing basic theoretical knowledge, and regarding clinical assessment tools, OSCE was preferred. Student feedback and advanced assessment techniques can help health education professionals overcome the flaws of either method.
Keywords: Perceptions and attitudes; Medical students; Assessment tools; Clinical competencies
Introduction
Medical education is the art and science of medical learning which has rapidly progressed in recent years. Adequately measuring core competencies of the medical students is a vital constituent of evaluation, providing reliable feedback, and improving medical education [1]. Assessment is an essential component of medical education because of its implications on the students, teachers, communities and the whole world after graduation from their medical schools [2]. Assessment is an integral component of overall educational activities and a vital tool, which drives student learning, because students usually tend to concentrate on the material to be assessed [3]. Furthermore, the selected assessment method should be consistent with the objectives of the curriculum. Studying medical curriculum requires a big deal of cognitive abilities, positive attitudes, time management, positive feelings, and reactions to the challenges that occur during the training [4]. Assessing student performance is a very important and complicated process [5], when the learning goals involve the acquisition of skills that can be demonstrated through action. The quality of academic performance and achievement among medical students are essential parts for the success of the educational process. The determinants of students’ performance have been the subject of current discussion among medical educators [6]. The use of a variety of assessment methods has become a characteristic of medical education, credentialing, and licensure since the 1950s [7]. However, the evaluation of competences using traditional examination has its limitations because of low validity and reliability [8]. Comparatively new non-traditional assessment methods (log book, open-book exam, simulations, self and peer assessments) have been introduced in medical education in the last decades. They are believed to be reasonable as they measure qualities, skills and competences. Clinical presentation models are intended to ensure that the medical students not only acquire appropriate scientific and clinical knowledge, but also the practical procedures and communication skills. This leads to obtaining most of the learning domains mainly cognitive, affective and psychomotor [9,10].
A new hybrid system-based curriculum was launched in 2011 at the Faculty of Medicine, Northern Border University in Arar [11]. Although evaluation of the perception of medical students regarding their assessment has an essential impact on the educational process, we plan to conduct such a study on this subject. The aim of the current study was to obtain perceptions from medical students of clinical years’ from 4th year to 6th year on the assessment methodologies used in the Faculty of Medicine, Northern Border University, Arar.
Material and Methods
This cross-sectional study was conducted in the college of Medicine from September to November 2020 after obtaining approval from the Local Committee of Bioethics at Northern Border University, Arar. A multistage stratified random sampling method was used to select 270 clinical year’s medical students (4th – 6th year) from the Faculty of Medicine. They were asked about the assessment methods, whether they are comprehensive, whether they reflect what they taught in the curriculum, and whether the assessment methods challenging the participants more than making them just memorize. Students’ perceptions of the preferred type of traditional written exams MCQs, short essay questions (SEQs) as good tools for assessing basic theoretical knowledge regarding the subject were determined. Moreover, the adequacy of the number of MCQs in each exam and the number of MCQs exams per course were also queried. Perceptions towards problem- based learning (PBL), Objective Structured Clinical Examination (OSCE), and Objective Structured Practical Examination (OSPE), clinical short and long cases were evaluated. Additionally, students’ perceptions towards relatively recent non-traditional methods such as log book, assignments, open-book exam, seminars and clinical presentations were also determined. The participants were requested to fulfill a validated, confidential, and self- administrated questionnaire to assess the degree of agreement on a 3- point Likert scale, with possible answers ranging from 1: “Agree, 2:neutral to 3: disagree”. The aim of this study was explained to the participants and re-assured them that the data gathered will remain confidential.
Data collected were entered in a master chart and analyzed using Excel-2019 with the help of a medical statistician. The data were summarized in the form of proportions and frequency tables in excel -2019 spreadsheet.
Results
This study included 270 medical students from clinical side 4th – 6th year, of whom, 162 (60%) were females and 108 (40%) were males. It was found that 27 %, 35%, 38 % of the participants enrolled in the fourth, fifth and sixth year, respectively. Only 49% of respondents agreed that their assessment methods are comprehensive, and 46% agreed that assessments reflect what is taught in the curriculum. Furthermore, 44% of them agreed that assessment strategies are more challenging than making them memorize. Concerning the preferred written examination assessment format, MCQs were the most commonly preferred exam formats by both genders, followed by the short essay question (SEQs). MCQs exam format was slightly more preferred by male students than females. On the other hand, both males (28%) and female (23%) students do not prefer the short essay question (SEQs) as an assessment format. Regarding written exams, 60% of respondents observed that MCQs exams are fair format, while (65.0%) agreed that the numbers of MCQs is enough in each exam. In terms of clinical assessment, 56.6% of participants agreed that OSCE is a good format for assessing clinical competencies, and that the number of OSCE stations is suitable. On the other hand, 42.8% of them agreed that the time assigned to each station is sufficient. However, 54.8% of applicants viewed that OSPE is a good format of clinical assessment, and 65% agreed that the number of OSPE stations are reasonable. On the other hand, only 45.5% of them viewed that the time allocated for each station is enough, as shown in Table 1.
In the current study, about more than one- half (56%) of the students examined by the OSCE preferred to be examined in real patients, followed by the simulated patients (30%) and on a model of the human body (manikin) (14%). However, 52.6% of students agreed that long and short clinical cases were real assessment tools for clinical competencies; male students (63%) preferred more than female students (37%). In the present study, there are no statistical differences between both genders regarding their preferences of other new non- traditional assessment methods as log book, assignments, open-book exams, clinical presentations and seminars, as shown in Table 2.
Discussion
In medical education, assessment is entering every phase of professional development. Validity and reliability are important criteria for a good assessment. For assessment to have any real impact on learning, it has to be context relevant. Students’ perceptions of their assessments can be used in the process of improving the quality of assessment, educational programs, student learning and performance [12]. The modern educational theory suggests that learning is facilitated when tasks are integrated [13]. The concept of “assessment drives learning” is accepted as one of the main pillars of high-quality assessment practice [14]. The majority of participants in the current study agreed that clarification of the assessment method from the beginning of the course improves their performance. It is essential that the assessment tasks mirror the learning objectives and curriculum contents [15]. The ability of students to retrieve data in assessments should follow Bloom’s taxonomy [16]. The current study found that about 49% of participants agreed that assessment methods are comprehensive, reflect what they taught in the curriculum (46%), and 44% of them agreed that assessment strategies are more challenging than making them memorize. Similar results (39.5%; 35.8%; 41.2%) were reported in the study by Ibrahim NK et al
This indicates that the assessment plan needs further improvement to meet the expectations of medical students. Multiple- choice questions have been widely used for summative assessment in undergraduate medical education because of their convenient standardization, efficient testing for large classes and a broad sampling of knowledge. In the current study, MCQs exams were preferred as a written assessment format more than short essay questions, which is consistent with other studies [17,18]. The females preferred MCQs slightly more (62.5%) than males (60%). Similar results (57.9% and 55.5%) were reported in a study by Ibrahim NK et al. [19]. Regarding clinical assessment, 56.6% of participants, agreed that the OSCE is a good format for assessing clinical competencies and that the numbers of OSCE stations are appropriate (65%), which coincides with many other studies by Hashmi NR et al and Raheel H et al.[20,21] Furthermore, only 42.8% of respondents reported that the time assigned for each OSCE station is adequate, which is consistent with the results of the study by Siddiqui FG et al [22]. The present study revealed that (54.8 %) of medical students agreed that OSPE is a good way of assessment of clinical competencies, and similar results were reported in the studies by Abraham RR et al and Menezes RG et al [23,24]. However, about 65% of our participants agreed that the number of OSCE stations is fair and the time allotted for each OSPE station was adequate, which coincides with the results of other study (66.3%) and (51.3%), respectively [19]. Regarding new assessment methods, recent literature has shown that females had significantly better perceptions towards peer assessment compared to males. In a study by Consorti F et al., female medical students showed higher levels of concern regarding peer assessment compared to males [25]. Concerning the students’ perception towards assignments or log book, our results illustrated that 72.5% of respondents agreed that it is a useful assessment format for knowledge of a subject. Similar results were reported in the study by Ibrahim NK et al., which found that log book was considered a useful way of assessment by 68.5% of respondents. Our results showed that most of the participants reported that receiving examinations feedback improves their performance. Clarification of assessment methods, formative assessment and feedback can enhance the performance of medical students.
The limitations of this study were medical students of basic sciences from 1st year to 3rd year.
Conclusion
The assessment plan needs further improvements and should be designed prospectively along with learning outcomes. The proposed Assessment directed medical education (ADME) curriculum is based on our knowledge that assessment drives learning. Adding more innovative methods of assessment as open book, self and peer assessment is required. Additional studies are recommended for a better understanding of students’ perceptions towards different innovative assessment formats. Our assessments need further improvement for better preparation of medical students for their future role as tomorrow’s young doctors.
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. Htwe TT, Sabaridah I, Low GK. Comparative assessment of students’ performance and perceptions on objective structured practical models in undergraduate pathology teaching. Singapore Med J. 2014;55(9):502–5. DOI:10.11622/smedj.2014121.
4. Sitticharoon C, Srisuma S, Kanavitoon S, Summachiwakij S. Exploratory study of factors related to educational scores of first preclinical year medical students. Adv Physiol Educ. 2014; 38(1):25-33.
5. Hashim Z, Miller A, Fahim N. The exam skills workshop as formative assessment for medical students. Int J Collab Res Intern Med Public Health. 2012; 4(5):1-11.
6. Salem RO, Al-Mously N, Nabil NM, Al-Zalabani AH, Al-Dhawi AF, Al-Hamdan N. Academic and socio-demographic factors influencing students’ performance in a new Saudi medical school. Med Teach. 2013; 35(Suppl. 1):S83-9.
7. Norcini JJ, Lipner RS, Grosso LJ. Assessment in the context of licensure and certification. Teach Learn Med. 2013;25(Suppl. 1):S62–67. DOI:10.1080/10401 334.2013.842909.
8. Guraya S, Alzobydi A, Salman S. Objective structured clinical examination: Examiners’ bias and recommendations to improve its reliability. J Med Sci. 2010;1:269–72.
9. Rehman R, Syed S, Iqbal A, Rehan R. Perception and performance of medical students in Objective Structured Practical Examination and viva voce. Pak J Physiol. 2012;8(2):33–6.
10. Axelson RD, Ferguson KJ. Bias in assessment of non-cognitive attributes. Virtual Mentor. 2012;14(12):998–1002. DOI:10.1001/virtualmentor.2012.14.12.
11. Ibrahim NK, Banjar S, Al-Ghamdi A, Al-Darmasi M, Khoja A, Turkistani J, et al. Medical students’ preference of problem-based learning or traditional lectures in King Abdulaziz University, Jeddah, Saudi Arabia. Ann Saudi Med. 2014;34(2):128- 33. DOI:10.5144/0256 4947.2014.128.
12. Al-Wardy NM. Assessment methods in undergraduate medical education. Sultan Qaboos Univ Med J. 2010;10(2):203-9.
13. Kromann BC, Jensen ML, Ringsted C. The effect of testing on skills learning. Med Educ. 2009;43(1):21–7.
14. Al Kadri HM, Al-Moamary MS, Van Der Vleuten C. Students’ and teachers’ perceptions of clinical assessment program: A qualitative study in a PBL curriculum. BMC Res Notes. 2009; 2:263.
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16. Khan JS. Assessment Driven Integrated Learning (ADIL): Assessment Directed Medical Education (ADME) curriculum. J Ayub Med Coll Abbottabad. 2010; 22(4):201-6.
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Muhammad Ayub Jat. Perceptions and attitudes of clinical year’s medical students towards assessment tools used in Northern Border University, Arar. Ann Clin Anal Med 2021;12(7):756-759
Citations in Google Scholar: Google Scholar
Investigation of factors affecting the intensity of chronic neck pain in young adult population
Aslan Telci E. 1, Öztop M. 1, Şekeröz S. 1, Tekin F. 1, Yağcı N. 1, Şenol H. 2
1 Pamukkale University School of Physical Therapy and Rehabilitation, 2 Department of Biostatistics, Pamukkale University Faculty of Medicine, Denizli, Turkey
DOI: 10.4328/ACAM.20443 Received: 2020-12-18 Accepted: 2021-01-19 Published Online: 2021-02-04 Printed: 2021-07-01 Ann Clin Anal Med 2021;12(7):760-764
Corresponding Author: Fatih Tekin, Pamukkale University, School of Physical Therapy and Rehabilitation Denizli, Turkey. E-mail: fzt.ftekin@hotmail.com P: +90 (258) 296 42 64 Fax: +90 (258) 296 44 94 Corresponding Author ORCID ID: https://orcid.org/0000-0001-7829-7957
Aim: Neck pain is a common health problem that most people experience throughout their lifetime. The aim of this study was to examine the factors associated with chronic neck pain intensity increasing in the young population over the last years.
Material and Methods: Two hundred and ninety- two young adults aged 18-30 years were included in the study. The severity of pain, disability level, general and spine-related quality of life, sleep quality and smartphone usage status of the participants were questioned. Binary logistic regression analysis was used to determine the factors affecting neck pain intensity.
Results: Smartphone usage in non-neutral position (Odds Ratio (OR): 2.116), decreased spine-related (OR: 0.980) and general quality of life (OR: 1.003), in- creased neck disability (OR: 1.079) are important factors that increase the severity of neck pain.
Discussion: Our results indicate the non-neutral position of the neck during a phone call, decreased level of spine-related quality of life and general quality of life, increased disability of the neck are major risk factors for moderate-severe neck pain. Informing the young population about these risk factors and provid- ing the necessary training will contribute to reducing the intensity of neck pain.
Keywords: Chronic neck pain; Intensity; Smartphone; Quality of life; Neck disability
Introduction
Neck pain is a common health problem that most people experience throughout their lifetime and is often encountered in different societies and at different ages [1]. The 1-year prevalence of neck pain was found to be 42-67% in young adults [2]. Additionally, between 2006 and 2016, neck pain population prevalence increased by 21%, making neck pain a global burden candidate [3]. There are studies in the literature examining risk factors for neck pain. However, there are no studies examining the factors that affect the intensity of neck pain in the way that this study targets.
Kim et al. (2018) in their systematic literature review reported that risk factors associated with neck pain included depressed mood, perceived muscular tension, and work in awkward/ sustained postures. In this study, Kim et al. mostly linked neck pain with psychological factors but physical factors should be considered too [4].
In addition to these risk factors, the increased use of technological tools with developing technology is seen as a risk factor for neck pain. Among these technological devices, the use of smartphones (SP) has increased greatly. Namwongsa et al. (2019) reported that SP users with neck pain use their SP with more neck flexion and produce more muscle activity in the cervical muscles compared to painless users, and in addition, as the neck flexion angle increases, the severity of neck pain increases. Prolonged use of the SP can lead to abnormal forward head posture and harm to cervical structure [5].
In addition, 7.7% of Turkish youth smoke, and smoking rates are increasing in the young adult population [6]. The association of smoking with neck pain has been a subject of research. Smoking was investigated as a risk factor or associated factor in several studies, with many studies reporting no statistically significant relationship with neck pain [7]. However, in many studies, weak relations between smoking and neck pain intensity were identified and reported [8-9].
As another risk factor, studies are examining the effect of sleep quality on the intensity of neck pain. According to Juan et al. (2019), poor sleep quality leads to worsening of neck pain intensity and depression in chronic neck pain patients. Also, Juan et al. stated that exercise is a positive mediator of the relation between depression and neck pain intensity. However, there is insufficient data in the current literature on the effect of sleep quality and exercise on the intensity of neck pain.
In the present literature, it is stated that chronic neck pain is very common among young adults, a serious burden for health care systems, and that the neck health of these individuals should be carefully examined for future periods. However, there is still uncertainty about the factors leading to neck pain in young adults, and more research is needed in this area [10]. The aim of this study, unlike other studies focusing on neck pain presence in the current literature, was to analyze the pain- related variables in individuals with chronic neck pain.
Material and Methods
Participants
This cross-sectional study was conducted on voluntary 292 students (192 females; 100 males; mean age: 22.72±2.75 years) aged 18-30 years who had neck pain for at least 3 months and
met the inclusion criteria at Pamukkale University School of Physical Therapy and Rehabilitation (Figure 1). Exclusion criteria were as follows: specific neck pain history, numbness in the arms, the presence of musculoskeletal pain in another part of the body, spinal disorders such as scoliosis and spondylolisthesis, musculoskeletal surgery, orthopedic and neurological disorders, and the presence of communication problems that may affect the assessment process. The study was approved by Pamukkale University Medical Ethics Committee. We informed all students about the study protocol. All individuals included in the study signed the informed consent form.
According to its anatomical localization, neck pain is defined as pain that extends posteriorly between the superior nuchal line and the spina scapula, laterally to the superior of the clavicle and anteriorly to the suprasternal notch and may spread to the head, trunk and arms [11]. Participants used a body diagram to mark the localization of their neck pain. Participants who reported pain outside the neck area were excluded from the study. Participants were informed about filling out the sociodemographic data form and questionnaires. In order to prevent missing data, the forms were checked quickly after the participants completed the forms, and all missing parts were completed.
Outcome Measures
Pain Intensity
The Visual Analogue Scale (VAS) was used to assess neck pain intensity. On the basis of the VAS scores, Boonstra et al. classified pain experienced by patients with chronic musculoskeletal pain as mild (≤3.4cm), moderate (3.5–7.4cm), and severe (≥7.5cm) [12]. According to VAS scores, participants were divided into two groups: mild neck pain (Group I; 0.5-3.4 cm) and moderate- severe neck pain (Group II; 3.5 cm and above).
Disability
The disability associated with neck pain was evaluated with the Neck Disability Index (NDI), a reliable and valid measurement instrument. The index consists of a total of 10 items (pain intensity, personal care, lifting, reading, headaches, concentration, work, driving, sleeping, and recreation). In the questionnaire, where each section is scored between 0-5, 50 points indicate the maximum disability [13]. The questionnaire has a Turkish reliability and validity study [14].
General Quality of Life
Nottingham Health Profile (NHP), which measures physical, psychological, and social effects and consists of 38 questions, was used to assess the general quality of life. This valid and reliable scale to measure the quality of life consists of six subtitles: pain, physical mobility, energy, sleep, social isolation, and emotional reactions. An increased score indicates a decrease in the general quality of life [15].
Spine-Related Quality of Life
The Spine Functional Index (SFI) was used to measure spine- related patient-reported outcomes, such as disability and quality of life. This index consists of 25 statements, represents spine functions as a percentage, and a high percentage expresses well spinal function [16].
Sleep Quality
To assess sleep quality and sleep disturbances, the Pittsburgh Sleep Quality Index (PSQI) that has 7 components (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction) was used. A total PSQI score higher than 5 indicates poor sleep quality [17].
Questioning Information Related to Smartphone Usage
SP usage habits have been assessed via 3 questions, including usage time in hours per day, screen sizes (below/above 5 inches) in inches, and position of the neck as neutral or non- neutral during calls. The neutral anatomical position of the neck was demonstrated to the participants in the picture and they were asked to compare their neck position during calls with this neutral position.
Statistical Analysis
The school where the study was conducted was accepted as the universe of the study and all students were reached. Therefore, there was no need for power analysis. Descriptive data are given as frequency, percentage, and mean ± standard deviation. Binary logistic regression analysis was used to determine the factors affecting neck pain intensity. The dependent variable is neck pain intensity; independent variables are Body Mass Index (BMI), gender, questions about smartphone usage, SFI, NDI, NHP and PSQI. The Mann-Whitney U test was also used to compare Group I and Group II. SPSS v22.0 package program was used for statistical analysis and to assess statistical significance, the level of α-error was accepted as 0.05.
Results
Descriptive data of the participants, questionnaire scores and smartphone usage variables are presented in Table 1.
The binary logistic regression analysis demonstrated that the non-neutral position of the neck during a phone call, decreased level of spine-related quality of life and general quality of life, and increased disability of neck are associated with neck pain for moderate-severe neck pain (Table 2).
Discussion
The key results obtained from this study in the young adult population indicated that neck position during phone calls, spine-related quality of life, disability status of the neck and general quality of life were important risk factors for chronic neck pain intensity. The aim of this study was to investigate the effects of factors such as cigarette use, smartphone use, increasing in the young population over the last years, on chronic neck pain intensity.
According to the results of our study, young individuals with mild neck pain had significantly higher levels of spine-related quality of life, general quality of life and sleep quality, and less neck disability than younger subjects with moderate-severe neck pain.
There is no evidence in the current literature about the relation between BMI and neck pain intensity. We investigated this relation, but found no effect of BMI on neck pain intensity. However, increasing BMI is associated with back pain and its intensity, but not neck pain [18].
Studies have shown that female gender is associated with neck pain, and this association is related to incidence [9]. In the present study, we did not investigate the incidence of neck pain according to gender, we investigated pain intensity distribution. After analysis, we found no significant differences between female and male genders in terms of neck pain intensity distribution in the young adult population.
The association of neck pain with smoking was corroborated in the study by Makela et al [18]. Also, there is a strong association between smoking and a herniated cervical intervertebral disc [19]. Coté et al. reported that in a population of 2184 adults aged 20-69 years, the prevalence of Grade II neck pain was also higher among current smokers. Grade I neck pain was more common in past smokers than in non-smokers, whereas current smokers were more likely to report Grades II and III to IV neck pain [8]. These studies show the effect of smoking on the incidence of neck pain, on the other hand, in the present study, we found that there was no effect of smoking on neck pain intensity in the young adult population. This result may be caused by acute small- to medium-sized analgesic effects of nicotine on pain intensity [20].
Studies on the prevalence of smartphone use have reported that the distribution of musculoskeletal symptoms or pain of any intensity was most common in the neck, followed by the upper back and then the shoulders. These results showed that the total time spent using a smartphone was significantly associated with any pain in the neck and shoulder. Consequently, the excessive use of a smartphone could produce considerable stress on the cervical spine and therefore cause neck pain [20]. However, in our study, there were no significant findings on the effect of SP usage per day on pain. This may be due to the approximation of the SP usage per day parameter between the groups.
According to our results, younger individuals using SP with a screen size of 5 inches and above have more risk of experiencing moderate to severe neck pain than those with a screen size of below 5 inches. Increasing cervical flexion and muscle activity with the increase in the size of the touch screen may cause this situation [21].
In this study, we found that the percentage of SP use in a non- neutral position of the neck was greater in young adults who suffer from moderate-severe neck pain than in group with mild neck pain. Using SP in a non-neutral position increases the risk of experiencing moderate-severe neck pain. In a study conducted on university students, it was reported that an increase in non-neutral neck and shoulder posture percentages may be responsible for the pain in these regions [22]. In a study conducted on young adults with mild neck pain and no neck pain, it was found that upper and lower cervical flexion angles were significantly higher in the mild neck pain group while using SP [23].
The relation between neck disability and pain is well described in the literature [24]. In our study, findings showed that disability level affects pain intensity. Subjects who suffer from neck pain might experience pain catastrophizing and may create a pain- disability vicious cycle for themselves by avoiding movements that may create pain. One of the limitations of our study is that we have not been able to examine pain catastrophizing.
Sleep quality is another aspect of chronic neck pain that may also affect pain intensity [25]. Pain and sleep relation may be double-sided. Since severe pain can affect sleep, poor sleep quality can affect pain intensity. Sleep disturbance has an increasing effect on pain intensity in women with fibromyalgia [25]. Although it is not a statistically significant difference, in our study, we found that the moderate-severe neck pain group have had poorer sleep quality than the mild neck pain group. Quality of life is closely related to chronic pain. The presence of neck pain has been reported to reduce the quality of life. There is a negative association between neck pain and quality of life [11]. Our findings showed that decreased quality of life worsened pain intensity. In spite of the gross measurement capacity of the general quality of life, spine-related quality of life is a specific outcome measure for patients with neck pain. In our study, the findings indicated that measured spine-related quality of life status and general quality of life had a negative effect on pain intensity.
The strengths of our study are as follows:
– examining the effects of variables not on the presence of pain, but on pain intensity
– investigating non-neutral neck position during SP calls
– conducting the study in a population most affected by SP usage
The limitations of the study are as follows:
– the measures were self reported, which might have caused some response bias
– the similarity between the groups in terms of some of the variables restricted the comparison
The conclusions obtained from our study are as follows:
– As the intensity of neck pain increases in young adult people, the rate of neck disability increases and the spine-related quality of life, the general quality of life and sleep quality decrease. In other words, decreased neck pain intensity increases the spine- related and general quality of life, and sleep quality.
– Smoking habit has no significant effect on neck pain intensity. – Young adults more often prefer SP with large screen sizes. The use of a larger screen SP often causes more severe chronic neck pain in younger individuals than a smaller screen.
– Young people who keep their necks in a neutral position during calls with SP suffer less neck pain than those who do not hold in a neutral position.
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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Aslan Telci E, Öztop M, Şekeröz S, Tekin F, Yağcı N, Şenol H. Investigation of factors affecting the intensity of chronic neck pain in young adult population. Ann Clin Anal Med 2021;12(7):760-764
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Comparison of short-term surgical and oncological outcomes of laparoscopic versus open surgery, in gastric cancer
Serdar Şenol 1, Servet Karagül 1, Oktay Karaköse 2
1 Department of Gastroenterological Surgery, SBÜ Samsun Training and Research Hospital, 2 Department of Surgical Oncology, SBÜ Samsun Training and Research Hospital, Samsun, Turkey
DOI: 10.4328/ACAM.20444 Received: 2020-12-21 Accepted: 2021-01-23 Published Online: 2021-02-08 Printed: 2021-07-01 Ann Clin Anal Med 2021;12(7):765-769
Corresponding Author: Serdar Şenol, Department of Gastroenterological Surgery, SBÜ Samsun Training and Research Hospital, Yenimahalle 3209.Sokak No:5 Atakum Samsun, Turkey. E-mail: serdarardaduru@gmail.com P: +90 5541164537 Corresponding Author ORCID ID: https://orcid.org/0000-0003-1193-1567
Aim: The aim of this study was to compare the short-term outcomes of gastrectomy operations performed using laparoscopic and open surgical methods in patients with gastric cancer in light of the current literature.
Material and Methods: This retrospective analysis included data of 65 patients with gastric cancer who underwent elective curative laparoscopic or open gastrectomy and D2 lymph node dissection between January 2017 and 2020 in the gastroenterological surgery and surgical oncology departments of the Samsun Training and Research Hospital.
Results: The open gastrectomy group included 31 patients with a median age of 63 (42–91) years. The laparoscopic gastrectomy group included 34 patients with a median age of 57 (24–81) years. There were no statistically significant differences between the two groups in terms of BMI, ASA score, tumor size, degree of invasion, or number of lymph nodes removed. Resection margin involvement was observed in 1 patient in the laparoscopic surgery group. Compared with the open gastrectomy group, the laparoscopic gastrectomy group demonstrated a significantly lower amount of intraoperative blood loss (75±15 mL vs 350±30 mL). The mean operative time was significantly longer(229±43 min vs 175±50 min). There was no statistically significant difference in the length of hospital stay (8 days vs 7 days) and mortality rates (5,8% vs 9,6%). Postoperative overall morbidity was lower (11% vs 16%, p>0,05). The surgical complication rate was lower in the laparoscopic group (2,9% vs 9,6%, p<0,05).
Discussion: Laparoscopic gastrectomy and D2 lymph node dissection may be a potential therapeutic option in patients with early and locally advanced tumors.
Keywords: Gastric cancer; Laparoscopic gastrectomy; Open gastrectomy; Short-term outcomes
Introduction
Gastric cancer is one of the leading causes of cancer-related deaths, and surgery continues to be the curative treatment option in over 90% of patients with early-stage gastric cancer [1]. Since Kitano [2] performed the first laparoscopic distal gastrectomy for gastric adenocarcinoma in 1994, this minimally invasive method has increased in popularity [3]. A meta-analysis and prospective randomized studies have indicated that laparoscopic total gastrectomy with D2 lymph node dissection is a safe procedure for the treatment of gastric cancer, reduces morbidity and hospital length of stay, and has no adverse effect on short-term oncological outcomes [4,5]. Similar studies have yielded comparable results with laparoscopic distal gastrectomy both in early-stage gastric cancer [6,7] and locally advanced gastric cancer [1].
The aim of our study was to compare short-term outcomes in patients who underwent laparoscopic or open gastrectomy and lymph node dissection for gastric cancer, in light of the current literature.
Material and Methods
This retrospective analysis included data of 65 patients with gastric cancer who underwent elective curative laparoscopic or open gastrectomy and D2 lymph node dissection between January 2017 and January 2020 in the gastroenterological surgery and surgical oncology departments of the Samsun Training and Research Hospital. The study protocol was approved by the Samsun Training and Research Hospital Ethics Committee (No: 2019/13). The laparoscopic and open surgery groups were evaluated retrospectively in terms of age, sex, ASA score, body mass index (BMI), tumor diameter, depth of tumor invasion within the gastric wall (pT), number of lymph nodes removed, resection margin, intraoperative blood loss, operative time, reoperation, length of hospital stay, mortality rate, and morbidity rate and causes.
Statistical Analysis
IBM SPSS Statistics version 21 (IBM Corp., Armonk, NY) software package was used for data analysis. The Kolmogorov–Smirnov test was used to test the normality of the data distributions. Since not all of the data were normally distributed, the data were presented as mean, median, minimum, and maximum values and compared between groups using the Mann–Whitney U test. The Chi-square test was used for between-group comparisons of percentage values.
Results
The open gastrectomy group included 31 patients (11 women and 20 men) with a median age of 63 (42–91) years. The laparoscopic gastrectomy group included 34 patients (9 women and 25 men) with a median age of 57 (24–81) years. There was no statistically significant difference between the groups in terms of gender, whereas the median age was significantly higher in the open surgery group. The median BMI was 25 (18–34) in open gastrectomy patients and 24 (17-40) in the laparoscopic gastrectomy patients. In the open gastrectomy group, 1 patient was ASA 4, 12 were ASA 3, and 18 were ASA
2. In the laparoscopy group, 14 patients were ASA 3, 13 were ASA 2, and 7 were ASA 1. There was no statistically significant difference between the two groups in terms of BMI or ASA. Among the 34 patients who underwent laparoscopic surgery, 20 underwent total gastrectomy and 14 underwent subtotal gastrectomy. Among the 31 patients who underwent open surgery, 22 underwent total gastrectomy while 9 underwent subtotal gastrectomy. The median tumor size was 5.5 (2–11) cm in the open surgery group and 5 (2–10) cm in the laparoscopy group. In the open surgery group, tumor stage was T4a in 19 patients, T3 in 8, T1b in 2, and T1a in 1 patient, while 1 patient was reported to have invasive cancer based on the result of the preoperative endoscopic biopsy and high-grade dysplasia was detected in the main surgical specimen. In the laparoscopy group, tumor stage was T4a in 21 patients, T3 in 6, T2 in 4, and T1a in 2 patients, and 1 patient was reported to have invasive cancer based on the result of the preoperative endoscopic biopsy, but no tumor was detected in the main surgical specimen. The median number of lymph nodes removed was 22 (8–48) in the open surgery group and 18 (6–45) in the laparoscopic surgery group. There was no significant difference between the two groups in terms of tumor size, degree of invasion, or the number of lymph nodes removed. Laparoscopic subtotal gastrectomy was converted to total gastrectomy in 1 patient due to the positive proximal resection margin. The operative time was 175±50 minutes for open surgeries and 229±43 minutes for laparoscopic surgeries. The difference in operative time between the groups was statistically significant (Table -1). Three patients in the open surgery group died due to postoperative acute respiratory distress syndrome, acute myocardial infarction, liver abscess and sepsis, while 2 patients in the laparoscopy group died due to postoperative acute myocardial infarction and cerebrovascular event. The prevalence of postoperative surgical and non-surgical complications in the open surgery group was 9,6% and 6,4% respectively and included pneumonia, pneumothorax, intraabdominal abscess, splenic infarction and abscess, and anastomotic leak. In the laparoscopic group, the rate of postoperative surgical and non-surgical complications was 2,9% and 8,8% respectively and the causes included intracranial hemorrhage, pneumonia, pulmonary embolism, intraabdominal hemorrhage. There was no significant difference between the groups in terms of mortality (for open and laparoscopic surgery, 9,67% vs 5,68%, respectively). The median length of hospital stay in the open and laparoscopic surgery groups was 7 (5–22) days and 8 (5– 42) days, respectively, which was not a statistically significant difference (Table 2).
In our patient population, the median follow-up was 18 months (3-34 months) in the laparoscopic gastrectomy group and 16 months (5-35 months) in the open gastrectomy group (p>0,05). In the laparoscopic and open groups, respectively, 4 and 3 patients were lost to follow-up. Four and 3 patients died during the follow-up respectively. In the laparoscopic group, 3 of them died because of cancer and 1 because of another disease. In the open group, 2 of them died because of cancer and 1 because of another disease.
Discussion
Gastrectomy is the cornerstone of curative treatment in gastric cancer. The popularity of minimally invasive techniques for gastrectomy has steadily increased over the last 10 years to improve the postoperative period [2].
Differences in age, BMI, ASA score between laparoscopic and open gastric cancer surgery, can be considered patient selection bias [8]. In our study, there was no statistically significant difference between the groups in terms of gender, BMI or ASA score. However, the median age was 63 years in the open surgery group and 57 in the laparoscopic surgery group, which is a statistically significant difference. When selecting patients, we also considered performance status, in addition to age. In terms of age range, the oldest patient in the laparoscopy group was 84 years old, compared to 91 years in the open surgery group. This difference stems from the fact that, anesthetists usually recommend open surgery for patients who is older and has a high ASA score to shorten the duration of surgery. With increased experience, however, their preferences have changed in recent times.
In our study, 20 gastric cancer patients underwent laparoscopic total gastrectomy, 14 underwent laparoscopic distal gastrectomy and D2 lymph node dissection. Laparoscopic distal gastrectomy was converted to total gastrectomy in 1 patient due to positive proximal resection margin. The majority of our patient population were patients with T3 and T4 tumors for both groups (79,4% for laparoscopic, 87,3% for open gastrectomy group). This represents the general characteristics of Western patients with gastric cancer [8]. The median number of lymph nodes removed was 18 (6-45) in the laparoscopic surgery and 22 (8-48) in the open surgery group (p>0,05). As mentioned in different studies [8-10], involving patients with early and locally advanced gastric cancer, our results support that the number of lymph nodes removed in the laparoscopic surgery is comparable with open surgery. In the laparoscopic surgery group, more than 15 lymph nodes, considered the minimum number of lymph nodes for accurate and adequate postoperative staging [11], were collected in 85,2% of our patients.
Intraoperative blood loss is associated with the incidence of early and late adverse effects of surgery and the prognosis of many malign tumors, including gastric cancer [12,13]. Therefore, careful operative techniques should be utilized to minimize intraoperative blood loss. In our study, the laparoscopic gastrectomy group exhibited a significantly lower amount of intraoperative blood loss (75±15 mL vs 350±30 mL, p<0,05). There are studies reporting similar findings for both early and locally advanced gastric cancer [6,8,9,14-16]. However, the use of laparoscopic gastrectomy in all patients with resectable gastric cancer can make the procedure more complex. As a result, more blood loss can be seen [15].
Operative time is an important variable, that reflects the difficulty of surgery and consequently the potential safety of the technique. Lack of tactile sensation, narrow surgical area, complicated vascular anatomy in the splenic hilum and difficulty of D2 lymph node dissection make laparoscopic surgery a time-consuming procedure [4,8]. Operative time was also significantly longer in the laparoscopic surgery group in our study.
In our study, no significant differences in the overall postoperative complication rates were observed between the laparoscopic group (4 patients, 11,7%) and the open group (5 patients, 16,1%, p<0,05). Different studies comparing laparoscopic and open surgery patients have demonstrated consistent morbidity rates (4,2 % – 23,3 %) [5,17-22]. In various studies, morbidity rates for open gastrectomy varied between 16,4% and 24,5% [5,23]. Moreover, in our study, in three out of the four laparoscopic cases, there were non-surgical complications due to pneumonia, pulmonary embolism and intracranial hemorrhage. Hence, the incidence of surgical complications in the laparoscopy group was quite lower and significant (2,9% vs 9,6%, p<0,05). Since the majority of our patient population comprised patients with locally advanced tumors, our study suggests that the advantages of laparoscopy for postoperative complications might be more substantial among locally advanced gastric cancers. In the laparoscopy group, there was only one surgical complication that required relaparotomy due to postoperative hemorrhage. Although, there was no statistical difference between the groups, there are studies [21,22] showing higher rates of reoperation and postoperative hemorrhage in laparoscopic surgeries. This was attributed to technical difficulties during laparoscopic gastrectomy, especially difficulty in forming the esophagojejunal anastomosis [24].
Mortality rates for laparoscopic gastrectomy have been reported between 0,6% to 0,8% [19,21]. In our study, postoperative mortality rates were higher (for open and laparoscopic surgery, 3 patients, 9,67% vs 2 patients, 5,68%, respectively). However, in the laparoscopic surgery group, two patients died due to cerebrovascular events and acute myocardial infarction, which can be classified as patient-related factors.
Better perioperative outcomes, such as less perioperative pain, earlier resumption of bowel movements and the resulting earlier oral intake were reported to reduce the time to discharge after laparoscopic surgery [8,20,25]. In our study, no significant difference was observed between the length of hospital stay in both patient groups for whom the regimen was initiated on the third postoperative day. However, one of our laparoscopic surgery patients with a previous history of cerebrovascular event had the longest hospital stay (42 days) due to postoperative intracranial hemorrhage. This unduly skewed our results due to the small number of patients in the study.
Our study has some limitations. Firstly, it is a single-center study with a limited patient size and designed retrospectively. Secondly, our follow-up period is not enough to make a conclusion for long term results. Thirdly, although the majority of our patients had locally advanced disease, systemic treatment could be applied as adjuvant therapy, due to the insufficient interpretation of computed tomography results. However, in recent times diagnostic laparoscopy and peritoneal washing cytology, neoadjuvant therapy, adjuvant hyperthermic intraperitoneal chemotherapy and cytoreductive surgery with intraperitoneal hyperthermic chemotherapy have been used in our patients by obtaining personal opinions of radiologists for the clinical staging.
Based on the short-term outcomes of our gastric cancer surgeries in our patient population, comprising mostly of locally advanced gastric cancer, laparoscopic gastrectomy with D2 lymph node dissection had lower blood loss, surgical complication rate and a comparable number of removed lymph nodes, resection margin, length of hospital stay, overall complication and mortality rates. However, it is associated with the longer operative time. This supports the use of laparoscopic gastrectomy with D2 lymph node dissection as a safe and effective method.
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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Serdar Şenol, Servet Karagül, Oktay Karaköse. Comparison of short-term surgical and oncological outcomes of laparoscopic versus open surgery, in gastric cancer. Ann Clin Anal Med 2021;12(7):765-769
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Comparison of reusable and single-use ureteroscopes for the treatment of medium-sized stones in the lower calyx: A prospective randomized study
Mehmet Yilmaz Salman 1, Goksel Bayar 2, Hakan Remzi Dincer 1, Orhun Sinanoglu 1
1 Department of Urology, Sancaktepe Prof Dr Ilhan Varank Training and Research Hospital, Istanbul, 2 Department of Urology, Mardin State Hospital, Mardin, Turkey
DOI: 10.4328/ACAM.20446 Received: 2020-12-22 Accepted: 2021-03-26 Published Online: 2021-06-17 Printed: 2021-07-01 Ann Clin Anal Med 2021;12(7):770-774
Corresponding Author: Mehmet Yilmaz Salman, Department of Urology, Sancaktepe Prof Dr Ilhan Varank Training and Research Hospital, Sarıgazi Emek, Namık Kemal street, No 54, 34785 Sancaktepe, Istanbul, Turkey. E-mail: mdmehmetyilmazsalman@yahoo.com P: +90 216 606 33 00 GSM: +90 532 723 47 78 Corresponding Author ORCID ID: https://orcid.org/0000-0002-9996-2300
Aim: Single-use flexible ureteroscopes (fURSs) were developed as an alternative in order to eliminate the cost disadvantages of reusable ureteroscopes in the treatment of kidney stones. The objective of this study was to compare single-use and reusable fURSs for the treatment of medium-sized stones in the lower calyx.
Material and Methods: The data of patients who underwent retrograde intrarenal surgery (RIRS) for medium-sized stones (10-20) mm in the renal pelvis were analyzed prospectively. The patients were divided into two groups according to the fURS model used during the operation. Uscope PU3022TM (Pusen®, China) was used as single-use fURS, and Flex X2TM (Karl Storz®, Germany) as reusable. Failed RIRS following Double-J stent insertion was considered as the first ses- sion and each RIRS operation as a separate session.
Results: The mean operation time was 20 minutes shorter in the reusable fURS group (53±17.4 vs 73.1±21.6, p< 0.001). The mean number of sessions was less in the reusable fURS group (1.3±0.46 vs. 1.6±0.59, p= 0.014). The stone-free rate was similar in both groups (77.5% vs. 72.5, p = 0.606).
Discussion: The success rates of reusable and single-use ureteroscopes in the treatment of medium-sized stones in the lower calyx were similar. However, the mean operation time was shorter and the number of sessions was less in the reusable ureteroscopy arm.
Keywords: Single-use; Ureteroscope; Reusable ureteroscope; RIRS; Medium sized
Introduction
Retrograde intrarenal surgery (RIRS), also known as flexible ureterorenoscopy (fURS), is a less invasive procedure with fewer complications compared to other procedures and is effective for medium-sized kidney stones (10-20 mm) even with complex anatomy and patients using anticoagulants [1]. With technological advancements, ureteroscopes used for these procedures gained the ability to allow irrigation and to actively deflect, which provides them with treatment features [2]. Over time, the fURS has evolved and has become an indispensable tool in renal stone treatment together with improvements in laser lithotripsy [3]. Stone-free rates (SFRs) of up to 90% have been provided with RIRS carried out using fURS [4]. With the widespread use of reusable fURSs, high initial and repair costs as well as sterilization and reprocessing expenditures became an apparent burden [5]. With the development in digital technologies, single-use fURS are marketed and used today, with test results comparable in terms of scope characteristics and vision [6]. However, these devices are relatively new in the market and therefore, currently, there are only limited comparative data in the literature about single-use fURS and reusable fURS in terms of clinical efficiency, costs and safety. The first digital single-use fURS, LithovueTM (Boston Scientific USA) was reported to be equivalent to standard reusable scopes in terms of performance and safety [7]. The UscopePU3022TM digital single-use fURS (Zhuhai Pusen Medical Technology Company Limited, China) has recently been introduced as a potential competitor to LithovueTM, with the claim of assuring comparable clinical performance, but at a lower cost [8]. Marchini et al. compared UscopePU3022 and Lithovue fURSs with the reusable Flex-X2 scope, but in this study, technical features were investigated rather than clinical performance [9]. Presentation
The objective of this study was to compare single-use with reusable fURS in terms of overall clinical performance in the treatment of medium-sized (10-20 mm) stones in lower calyx under similar conditions.
Material and Methods
A total of 80 patients who presented to our hospital and were treated with RIRS due to 10-20 mm sized stones in the lower calyx between May 2018 and December 2018 were included in the study. The patients were divided into two groups according to the fURS model used during the operation. Reusable fURS (7.5 Fr) was used in the first group, and single-use fURS (9.5 Fr) in the second group. Patients’ demographics such as age and gender, stone size and surface area, operation time, number of sessions, success and complications were recorded. Patients with stones localized other than lower calyx, a history of prior stone surgery or extracorporeal shock-wave lithotripsy (SWL) or RIRS for significant residual stone, pediatric patients, those with comorbidities such as diabetes mellitus, hypertension, and ischemic heart disease, patients on anticoagulants, and those with prior nephrostomy or double-j stent due to infection were excluded from the study. The study protocol was approved by the local ethics committee (Decision No: 2021/99). Written informed consent was obtained from all patients before operation. The study was conducted in compliance with the ethical principles of the Declaration of Helsinki.
Surgical Technique
Urine culture was taken in addition to routine laboratory examinations, and the operation was performed when urine culture became negative. Preoperative 1 g ceftriaxone was administered intravenously. An attempt was made to insert access sheath in all patients in the first session. If the access sheath could not be inserted during the first attempt with single- use fURS, the operation was discontinued considering that the device rigidity was not sufficient to provide access over the guide wire, a double-j (DJ) stent was inserted and operation was performed 2 weeks later. Whereas in the reusable fURS, access was attempted through the guide wire, even if the access sheath could not be placed. The Zebra guide wireTM (Boston Scientific®, USA) was inserted into the ureter with reusable fURS, and the intramural ureter was dilated with reusable fURS up to the mid ureter, then the access sheath was tried over the guide wire. UscopePU3022TM (Pusen®, China) was used as single-use fURS, and Flex X2TM (Karl Storz®, Germany) as reusable. Access sheaths of Flexor-Regular (R; 9.5/11.5 Fr, Cook Medical, USA) and Flexor Ureteral Access Sheath Hydrophilic Coating (R; 10.7/ 12.7 Fr, Cook Medical, USA) were used in reusable fURS and single-use fURS, respectively. DJ stent was inserted into all patients at the end of the first procedure.
Evaluation of Outcomes and Complications
A failed RIRS following DJ insertion was considered as the first session and each RIRS operation as a separate session, while removal of DJ stents was not counted as a session. Complete SFR status or clinically insignificant stones (≤ 3 mm) on non-contrast CT three months after the last operation was considered successful. Operation time was defined as the duration from the insertion of fURS through urethral meatus up to DJ stent placement. All operations were carried out by a single urologist experienced in fURS. The stone surface area was determined by computed tomography by measuring the length of the three dimensions.
Statistical Analysis
Data obtained in the study were analyzed using the SPSS for Windows version 21.0 statistical software. The normality of the data was tested using the Kolmogorov-Smirnov method. Comparison between the groups was made using the Mann- Whitney U test for continuous variables and the Chi-square test for categorical variables. Continuous variables were expressed as mean ± standard deviation, min and max descriptive values, and categorical values as the number and percentage p<0.05 values were statistically significant.
Results
Eighty patients were included in the study with 47 of whom were males (58.8%) and 33 (41.2%) females. The mean age of the patients was 46.4 ± 13.1 (25-75) years. At the end of three months, 60 patients were stone-free (75%), of whom, 31 (77.5%) were in the reusable fURS and 29 (72.5%) in the single-use fURS group. No statistically significant difference was found between the two groups in terms of SFR (p=0.606). Five patients developed complications with two being in the reusable and three in the single-use fURS group. The operation was terminated in three patients due to ureteral injury, and in two patients because of bleeding. These five patients had no additional intervention except for DJ stent placement, and the stones were removed in the second session. The mean stone surface areas were similar between both groups (p =0.267) (Table 1).
In the reusable group, 12 patients underwent the second session, three of which were due to failed access in the first intervention and nine for residual stone. A total of 22 additional sessions were performed in the single-use fURS group: two sessions in 20 patients and three sessions in two patients; of these 22 additional sessions, eleven were performed due to residual stone, and the remaining eleven since the first access was unsuccessful. The need for additional sessions due to failure of the first attempt was significantly lower in the reusable fURS group compared to the single-use fURS group (p=0.005) (Figure 1).
Additional session for residual stone was similar in both groups (22.5% vs. 27.5%, p = 0.317). The successful access rate in the first session was higher in the reusable fURS group (92.5% vs 72.5%, p = 0.03). The mean operation time was 20 minutes shorter in the reusable fURS group (53±17.4 vs 73.1±21.6, p< 0.001) (Figure 2).
The mean number of sessions was less in the reusable fURS group (1.3±0.46 vs. 1.6±0.59, p= 0.014). The stone-free rate was similar in both groups (77.5% vs. 72.5%, p = 0.606). Treatment outcomes of both groups are given in Table 2.
Discussion
Flexible ureteroscopy has been performed with increasing frequency over the last two decades, with stone-free rates equal to the PCNL for stone sizes ≤ 2 cm [10, 11]. With this method, SFR was achieved by 95% in previous reports regardless of kidney stone location. The Clinical Research Office of the Endourological Society (CROES) study has prospectively collected data from more than 10,000 patients. The authors of this study found SFRs of 90% and 80% for stones <10 mm and <15 mm in size, respectively, after a single session of RIRS [12]. As to data with PolyscopeTM, Bader et al. performed an in vitro and clinical assessment with this single-use fURS, the field of view and image quality were comparable to reusable fURS [13]. During clinical evaluation, they described the facility to insert this ureteroscope over a guidewire or through an access sheath, with an 89.5% SFRs in 40 laser lithotripsy procedures (mean stone size 1 cm), mean operation time of 26 minutes and no intraoperative complications. In another study, Gu et al. reported their experience with PolyscopeTM, in which SFR was 89.5% in 86 patients (median stone size 1.23 cm) with nine patients requiring secondary procedures [14]. In our study, the overall SFR was 75%, while this rate was 77.5% in the reusable fURS group and 72.5% in the single-use fURS group. This rate was higher in the reusable group, although the difference was not statistically significant (p=0.606).
To avoid the costs associated with the repair and sterilization of conventional reusable fURS, many institutions are now using single-use alternatives. Reduced costs at initial purchase of equipment and reliability are advantages of single-use fURS. Furthermore, single-use fURS has comparable SFRs with reusable fURS for treating nephrolithiasis [15]. A recent retrospective study incorporated LithoVueTM data from 159 cases across 14 care centers to evaluate the clinical efficacy of this single-use fURS [16]. Investigators reported a 96.8% first-treatment success rate in terms of ability to access stone, structure, and upper urinary tract urothelial carcinoma lesion. In our study, the operation time was 53±17.4 minutes in the reusable fURS and 73.1±21.6 minutes in the single-use fURS group (p<0.001). Similarly, Salvado et al. found that the mean operation time was 76.4 minutes with single-use fURS in middle-sized stones [10]. Usawachintachit et al. found that single-use LithoVueTM fURS cases were, on average, 10-15 minutes shorter and resulted in almost a quarter of an hour less total time in the operating room compared to reusable fURS [7]. Single-use fURS displays more success in complex lower calyceal stones, as SFR following single-use fURS was slightly higher than rates reported in RIRS studies with reusable fURS [17]. A possible explanation for the higher SFR in lower pole stones could be the fact that when using single-use equipment, the surgeon may be less concerned about damaging the fURS and, therefore, could maximally deflect the scope without fear [18]. Salvado et al. inserted DJ stent preoperatively in 10 patients with medium-sized stones, which means 45.5% additional operative session due to failed access. The clinical data observed in this series does not differ from the previous results traditionally obtained with other reusable devices, however, the study did not compare outcomes with reusable equipment under similar conditions [10].
Usawachintachit et al. reported that single-use fURS was associated with a statistically significantly decreased complication rate compared to the use of reusable scopes. Their reusable fURS group experienced a three-fold increased rate of complications compared to single-use fURS [7]. Whereas in our study, no significant difference was found between the reusable and single-use groups in terms of complication rates (p=0.644). Our complication rates are lower than those of the previous studies [19, 20]. Mager et al. prospectively compared 68 reusable flexible uretero-renoscopies (Flex-X2S, Flex-XC, Karl Storz) and 68 single-use fURSs (LithoVue, Boston Scientific) [21]. Comparing clinical outcomes of reusable vs. single-use instruments revealed no significant difference for overall success rates (81 vs. 87%), stone-free rates (82 vs. 85%), mean operation time (76.2 vs. 76.8 min), radiation exposure time (3.83 vs. 3.93 minutes) and complication rates (7 vs. 17%) (p > 0.05). The above cited studies compared clinical performance of different fURS devices regarding overall urinary stone clearance. However, no study was found in the literature comparing reusable and single-use fURSs in the treatment of lower calyx stones. To the best of our knowledge, the present study is the first trial evaluating both types of instruments in the treatment of lower calyx stone. In our series, SFRs, operation time and preoperative DJ stent placement were 72.5% vs 77.5%, 73.1 vs. 53 minutes (p<0.001) and 27.5% vs. %7.5 (p= 0.005), respectively for the single use fURS vs. reusable fURS, which seem to be in contrast to recently published studies. We found that additional session number and operation time was statistically significantly higher in the single-use fURS group. On the other hand, larger access sheath and instrument sizes requires an initial DJ insertion in many cases to assure dilation for the following single-use fURS session. The second issue is that the quickly worsening visibility during a fURS session prolongs the operation time. A prospective cohort study carried out with the UscopePU3022TM across 11 centers in 2017 suggested that this assumption may be true. The authors concluded that the UscopePU3022TM performed well with regards to maneuverability, deflection and limb fatigue and appears to be comparable to standard fURS; however, poor visibility is a concern for UscopePU3022TM with receiving a low overall performance rating compared to standard fURS. The image was reported to be too dark, especially at the periphery, which was evident when navigating the renal pelvis. In order to improve vision, we attached a triple port to the single-use fURS to suction turbid fluid in the renal pelvis and therefore, a certain time elapsed when manipulating the port from inflow to outflow and vice versa. Finally, in our study the mean number of sessions was significantly lower in the reusable group (p=0.014). In general, looking at our results, reusable fURS seem advantageous compared to simple-use fURS in terms of treatment performance with shorter operation time and fewer additional sessions. Given fluoroscopy exposure with fURS, reusable devices seem to decrease this advantage with shorter operation time. However, considering cost factor reusable fURS brings both initial and repair costs increasingly with the widespread use of TIRS operations worldwide. We believe that technological advancement will eliminate the cost disadvantage of relatively new single-use fURSs, making that devices more practicable in the treatment of middle-sized kidney stones. Limitations
There are also limitations to our study. We could not measure fluoroscopy time and stone density, and could not perform a cost analysis among comparative clinical data. However, being the first study comparing these two devices is the strength of our study.
Conclusions
The success rates of reusable and single-use ureteroscopes in the treatment of medium sized stones in lower calyx were comparable. However, the mean operation time was shorter and the number of sessions was less with the reusable ureteroscopy arm. The routine clinical use of single-use fURSs is still a matter of investigation and discussion worldwide; however, their real potential and economic advantages remain to be elucidated with comprehensive studies. Thanks to advancements, similar results can be obtained if single-use fURS vision achieves better visual quality and smaller calibrations.
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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Mehmet Yilmaz Salman, Goksel Bayar, Hakan Remzi Dincer, Orhun Sinanoglu. Comparison of reusable and single‐use ureteroscopes for the treatment of medium‐sized stones in the lower calyx: A prospective randomized study. Ann Clin Anal Med 2021;12(7):770‐774
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Is subclinical hypothyroidism a risk factor for myocardial infarction? A comparative study of a cohort of young Pakistani men
Muhammad Imran Aftab 1, Madiha Ali 2, Bushra Anam Ali 3, Bilal Habib 4, Inamul Haq 5, Syed Imran Ali Shah 6
1 Department of Physiology, Independent Medical College, Faisalabad, Pakistan, 2 Department of Anatomy, Independent Medical College, Faisalabad, Pakistan, 3 Department of Pathology, Fazaia Medical College, Islamabad, Pakistan, 4 Department of Physiology, Rai Medical College, Sargodha, Pakistan, 5 Department of Physiology, University of Hafr Al-Batin, Hafar Al Batin, Saudi Arabia, 6 Department of Biochemistry, University of Hafr Al-Batin, Hafar Al Batin, Saudi Arabia
DOI: 10.4328/ACAM.20448 Received: 2020-12-23 Accepted: 2021-01-23 Published Online: 2021-02-05 Printed: 2021-07-01 Ann Clin Anal Med 2021;12(7):800-803
Corresponding Author: Syed Imran Ali Shah, Department of Biochemistry, University of Hafr Al-Batin, Hafar Al Batin, Saudi Arabia. E-mail: simranali@uhb.edu.sa / s.shah10@alumni.imperial.ac.uk P: +966534510690 Corresponding Author ORCID ID: https://orcid.org/0000-0002-0833-0771
Aim: Myocardial infarction (MI) is a major cause of death globally with a rising incidence at a younger age. Subclinical hypothyroidism (SCH) is an asymptom- atic condition with raised serum thyroid-stimulating hormone (TSH) and normal free thyroid hormones. SCH has been linked with MI previously, but local data are not available. The present study was done to determine the relation between SCH and MI in young men from the local population.
Material and Methods: The cross-sectional study compared male patients with MI (n=75) with age-matched controls (n=75) for the presence of subclinical hypothyroidism and other clinical risk factors including blood pressure, waist circumference and fasting blood glucose (FBG). For the assessment of SCH, serum thyroid hormone profile was done, including TSH, free tri-iodothyronine (fT3) and free thyroxine (fT4) levels.
Results: The incidence of SCH in MI patients and healthy control subjects were 12% and 5%, with the difference being statistically insignificant (p=0.15.). No differences were observed between the two groups in thyroid hormone profile and other clinical risk factors studied.
Discussion: SCH does not appear to be associated with an increased risk of MI in local population of Pakistani men. Considering the study limitations, larger prospective trials are warranted to inform robust outcomes.
Keywords: Thyroid hormones; Subclinical hypothyroidism; Myocardial infarction; Cardiovascular diseases
Introduction
Myocardial infarction (MI), a condition characterized by irreversible ischemic damage of the myocardium due to obstruction to coronary blood flow, is a major cause of death and compromised quality of life of survivors globally. Many modifiable and non-modifiable risk factors of MI have been recognized over the years, including family history, smoking, obesity, dyslipidemia and psychosocial disorders [1, 2]. Subclinical hypothyroidism (SCH) is an asymptomatic condition characterized by raised serum thyroid-stimulating hormone (TSH) levels and normal free thyroid hormones, including free triiodothyronine (fT3) and thyroxine (fT4). SCH and overt hypothyroidism share causes, which include iodine deficiency, autoimmune thyroiditis, surgical or ablative procedures induced, and certain medications [3]. SCH has been proposed as a risk factor for hypertension, hyperlipidemia and hyperhomocysteinemia, which are also associated with the pathophysiology of cardiovascular diseases [4-6]. Overt thyroid disease is a known cause of atherosclerotic cardiovascular abnormalities [7]. Subclinical thyroid dysfunction itself is linked with cardiac diseases due to the sensitivity of the cardiovascular system to thyroid hormones at the cellular and molecular levels [8]. Thyroid hormones influence cardiac myocytes via both genomic and non-genomic mechanisms and stimulate or suppress the transcription of specific target genes involved in the maintenance of cardiac integrity [9]. Nonetheless, adverse cardiovascular outcomes due to subclinical thyroid abnormalities remain contentious and unclear, and local data on this aspect are missing. Furthermore, the benefits of mild SCH treatment in the prevention of MI remain controversial. The present study was conducted to highlight any potential nexus between SCH and MI in the local population of Pakistan.
Material and Methods
The cross-sectional comparative study was conducted in compliance with the ethical principles outlined in the Declaration of Helsinki. Adult male patients (n=75), between the ages of 18 to 55 years, admitted to Punjab Institute of Cardiology, Lahore, Pakistan following an acute MI (Group 1) were recruited through a non-random convenience sampling. There is growing evidence of increasing risk of MI in young males, hence a younger age group was included in the study [10]. Age-matched healthy males (n=75) without any history of MI were enrolled as controls (Group 2). A relatively young age group was chosen, as the incidence of MI is drastically increasing in young Pakistani men [11]. Subjects with a previously known medical history of diabetes mellitus (either on insulin therapy or using oral hypoglycemic agents), hypertension, alcoholism, overt thyroid disease, or cardiovascular diseases were excluded from the study.
Written informed consent was taken from the subjects on the study proforma before commencing the study procedures. Complete confidentiality of all data was ensured. Clinical history, examination and laboratory tests of patients were recorded. Assessments were done for comorbidities like diabetes mellitus, hypertension and obesity, which are implicated in the pathophysiology of MI, in order to eliminate the potential skewing of the data due to confounders. Blood pressure (BP) was measured from the brachial artery using a mercury sphygmomanometer after ensuring that the subject had 10 minutes of rest. Two readings were taken 10 minutes apart and their mean was recorded. Waist circumference (WC) was measured with a standard measuring tape, at the end of normal expiration to the nearest 0.1 inch, measuring at the narrowest point between the lower ribs and the iliac crest. WC, a constant measure of abdominal obesity, was employed due to ease of measurement. Unlike the waist-hip ratio, WC avoids taking hips into account as in addition to fat, hips comprise of skeletal muscle and bone, which do not have an adverse relationship with atherosclerosis, hypertension and diabetes. Independent of body mass index (BMI), WC has a strong association with mortality risk and is one of the criteria for metabolic syndrome [12]. Blood samples were collected in the morning between 8-10 am from subjects who were fasting for at least 6 hours. Blood (5 ml) was drawn from each subject in a 5cc syringe by venipuncture following aseptic measures. Serum was separated by centrifugation, collected in serum cups and stored at -20 oC until analysis. Fasting blood glucose (FBG) was checked by enzymatic-colorimetric GOD-PAP end-point method using standard reagent (Glucose PAP SL, ELITech Clinical Systems, Sées, France) and reading was taken on the Microlab 300 (ELITech Group, Puteaux, France) semi-automated clinical chemistry analyzer. Serum levels of fT3, fT4 and TSH were measured using standard enzyme-linked immunosorbent assay (ELISA) kits (CTK Biotech, Inc., Poway, California, United States) and read on an Epoch microplate spectrophotometer (BioTek Instruments, Inc., Winooski, Vermont, United States). SCH was defined as TSH above the upper limit of normal (4 mU/L) and fT4 within the normal range (9-25 pmol/L) ( Your guide to thyroid function tests. Harrogate, United Kingdom: British Thyroid Foundation; 2018. Available at: https://www.btf-thyroid. org/thyroid-function-tests).
The data were statistically analyzed using Statistical Product and Service Solutions (SPSS; formerly statistical package for social sciences) version 20 (IBM® SPSS® Statistics 20.0 for Desktop Windows, IBM Corporation, Armonk, New York, United States). The Shapiro-Wilk test was applied to assess data normality. Data were described as mean ± standard deviation (SD) for normally distributed continuous variables including fT3, fT4, TSH, FBG, diastolic and systolic blood pressure, and waist circumference. For categorical variables like the presence or absence of SCH, frequencies and percentages were given. Differences in categorical variables were evaluated by a 2×2 contingency chi-square test, while group means were compared using the independent sample t-test. A p-value of less than 0.05 was considered significant.
Results
The mean age (in years) in Group I was 43.59±7.42 years and in Group II was 42.28±8.96 years, with no difference between the groups (p=0.332). The two groups were compared for BP, FBG and waist circumference, but no difference was found since patients having hypertension, diabetes mellitus and obesity have already been excluded from the study. The systolic BP (mm Hg) in Group I was 123.80±15.22 compared to 123.33±14.8 in Group II (p=0.849). The diastolic BP (mm Hg) was 77.73±12.26 in Group I as compared to 78.13±10.23 in Group II (p=0.828). The waist circumference (in inches) was 36.6±2.94 in Group I as compared to 35.6±3.26 in Group II (p=0.47). FBG (mg/ dL) in Group I was 97.17±40.17 compared to 89.06±26.36 in Group II (p=0.15). In Group I, the frequency of SCH was 12% and in Group II it was 5%. Levels of TSH (mIU/L) in Group I (2.51±1.40) and Group II (2.13±1.16) showed no difference (p >0.05). No difference was found in the levels (pmol/L) of fT3 (Group I 4.58±0.42 vs. Group II 4.51±0.67, p=0.44) and fT4 (Group I 17.16±1.06 vs. Group II 17.41±2.77, p=0.46). Table 1 summarizes the comparison of various study parameters between the two groups.
Discussion
MI is a longstanding global health threat with more and more younger individuals becoming its victim. It is estimated that nearly one-fifth of all deaths in Pakistan are due to MI and its complications [13]. Besides the well-known risk factors, South Asian ethnicity has been identified as a predisposing factor for developing cardiovascular diseases at a younger age [14]. SCH has also been linked to the development of cardiovascular diseases by influencing lipid metabolism [15]. This study attempted to identify the link between MI and SCH in young Pakistani males. The overall prevalence of SCH in the present study population was 8.6 %, which is similar to the prevalence reported previously [16]. The prevalence of SCH in healthy individuals observed in the present study was also consistent with the findings of Alam et al. who reported a similar prevalence of SCH in the general Pakistani population [17]. Another study reported a slightly higher prevalence of SCH in the Dera Ismail Khan region of Pakistan [18], which could be attributed to a difference in the age group, as that study population included school-going children only. In the present study, 12% of the patients with MI have SCH, which is in accordance with the prevalence reported in the Rotterdam study [19].
The association of SCH with ischemic heart disease is a matter of debate. The present study did not demonstrate any link between SCH with MI. Previously, a longitudinal study with a 20-year follow-up also did not show any increase in cardiac mortality from SCH [20]. More recently, no association has been demonstrated between unrecognized SCH and cardiovascular events or mortality [21]. In a meta-analysis by Rodondi et al., only severe SCH (TSH > 10 mIU/L) was found to be associated with cardiovascular diseases, but moderate SCH (TSH levels between 4.5-10 mIU/L) was not shown to correlate with MI [16]. No case of severe SCH was found in the present study, so the association of severe SCH with MI could not be analyzed. Contrary to the present findings, some studies have found a significant correlation between SCH and MI, possibly owing to age and gender differences between their study populations and ours, as well as their prospective design, which allowed for longitudinal assessment of cardiovascular outcomes in SCH [19, 22, 23]. Based on the current findings, the role of the treatment of mild to moderate SCH in the prevention of MI cannot be suggested. Judicious prophylactic use of thyroxine in SCH has been shown to carry potential benefit, yet unwarranted administration of the same can lead to SCH [24].
The present study explored the role of SCH in MI in young men, as the risk of MI in young Pakistani males is on the rise. Most such studies have previously been conducted on females exclusively or on mixed populations [19, 23]. To the best of our knowledge, no such study has thus far been conducted to establish the correlation of MI with SCH exclusively in males, particularly in the local context. The present study is novel as it targeted a less explored aspect of MI pathophysiology in this part of the world, where the awareness of different manifestations of thyroid abnormalities is still lacking. Being a cross-sectional study, it could not suggest a cause-effect relationship. The study population comprised of male subjects only, so gender-based differences could not be assessed. The low frequency of SCH in both groups made it difficult to comprehensively study the correlation of SCH with MI. The majority of the study population belonged to areas that are not endemic for thyroid abnormalities, particularly related to iodine deficiency [25], hence the results may not be representative of the overall Pakistani population.
Conclusion
No relationship between SCH and MI could be inferred from the study and therefore, the treatment of SCH for cardioprotective benefits cannot be suggested. Whether to treat SCH to reduce the risk of future cardiovascular events still remains a controversial matter. The association of SCH with ischemic heart disease should be studied longitudinally on a larger cohort of the Pakistani population, with the inclusion of females and having a wider age range.
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: The authors extend their appreciation to the Deanship of Scientific Research, University of Hafr Al-Batin for funding this work through the research group project No. G-121-2020.
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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Muhammad Imran Aftab, Madiha Ali, Bushra Anam Ali, Bilal Habib, Inamul Haq, Syed Imran Ali Shah. Is subclinical hypothyroidism a risk factor for myocardial infarction? A comparative study of a cohort of young Pakistani men. Ann Clin Anal Med 2021;12(7):800-803
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Are incidental IMRT doses to internal mammary lymph nodes reliable enough, as they were in the past with conformal RT in breast cancer?
Necla Gurdal 1, Selami Eken 2, Ugur Akbayırlı 2, Neslihan Kurtul 3
1 Department of Radiation Oncology, Istanbul Prof.Dr.Cemil Taşcıoğlu City Hospital, Istanbul, 2 Department of Medical Physics, Sutcu Imam University, Faculty of Medicine, Kahramanmaraş, 3 Department of Radiation Oncology, Sutcu Imam University, Faculty of Medicine, Kahramanmaraş, Turkey
DOI: 10.4328/ACAM.20449 Received: 2020-12-25 Accepted: 2021-02-10 Published Online: 2021-02-21 Printed: 2021-07-01 Ann Clin Anal Med 2021;12(7):804-808
Corresponding Author: Necla Gurdal, Istanbul Prof.Dr.Cemil Taşcıoğlu City Hospital, Department of Radiation Oncology, Şişli, 34384, Istanbul, Turkey. E-mail: gurdalnecla@hotmail.com P: +90 506 478 1440 Corresponding Author ORCID ID: https://orcid.org/0000-0001-5627-3436
Aim: Intensity-modulated radiotherapy (IMRT), applied in combination with several other methods, has gradually become common practice in breast cancer treatment. The dose distribution in this area has become even more critical since the benefits of regional lymph node irradiation were demonstrated in disease- free survival (DFS) and distant metastasis-free survival (DMFS) rates, particularly in the early phase of the disease. Our main aim in this dosimetric study was to compare IMRT and conformal RT plans, excluding internal mammary lymph node field (IMLN) planning, and to investigate the dose distribution incidentally received by the IMLN.
Material and Methods: A PTV-total was created excluding the IMLN field in 15 right-sided and 15 left-sided breast cancer patients, and two different plans were designed for each patient to receive the defined target doses using both conformal and IMRT techniques. The incidental IMLN field dose distributions in the conformal and IMRT plans were compared in regards to the D95, Dmax, Dmin, Dmean, V40, V45, V47.5, and homogeneity index (HI) values.
Results: The incidental distributions of D%95, D%98, D%2, maximum dose, minimum dose, mean dose, V40, V45, and V47.5 in IMLN were found to be signifi- cantly lower in the IMRT plans compared to the conformal plans.
Discussions: IMRT requires a more careful reevaluation of the incidental doses received by the IMLN field. The use of IMRT in breast cancer radiotherapy may lead to a potential for increased recurrence rates in the internal mammary lymph nodes area compared to the rates observed in the conformal technique due to the lower doses received by the adjacent tissues.
Keywords: Breast cancer; Radiotherapy; Incidental doses; Nodal irradiation
Introduction
The contribution of radiation therapy (RT) in breast cancer treatment has long been the subject of investigation. Another major issue is to determine the characteristics of the patients, in whom IMLN field will be treated [1,2]. The characteristics of patient subgroups, in which the contributions of the IMLN field RT are observed in the rates of local control (LC), overall survival (OS) or disease-free survival (DFS) rates, have been among the major questions waiting to be answered today. The IMLN field is difficult to reach surgically, which increases the duration of the intervention associated with increased risks [3]. In addition, due to the potential of additional pulmonary and cardiac toxicity associated with the IMLN RT, the benefit-to- risk ratio should be studied with care for every patient during the planning phase.
The doses, to which the surrounding tissues are exposed, have been reduced currently, owing to the advances in technology during the evolution of breast RT from 2D to 3D, as well as towards IMRT. Although the inverse planning period is longer in IMRT, side effects are less frequently observed because the surrounding tissues are exposed to lower doses [3].
The exposure of the surrounding tissues to lower doses by means of IMRT requires a more careful re-evaluation of the incidental doses received by the IMLN field. Then, the question arises, could this modification in the technique of the treatment lead to a change (potential increase) in the IMLN recurrence rates? In this article, we tried to shed light on the answer to this question.
Material and Methods
Patient selection
Patients previously irradiated at our center were reviewed and 30 cases were selected for the present study. Three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) were retrospectively planned for 15 right- sided and 15 left-sided breast cancer patients treated with breast-conserving surgery and whole breast radiation therapy. Simulation, volume definition, and radiotherapy technique
CT simulations were done with a GE Light Speed16 CT scanner in the supine position with a slice thickness of 2,5 mm. Target volumes and organs at risk were delineated by a single radiation oncologist using Varian Eclipse TPS station Version 13.0.1 (Varian Medical Systems, Sao Paulo).
Regardless of tumor stage and lymph node involvement, axillary levels I- II-III, supraclavicular region and internal mammary lymph nodes were retrospectively contoured in all cases, according to radiation therapy oncology group (RTOG) breast cancer atlas.
The contralateral breast, heart, lungs were delineated as organs at risk (OAR). Dose constraints for OAR are shown in Table 1. For whole breast radiation planning, PTV-total (PTV-breast and PTV-lymphatic) included ipsilateral breast, axillary levels I- II- III, and supraclavicular lymphatic (except internal mammary lymph nodes ) with a 3 mm expansion and the PTV-boost included lumpectomy cavity with a 10 mm expansion limited to 3 mm from the patient’s surface. The prescribed doses were 50 Gy to PTV-total and 60Gy to PTV-boost at 2Gy per fraction. The IMLN field was delineated in every patient to cover the first three intercostal spaces extending to the margin of the 4th rib. The margins of IMLN were defined as a distance of 5 mm mediolaterally and 2 mm anteroposteriorly around the vessels. A PTV-total was created excluding the IMLN field in every patient as described above, and two different plans were designed for each patient to receive the defined target doses using both conformal and IMRT techniques. The incidental IMLN field dose distributions in the conformal and IMRT plans were compared in regards to the D95, Dmax., Dmin., Dmean, V40, V45, V47.5, and homogeneity index (HI) values. The HI was calculated according to the (D2-D98)/Dp formula. The DVH parameters, on which the plans were based, are presented in Table 2. A boost plan to be directed to the lumpectomy cavity was designed in each patient to ensure that the closest doses to real ones would be received by the adjacent tissues. Radiotherapy Planning:
3DCRT plans with field-in-field technique
A single isocentric treatment approach was used in this planning. For this purpose, two parallel tangential fields covering the target breast tissue together with the regional lymphatics (level I-II-III) and two opposing anterior-posterior (AP) parallel fields covering the supraclavicular region were used. The isocenter of these four basic fields was primarily located inferior to the clavicular head. Then the isocentre was revised to match it inferiorly to the field, as it was predicted that the tangential field distance would be a maximum of 20 cm on the superior-inferior plane when the jaw was completely closed and located superiorly to the isocenter. Gantry angles of the tangential fields were determined, selecting the angles to show none or the least of the posterior breast tissue volume in the “beam’s eye view”. The source-to-skin distance (SSD) on the forehead was equalized on both sides. The tangential field distance was set to zero for superior jaws, but a 2 cm-width was set at the outer margin of the PTV inferiorly to compensate the respiratory motion. The subfields were created within the total calculated field with MLCs, primarily to cover the volumes receiving a dose over 110% and then to reduce the volumes subject to doses 107% and 105%. The sum of the weights of the subfields was designed in such a way that it would not be over 20% of the weight of each plan.
Seven-Field Inverse IMRT Plans
Seven fields were used in inverse IMRT plans, created at the gantry angles of three internal and three external tangential fields and one vertical field with respect to PTV breast. After the tangential areas used in 3DCRT plans were diverted externally in the range of 5-15 degrees, two more areas were selected, directed internally at 15-20 degrees. The last field was selected at an angle so that it would be positioned perpendicularly. The coach angles were set to zero in the field configurations. Aligning all created fields to the point where all targeted PTVs were intersected, the centre of gravity for the total PTV was selected to be the isocenter. Fluence smoothing of all fields was designed to be proportional to the maximum and minimum optimization priority values defined for PTVs. In addition, normal tissue optimization was set to equal values to those of the PTV priority values in the automatic mode. Statistical methods:
Frequencies and statistics were performed using SPSS 20 (SPSS Inc.) statistical software. The statistically significant threshold was accepted as p=0.05. As the data set was not distributed normally, the Wilcoxon signed rank test was used to compare the doses delivered by the conformal and IMRT plans to the IMLN regions.
Results
The long and short median diameters of the target volume of IMLN were 1.5 cm and 0.8 cm, respectively, based on the anatomical section. The median height of the patients was 160 cm (range: 141-168 cm) and their median body weight was 73 kg (range: 43-125 kg). The median volume of the breast tissue was 1200cc (range: 443-2339 cc). According to the body mass index (BMI) classification, 33% of the patients were obese or extremely obese. The median BMI was 29 (range: 21-46). The doses received by the target volumes and organ-at-risk (OAR) doses are presented in Table 1.
The incidental distributions of D%95, D%98, D%2, maximum dose, minimum dose, mean dose, V40, V45, and V47.5 in IMLN were found to be significantly lower in the IMRT plans compared to the conformal plans (Figure 1). The homogeneity of the incidental dose distributions was found to be more favorable in the conformal plans in 63% of the patients compared to IMRT plans, however, no statistically significant difference was observed (Figures 2, 3).
Discussion
IMLN positivity reaches 40-65%, especially in the presence of centromedial localization, axillary involvement or large tumor. Furthermore, the involvement of IMLN reached a “5-7%” rate even in an N0 disease [4]. Such factors strengthen the rationale of applying an elective IMLN RT [3,5-7]. However, the RT field widens by including the IMLN area, leading to increases in toxicity primarily in the heart and lungs [1]. The incidence of adverse coronary events has been reported to increase by 7.4% with an increase in one Gray unit in the mean dose to which the heart was exposed [8]. Furthermore, IMNL RT has been shown to be associated with an 18%-increased risk of coronary artery disease compared to a 7% increase in breast radiotherapy without IMLN RT [9]. These findings have long caused the MILN RT indication to be decided cautiously and limitedly. In addition, the prevalence of recurrence in the IMLN field is 1% [10], with the conformal RT technique, which has a common use today. This recurrence rate was associated with the incidental IMLN doses received during the breast radiotherapy [3]. Due to these reasons, the evaluation of the doses to which the IMLN area was exposed, has always been a subject of primary importance, even in selected patients, in whom the IMLN area was not included in the target treatment field in the RT plans.
In the MA 20 study [11], one of the studies providing the strongest evidence for the importance of MILN field RT, showed favorable results in DFS (77% vs 82%, respectively) and regional recurrence rates (2.7% vs 0.7%, respectively) in patients receiving IMLN + SCV + Level- III irradiation compared to the remaining patients who did not receive this treatment at an early stage of the disease with 1-3 positive nodes or in the node-negative patients with T2-T3 unfavorable disease (disseminated LVSI, inadequate axillary dissection, etc.). In EORTC 22922 [12], patients with positive axillary lymph nodes or patients with central/medial tumors were examined based on the treatment with IMLN + SCV RT. The study reported that the mortality of breast cancer was reduced, and the DFS and distant DFS rates were improved. With the addition of improved OS rates, these results were highlighted in a meta- analysis, including a French study, too [13], In the light of these randomized studies, the NCCN (National Comprehensive Cancer Network) guidelines were updated, strongly considering the irradiation of the regional lymph nodes, including the IMLN region, in the patients who underwent breast-conserving surgery and had 1-3 positive lymph nodes. Furthermore, even in patients with central/medial tumors without any positive lymph nodes or in patients having a tumor size larger than 2 cm with disseminated LVSI, the importance of “regional nodal RT” was stressed. This is a major milestone in the evolution of breast cancer radiotherapy. In the near future, we may even discuss the usefulness of IMLN RT intensively in some selected node-negative patients or patients with micrometastatic involvement, as well as patients with 1-3 positive lymph nodes.
Radiotherapy planning is a major challenge for the treatment team in widely separated large-volume breasts, in which homogeneity is difficult to achieve in daily practice. In these patients, IMRT provides a more homogeneous dose distribution in this type of breast tissue having a characteristic convex anatomical structure. Despite the long planning time and associated high costs, the use of IMRT has gradually become more common owing to the benefits including the esthetic/ long- term cosmetic effects, reduction in the cardiac dose, and lower acute or late toxicity [14,15]. However, we must realize during the evolution of RT practices that more effective elimination of the microscopic disease associated with the incidental doses of the 3D conformal therapy may not be achieved with IMRT, because, based on the algorithm plans, the reduction in the dose is faster at the margins of the treatment field in IMRT, compared to the conformal therapies [4,16]. Therefore, it is anticipated in the patients receiving IMRT that IMLN area will receive lower doses along with the adjacent tissues. Therefore, at least in the planning phase, it would be beneficial to contour the IMLN site to review the received incidental doses, even though it is not included in the PTV, especially for the grey-zone patients with relatively high risk; these reliable IMLN doses in the conformal therapy might lose their effect in IMRT. This condition reminds the question of whether an increase in the recurrence rates will occur in IMLN in the near future.
The results of our study supported a positive answer to this question. Several previous results are available in the literature examining the incidental doses received by IMLN during 2D or 3D conformal therapies [17-19]. Despite the limitations, our study is one of the first studies to investigate the incidental doses of IMRT and to compare their distribution with those of conformal RT. The patient population in our study included patients with a larger volume of breast and high BMI, in whom homogeneity was difficult to achieve in daily clinical practice, so we tended to apply IMRT. The median breast volume in the study patients was 1200cc (443-2339 cc). According to the the BMI classification, 33% of the study patients were extremely obese. IMRT is preferred more in these patients, in whom RT planning is challenging and dose constraints are difficult to achieve. Within this scope, we may emphasize that the incidental doses received by the OAR and IMLN were close to the ones applied in real clinical practice. The incidental dose distributions in the IMRT plans in our study was significantly lower in terms of D%95, D%98, D%2, maximum dose, minimum dose, mean dose, V40, V45, and V47.5. Thus if we discuss the enhancing benefits of the IMLN field RT, and, in the light of the randomized studies, if we recognize the benefits of IMLN field RT in some selected subgroups of patients with 1-3 positive nodes, or even the ones without positive nodes, we may conclude that we must exercise extra care in observing the doses received by the IMLN field in IMRT plans, or we must consider including this region to PTV and not rely on the incidental doses to be received in the presence of robust indications. Unfortunately, robust data on the recurrence rates in the IMLN field are not available today as IMLN field is excluded from PTV in current IMRT practice. In order to be able to conclude stronger recommendations, further large-scale studies providing more robust data are required. Conclusion:
In light of the results of large-scale randomized studies, it has been observed that the inclusion of the internal mammary lymph node area to RT plans is associated with reductions in local or distant overall recurrence rates and cancer-related mortality rates, especially in the early-stage breast cancer [11,12,20]. Associated treatment benefits have been reported in patients with 1-3 positive axillary nodes or even in patients without axillary node involvement but having the tumor centrally or in the inner quadrant, as well as benefits observed in patients with four or more positive lymph nodes [21,22]. This is a promising result in the sense that the local benefits of IMLN field RT can be observed in larger patient subgroups. Particularly in patients with the involvement of 1-3 nodes or in the high-risk patients without positive nodes (such as central/medial location, T2-3 tumor, etc.), it is more important to achieve a balance between the benefits of RT on survival rates, DFS, and LC rates; and its potential pulmonary or cardiac, etc. toxicity. In this context, it will be useful to consider that, with IMRT in breast cancer radiotherapy, there may be a potential of increased recurrence rates in the internal mammary lymph nodes area compared to the rates observed in the conformal technique due to the lower doses received by the adjacent tissues. Therefore, contouring the IMLN area and a careful evaluation of the doses to which this area is exposed will provide treatment benefits.
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. Nikolaevich NS, Vasilevich KS. Why do we need irradiation of internal mammary lymph nodes in patients with breast cancer: Analysis of lymph flow and radiotherapy studies. Rep Pract Oncol Radiother. 2017;22(1):37-41.
3. Vrana D, Gatek J, Cwiertka K, Lukesova L, Koranda P. Internal mammary node management in breast cancer. A review.Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2013;157(3):261-5.
4. Intensity Modulated Radiation Therapy Collaborative Working Group. Intensity- modulated radiotherapy: current status and issues of interest. Int J Radiat Oncol Biol Phys. 2001; 51(4):880-914.
5. Leidenius MH, Krogerus LA, Toivonen TS, Leppänen EA, von Smitten KA. The clinical value of parasternal sentinel node biopsy in breast cancer.Ann Surg Oncol. 2006; 13(3): 321-6.
6. Van der Ent FW, Kengen RA, van der Pol HA, Povel JA, Stroeken HJ, Hoofwijk AG. Halsted revisited: internal mammary sentinel lymph node biopsy in breast cancer. Ann Surg. 2001;234(1):79-84.
7. Heuts EM, van der Ent FW, von Meyenfeldt MF, Voogd AC. Internal mammary lymph drainage and sentinel node biopsy in breast cancer – A study on 1008 patients. Eur J Surg Oncol. 2009;35(3):252-7.
8. Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Brønnum D, et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med. 2013;368(11):987-98.
9. Harris EE, Correa C, Hwang WT, Liao J, Litt HI, Ferrari VA, et al. Late cardiac mortality and morbidity in early-stage breast cancer patients after breast- conservation treatment.J Clin Oncol. 2006;24(25):4100-6.
10. Xie L, Higginson DS, Marks LB. Elective regional nodal irradiation in patients with early-stage breast cancer. Semin Radiat Oncol. 2011;21(1):66-78.
11. Whelan TJ, Olivotto IA, Levine MN. Regional Nodal Irradiation in Early-Stage Breast Cancer. N Engl J Med. 2015;373(19):1878-9.
12. Poortmans PM, Collette S, Kirkove C, Van Limbergen E, Budach V, Struikmans H, et al. EORTC Radiation Oncology and Breast Cancer Groups. Internal Mammary and Medial Supraclavicular Irradiation in Breast Cancer. N Engl J Med. 2015;373(4):317-27.
13. Budach W, Bölke E, Kammers K, Gerber PA, Nestle-Krämling C, Matuschek C. Adjuvant radiation therapy of regional lymph nodes in breast cancer -a meta- analysis of randomized trials-an update. Radiat Oncol. 2015;10:258.
14. Freedman GM, Anderson PR, Li J, Eisenberg DF, Hanlon AL, Wang L, et al. Intensity modulated radiation therapy (IMRT) decreases acute skin toxicity for women receiving radiation for breast cancer. Am J Clin Oncol. 2006;29(1):66-70.
15. Yang Z, Zhang L, Chen X, Ma J, Mei X, Chen J, et al. Multibeam inverse intensity-modulated radiotherapy (IMRT) for whole breast irradiation:a single center experience in China. Oncotarget. 2015;6(33):35063-72.
16. Caudrelier JM, Meng J, Esche B, Grimard L, Ruddy T, Amjadi K. IMRT sparing of normal tissues in locoregional treatment of breast cancer. Radiat Oncol. 2014;9:161.
17. Leite ET, Ugino RT, Santana MA, Ferreira DS, Lopes MR, Pelosi EL, et al. Incidental irradiation of internal mammary lymph nodes in breast cancer: conventional two-dimensional radiotherapy versus conformal three-dimensional radiotherapy. Radiol Bras. 2016;49 (3):170-5.
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Necla Gurdal, Selami Eken, Ugur Akbayırlı, Neslihan Kurtul. Are incidental IMRT doses to internal mammary lymph nodes reliable enough, as they were in the past with conformal RT in breast cancer? Ann Clin Anal Med 2021;12(7):804-808
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Relationship between resting VO2max consumption, functional independence, and physical activity levels in mothers of children with immobile cerebral palsy
Fatih Tekin 1, Furkan Bilek 2
1 Pamukkale University, School of Physical Therapy and Rehabilitation, Denizli, 2 Department of Physiotherapy and Rehabilitation, Fırat University, Faculty of Health Sciences, Elazığ, Turkey
DOI: 10.4328/ACAM.20452 Received: 2020-12-23 Accepted: 2021-02-01 Published Online: 2021-02-10 Printed: 2021-07-01 Ann Clin Anal Med 2021;12(7):809-813
Corresponding Author: Fatih Tekin, Pamukkale University, School of Physical Therapy and Rehabilitation, Denizli, Turkey. E-mail: fzt.ftekin@hotmail.com P: +90 258 2964264 Corresponding Author ORCID ID: https://orcid.org/0000-0001-7829-7957
Aim: In the current literature, there is no study investigating the relationship between oxygen consumption in children with Cerebral Palsy (CP) and the physical activities of their parents. In this study, we aimed to investigate the relationship between resting VO2max consumption and functional independence and physical activity levels in mothers of children with immobile CP.
Material and Methods: Thirty cerebral palsied cases (F:16, M:14) with a mean age of 6.63±2.68 years (3-12 years) were included in the study with their mothers. Registration forms were filled out for each case. Children were evaluated with the Functional Independence Scale for Children (WeeFIM). Resting VO2max measurements were performed with the Cosmed Fitmate Protm device. International Physical Activity Questionnaires (IPAQ) were completed for mothers.
Results: There are no statistically significant differences between the mean resting VO2max values of quadriplegic and diplegic CP cases (p>0.05), and there are no statistically significant differences in mean resting VO2max values of the cases with CP in terms of gender (p>0.05). There is a significant correlation between resting VO2max values of patients with CP and their mothers’ physical activity levels (p<0.05). Likewise, there is a significant correlation between functional independence levels in daily living activities of patients with CP and their mothers’ physical activity levels (p<0.05).
Discussion: Physical activity levels of mothers with CP are lower in all areas compared to mothers who do not have a disabled child. Resting VO2max values and functional independence of children with CP are better in mothers with high physical activity levels.
Keywords: Cerebral palsy; Physical activity; Functional independence; Oxygen consumption
Introduction
Cerebral Palsy (CP) is a permanent disorder of motor function, posture and movement development that occurs due to a non-progressive lesion in the brain in the maturation period, but can change with age and cause limitations in activities. Sensory, cognition, communication, perception, epilepsy, behavioral disorders and secondary musculoskeletal problems may accompany this motor disorder [1]. As a result of all these problems, children’s functional independence levels may decrease in daily life [2]. Some cases with CP may also be immobile due to these problems [3]. As a result, problems such as a decrease in muscle strength and mass, decrease in bone mineral density, various orthopedic problems and decrease in resting VO2max may occur secondary to immobilization [4-6]. Alterationsofthecentralnervoussystem,whichproducethe characteristic features of CP, result in functional deviations that require greater oxygen consumption than typical functions. For this reason, oxygen consumption can be considered a useful tool for the assessment of functional ability, because its interpretation provides an indication of endurance, fatigue and ability to accomplish routine daily tasks. Then, quantification of the oxygen consumpted while resting and doing daily tasks can provide objective data in order to help evaluation of patients with walking and other locomotor system disabilities and help assess the effectiveness of therapeutic interventions, such as ambulatory aids, orthotic prescriptions, physical therapy or surgery [7].
VO2max is the maximum level of O2 usage per minute in liters with exercise. Resting VO2max is the maximum O2 usage level per minute by a person in a sitting position and resting state without any physical activity [8]. Resting VO2max can provide information with physical activities [9].
It has been shown that the contribution of parents in the process of caring for a child with CP is important in the treatment process and affects the success of rehabilitation [10]. There are studies showing that the inclusion of parents in the treatment process increases success [11]. However, in the current literature, there is no study investigating the relationship between the resting VO2max consumption by a child with CP and the physical activity levels of the parents.
The aim of this study is to investigate the relationship between resting VO2max consumption and functional independence and physical activity levels in mothers ofchildren with immobile CP.
Material and Methods
This study was conducted at Fırat University Hospital and was done in March 2020. The study, which was conducted according to the principles stated in the Declaration of Helsinki, was ethically appropriate and it was decided by Fırat University Non-Invasive Research Ethics Committee with the number of 97132852/050.01.04.
Study Design and Cases
This study is a prospective and cross-sectional study. Thirty children and their mothers who met the inclusion criteria were included in the study. While the inclusion criteria for the study were diagnosis of CP in children, the ages from 2 to 18, and the inability to provide independent ambulation, the exclusion criteria were the presence of another neurological disease and the presence of a disease that would affect resting oxygen consumption. For mothers, the inclusion criterion was living with the child, while the exclusion criterion was the presence of any disease that could affect the level of physical activity. Participation in the study was voluntary, and consent forms were obtained from all subjects for participation in the study. Thirty cases (F:16, M:14) whose mean age was 6.63±2.68 years (min-max: 3-12 years), were included in the study with their mothers.
A registration form containing various clinical and demographic data was filled in for the cases with CP included in the study, and they were evaluated with the Functional Independence Scale for Children (WeeFIM). Then, resting VO2max measurement was performed with the Cosmed Fitmate Protm device. The International Physical Activity Questionnaire (IPAQ) was completed by the mothers of the cases. The data obtained were analyzed.
Evaluations
Demographic Data Form
Demographic data forms were filled in, containing the age, height, weight, gender and clinical type of the children with CP and the maternal age.
Resting VO2max Measurement
The measurements were made with the Cosmed Fitmate Protm device. Before taking the measurement, the children were kept in a sitting position for at least 20 minutes. Afterwards, resting VO2max was measured for 10 minutes. The highest VO2 value seen in this 10 minute period was recorded. Care was taken to ensure that the children did not exercise heavily in the last 24 hours before the time of measurement and their sleep patterns were not disturbed. Figure 1 shows the Cosmed Fitmate Protm device and the application position for resting VO2max measurement (available at: www.cosmed.com/en/products/ cardio-pulmonary-exercise-test/fitmate-pro).
Functional Independence Measure for Children
It was created in 1993 using the Functional Independence Scale (FIM). It is a useful, short, comprehensive measurement method [12] that determines developmental, educational and social functional limitations in children with CP and other developmental disorders.
Functional Independence Measure for Children (WeeFIM) includes a total of 18 items in 6 areas: self-care, sphincter control, transfers, locomotion, communication, social and cognitive. In this sense, it is an effective measure that is widely used in the evaluation of transfers and locomotion, providing posture smoothness and balance in children with CP. While performing the function in each item in the areas evaluated, the child’s abilities of whether he received assistance, on time, or whether an assistive device was required are scored from 1 to 7. A score of 1 is given when the child performs the task with a complete help, and 7 points when the child does it independently and safely. Accordingly, a minimum of 18 (fully dependent) and a maximum of 126 (fully independent) points can be obtained [13].
International Physical Activity Questionnaire
The International Physical Activity Questionnaire (IPAQ) was first developed in Geneva in 1998 in order to determine the level of physical activity that individuals reported, and in 2003, it created the idea that it could be used in the international arena with validity and reliability studies in 12 countries [14]. The short-form version of the IPAQ, which validity and reliability in Turkish was performed by Öztürk et al. in 2006, consists of 7 questions [14, 15].
IPAQ provides information about the walking activity, the time they spend in moderate and vigorous activities, and the time they spend while sitting. In order to calculate the total score of the IPAQ form, it is necessary to determine the total number of days in minutes and weekly days of walking activity, moderate activity and vigorous activity. The total energy expended for the activities is calculated with the MET-minute score. Classification according to the calculation of the total MET-minute/week = (walking + moderate + vigorous + sitting) MET-minute/week is as follows:
1. Inactive Category: The lowest level of physical activity is in this group.
2. Minimal Active Category: Those that meet any of the criteria below are defined as minimal active.
a. Vigorous activity for a minimum of 3 days and a minimum of 20 minutes.
b. Moderate intensity activity or walking activity for a minimum of 30 minutes per day at least 5 days a week
c. At least 5 days a week, a combination of walking activity and moderate-intensity activity at a minimum of 600 MET-minutes/ week.
3. Very Active Category: Equal to moderate activity for at least an hour or more per day. This is the level of activity required to see the health benefits of physical activity.
a. Vigorous activity at least 3 days a week, equivalent to a minimum of 1500 MET-min/week
b. 7 or more days, a combination of walking activity, moderate activity, or vigorous activity at a minimum equivalent to 3000 MET-min/week [14-16].
Statistical Analysis
As a result of the samples taken from the current literature and the power analysis, it was calculated that when 25 cases were taken into the study, a 90% power would be reached with 95% confidence. The data were analyzed with the SPSS 25 (IBM SPSS Statistics 25 software (Armonk, NY: IBM Corp.)) package program. Continuous variables were given as mean ± standard deviation, and categorical variables as numbers and percentages. Relationships between continuous variables were evaluated using Spearman’s correlation analysis.
Results
The mean age of the patients with CP (F: 16 M: 14) included in the study was 6.63±2.68 years (min-max: 3-12 years), the mean weight was 27.8±11.18 kg (min-max: 12-52 kg), and the mean height was 111.6±14.99 cm (min-max: 83-139 cm). Mean BMI was calculated as 21.42±4.71 kg/m2. The mean maternal age was 37.83±4.42 years (min-max: 22-45 years).
Thirteen (43.3%) cases were quadriplegic and 17 (56.7%) were diparetic type.
The mean score of resting VO2max of the cases was 7,12±1,37 ml/kg/min (min: 4,7 – max: 9,7) and the mean score of WeeFIM was 65,2±14 (min: 38 – max: 97).
In Table 1, the mean resting VO2max values of quadriplegic and diplegic CP cases and the difference between them are given. According to Table 1, there is no statistically significant difference between the mean resting VO2max values of quadriplegic and diplegic CP cases (p>0.05).
In Table 1, the mean resting VO2max values of the cases and the difference due to gender are given.
According to Table 1, there is no statistically significant difference in the mean resting VO2max values of the cases with CP in terms of gender (p>0.05).
In Table 2, the maternal IPAQ scores are given according to their vigorous, moderate, walking and sitting activities.
Table 2 shows that there are mothers who have no moderate and vigorous activities. This is probably due to the burden of caring for a disabled child.
In Table 3, the relationship between resting VO2max values of the cases with CP and their level of independence in activities of daily living with the physical activity levels of their mothers is given.
According to Table 3, there are significant relationships between resting VO2max values of patients with CP and their mothers’ physical activity levels (p<0.05). Likewise, there are significant relationships between functional independence levels in daily life activities of patients with CP and their mothers’ physical activity levels (p<0.05).
Discussion
This study is important because it is the first study investigating the relationship between resting VO2max consumption in children with CP and physical activity levels of mothers. This study, which aimed to investigate the relationship between resting VO2max consumption and functional independence and physical activity levels of mothers in children with immobile CP, was completed with the participation of 30 patients with CP and their mothers. As a result, the resting VO2max consumption of children with immobile CP is lower than their healthy peers; It was observed that the physical activity levels of mothers were lower in all areas compared to mothers who did not have a disabled child. In addition, it was observed that children of mothers with lower physical activity levels were also more functionally dependent on daily living activities.
Consumption of VO2max and resting VO2max peaks between the ages of 17-21 in men, and then decreases with age. In women, it reaches its highest values between the ages of 12-15, and then decreases with age. In general, the values of VO2max and resting VO2max consumption of men are higher in all periods. Absolute, independent of body weight, VO2max values are lower in children than in adults. When expressed in proportion to body weight, the difference with adults decreases. While the average VO2max value is 50 ml/kg/min at the age of 5 in healthy boys and girls, it increases to 52 ml/kg/min in boys around the age of 9-10. In girls, it decreases to 45 ml/kg/min [17].
According to the data obtained from this study, the resting VO2max values of children with CP are much lower than their healthy peers. The mean resting VO2max of these patients, whose mean age was 6.63±2.68 years, was calculated as 7.12±1.37 ml/kg/min. Considering the fact that the cases are functionally dependent on their daily activities, it is understood that immobilization explains the low resting VO2max values. Information on the energy expended during walking by children with cerebral palsy can provide objective data to help assess ambulatory aids, orthotic prescriptions or surgical intervention [18]. Generally, the rate of oxygen uptake is used to measure energy expenditure, but heart rate is more easily measured and has been shown in adults to be an accurate and convenient estimate of energy expenditure [19]. Heart rate has also been suggested for estimating energy expenditure by normal and disabled children [20]. It is shown previously that there is a linear relationship between heart rate and oxygen uptake over a wide range of walking speeds for normal children and for children with cerebral palsy [21].
Although the mean resting VO2max value was higher in girls compared to boys, there was no significant difference between them. In this case, it can be interpreted that there is no difference in terms of gender between the resting VO2max values of the CP cases between the ages of 3-12.
According to the data obtained from this study, there is no difference between the resting VO2max values of quadriplegic and diplegic CP cases. Although it is expected that the physical capacity of diplegic patients is higher than quadriplegics, it is thought to be due to the greater effect of mobility on resting VO2max. The fact that all of the cases included in the study were immobile prevented this difference from occurring.
The energy expenditure index based on oxygen uptake (EEI) varied with walking speed, and the EEI curve reflects the energy requirements at various walking speeds. At slow speeds, the EEI for both groups of children was high, indicating poor economy. With increasing walking speed, the EEI decreased until an optimum range of maximum economy was reached. For normal children who could walk beyond this speed, the EEI increased, reflecting less economy at the fastest speeds. This pattern was the same for both the oxygen-uptake and heart- rate indices [22].
It was observed that the physical activity levels of mothers of the cases with CP included in the study were lower in all areas compared to mothers without a disabled child [23, 24]. Having a disabled child and taking care of him has led to this situation. Caring for a disabled child with a lower resting VO2max and less functional independence in daily living activities, compared to their healthy peers, causes a decrease in the level of physical activity. Supporting this situation, according to the data obtained from this study, there is a correlation between the physical activity levels of the mothers and the resting VO2max and daily living independence of their children. From another point of view, resting VO2max values and functional independence of children with CP of mothers with high physical activity levels are better. Therefore, it is necessary to advise mothers to increase their physical activity levels.
A mother who is more physically active and who is aware of the importance of physical activity will also provide care to a disabled child, as the high physical activity levels of mothers can positively affect the resting VO2max values of the child with CP and functional independence in daily life activities and factors such as being able to cope more easily with the burden of raising it.
The limitation of our study is that, first of all, we did not evaluate mothers’ working status or weekly working hours. Secondly, in order to generalize the results, the inclusion of different types of CP and a control group consisting of healthy children and their mothers into the study could make the study stronger. In addition, the objective of the measurements and the inclusion of more cases than the number of cases determined in the power analysis are the strengths of the study.
As a result, the resting VO2max values of children with CP are much lower than their healthy peers, and there is no difference in terms of gender. Likewise, there is no difference between the resting VO and diplegic types of CP. Physical activity levels of mothers with CP are lower in all areas compared to mothers who do not have a disabled child. This situation was caused by having a disabled child and taking care of him. The resting VO2max values and functional independence of the children with CP of mothers with high physical activity levels are better.
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. Rose J, Medeiros JM, Parker R. Energy cost index as an estimate of energy expenditure of cerebral-palsied children during assisted ambulation. Dev Med Child Neurol. 1985;27(4):485-90.
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22. Rose J, Gamble JG, Burgos A, Medeiros J, Haskell WL. Energy expenditure index of walking for normal children and for children with cerebral palsy. Dev Med Child Neurol. 1990;32(4):333-40.
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Effects of serum biochemical parameters on the prevalence of colon polyps
Muhammet Fatih Aydin
Department of Gastroenterology, Altinbas University, Bahcelievler Medical Park Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.20521 Received: 2021-02-05 Accepted: 2021-03-20 Published Online: 2021-04-02 Printed: 2021-07-01 Ann Clin Anal Med 2021;12(7):775-779
Corresponding Author: Muhammet Fatih Aydin, Altinbas University, Bahcelievler Medical Park Hospital, Department of Gastroenterology, Mahmutbey Dilmenler street, No:26, 34217, Istanbul, Turkey. E-mail: mdfatihaydin@gmail.com P: +90 212 604 01 00 F: +90 212 445 81 71 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6056-9360
Aim: Early detection of colorectal polyps is important to prevent malignant transformation. The levels of several metallic and hematologic parameters may be indicators of these polyps. The objective of this study was to investigate whether iron levels may indicate the presence of colorectal polyps.
Material and Methods: A total of 897 patients who underwent routine biochemical analysis and colonoscopy were retrospectively evaluated. Patients were grouped as polyp (-) and polyp (+) and further divided into two groups as those with neoplastic polyps and the patients with non-neoplastic polyps. The levels of iron, ferritin, hemoglobin, glucose, cholesterol, triglycerides and vitamin D were compared between the groups.
Results: Males accounted for 60.5% of all patients, and 39.5% were females. The mean age of the patients was found as 43.3±11.9 years. The mean iron (p=0.023), ferritin (p=0.002), cholesterol (p=0.008) and triglycerides (p=0.005) levels were significantly higher in patients with polyps compared to those without polyps. The mean iron (p=0.001), ferritin (p<0.001), hemoglobin (p<0.001) and triglyceride (p=0.007) levels were higher in the males compared to the females. The mean iron (p<0.001), ferritin (p<0.001) and cholesterol (p=0.020) levels were significantly higher in patients with neoplastic polyps compared to those with non-neoplastic polyps.
Discussion: Iron levels were elevated in individuals with colorectal polyps and further elevated in patients with neoplastic polyps. Determination of cut-off values of iron and other parameters in predicting colorectal polyps will enable early detection of colorectal polyps and proper intervention.
Keywords: Colorectal polyps; Neoplastic; Non-neoplastic; Iron; Ferritin; Hemoglobin
Introduction
Colorectal cancer (CRC) is the second most common cancer in women and the third most common cancer in men worldwide [1]. The incidence and the rate of mortality from CRC are increasing all over the world due to several reasons, including urbanization, sedentary life, smoking, excessive alcohol consumption, changed dietary habits and obesity. The pathogenesis of CRC has been well-defined and colorectal polyps play a major role in the etiology of CRC [2]. The association between colorectal polyps and CRC has been reported in epidemiological, clinical and molecular research [3].
Colorectal polyps can be defined as visible protrusions over the surrounding large intestine mucosa. They present as isolated, multiple or diffuse lesions. Colorectal polyps are histologically classified as neoplastic (adenomatous) and non-neoplastic. CRC mainly develops from adenomatous polyps through a process known as adenoma-to-carcinoma sequence [4]. Non- neoplastic polyps do not have malignant potential. Although all adenomatous polyps have malignant potential when detected early enough, most are benign. For polyps that develop into CRC, the time until the development of CRC is accepted as >10 years [5]. This gives enough time to clinicians to perform interventional strategies in order to prevent the transformation of the polyp into cancer [5]. Therefore, it is of paramount importance to start colonoscopy scans to detect colorectal polyps timely. It has been proven that early detection and resection the map of these polyps prevent mortality due to CRC [6].
In general, a routinely ordered blood test sometimes can give abnormal values in certain parameters. It is important to study blood parameters that can be associated with polyps. Screening of these abnormal parameters may help identify populations at high risk for colorectal polyps [7].
Determination of the association between blood parameters and the presence of colorectal polyps may be helpful in the timely intervention to and management of these polyps. However, publications on this issue are limited except for a few studies that have directly investigated the relationship between blood parameters levels and the presence of colorectal polyps [8, 9].
It is known that some metals are involved in the process of polyp formation [10]. Iron is one of the metals found abundantly in the colon. The number of studies in the literature demonstrating the relationship between iron levels and the presence of colorectal polyps is limited. Therefore, the objective of this study was to investigate the relationship between serum iron concentrations and colon polyps, and specifically, neoplastic polyps.
Material and Methods
Patients who presented to our hospital with gastrointestinal complaints and underwent colonoscopy between January 2018 and December 2019 were retrospectively evaluated. Data of the patients were obtained from the information processing system of the hospital. Patients who underwent metabolic panel test and colonoscopy were included in the study. Patients with a history of colorectal surgery, those with a personal or family history of colonic diseases including CRC and inflammatory bowel disease, patients with active infectious disease, rheumatic disease, those who were regularly using vitamin and/ or mineral supplements and patients with an elevated CRP level were excluded from the study. In addition, patients with missing data were also excluded. Patients’ demographic data such as age and gender, presence of polyps, type of polyps (neoplastic or non-neoplastic), serum levels of iron, ferritin, glycated hemoglobin (HbA1C), blood glucose, cholesterol, triglycerides, and vitamin D were recorded and analyzed.
For the metabolic panel test and serum biochemical analysis, after one-night fasting, blood samples were collected from all patients. Colonoscopy procedures were performed by an experienced endoscopist after bowel preparation with self- administration of 2-4 L of polyethylene glycol solution before the colonoscopy. The sufficiency of bowel preparation was assessed by the endoscopist based on the Boston Bowel Preparation Scale. The samples of all resected polyps were sent to the pathology laboratory for biopsy. Patients were divided into two groups as the patients with and without colon polyps. The patients with polyps were further divided into two groups as those with non-neoplastic polyps and the patients with neoplastic polyps that have malignancy potential. The obtained biochemical parameters were compared between these groups. Ethics Considerations
Before the beginning of the study, ethics approval was obtained from the local ethics committee of our hospital (Decision No: 71522473/050.01104/404; Date:10/07/2020). The study was conducted in accordance with the ethical guidelines of the Declaration of Helsinki.
Statistical Analysis
The data obtained in this study were statistically analyzed utilizing SPSS 23.0 software for Windows (SPSS Inc., Chicago, IL, USA). The normality of the data was evaluated with the Kolmogorov-Smirnov test. Non-normally distributed variables were compared between two groups using the Mann-Whitney U test. Numerical variables were expressed as mean ± standard deviation, median, minimum and maximum descriptive statistics, while categorical variables are given as frequency (n) and percentage (%). The p-values <0.05 were considered statistically significant.
Results
A total of 897 patients who underwent a colonoscopy procedure in our gastroenterology clinic due to various indications between January 2018 and December 2019 were included in this study. Among all patients, 543 (60.5%) were male. The mean age of the patients was 43.3±11.9 years.
Laboratory parameters were compared between the patients with polyps and those without polyps detected during the colonoscopy procedure. Accordingly, the mean iron level was found as 84.8±37.8 mg/dL (range: 5-256) in the polyp (+) and 71.2+30.8 mg/dL in the polyp (-) group. The mean iron level was statistically significantly higher in the polyp (+) group. In addition, the mean levels of ferritin, cholesterol and triglycerides were also statistically significantly higher in the polyp (+) group compared to the polyp (-) group. Whereas, the levels of HbA1C, glucose and vitamin D did not show a significant difference between the two groups. The comparison of the laboratory parameters between the two groups is given in Table 1.
The laboratory parameters included in the study were compared between male and female patients. The mean iron value was 86,5+32,5 (range: 5-181) for males and 71,3+39 (range: 12- 256) for females. The difference between male and female patients in terms of iron levels was statistically significant (p=0.001). In addition, mean levels of ferritin, hemoglobin, and triglycerides were also significantly higher in male patients.
Comparison of the laboratory parameters between male and female patients is shown in Table 2.
The mean iron and ferritin levels were also compared between the female patients with and without polyps. There was no statistically significant difference between them (Figure 1). The patients with polyps were further divided into two groups according to the classes of the polyps as neoplastic and non-neoplastic. The laboratory parameters were compared between these two new patient groups. Accordingly, the mean iron, ferritin and cholesterol levels were statistically significantly higher in the neoplastic group compared to the non-neoplastic group. Comparison of these three significant parameters between the two groups is given in Table 3.
Lastly, Figure 2 shows the mean iron levels in polyps (-), polyps (+) patients and those with neoplastic polyps.
Discussion
Metabolic abnormalities are often encountered in individuals with colorectal polyps [7]. Providing insight into the role of essential and non-essential elements involved in the development of polyps is of importance for better understanding of the transformation of colonic polyps into CRC. This can encourage researchers to focus on the elements involved in neoplastic polyps and provide an opportunity for more efficient management of CRC. Unfortunately, so far studies in the literature have focused on metal contents in colorectal cancer [11] and only reported rare data on metal contents of precancerous lesions, namely polyps.
Studies have suggested that high levels of iron increased the risk of CRC in humans through the formation of OH radicals and suppression of cellular immune functions [10]. Another proposed mechanism is that iron-induced oxidative stress and resultant antioxidant depletion, thus oxidant/ antioxidant balance promotes carcinogenesis [12]. Iron can accelerate oxidative damage in macromolecules, causing both inflammatory and neoplastic disorders. The concentration of iron is high in the colon, suggesting that this may be associated with the formation of polyps. Iron is involved in the biological function in both normal and cancerous tissue. Ferritin is a major iron storage protein, and its serum levels are associated with body iron stores [13].
In our study, we examined whether iron levels change in polyps, and specifically neoplastic polyps. We found significantly higher ironandferritinlevelsinthepatientswithpolypscomparedto those without. This result suggests that the level of iron that can be readily obtained as a laboratory parameter, may be an indicator of the presence of colorectal polyps. In a special article, Nelson reported the presence of an association between body iron stores and the development of precancerous lesions in the colon, namely colorectal polyps [14]. Alimonti et al. showed that polyp tissues had a higher level of iron compared to the healthy tissues [10]. Lorenzi et al. found a correlation between high serum ferritin levels and biological events that are closely related to colorectal tumors, such as the growth and proliferation of tumor cells [13]. In our study, iron and ferritin levels were also statistically significantly higher in patients with neoplastic polyps compared to the patients with non-neoplastic polyps. Kucharzewski et al. also reported higher iron levels in colorectal cancer than in polyps [15]. As clearly found in our study (Figure 2), iron levels showed an increase from normal to polyp tissues and then to neoplastic polyp tissues, suggesting that iron may play a role in the adenoma-to-carcinoma sequence of CRC. A cut-off value of iron level can be found with further studies to distinguish neoplastic polyps from non- neoplastic ones.
Hemoglobin, an iron-containing metalloprotein has been shown to be higher in patients with colorectal polyps [16]. In addition, some studies have shown elevated hemoglobin levels in metabolic diseases that are known to be associated with colorectal polyps, such as metabolic syndrome and non- alcoholic fatty liver [8, 17, 18]. In our study, although there was no significant difference between patients with and without colorectal polyps in terms of hemoglobin levels, these levels were significantly higher in patients with neoplastic polyps compared to those with non-neoplastic polyps. This finding may indicate that hemoglobin is involved more in malignant transformation of the colorectal polyp. Similarly, Kim et al. reported that elevated hemoglobin levels were useful in predicting the presence of adenomatous polyps [19].
In the present study, the levels of several metabolic and hematologic elements/parameters were also investigated in colorectal polyps. In addition to iron and ferritin, cholesterol and triglyceride levels were significantly higher in the patients with polyps, while glucose and vitamin D levels did not show statistical significance. Furthermore, cholesterol levels were also significantly higher in patients with neoplastic polyps compared to those with non-neoplastic polyps. The mean levels of iron, ferritin, hemoglobin, and triglycerides were also significantly higher in male patients. This might be caused by the higher overall incidence of colorectal polyps in men compared to women[20].Duetotheabundanceofmetallicandhematologic parameters that can play a role in the development of the polyp, studies have investigated a wide spectrum of parameters. A systematic review or a meta-analysis to compile the literature on this issue can be of benefit.
In a study by Yang et al., a weak correlation was found between lipids including vitamin D, and the presence of colorectal polyps [21]. Sun et al. studied serum albumin levels and found lower values in patients with colorectal polyps [22]. Magnesium has been shown to exert protective effects against the risk of adenomatous polyps [23, 24]. Alimonti et al. found increased levels of selenium and decreased values of copper and mercury in polyp tissues, while zinc and manganese levels remained unchanged [10]. These metabolic and hematologic parameters can readily be obtained with routine blood analysis, and determination of the association between some of these elements and colorectal polyps can enable developing risk stratification systems to be used in the early detection of colorectal polyps.
Study Limitations
The retrospective and single-center nature of this study may be considered the main limitation. However, the major objective of this study was to investigate the relationship between iron levels and polyps. The number of patients was satisfying for a study of such structure. Finally, given the scarcity of studies in the literature on this issue,we think that our results will be encouraging for future detailed research on metal contents of colorectal polyps.
Conclusions
The results of this study indicate that iron levels were elevated in individuals with colorectal polyps and further elevated in patients with neoplastic polyps. This should prompt clinicians to evaluate iron levels among the other metabolic and hematologic
laboratory parameters in patients suspected to have colorectal polyps. On the other hand, the determination of cut-off values of iron and other parameters in predicting colorectal polyps will be helpful in the development of new risk scoring systems, facilitating early detection of colorectal polyps. Further comprehensive studies are needed in order to enlighten the role of iron in the development of colorectal polyps and to support the findings of 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: 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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Fractionated stereotactic radiotherapy with Cyberknife® for primary spinal cord tumors
Ebru Atasever Akkas 1, Yildiz Guney 2
1 Department of Radiation Oncology, Medical Faculty of Saglik Bilimleri University, Dr.Abdurrahman Yurtarslan Oncology Research and Training Hospital, 2 Radiation Oncology Clinic, Memorial Ankara Hospital, Ankara, Turkey
DOI: 10.4328/ACAM.20668 Received: 2021-04-24 Accepted: 2021-06-18 Published Online: 2021-07-02 Printed: 2021-07-01 Ann Clin Anal Med 2021;12(7):780-783
Corresponding Author: Ebru Atasever Akkas, Department of Radiation Oncology, Medical Faculty of Saglik Bilimleri University, Dr.Abdurrahman Yurtarslan Oncology Research and Training Hospital, Ankara, Turkey. E-mail: eakkasatasever@gmail.com P: +90 532 0551977 Corresponding Author ORCID ID: https://orcid.org/0000-0003-4164-7196
Aim: This study aimed to evaluate the efficacy and safety of Cyberknife® (Accuray, Sunnyvale, CA, USA) fractionated stereotactic radiotherapy (FSRT) in pri- mary spinal cord tumors. The secondary aim is to present local control, post-treatment pain, neurological, and radiological response, and overall survival (OS) in the patients with spinal cord tumors.
Material and Methods: Fourteen patients with primary spinal cord tumors who underwent FSRT between July 2009 and October 2015 were retrospectively analyzed.
Results: The median dose delivered was 20 Gy (16-40), the median was 5 (3-6) fractions. The average follow-up period was 91 ± 40 months. After the treat- ment, in the evaluation of the first clinical response, it was determined that 5 (35.7%) patients had a decrease in symptoms, 6 (42.9%) patients were stable, 3 (21.4%) patients had no complaints. In the first radiological response evaluation, 2 (14.3%) patients had a complete response and 12 (85.7%) patients had a stable response. Vertebral compression fracture was detected as a late treatment side effect in one patient. According to the Kaplan-Meier analysis, the median five- and 10-year OS for patients with benign tumors was 115 months, 90% and 67.5 %, respectively; and the median five- and 10-year OS for the malign tumors patients was 76 months, 50 % and 25 %, respectively.
Discussion: FSRT appears to be a safe treatment modality, given the potential for late toxicity in patients with primary spinal cord tumors with high long-term survival rates, with few studies and limited follow-up time.
Keywords: Primary Spinal Cord Tumors; Cyberknife®; Fractionated Stereotactic Radiotherapy; Toxicity
Introduction
Primary spinal cord tumors are rare tumors that represent only 3% of all central nervous system malignancies. It frequently located intradural or intramedullary, which distinguishes them from spinal cord metastases that are anatomically extradural [1].
Localization, cellular types, growth pace of spinal tumors and neurological status at presentation are essential parameters that determine the prognosis.
Complete surgical resection should be considered for most primary spinal tumors except for spinal lymphomas, if it is technically safe and available. Generally, only complete resection is curative for patients with low-grade histologies. Definitive radiotherapy is considered in medically inoperable patients, or definitive resection cannot be performed by preserving neurological function. Radiotherapy is indicated for tumors that are often incompletely resected, for those with nerve root transplantation, for high-grade tumors regardless of the resection size, and for most recurrent tumors [2].
In this case, standard fractionated external beam radiotherapy (EBRT) is used, but the adequate therapeutic radiation dose cannot be given due to dose limitations to spinal cord. Most primary tumors require high radiotherapy doses above the known spinal cord tolerance dose. To limit potential toxicities, guidelines recommend the bioequivalent dose (BED 2 Gy equivalent fractions) of 50 Gy [3]. In this case, it was reported that local failure rates due to EBRT may be relatively high [4]. The mechanism of fractionated stereotactic radiotherapy (FSRT) is specific for spinal cord tumors and is entirely different from the EBRT mechanism. It creates more double-strand breaks in DNA, repairs minor DNA damage, and even has anti- vascular effects, in situ vaccine effects, and abscopal effects [5,6]. Therefore, stereotactic radiotherapy provides effective local ablation therapy, and thus increases local control of the disease and overall survival (OS).
This study aimed to evaluate the efficacy and safety of Cyberknife® (Accuray, Sunnyvale, CA, USA) FSRT in spinal cord tumors. The secondary aim is to present local control and OS in patients with spinal cord tumors.
Material and Methods
Patients
This retrospective study was approved by the Medical Specialty Training Board of Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital (approval decision number: 08.10.15/1).
This retrospective study included 14 patients treated for primary spinal cord tumors who applied to the University of Health Sciences and the Dr Abdurrahman Yurtaslan Oncology Training and Research Hospital of Radiation Oncology between July 2009 and October 2015.
Treatment
According to the localization of the primary spinal cord tumor, patients wore a head-neck mask (Radon® Thermoplastic IMRT-A Head Shoulder Mask) and for planning purposes, immobilization devices with 4-dimensional Computed Tomography (4DCT) without contrast and 1.5 mm slice thickness CT were used. Determination of the patients’ target volume (TV) was achieved by fusing the images obtained by 3 mm slice thickness magnetic resonance imaging (MRI) scanning. The contrast-enhancing lesion on the MRI was delineated as gross tumor volume (GTV). The planned target volume (PTV) was created by giving a 1 mm margin around the GTV from all directions. T2-weighted magnetic resonance images delineate the spinal cord 6 mm above and 6 mm below the defined TV.
All patients were treated with the Cyberknife® device. The X-sight spine and 6D skull tracking technique were used. The plan of cyberknife ® FSRT isodose line of the patients is shown in Figure 1.
CT of bone structure, MRI of soft tissue and PET-CT for metabolic activity were used to evaluate the radiographic response using the Updated Response Evaluation Criteria in solid tumors (RECIST) [7]. The first follow-up imaging method was performed approximately three months after FSRT. Clinical response was assessed concurrently with imaging follow-up. The 0-10 Numerical Rating Pain Scale (NRPS) was used to measure the pain response. In addition, various methods were used to assess neurological function, including the Medical Research Council (MRC) scale of 0-5 points for motor strength, the stinging test for numbness, the Romberg assessment for balance, and the test of the cranial nerves.
Statistical Analysis
All data were analyzed using the SPSS version 22 (IBM Corp., Armonk, New York, USA) statistical program. Descriptive statistics were calculated to determine the general characteristics of the groups. Frequency tables were used for ordinal variables, median and minimum/maximum values for non-normally distributed variables, mean ± standard deviation values for normally distributed variables. OS ratios were analyzed using the Kaplan – Meier method.
Results
The demographic and pathological features of the patients are shown in Table 1. A patient with recurrent (time of relapse after the first treatment was 62 months) medulloblastoma previously received RT to the craniospinal and posterior fossa. No surgery is considered in relapse, and FSRT is primarily applied in relapse. Chemotherapy was administered only to the case of recurrent medulloblastoma. Three patients with recurrent (relapse times after the first treatment are 48, 62 and 168 months, respectively) spinal ependymoma also received postoperative limited field-spinal RT in their initial treatments, and FSRT was performed as secondary irradiation.
After the treatment, when evaluating the first clinical response, it was determined that 5 (35.7%) patients had a decrease in symptoms, 6 (42.9%) patients were stable, 3 (21.4%) patients had no complaints. At the first radiological response evaluation, 2 (14.3%) patients had a complete response, and 12 (85.7%) patients had a stable response. Vertebral compression fracture was detected as a late treatment side effect in one patient. During the median follow-up period of 91 ± 40 months (calculated from the time of each patient’s first FSRT treatment), local recurrence occurred in 4 (28.6 %) patients.
According to the Kaplan-Meier analysis, the median, five- and 10-year OS for the benign tumors patients was 115 months (range: 25 -131 months), 90 % and 67.5 %, respectively, and the median five- and 10-year OS for the malign tumors patients was 76 months (range: 12 -85 months), 50 % and 25 %, respectively. The properties of FSRT treatment and critical organ doses are showed in Table 2.
Discussion
Due to the rarity of primary spinal cord tumors, there are few articles in the current literature on Stereotactic Radiosurgery (SRS) and FSRT for the treatment of these tumors. In our study, we aimed to evaluate the role of FSRT in the treatment of a limited number of patients with primary spinal cord tumors in our clinic.
Elibe et al., in their study on 30 patients with primary spinal cord tumors, reported SRS indication for pain in 19 (63.3%) patients, neurological deficit in 19 (63.3%), and asymptomatic only for radiological progression in 4 (13.3%) patients. Pain relief was observed in all patients presenting with pain during the follow- up of symptoms of patients who were given the median SRS dose of 16 Gy (10-24) (67% partial relief and 33% complete relief). In neurological deficit, it was reported that it was stable in 5 (31%) patients, and improvement was observed in 11 (69%) [8]. In a study conducted by Kufeld et al. with 39 patients with spinal meningioma and schwannoma, the median prescription dose of radiosurgery applied was 14 Gy. A decrease in pain level was reported in 8 of 19 patients with pain symptoms [9]. In our study, FSRT was indicated in 8 (57.1%) patients due to pain and 6 (42.9%) due to neurological deficit. These patients were monitored for symptoms. Partial symptom response was in 5 (35.7%) patients, stable response in 6 (42.9%) patients, and complete response in 3 (21.4%) patients.
Elibe et al., while providing local radiological control in 77% of the treated patients, they detected local-regional recurrence in 23% of them [8]. According to Kufeld et al., 19 lesions regressed in size, and 20 lesions were stable [9]. Chang et al. also reported their radiosurgery experience in 20 patients with 30 spinal cord lesions. Stereotactic radiotherapy/radiosurgery was applied in 1-5 fractions at doses of 14-33 Gy. While 57% of the lesions regressed, 33% were stable and 10% had progression [10]. Nineteen benign tumors were evaluated during a 25-month follow-up period after radiosurgery by Saghal et al. Tumor size was stable in 13 patients, regression in three patients, and progression in three patients. The patients who progressed were diagnosed with two neurofibromas and one hemangioblastoma [11]. In our study, while local radiological control was achieved in 71.4% of cases, local regional recurrence was detected in 28.6% of cases.
Elibe et al. found long-term toxicity in two patients, which is thought to be associated with SRS. One of these patients had erector spine radionecrosis (patient received 16 Gy for S1 desmoid tumor), and the other had foot drop (patient received 10 Gy for L1-L2 glioma). Sixteen vertebral compression fractures were observed, none of which were associated with SRS [8]. In our study, a compression fracture was detected in a patient with long-term toxicity, which we think is associated with treatment (the patient received 40 Gy / 5 fraction therapy for L2 chordoma).
In our study, the median, five- and 10-year OS for the benign tumors patients was 115 months, 90% and 67.5%, respectively, and the median, five- and 10-year OS for the malign tumors patients was 76 months, 50 % and 25%, respectively. The limitation of our study is the small number of patients with different tumor histology. However, according to the publications in the literature, the follow-up period is a lengthy study.
Conclusion
FSRT appears to be a safe treatment modality, given the potential for late toxicity in patients with primary cord tumors with high long-term survival rates, with few studies and limited follow-up time. Studies with a higher number of patients and long-term follow-up are needed.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or 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
1. Duong LM, McCarthy BJ, McLendon RE, Dolecek TA, Kruchko C, Douglas LL,et al. Descriptive epidemiology of malignant and nonmalignant primary spinal cord, spinal meninges, and cauda equina tumors, United States, 2004-2007. Cancer. 2012; 118(17):4220-7.
2. Kotecha RR, Bovi JA, Angelov L. Spinal Cord Tumors. In: Tepper JE, Foote RL, Michalski JM, editors. Gunderson & Tepper’s clinical radiation oncology. Philadelphia: Elsevier; 2021. p.551-70.
3. Schultheiss TE, Kun LE, Ang KK, Stephens LC. Radiation response of the central nervous system. Int J Radiat Oncol Biol Phys. 1995; 31(5):1093-12.
4. Boriani S, Saravanja D, Yamada Y, Varga PP, Biagini R, Fisher CG. Challenges of local recurrence and cure in low grade malignant tumors of the spine. Spine. 2009; 34(22 Suppl.):48-57.
5. Brooks ED, Chang JY. Time to abandon single-site irradiation for inducing abscopal effects. Nat Rev Clin Oncol. 2019; 16(2):123–35.
6. Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science. 2015; 348:69–74.
7. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009; 45(2):228-47.
8. Elibe E, Boyce-Fappiano D, Ryu S, Siddiqui MS, Lee I, Rock J, et al. Stereotactic radiosurgery for primary tumors ofthe spine and spinal cord. J Radiosurg SBRT. 2018; 5(2):107-13.
9. Kufeld M, Wowra B, Muacevic A, Zausinger S, Tonn JC. Radiosurgery of spinal meningiomas and schwannomas. Technol Cancer Res Treat. 2012; 11(1):27-34.
10. Chang UK, Rhee CH, Youn SM, Lee DH, Park SQ. Radiosurgery using the Cyberknife for benign spinal tumors: Korea Cancer Center Hospital experience. J Neurooncol. 2011; 101(1):91-9.
11. Sahgal A, Chou D, Ames C, Ma L, Lamborn K, Huang K, et al. Image-guided robotic stereotactic body radiotherapy for benign spinal tumors. The University of California San Francisco preliminary experience. Technol Cancer Res Treat. 2007; 6(6):595–604.
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Ebru Atasever Akkas, Yildiz Guney. Fractionated stereotactic radiotherapy with Cyberknife® for primary spinal cord tumors. Ann Clin Anal Med 2021;12(7):780- 783
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Effect of 4-prothrombin complex concentrate on mortality in patients presenting to the emergency department with warfarin-induced bleeding
Haydar Karahan
Department of Emergency Medicine, Ministry of Health Mardin Province Nusaybin State Hospital, Mardin, Turkey
DOI: 10.4328/ACAM.20700 Received: 2021-05-11 Accepted: 2021-06-29 Published Online: 2021-07-04 Printed: 2021-07-01 Ann Clin Anal Med 2021;12(7):784-787
Corresponding Author: Haydar Karahan, Department of Emergency Medicine, Ministry of Health Mardin Province Nusaybin State Hospital, Mardin, Turkey. E-mail: haydarkarahan@hotmail.com P: +90 532 135 87 36 Corresponding Author ORCID ID: https://orcid.org/0000-0002-5114-5969
Aim: Today, it has been observed that the increase in the use of vitamin K antagonists (VKA) causes various complications, from acute bleeding to death. Fresh frozen plasma and 4-prothrombin complex concentrate (4-PCC) are still used in the treatment of these patients. In our study, we aimed to investigate the effect of 4-PCC use on early mortality in patients presenting with bleeding due to VKA.
Material and Methods: Our study was conducted in a district state hospital with a retrospective and single-center design. It enrolled a total of 89 patients with a history of vitamin K antagonist drug use; patients with a history of trauma-induced hemorrhage or hematological disease were excluded.
Results: Out of 89 patients with a mean age of 71.00±10.79 years, 51.7% were male and 51.7% had a major hemorrhage and 48.3% had minor hemorrhage. Twenty-seven percent of the patients died despite treatment. The mean post-admission INR level was 9.48±5.8. Post-treatment and 24-hour INR levels were significantly lower in both patient groups treated with 4-PCC and FFP. It was determined that the administration of vitamin K did not lead to any significant difference in both patient groups treated with FFP and 4-PCC. Additionally, the treatment lasted 4 times longer, and the mortality rate was 4 times higher among patients treated with FFP than those treated with 4-PCC.
Discussion: We detected that the use of 4-PCC to reverse the anticoagulant effect will provide more rapid treatment, less volume loading, and lower mortality among patients using VKAs.
Keywords: Hemorrhage; Vitamin K Antagonist; Prothrombin Complex Concentrate
Introduction
Vitamin K antagonists (VKAs) are currently among widely prescribed medications. Many studies in the literature have reported that these agents effectively treat and prevent many thromboembolic events [1]. However, these agents have a narrow therapeutic range, which may cause complications [2,3]. These complications include major hemorrhages such as intracranial hemorrhage and gastrointestinal hemorrhage and minor hemorrhages such as epistaxis, gingival bleeding, and hematuria [4,5]. The risk of hemorrhage particularly increases when the international normalized ratio (INR) level rises above 5.0 [5]. Therefore, patients using these agents frequently present to the emergency department with hemorrhage [6]. There are times when rapid intervention is required in patients who present to the emergency department with VKA-induced hemorrhage. In some of these conditions, such as intracranial bleeding requiring surgery or massive gastrointestinal bleeding requiring interventional procedures, it may be necessary to reverse the effect of CVA [7]. Although vitamin K administration is part of the routine procedure in such patients, it may take up to 4 hours in intravenous administration and 24 hours in oral administration for INR starting to fall [8-10].
Currently, fresh frozen plasma (FFP) is widely used to reverse the effects of VKAs. However, FFP has some disadvantages such as long preparation time, risk of transfusion reactions, and volume loading [11,12].
Four-prothrombin complex concentrate (4-PCC) contains factor 7 in addition to vitamin K-dependent coagulation factors 2, 9, and 10 [11,13]. Whereas normalizing INR with FFP is often difficult and takes a long time, 4-PPC fulfills this task quickly and effectively [11,14]. 4-PPC has been used to reverse the effect of VKAs for a long time now. International guidelines also recommended the use of 4-PPC for an urgent reversal of INR in VKA-induced hemorrhage [15].
In this study, we aimed to investigate the effect of the use of 4-PCC on early mortality among patients presenting with VKA- induced hemorrhage.
Material and Methods
Study Design
Our study retrospectively recorded the medical data of successive patients older than 18 years of age who presented to the emergency department with VKA-induced hemorrhage. The study participants were those who were known to be previously administered VKA agents against thromboembolic events. Early in-hospital mortality was recorded from patient records during the hospital stay.
Study Settings and Population
This study was designed to be conducted between January 1, 2018, and January 1, 2020, in the emergency department of a district state hospital with a capacity of approximately 500 emergencies per day and 150 beds. The study population was composed of patients older than 18 years with complete medical records, who presented to the emergency with VKA- induced hemorrhage. A hemorrhage was detected by an emergency medicine specialist.
Our study design excluded patients with traumatic hemorrhage, a history of the hematological disease, and an unclear history of VKA use.
Patient records were obtained from the hospital automation system and medical records archive. In-hospital mortality was defined as death occurring within 7 days after hospital admission.
Study Protocol
Before the collection of the patients’ data, an ethics committee approval was obtained (ethics committee no. E-37201737- 806.02.02). Patients using VKA who presented to the emergency department with acute hemorrhage were retrospectively identified with the help of the hospital data management system. Their age, sex, indications for VKA use, and outcomes were recorded from the hospital data management system. The same system was also used to record the treatments administered to the patients (vitamin K, fresh frozen plasma (10mL/kg), and 4-PCC (50 IU/kg)) and their duration of administration, patient outcomes (admission to a regular ward, admission to intensive care unit, or discharge), and mortality data. All data were recorded on previously prepared study forms.
Statistical Analysis
SPSS (Statistical Package for Social Sciences) for Windows 20.0 software was used for the statistical analysis of all the data obtained. All data were summarized in tables during evaluation. The Mann-Whitney U test was used to compare the mean values of the data obtained, and the Pearson Chi- Square (and the Fisher’s exact test when required) was used to compare non-parametric data.
The results were considered significant at p<0.05, with a 95% confidence interval.
Results
Our study included 89 patients, of whom 43 (48.3%) were female and 46 (51.7%) were male. The mean age of the study population was 71.00±10.79 years. The indications for VKA use was a history of atrial fibrillation (AF) in 29.2% of the patients, valve replacement in 40.4%, cerebrovascular disease (CVD) in 10.1%, pulmonary thromboembolism (PTE) in 4.5%, deep vein thrombosis (DVT) in 6.7%, and other causes in 9%. Forty-five (51.7%) patients were found to have major hemorrhage and 44 (48.3%) had minor hemorrhage at emergency department admission. Among patients with major hemorrhage, 21 (46.6%) had intracranial hemorrhage, 20 (44.4%) had gastrointestinal system (GIS) hemorrhage, and 4 (8.9%) had a pericardial hemorrhage. Minor hemorrhage included hematuria in 18 (40.9%) patients and gingival hemorrhage in 26 (59.1%). Twenty-five percent of the patients died despite treatment (Table 1).
After admission, patients were evaluated, their laboratory tests were ordered, and treatment was started. The mean INR on admission was 9.48±5.8 (Table 1). VKA-induced bleeding was treated with 4-PCC (50 IU/kg) in 38.2% of patients and FPP in 61.8%. Vitamin K was administered to 44.9% of patients, but not to 55.1% of them. Patients treated with 4-PCC had a mean pre-treatment INR level of 8.68±5.51, a mean immediate post-treatment INR level of 1.91±0.93, and a mean 24th hour INR level of 2.44±1.31. Patients treated with FFP had a mean pre-treatment INR level of 9.98±5.96, a mean immediate post-treatment INR level of 3.03±1.53, and a mean 24th hour INR level of 2.88±2.10. An analysis of the change in INR levels showed that patients treated with FFP (10 mL/kg) had significantly lower post-treatment INR than the admission INR. Similarly, patients treated with 4-PCC also had a significantly lower post-treatment INR level than the admission INR. However, the analysis of the 24th hour INR levels showed a significant rise in the INR level in the 4-PCC group but not in the FFP group (Table 2).
An analysis of INR levels by the status of treatment with vitamin K showed a mean post-treatment INR level of 1.82±0.35 and a mean 24th hour INR level of 2.33 ±0.44 in patients treated both with vitamin K and FFP, and a mean post-treatment INR level of 1.20±0.22 and a mean 24th hour INR level of 1.87 ±0.35 in patients treated with FFP alone. Among patients treated with FFP, the mean post-treatment INR level and the mean 24th hour INR level showed no significant difference from the mean admission INR level with respect to the treatment with vitamin K (Table 3). An analysis of the INR levels by the status of treatment with vitamin K showed a mean post-treatment
INR level of 1.87±0.83 and a mean 24th hour INR level of 2.31 ±1.10 in patients treated with both vitamin K and 4-PCC, and a mean post-treatment INR level of 6.41±1.39 and a mean 24th hour INR level of 2.53 ±1.44 in patients treated with 4-PCC alone. Among patients treated with 4-PCC, the mean post- treatment INR level and the mean 24th hour INR level showed no significant difference from the mean admission INR level by the status of treatment with vitamin K (Table 3).
Comparison of post-treatment mortality rates showed a mortality rate of 36.4% among patients treated with FFP and only 14.4% in patients treated with 4-PCC, with the difference being statistically significant (p=0.031) (Table 1). In addition, comparison of the duration of administration revealed a significant difference between the 4-PCC treatment and the FFP treatment (Table 1).
Discussion
Warfarin is the most widely used VKA drug. It acts by preventing the synthesis of vitamin K-dependent coagulation factors (factor 2, 7, 9, 10), with effective anticoagulation being determined by the therapeutic INR range [16]. 4-PCC and FFP are among the current treatments for the reversal VKAs’ effects in patients presenting with acute hemorrhage. Our study showed that 4-PCC reduced admission INR level to lower post-treatment levels compared with FFP among patients using VKAs and presenting with acute hemorrhage. Demeyere et al. reported that 4-PCC provided a quicker and more effective reversal of VKAs’ effects compared with FFP in patients with a history of cardiopulmonary bypass [17]. Similarly, Hickey et al. detected that 4-PCC reversed the effect of VKAs more quickly and more effectively than FFP in the emergency department [18]. In addition to the treatment efficacy, the duration of the treatment also guides the clinician in the choice of treatment in patients with acute hemorrhage. Due to the need for blood group determination and longer preparation and infusion times, it is very unlikely for FFP to have a shorter duration of administration than 4-PCC. Hence, our study demonstrated a significantly shorter time to start 4-PCC treatment than FFP. Similarly, there is a consensus among prior studies in the literature that 4-PCC is associated with a shorter time to start treatment [19, 20]. Our findings support the literature data. Our study demonstrated that administering vitamin K did not cause any significant difference in INR reversal in patients treated with FFP or 4-PPC. In addition, we did not find any significant difference regarding whether the administration of vitamin K was a cause of rebound INR elevation in both FFP and 4-PCC groups. Comparison of the study groups in terms of volume overloading showed that FFP caused a greater volume load compared with 4-PCC. Therefore, we believe that 4-PCC would be beneficial in terms of volume overload. Our study found a mortality rate of 28.1% in our study population; of those who died, 20 patients were treated with FFP, and the remaining 5 with 4-PCC. Comparison of the mortality rates in both groups showed that the mortality rate was significantly lower in the 4-PCC group. We suggest that more rapid administration and less volume overload with 4-PCC caused this difference in mortality rates. In a nationwide study, Zeeshan et al. found that 4-PCC significantly increased survival among trauma victims [21].
Limitations
Our study has some limitations. Firstly, it was inevitable to have some missing data due to the retrospective nature of the study. Patients lost to follow-up may have died in other hospitals. Secondly, this was a single-center study, and thus our sample size was small. Lastly, physiological vital signs could not be used due to incomplete records at the time of admission. Conclusion
We concluded that the use of 4-PCC to reverse the anticoagulant effect among patients using VKAs will ensure a more rapid treatment, cause less volume overloading, and result in a lower mortality rate. We believe that FFP may be life-saving when 4-PCC is unavailable or contraindicated; otherwise, 4-PCC should be kept in mind as the first option for the treatment of patients with acute hemorrhage.
Acknowledgment
The author appreciate kind support of Ministry of Health Mardin Province Nusaybin State Hospital.
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
1. Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ, et al. Evidence-based management of anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012; 141(Suppl. 2):S152-84.
2. Hanley JP. Warfarin reversal. J Clin Pathol. 2004; 57(11):1132–9.
3. Schulman S, Beyth RJ, Kearon C, Levine MN. Hemorrhagic complications of anticoagulant and thrombolytic treatment: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition) Chest. 2008; 133(Suppl. 6):257-98.
4. van der Meer FJ, Rosendaal FR, Vandenbroucke JP, Briet E. Bleeding complications in oral anticoagulant therapy. An analysis of risk factors. Arch Intern Med. 1993; 153(13):1557–62.
5. Leissinger CA, Blatt PM, Hoots WK, Ewenstein B. Role of prothrombin complex concentrates in reversing warfarin anticoagulation: a review of the literature. Am J Hematol. 2008; 83(2):137–43.
6. Leendertse AJ, Egberts AC, Stoker LJ, van den Bemt PM. Frequency of and risk factors for preventable medication-related hospital admissions in the Netherlands. Arch Intern Med. 2008; 168(17):1890–6.
7. Levi M. Emergency reversal of antithrombotic treatment. Intern Emerg Med. 2009; 4(2):137–45.
8. Keeling D, Baglin T, Tait C, Watson H, Perry D, Baglin C, et al. Guidelines on oral anticoagulation with warfarin—fourth edition. Br J Haematol. 2011; 154(3):311– 24. DOI: 10.1111/j.1365-2141.2011.08753. x.
9. Lubetsky A, Yonath H, Olchovsky D, Loebstein R, Halkin H, Ezra D. Comparison of oral versus intravenous phytonadione (vitamin K1) in patients with excessive anticoagulation: a prospective randomized controlled study. Arch Intern Med. 2003; 163(20):2469–73.
10. Crowther MA, Ageno W, Schnurr T, Manfredi E, Kinnon K, Garcia D, et al. Oral vitamin K produces a normal INR within 24h of its administration in most patients discontinuing warfarin. Haematologica. 2005; 90(1):137–9.
11. Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G. Oral anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012; 141(Suppl. 2):S44–88. DOI: 10.1378/chest.11-2292.
12. Yang L, Stanworth S, Hopewell S, Doree C, Murphy M. Is fresh-frozen plasma clinically effective? An update of a systematic review of randomized controlled trials. Transfusion. 2012; 52(8):1673–86. DOI: 10.1111/j.1537- 2995.2011.03515.x.
13. Holland L, Warkentin TE, Refaai M, Crowther MA, Johnston MA, Sarode R. Suboptimal effect of a three-factor prothrombin complex concentrate (Profilnine-SD) in correcting supratherapeutic international normalized ratio due to warfarin overdose. Transfusion. 2009; 49(6):1171–7. DOI: 10.1111/j.1537- 2995.2008.02080.x.
14. Vigue B. Bench-to-bedside review: optimising emergency reversal of vitamin K antagonists in severe haemorrhage—from theory to practice. Crit Care. 2009; 13(2):209. DOI: 10.1186/cc7701.
15. Baker RI, Coughlin PB, Gallus AS, Harper PL, Salem HH, Wood EM. Warfarin reversal: consensus guidelines, on behalf of the Australasian Society of Thrombosis and Haemostasis. Med J Aust. 2004; 181(9):492–7.
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19. Jones CA, Petrozzino JJ, Hoesche J, Krol EM, Freeman K. Perceptions about time for normalization of international normalized ratio in patients requiring acute warfarin reversal when using fresh-frozen plasma. Am J Emerg Med. 2013; 31:878–79.
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Haydar Karahan. Effect of 4-prothrombin complex concentrate on mortality in patients presenting to the emergency department with warfarin-induced bleeding. Ann Clin Anal Med 2021;12(7):784-787
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Colonoscopy screening for colon polyps: Can it be useful at an earlier age for preventing malignant transformation?
Muhammet Fatih Aydin 1, Mehmet Akif Aydin 2
1 Clinic of Gastroenterology, 2 Clinic of General Surgery, Altinbas University Bahcelievler Medikal Park Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.20708 Received: 2021-05-18 Accepted: 2021-07-08 Published Online: 2021-07-10 Printed: 2021-07-01 Ann Clin Anal Med 2021;12(7):788-793
Corresponding Author: Muhammet Fatih Aydin, Clinics of Gastroenterology, Altinbas University Bahcelievler Medikal Park Hospital, Kultur Sok. No: 1 Bahcelievler, 34180, Istanbul, Turkey. E-mail: mdfatihaydin@gmail.com P: +90 505 774 55 52 F: +90 212 484 16 90 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6056-9360
Aim: The aim of this study was to investigate whether colonoscopy screening should be performed at an earlier age than specified in the current guidelines.
Material and Methods: Data of 1882 patients who presented to the gastroenterology clinic of our hospital and underwent colonoscopy were retrospectively evaluated. Polyps detected during colonoscopy were excised and sent to the pathology laboratory for histopathological examination. Patients were divided into two groups as <45 years old and ≥45 years old, and the data were compared between the groups.
Results: The most common indications for colonoscopy were abdominal pain in 40.6% of the patients, rectal bleeding in 18.6%, constipation in 14.2%, anemia in 10.5%, diarrhea in 3.1%, and other reasons in 6.8%. The rate of polyps was statistically significantly higher in patients aged ≥45 years (43.3%) compared to patients aged <45 years (32.1%). The rate of neoplastic polyps was statistically significantly higher in the group aged ≥45 years compared to the group aged <45 years. The most common localizations of polyps were rectum and sigmoid colon in all age groups.
Discussion: Based on our findings, we believe that the onset age of screening for colon polyps should be 45 years, as recommended by the updated guidelines. Also, colonoscopy screening should be performed in young adults without alarm symptoms who present with lower gastrointestinal complaints.
Keywords: Colon Polyps; Colonoscopy; Neoplastic; Hyperplastic; Age
Introduction
Colon polyps are considered a bridge to colorectal cancer (CRC) because of their potential for malignant transformation. Early detection and endoscopic removal are essential in the prevention of CRC. CRC is one of the most common cancer types in Western countries, with 446.000 new cases reported in Europe annually. The annual mortality from CRC is 214,000 for both sexes (available at: https://ecis.jrc.ec.europa.eu/). CRC cases are estimated to reach 1.36 million in men and 1.08 million in women worldwide by 2035 [1]. Recently, a change has been found in the incidence of polyps with increasing localization in the proximal colon in Western countries, accompanied by an increased number of sessile serrated polyps (SSP).
Most polyps are asymptomatic and remain unrecognized, but major clinical presentations in symptomatic cases include gastrointestinal bleeding, abdominal pain, intestinal obstruction, rectal prolapsus, and changes in bowel habits [2]. Polyps are histologically classified as neoplastic and non-neoplastic [3]. Non-neoplastic colon polyps may be inflammatory hyperplastic and cystic polyps, whereas neoplastic polyps can be benign such as tubular and tubulovillous adenomas or malignancies, and these polyps are precursors of colon cancers. Recent studies have shown that hyperplastic polyps at the right side of the intestines may have malignant potential and should be closely followed up [4]. These polyps have adenomatous components; they show a serrated, sawtooth-like surface epithelium and have BRAF mutations [5].
Colon polyps are curable if excised. If left untreated, patients may develop complications such as bleeding, and the condition may be fatal because of malignant transformation. Styrker et al. suggested that the risk of developing cancer because of sporadic colon polyps of 1 cm is 8% in 10 years and 24% in 20 years [6]. Therefore, removal of polyps is important to avoid the development of malignant polyps [7]. Interestingly, recent studies have reported an increase in the incidence of CRC in people younger than 40 years [8].
Colonoscopy is considered the best screening modality for colon cancer and adenomatous polyps by most gastroenterologists [9]. Current guidelines recommend that colonoscopy screening begin at 50 years of age and should continue until 75 years (available at: https://www.uspreventiveservicestaskforce.org/ Page/Document/UpdateSummaryFinal/colorectal-cancer- screening). Given the benefits of colonoscopy screening in adults and the increasing incidence of CRC in younger ages, there is a debate in the literature about whether colonoscopy screening for CRC should be started at an earlier age [10]. However, there is no empirical data on the effects of colonoscopy performed in patients <45 years of age.
The aim of this study was to investigate whether colonoscopy screening should be performed at an earlier age than specified in the guidelines.
Material and Methods
Study Design
The data of patients who presented to the gastroenterology clinic of our hospital due to various reasons, who had a positive stool screening test, and underwent colonoscopy from 2017 to 2019, were obtained from the hospital records and
retrospectively evaluated. Patients with a severe cardiac or hepatic condition, respiratory failure, hemodynamic instability and serious systemic diseases, those at an advanced stage of disease, patients with active gastrointestinal bleeding, and those with known colorectal cancer were excluded from the study.
Data Collection
Patient demographics such as age and sex, smoking and alcohol consumption status, presence of alarm symptoms (weight loss, anemia, etc.), and family history were recorded. Besides, indications for colonoscopy, bowel cleanliness, pathologic findings, presence of polyps, localizations of polyps, type, number, and size of polyps, and presence of dysplasia were recorded and analyzed.
Data Analysis
The data obtained were analyzed in detail. Colonoscopy procedures were performed by three experienced gastroenterologists. All polyps detected during colonoscopy were excised and sent to the pathology laboratory for histopathological examination. Polyp specimens were fixed in buffered formalin. Following staining with hematoxylin eosin, one or two sections of 4 μm were examined depending on the polyp size.
The patients were divided into two groups as <45 years old and ≥45 years old and data were compared between these two groups.
Ethical Considerations
Before the study, ethical approval was received from the local ethics committee of the Sakarya University Training & Research Hospital dated 07/10/2020 and 71522473/050.01.04/402 numbered decision. The study was conducted in line with the ethical principles of the Declaration of Helsinki.
Statistical Analysis
Statistical analysis was performed using the MedCalc Statistical Software version 12.7.7 (MedCalc Software bvba, Ostend, Belgium; http://www.melcalc.org; 2013). Continuous variables were expressed as descriptive statistics (mean and standard deviation). Categorical variables were evaluated using the Chi- Squared test and Fisher’s Exact test when necessary, and were expressed as frequency (n) and percentage (%). P<0.05 values were considered statistically significant.
Results
Demographic Data
A total of 1882 patients who underwent colonoscopy due to various reasons in the gastroenterology clinic of our hospital from 2017 to 2019 were included in the study; of all patients, 990 (52.6%) were male and 892 (47.4%) were female. The demographic data of groups are shown in Table 1. No significant difference was found between the groups in terms of age or sex (p>0.05).
The rate of smoking was found to be 13.9% in the group aged ≥45 years and 15% in the group aged <45 years. The rate of alcohol consumption was found to be 2.5% in the group aged ≥45 years and 3.9% in the group aged <45 years.
Colonoscopy Data
When data about colonoscopy procedures were examined, a family history was found in 124 (6.6%) patients and 1870 (99.4%) patients underwent their first colonoscopy. Table 2 shows bowel cleanness status, family history, number of colonoscopies, and whether colonoscopy was completed for both groups.
The most common indications for colonoscopy were abdominal pain in 40.6% of the patients (n=764), rectal bleeding in 18.6% (n=350), constipation in 14.2% (n=268), anemia in 10.5% (n=198), diarrhea in 3.1% (n=58), and other reasons in 6.8% (n=128). The distributions of colonoscopy indications according to the groups are shown in Figures 1 and 2.
Colonoscopy Findings
Colonoscopy examination was normal in 834 patients (44.3%), while pathologic findings were found in 1048 (55.7%). When all patients were evaluated, the most common pathologic findings were polyps (36.9%) and hemorrhoids (9.9%). The distribution of pathologic findings for both groups is presented in Table 3.
Localization of pathologic findings was in the rectum in 370 patients (19.6%), in the sigmoid colon in 216 (11.5%), in the descending colon in 136 (7.2%), in the transverse colon in 114 (6.1%), in the ascending colon in 104 (5.5%), and in the cecum in 62 (3.3%). Pathologic findings were observed in rectum in 19.2%, in the sigmoid colon in 16.4%, and in the descending colon in 10.2% of patients aged ≥45 years. Localization of pathologic findings was in rectum in 20% and sigmoid colon in 7.8% of patients aged <45 years.
Colonic polyps were found in 36.9% of all patients included in this study. The rate of polyps was statistically significantly higher in patients aged ≥45 years (43.3%) compared to patients aged <45 years (32.1%) (p<0.001).
Regarding the types of polyps detected during colonoscopy, in the group aged ≥45 years, neoplastic polyps were found in 178 patients, and non-neoplastic polyps were found in 170. In the group aged <45 years, neoplastic polyps were found in 114 patients, and hyperplastic polyps were found in 232. The rate of neoplastic polyps was statistically significantly higher in the group aged ≥45 years compared to the group aged <45 years (p<0.001). No statistically significant difference was found between the two groups in the incidence of non-neoplastic polyps (p=0.309).
Regarding the localizations of hyperplastic polyps, the most common polyp localizations were the rectum and sigmoid colon in all age groups. In patients under 45 years of age, we observed 6 tubular polyps in the rectum and sigmoid colon and 16 high- grade dysplasia polyps and 1 colon cancer in the ascending colon. In patients over 45 years of age, we found 34 high-grade dysplasia polyps and 2 colon cancers. The rate of having more than 3 polyps was found as 24.9% in patients aged ≥45 years and 18.1% in patients aged <45 years. The difference between the groups was statistically significant (p=0.002).
There was a statistically significant difference between patients aged ≥45 years and <45 years in the number of polyps found by three examiners. Accordingly, the number of polyps found by the first examiner was significantly higher compared to the second and third examiners (p<0.001). There was a statistical significance in the numbers of neoplastic and hyperplastic polyps found by the three examiners. The rate of detection of neoplastic and hyperplastic polyps was statistically significantly higher in the first examiner compared to the other examiners (p<0.001 for all). Colonoscopy durations were evaluated by an independent nurse and the mean colonoscopy duration was found to be longer in the first examiner compared to the other examiners.
The numbers of polyps were evaluated according to the demographic data of the patients. No statistically significant difference was found between the sexes in the number of polyps (p=0.088). Also, no significant difference was found in polyp numbers according to smoking or alcohol use (p=0.874 and p=0.488, respectively). Similarly, there was no significant difference in polyp numbers according to family history (p=0.222). Again, no significant difference was found between patients with and without alarm symptoms in terms of polyp numbers (p=0.306).
According to the results of the ROC analysis performed to determine the critical age that can pose a risk for the number of polyps, a cut-off value of 29.5 years was found to create a risk for a high number of polyps with a sensitivity of 98.6% and a specificity of 91.4% (AUC=0.590, p=0.018) (Figure 3).
Discussion
Most current international guidelines recommend the onset age of colonoscopy screening as 50 years of age in people with moderate risk. This is based on an increase of CRC incidence around 50 years of age. In 2009, the diagnosis of CRC was established in people aged 50 years and over by 90% [11]. In a study by Chen et al., one colonoscopy screening in an unscreened 50-65-year-old population was expected to prevent mortality from CRC by 49% [12]. In the Canadian Task Force on Preventive Health Care (CTFPEC) guidelines (Canada), colonoscopy screening onset age is recommended as 50 years, allowing postponing of screening until 60 years of age [13].
In 2018, US Preventive Services Task Force (USPSTF) updated the onset age of colonoscopy screening as 45 years in patients with moderate risk (available at: https:// www.uspreventiveservicestaskforce.org/Page/Document/ UpdateSummaryFinal/colorectal-cancer-screening). In Saudi Arabia, the onset age of colonoscopy screening is recommended as 45 years, because the diagnosis of CRC is made in 55 years of age in Saudi women and 60 years of age in Saudi men [14]. Studies in the literature have reported that the incidence of CRC is increasing in parallel with the increasing incidences of a sedentary lifestyle, obesity, and diabetes mellitus in young adults [10].
Studies from various countries have reported the incidence of CRC in people aged under 40 years. The incidence of CRC under 40 years of age was reported as 52% in a study from Pakistan [15], 39% in a study from India [16], and 22% in a study from Korea [17]. In a study from Turkey, the incidence of early-onset CRC was reported as 20% in people aged under 40 years [18]. On the other hand, the incidence of CRC under 50 years of age was reported as 10% in a study from the USA [19], while this rate was reported as 5% in a study from the UK [20]. It is seen that the incidence of CRC in young adults is higher in developing countries compared to developed countries. We attribute this to the fact that colonoscopy screening programs are more common in developed countries.
The European Society of Gastrointestinal Endoscopy (ESGE) recommends to evaluate bowel cleanness during colonoscopy, and appropriate or good cleanliness should be reported in at least 90% of screenings [21]. In our study, bowel cleanliness, which is among the factors affecting the quality of colonoscopy, was near 100% in all patients.
In a recent study, it was reported that at least 1 polyp was detected in 34.3% of patients undergoing colonoscopy screening [22]. Similarly, in our study, we found at least 1 polyp in 36.9% of patients undergoing colonoscopy.
In our study, the most common indications of colonoscopy in patients aged <45 years were abdominal pain in 43%, changed bowel habits in 21%, rectal bleeding in 20%, and anemia in 10%. In a study by Mikaeel et al. on colorectal cancer in young adults, indications for colonoscopy in patients aged under 50 years were found as rectal bleeding in 51%, abdominal pain in 16%, anemia in 16%, and changes in bowel habits in 13% [23]. We believe that although the indications in our study were similar to those of the mentioned study, the differences between the rates might have resulted from different sociocultural characteristics and lifestyles between the countries.
Based on the updated recommendations in recent guidelines for performing colonoscopy at an earlier age, we divided our patients into two groups as ≥45 years old and <45 years old, and evaluated the data again between these two groups. The presence of polyps and neoplastic polyps was statistically significantly higher in the ≥45- year-old group compared to the <45- year-old group. However, colonoscopy was performed in 1078 patients in the <45 -year-old group (52.3%), and pathologic findings were detected in 55.3% of these patients. In a study by Peñaloza et al. in 2017, a total of 411 colonoscopies were analyzed, and pathologic findings were observed in 44% of cases. The highest rate of pathologic findings was found in the 41-50-year-old age group [24].
In our study, the most common localization of pathologic findings was the rectum (19.6%), followed by the sigmoid colon (11.5%). In a study by Peñaloza et al., the most common localization was in the sigmoid colon as well [24]. Given that serrated adenomas are more common on the right side, the rate of pathologic findings detected in the sigmoid colon was remarkable. Also, recent studies have shown that hyperplastic polyps on the right side of the intestines may have malignant potential and should be closely followed up [4]. In our study, more than 5% of the hyperplastic polyps were localized in the cecum, ascending colon, and transverse colon on the right side. Overall, no statistically significant difference was found between patients with and without alarm symptoms (weight loss, anemia, etc.). This indicates that performing colonoscopy screening only in patients with alarm symptoms brought the possibility of missing polyps in other patient groups. Therefore, we think that colonoscopy screening should be performed not only in patients with alarm symptoms, but in all patients presenting with lower gastrointestinal complaints.
In our study, there was a significant difference between the numbers of polyps detected by the three examiners. Accordingly, the first examiner found a higher number of polyps than the other examiners. We believe this was the result of longer colonoscopy durations.
The ROC analysis was performed to determine the cut-off value for the age at risk for a high number of polyps. As a result of this analysis, a cut-off value of 29.5 years was found to create a risk for a high number of polyps with a sensitivity of 98.6% and a specificity of 91.4%. We think that this result suggests the importance of colonoscopy screening at an earlier age. Limitations of the Study
This study has some limitations. It has a retrospective design and was conducted in a single center. Longer term results could not be obtained. On the other hand, as a strength, it claims a younger age as a threshold value for colonoscopy screening. However, our results need to be supported by further comprehensive studies.
Conclusions
Given the increasing incidence of early-onset CRC worldwide, colonoscopy screening should be performed in young adults without alarm symptoms who present with lower gastrointestinal complaints. Current guidelines recommend the age of starting colonoscopy screening as 50 years. However, as seen in our study, polyps can be found at an earlier age. Therefore, based on our findings, we believe that colonoscopy screening should be started at 45 years of age, given the increasing incidence of early-onset colorectal cancer. In order to update current guidelines and to set an earlier age for colonoscopy screening for polyps, sufficient evidence should be accumulated in the literature on this subject. We believe that our paper will contribute to further comprehensive research on the matter.
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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Muhammet Fatih Aydin, Mehmet Akif Aydin. Colonoscopy screening for colon polyps: Can it be useful at an earlier age for preventing malignant transformation? Ann Clin Anal Med 2021;12(7):788-793
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Recruitment maneuver application following pulmonary endarterectomy; does it have any impact on reperfusion lung injury and outcome?
Mustafa Emre Gürcü 1, Pınar Karaca Baysal 1, Karolin Yanar 2, Nural Bekiroğlu 3, Atakan Erkılınç 1, Bedrettin Yıldızeli 4
1 Department of Anesthesiology, Koşuyolu High Speciality Educational and Research Hospital, 2 Department of Biochemistry, Cerrahpaşa Faculty of Medicine, Istanbul University, 3 Department of Biostatistics, Faculty of Medicine, Marmara University, 4 Department of Thoracic Surgery, Faculty of Medicine, Marmara University, İstanbul, Turkey
DOI: 10.4328/ACAM.20751 Received: 2021-06-17 Accepted: 2021-07-02 Published Online: 2021-07-06 Printed: 2021-07-01 Ann Clin Anal Med 2021;12(7):794-799
Corresponding Author: Mustafa Emre Gürcü, Koşuyolu High Speciality Educational and Research Hospital, Department of Anesthesiology, Cevizli Mahallesi, Denizer Caddesi, No:2 İstanbul/Turkey. E-mail: emregurcu@gmail.com P: +90 5058917800 Corresponding Author ORCID ID: https://orcid.org/0000-0002-5434-9932
Aim: The only curative treatment of chronic thromboembolic pulmonary hypertension is Pulmonary Endarterectomy. This surgery, may result in ischemia- reperfusion lung injury, which may be related with higher mortality. The aim of the study was to assess the effect of intraoperative recruitment maneuver on ischemia-reperfusion lung injury following Pulmonary Endarterectomy.
Material and Methods: The study was designed as a randomized prospective study with the approval of the Clinical Trials Ethics Committee of our hospital. Between January 2019 and December 2019, 60 patients were included in the study. Randomization was performed using a computer program. The patients were divided into two groups: the study group, in which the recruitment maneuvers were performed and the control group. The primary outcome of this study was to compare the biochemical markers of ischemia-reperfusion injury and oxygenation in patients with and without recruitment maneuvers.
Results: In the recruitment group, arterial pO2 value was 312±82 mmHg, while it was 268±85 mmHg in the control group (p: 0.044). Malondialdehyde, a biomarker of ischemia-reperfusion injury in Broncho Alveolar Lavage fluid were 5±1 and 4±0 (p:0.008) in the control and recruitment groups, and Superoxide Dismutase were 10±2 and 11±1 (p: 0.011) in the control and recruitment groups, respectively.
Discussion: During pulmonary endarterectomy operations, the application of recruitment maneuvers at high inflation pressures after cardiopulmonary bypass, where reperfusion injury may occur, results in a decrease in ischemia-reperfusion injury markers especially in broncho alveolar lavage fluid, and an increase in antioxidant molecules.
Keywords: Chronic Thromboembolic Pulmonary Hypertension; Pulmonary Endarterectomy; Recruitment Maneuver; Reperfusion Lung Injury; Antioxidant Molecule
Introduction
Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a rare disease characterized by the progression of thromboembolism as an organized tissue in the pulmonary arteries[1]. Pulmonary Endarterectomy (PEA) is the only curative treatment option for CTEPH. Following operation, reperfusion of the occluded pulmonary artery may result in ischemia-reperfusion lung injury and right ventricular failure [2]. Reperfusion lung injury is characterized by arterial hypoxia caused by focal pulmonary infiltrates in the regions distal to the endarterectomy[3].
Understanding the process is extremely important to develop a new treatment strategy or procedure that can reduce tissue injury[4]. The mechanisms that cause ischemia-reperfusion injury are very complex and mainly involve a number of events, such as the production of molecular oxygen due to the improvement of blood flow within the ischemic tissue, and consequently the release of reactive oxygen derivatives, prominent inflammatory response and endothelial dysfunction [5].
To prevent reperfusion lung damage that may develop after operation, pre- and post- operative fluid restriction [6], avoidance of high-dose catecholamine and vasodilator therapy, low tidal volume (TV) and inspiratory peak pressures, and recruitment maneuvers (RM) with high PEEP in the postoperative period have been proposed [7].
High PEEP and RM have resulted in better survival and are associated with decreased inflammatory mediator levels in plasma and Broncho Alveolar Lavage (BAL) fluids [8,9], increased oxygenation and decreased Pulmonary Vascular Resistance (PVR)[10-12].
The aim of this study was to investigate the effect of intraoperative lung protection with RM maneuver in patients undergoing PEA for ischemic reperfusion lung injury. The primary outcome of this study was to compare the biochemical markers of ischemia-reperfusion injury and oxygenation in patients with and without RM. The secondary outcome was a comparison of hemodynamics, lung damage, intensive care and hospital stay in patients with and without RM.
Material and Methods
Patient Selection:
The study was designed as a randomized prospective study and approved by the Institutional Review Board (IRB) of Kartal Koşuyolu High Speciality Educational and Research Hospital (IRB#: 2018.6.62). Written informed consent was obtained from all patients participating in the trial, a legal surrogate, parents or legal guardians for minor subjects. Between January 2019 and December 2019, 60 patients were included in the study. Randomization was performed through a computer program. The patients were divided into two groups: the study group, in which RM was performed (RM, n=30), and the control group (C, n=30). Patients with chronic inflammatory disease, chronic liver and kidney failure, patients who had postoperative complications requiring Extracorporeal Membrane Oxygenation (ECMO), and patients who died after surgery were excluded from the study.
Anesthetic and Surgical Procedure:
Central venous and pulmonary artery catheterization were performed with an 8F catheter from the internal jugular vein, and cardiac output was measured with the Thermodilution (Arrow®ThermodilutionCatheters) method in all patients. Anesthesia maintenance was achieved with 2% sevoflurane in 60% oxygen-air mixture. Pulmonary endarterectomy was performed during Total Circulatory Arrest (TCA) at 18Co.
The recruitment maneuver was performed in patients in the study group for 45 seconds at 35 cmH2O PEEP, FiO2:%100 PCV mode after cardiopulmonary bypass (CPB) with open chest. Throughout the RM, mean arterial pressure, central venous pressure (CVP) and transesophageal echo (TEE), right ventricular function and septum position, and signs of RM- related right ventricular overload were monitored. Following the RM, we decreased PEEP to 6-8 cm H2O in one step and returned mechanical ventilation to baseline values. Patients in the control group were ventilated in the PCV mode at 6-8 ml/kg tidal volume, 6-8 cmH2O PEEP, FiO2 :%60 (pO2>100 mmHg) and 12-15/min respiratory rate. All patients received 20-30 ppm inhaled nitric oxide therapy throughout the surgery. Patients were transferred to the intensive care unit after the operation. The patients were kept anaesthetized and sedated postoperatively in the intensive care unit. Extensive ventilatory and circulatory monitoring were continuously performed, including online measurement of pulmonary artery pressure with an oxymetric Swan-Ganz catheter, cardiac output, mixed venous oxygen saturation, and arterial blood gases. Pressure- controlled mechanical ventilation with PEEP of 6-8 cmH2O, FiO2: %60 (pO2>90-100 mmHg) and tidal volume of 6-8 ml/ kg was applied to all patients. Depending on blood gas values (pH>7.30, pO2>90-100 mmHg), high PEEP values were reduced to 3 cmH2O before extubation by PEEP titration. Inhaled nitric oxide, which started in the intraoperative period was reduced for the first 4-6 hours postoperatively and weaned. PaO2/FiO2 ≥150 or SpO2 ≥92% (FiO2 ≤ 40%) and positive end expiratory pressure (PEEP) ≤3 cmH2O, pH> 7.25, hemodynamic stability (no vasopressor drugs or low dose), can initiate inspiratory effort and neurologically awake patients were extubated. Postoperative fluid treatment of all patients was planned to have a negative fluid balance and chest radiographs were taken daily. Postoperative chest radiographs of all patients at 24 hours were evaluated by a single radiologist. According, both lungs were divided into three parts: the lower, middle and upper zones. Parenchyma infiltration images were scored 1 point and airspace images were scored 3 points. The total reperfusion score was accepted as a total of 18 points for both lungs [13]. Measurement of Biochemical Parameters:
Blood and BAL fluid samples were collected from all patients 4 hours following the operation. Иlood and BAL samples were centrifuged, and their plasmas were separated, and this plasma was stored in the deep-freezer at -200C until biochemical measurements were performed in Eppendorfs. Biochemical measurements were performed at the end of the study by dissolving all plasmas at once.
Measurement of malondialdehyde (MDA) levels:
The rate of lipid peroxidation was measured using the Buege and Aust procedure. MDA and its products formed a colored product by reacting with thiobarbituric acid. 250 μL of plasma and BAL were boiled at 950C for 15 minutes by adding 1 mL of thiobarbituric acid, 1.5 mL of trichloroacetic acid and 200 μL of hydrochloric acid. Following the centrifugation process, the absorbances of the supernatants were read at 532 nm wavelength.
Measurement of superoxide dismutase (SOD) activity:
Superoxide dismutase (SOD) activity was measured with modification using the method of Sun et al. This method has been used in the inhibition of nitrobluetetrosolium reduction. Xanthine oxidase was used as a superoxide stimulant. SOD reagent (100 μL) and 20 μL xanthine oxidase were pipetted onto the 20 μL sample. After twenty minutes of incubation, 20 μL of copper 2 chloride was added to stop the reaction. Absorbances were read against the reagent blind at 560 nm wavelength. The activity of 1 unit Cu, Zn-SOD was defined as the inhibition of 50% xanthine oxidase activity.
Determination of advanced oxidation protein products (AOPP) concentration:
Advanced oxidation protein products (AOPP) were made according to Hanasand’s method. Citric acid (200 μL) was added to 20 μL of the sample pipetted into UV plates. One minute later, 10 μL of potassium iodide was pipetted, and the reading was performed at a wavelength of 340 nm. In order to make concentration calculations, Chloramine-T equivalents were used as a standard in the 0-100 μmol/L concentration range.
Measurement of the level of thiol groups:
Plasma and BAL total thiol (T-SH) and non-protein thiol (NPSH) concentrations were analyzed using 5.5 dithiobis (2- nitrobenzoic acid) (DTNB) with the method developed by Sedlak and Lindsay. Plasma aliquots of 20 μL were treated with 400 μLof0.2Mtrisbuffer,pH8.2and20μLof0.01MDTNBto determine the T-SH groups. NPSH samples were measured in the following way: 20 μL plasma was mixed with 400 μL 50% TCA. The tubes were centrifuged at 3000g for 15 minutes. Supernatant fractions were studied as the T-SH method mentioned above. The absorbance values of the samples were read at 412 nm wavelength against the reactive blind. The molar extinction coefficient of thiol (SH) groups at 412 nm wavelength was considered to be approximately υ=13,100 m-1/ cm-1. P-SH groups were calculated by subtracting NP-SH from T-SH.
Statistical Analysis:
Results were expressed as either mean (SD) or frequencies. The Chi-square test was used for the comparison of the categorical variable. Continuous random variables were tested for normality of the data distribution using a histogram or Shapiro- Wilk test. The primary outcomes, which were continuous random variables, were compared between the groups using the Unpaired t-test. For the secondary outcomes, which were also continuous random variables; Paired t-tests were used in each group, then a new variable which was named as “percent of change” was calculated in order to determine the amount of change between pre and post measurements. Therefore, an Unpaired t-test was used to compare the mean percentage of change between the groups. To test the differences in hemodynamic parameters between groups (RM-Control group), we carried out ANCOVA analysis using baseline variables. Analyses were performed using SPSS Statistics version 15.0 software (SPSS Inc., Chicago, IL, USA). A P-value of 0.05 was considered statistically significant.
Results
The demographic characteristics of the patients are shown in Table 1. The mean age of the patients was 49±16 years, and 52.5% (n: 31) were female. There were no differences between the two groups in terms of demographic characteristics (Table 1). The mean cardiopulmonary bypass duration, aortic cross-clamp and total circulatory arrest duration were 191±3, 40±2 and 21±1 min, respectively, and there were no differences between the two groups. The comparison of two groups in terms of the postoperative 4th -hour arterial blood gas values and the postoperative 24th -hour ischemia-reperfusion injury score in the chest X-ray are given postoperative arterial pO2 value was significantly higher in the recruitment group compared to the control group (312±82 vs 268±85 mmHg; p: 0.044) (Table 1). Preoperative and postoperative hemodynamic data are summarized in Table 3. When pre-postoperative changes of hemodynamic values were compared within each group (RM ve control) mAP, mPAP, CO, CI and PVR, which were hemodynamic parameters, significantly decreased. However, after the adjustment of absolute change, % change, and pre- postoperative changes according to baseline values with ANCOVA, changes in these hemodynamic parameters were detected to be non-significant (Table 2, Figure 1).
The comparison of biochemical markers due to ischemia- reperfusion injury in BAL and blood sample is shown in Table 3. MDA, the most important marker of ischemia-reperfusion injury, especially in BAL, was found to be significantly higher in the control group than in the recruitment group (5±1 and 4, respectively) (p: 0.008), and SOD, which reduces ischemia- reperfusion injury, was found to be low in the control group, and the difference between the two groups was significant (10±2 and 11±1, respectively) (p: 0.011) (Table 3).
Clinically, there were no differences between the RM and Control groups, in terms of duration of mechanical ventilation (19±18 hours vs 18±7 hours; p:0.868, respectively), intensive care unit (2±1 days vs 3±1days; p:0.863 ,respectively) and hospital stay (8±2 days vs 10±5 days; p: 0.146, respectively).
Discussion
In this study, the biochemical and clinical effects of two different ventilator strategies applied to patients after PEA on ischemia-reperfusion lung injury were investigated. The most important and primary findings of the study were that the RM, applied in the early period of reperfusion reduced MDA in BAL samples of the patients and increased SOD, an antioxidant molecule, and oxygenation in arterial blood gas samples. No significant difference was observed in the findings of ischemia- reperfusion injury on the chest X-ray, intensive care unit, and hospital stay of the patients.
Ischemia-reperfusion lung injury following PEA is an important risk factor for early mortality. Pulmonary artery pressure increases when >40% of the pulmonary vascular bed is occluded. Secondary to the arterial thrombus, the ‘hypoxic pulmonary vasoconstriction’ mechanism is activated. This situation results in CTEPH in the long run, and the only curative treatment option for CTEPH is PEA operation. Cardiopulmonary bypass and deep hypothermic circulatory arrest are mandatory for successful PEA surgery, however, they increase inflammatory response following the surgery. The lungs are the only organ that receives the entire CO and are exposed to severe ischemia-reperfusion injury during CPB[14]. During total CPB, pulmonary blood flow stops completely. Bronchial blood flow is severely reduced. This event causes the development of inflammatory ischemia-reperfusion injury in the lungs [6]. After revascularization and endarterectomy, reperfusion injury is seen at the alveolocapillary level in the occluded lung segments. Plasma MDA is a product of lipid peroxidation, which results from ischemia and reperfusion in humans, and plasma levels increase with reperfusion. It is therefore a useful biomarker in determining oxidative stres[15]. SOD specifically converts the superoxide radical into hydrogen peroxide, preventing the formation of hydroxyl radical and peroxynitrite [16]. SOD is commonly found in many cell types in the lung [17]. When compared to other tissues, especially extracellular SOD has a high activity in the lung and is the predominant form of SOD in vascular tissues [18]. It was reported that SOD completely prevents the increase of hypoxic pulmonary vasoconstriction caused by reperfusion, which occurs after 30 minutes of ischemia, and pulmonary capillary leakage [19].
In the pre-postoperative period, it has been suggested to avoid excessive fluids, especially to prevent the development of pulmonary edema [6]. Different ventilator strategies are also applied, since they decrease mortality and morbidity by reducing reperfusion injury in the lung tissue. Although the optimum ventilation strategy is not fully known, these strategies have been developing based on the experience gained from both lung transplantation and PEA operations. It has been reported that performing RM before reperfusion of ischemic lungs protects the lungs from reperfusion lung injury [20], and early administration of optimal PEEP reduces extravascular lung water in oleic acid lung injury [21]. In PEA operations, avoiding vasoactive and vasodilator treatments following CPB, the use of low TV and low peak inspiratory pressures reduce reperfusion lung injury and the development of right ventricular failure [3]. After PEA operation, the application of RM and high PEEP in the intensive care unit reduce pulmonary edema caused by reperfusion injury or lung injury due to atelectasis [7]. The results obtained from this study indicated that RM, performed in the early period of reperfusion injury, significantly increased SOD and reduced the reperfusion lung injury at the cellular level by decreasing MDA caused by ischemia-reperfusion. Application of RM with PEEP and subsequent maintenance of high PEEP levels prevent alveolar micro atelectasis and repair the oxygenation [22]. In patients with mechanical ventilation support, PEEP may increase hyperinflation in the non-dependent lungs, while clearing off closed alveoli in the dependent lungs. Thus, high PEEP has positive effects in reversible ARDS patients [23]. In particular, it reduces hospital and intensive care mortality rates [24], and significantly increases oxygenation in patients after CPB [25]. In hypoxemic patients with pulmonary hypertension who underwent PEA operation due to chronic pulmonary thromboembolism, there is an increase in oxygenation with the RM application and subsequent application of high PEEP [8]. In this study, it was found that the application of recruitment maneuver at high inflation pressures in PEA operations in the early period immediately after weaning from CPB caused a significant increase in oxygenation compared to the control group. Patients in both groups were extubated on average on the first operative day. It was determined that the intensive care and a hospital stay of the patients and reperfusion injury findings in chest X-ray were less in the recruitment group, who were applied high PEEP, although there was no statistically significant difference between the two groups.
The limitations of our study are the low number of patients and the role of the surgical procedure itself as a primary driver of the observed physiological changes. While the study demonstrated an increase in superoxide dismutase and a decrease in malondialdehyde, both of which indicate a decrease in reperfusion injury, we did not find any significant difference between measurable clinical outcomes, such as chest X-ray score findings, ICU and hospital length of stay. The RM itself potentially “washes” out or dilutes the alveolar content, and this may be the reason why SOD activity and MDA were marginally reduced in BAL of the RM group. The measurement of BAL total protein concentration could help determine whether such a washout effect might have happened. In this study we used sample sizes of 30 in each group by holding to the Central Limit Theorem and Law of Large Numbers because the incidence of CTEPH patients in the society is limited.
In conclusion, during PEA operations, the application of RM at high inflation pressures after CPB, where reperfusion injury begins, resulted in a decrease in ischemia-reperfusion injury markers, especially in BAL fluid, and an increase in antioxidant molecules. While application of RM provided a significant increase in oxygenation without causing hemodynamic instability, noclinical important differences were detected
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. Mayer E, Dahm M, Hake U, Schmid FX, Pitton M, Kupferwasser I, et al. Mid- term results of pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension. Ann Thorac Surg. 1996; 61(6):1788-92. DOI: 10.1016/0003-4975(96)00169-5.
3. Mares P, Gilbert TB, Timothy EM, Hiesmayr M, Muhm M, Herneth A, et al. Pulmonary Artery Thromboendarterectomy: A Comparison of Two Different Postoperative Treatment Strategies. Anesth Analg. 2000; 90(2):267-73. DOI: 10.1097/00000539-200002000-00006.
4. Bonservizi WGS, Koike MK, Saurim R, Felix GAA, da Silva SM, Montero EFS, et al. Ischemic preconditioning and atenolol on lung injury after intestinal ischemia and reperfusion in rats. Transplant Proc. 2014; 46(6): 1862–6. DOI:10.1016/j. transproceed.2014.05.054.
5. Yellon DM, Hausenloy DJ. Mechanisms of Disease Myocardial Reperfusion Injury. N Engl J Med. 2007; 357(11):1121-35.
6. Young RW. Prevention of Lung Injury in CardiacSurgery: A Review. J Extra Corpor Technol. 2014; 46(2):130-41.
7. Takeuchi M, Imanaka H, Tachibana K, Ogino H, Ando M, Nishimura M. Recruitment maneuver and high positive end-expiratory pressure improve hypoxemia in patients after pulmonary thromboendarterectomy for chronic pulmonary Thromboembolism. Crit Care Med. 2005; 33(9):2010-4. DOI: 10.1097/01.ccm.0000178174.53373.da.
8. Crotti S, Mascheroni D, Caironi P, Pelosi P, Ronzoni G, Mondino M, et al. Recruitment and derecruitment during acute respiratory failure: A clinicalstudy. Am J Respir Crit Care Med. 2001; 164(1):131-40. DOI: 10.1164/ ajrccm.164.1.2007011.
9. Hess DR, Bigatello LM. Lung recruitment: The role of recruitment maneuvers. Respir Care. 2002; 47:308–17.
10. Fischer LG, Aken HV, Burkle H. Management of pulmonary hypertension: Physiological and pharmacological considerations for anesthesiologists. Anesth Analg. 2003; 96(6):1603-16. DOI: 10.1213/01.ane.0000062523.67426.0b.
11. Rothen HU, Sporre B, Engberg G, Wegenius G, Hedenstierna G. Reexpansion of atelectasis during general anesthesia: A computed tomography study. Acta Anaesthesiol Scand. 1995; 39(1):118-25. DOI:10.1111/j.1399-6576.1995. tb05602.x.
12. Duggan M, McCaul CL, McNamara PJ, Engelberts D, Ackerley C, Kavanagh BP. Atelectasis causes vascular leak and lethal right ventricular failure in uninjured rat lungs. Am J Respir Crit Care Med. 2003; 167(12):1633-40. DOI: 10.1164/ rccm.200210-1215OC.
13. Kundu S, Herman SJ, Winton TL. Reperfusion Edema after Lung Transplantation: Radiographic Manifestations. Radiology. 1998; 206(1):75-80.
14. Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol. 1978; 52:302-10. DOI: 10.1016/s0076-6879(78)52032-6.
15. Singh Z, Karthigesu IP, Singh P, Kaur KR. Use of Malondialdehyde as a Biomarker for Assessing Oxidative Stress in Different Disease Pathologies: a Review. Iranian J Publ Health. 2014; 43(3):7-16.
16. Oury TD, Day BJ, Crapo JD. Extracellular superoxide dismutase: a regulator of nitricoxide bioavailability. Lab Invest. 1996; 75(5):617-36.
17. Chang LY, Kang BH, Slot JW, Vincent R, Crapo JD. Immunocytochemical localization of the sites of superoxide dismutase induction by hyperoxia in rat lungs. Lab Invest. 1995; 73(1):29-39.
18. Oury TD, Chang LY, Marklund SL, Day BJ, Crapo JD. Immunocytochemical localization of extracellular superoxide dismutase in human lung. Lab Invest. 1994; 70(6):889-98.
19. Messent M, Griffiths MJ, Quinlan GJ, Gutteridge JM, Evans TW. Ischaemia- reperfusion injury in the rat is modulated by superoxide generation and leads to an augmentation of the hypoxic pulmonary vascular response. Clin Sci (Lond). 1996; 90(1):47-54. DOI: 10.1042/cs0900047.
20. Borges JB, Okamoto VN, Matos GFJ, Caramez MPR, Arantes PR, Barros F, et al. Reversibility of lung collapse and hypoxemia in early acute respiratory distress syndrome. Am J Respir Crit Care Med. 2006; 174(3):268-78. DOI: 10.1164/ rccm.200506-976OC.
21. DeCampos KN, Keshavjee S, Slutsky AS, Liu M. Alveolar recruitment prevents rapid reperfusion induced injury of lung transplants. J Heart Lung Transplant. 1999; 18(11):1096-102. DOI: 10.1016/s1053-2498(99)00082-0.
22. Ruiz-Bailén M, Fernández-Mondéjar E, Hurtado-Ruiz B, Colmenero-Ruiz M, Rivera-Fernández R, Guerrero-López F, et al. Immediate application of positive- end expiratory pressure is more effective than delayed positive-end expiratory pressure to reduce extravascular lung water. Crit Care Med. 1999; 27(2):380-4. DOI: 10.1097/00003246-199902000-00046.
23. Gattinoni L, Caironi P, Cressoni M, Chiumello D, Ranieri VM, Quintel M, et al. Lung recruitment in patients with the acute respiratory distress syndrome. N Engl J Med. 2006; 354(17):1775-86. DOI: 10.1056/NEJMoa052052.
24. Lanqi Guo, Jianfeng Xie, Yingzi Huang, et al. Higher PEEP improves outcomes in ARDS patients with clinically objective positive oxygenation response to PEEP: a systematic review and meta-analysis. BMC Anesthesiol. 2018; 18(1):172. DOI:10.1186/s12871-018-0631-4.
25. Dyhr T, Laursen N, Larsson A. Effects of lung recruitment maneuver and positive end-expiratory pressure on lung volume, respiratory mechanics and alveolar gas mixing in patients ventilated after cardiac surgery. Acta Anaesthesiol Scand. 2002; 46(6):717-25. DOI: 10.1034/j.1399-6576.2002.460615.x.
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Mustafa Emre Gürcü, Pınar Karaca Baysal, Karolin Yanar, Nural Bekiroğlu, Atakan Erkılınç, Bedrettin Yıldızeli. Recruitment maneuver application following pulmonary endarterectomy; does it have any impact on reperfusion lung injury and outcome? Ann Clin Anal Med 2021;12(7):794-799
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Herpes Zoster oticus with multiple cranial nerves involvement: A case series
Oui Ting Jie, Mawaddah Azman, Balwant Singh Gendeh, Hardip Singh Gendeh
Department of Otorhinolaryngology, Head and Neck Surgery, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
DOI: 10.4328/ACAM.20369 Received: 2020-10-11 Accepted: 2021-02-18 Published Online: 2021-06-24 Printed: 2021-07-01 Ann Clin Anal Med 2021;12(7):814-818
Corresponding Author: Hardip Singh Gendeh, Department of Otorhinolaryngology, Head & Neck Surgery, The National University of Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Kuala Lumpur, Malaysia. E-mail: hardip88@gmail.com P: +6-03-91456202 F: +6-03-91456684 Corresponding Author ORCID ID: https://orcid.org/0000-0001-9679-3495
This case series aims to describe the clinical presentations, management and patient outcomes in four cases of Ramsay Hunt Syndrome describe the clinical presentations, management and patient outcomes in four cases of Ramsay Hunt Syndrome (RHS) with multiple cranial nerve involvement. A review of four cases of RHS with a variety of cranial nerve involvement in different age groups (paediatric, adult and elderly) was conducted. The patients were followed up at the otorhinolaryngology outpatient clinic and the response to oral antiviral and steroid therapy was assessed. We observed good responses to combination antiviral-steroid treatment in all 4 cases. There was complete resolution of cranial nerve palsies in 3 out of 4 of the cases within 1-2 weeks. In the remaining 1 case, the symptoms also completely disappeared after 3 months. Relevant clinical and radiological findings were documented. Several theories have been proposed to explain the pathophysiology of other cranial nerve palsies (eg. V, XI, IX, X, XI, and XII) secondary to a Zosterian infection. The described pathways form the basic principles of RHS treatment which involve the usage of oral antivirals and steroid therapies in RHS. There has been some controversy regarding the efficacy of antiviral and steroid therapies in RHS. However, this case series review showed that the combination therapy of antiviral-steroid improved the patients’ overall prognosis. Hence, such treatment should be considered in all patients without contraindications.
Keywords: Ramsay hunt; Herpes Zoster; Cranial nerves; Antiviral therapy; Steroid therapy
Introduction
The Varicella-Zoster virus (VZV) is one of nine herpesviruses known to be capable of infecting human beings. The well- known medical condition it causes is varicella (commonly known as “chickenpox”) as its initial presentation. This infective but self-limiting disease normally presents with a characteristic skin rash consisting of small, itchy, blisters widely distributed over the patient’s back, chest and face. After the primary infection is resolved, the virus resides dormant in the spinal and cranial nerve ganglia lifelong. There is a possibility for the virus to reactivate and replicate subsequently in life, leading to the development of shingles. This occurs as a result of the inflammation caused by the virus as it travels from the affected ganglions through the sensory nerve fibres into the respective dermatomes. This secondary Varicella-zoster viral infection typically presents with the presence of pain and vesicular rash according to its dermatomal distribution. If a patient presents with unilateral otalgia and an eruption of painful, herpetiform skin lesions over the external ear unilaterally, then a clinical diagnosis of herpes zoster oticus (HZO) can be made.
In HZO, the virus arises from the geniculate ganglion of the facial nerve, which consists of sensory, motor and parasympathetic nerve fibres. Following reactivation, neural inflammation, combined with its anatomical location within the petrous temporal bone, may lead to debilitating neurological sequelae, namely, unilateral lower motor neuron facial nerve palsy. [1] This constellation of clinical findings was first described by Ramsay Hunt and since then has been dubbed “Ramsay Hunt Syndrome” (RHS). [2] There have been variations in the way RHS has been defined, however the triad of clinical features include the typical dermatomal distribution of rash (often preceded by pain) and acute peripheral palsy of the 7th cranial nerve on the same side. [1] It is worth noting that the pioneer, Dr. Hunt, himself noticed the involvement of symptoms such as vertigo and tinnitus, which imply other cranial nerve involvement, namely the 8th cranial nerve. Furthermore, there have been reports of RHS affecting other cranial nerves (albeit less commonly) such as V, VI, IX, X, XI and XII. Sometimes several cranial nerves are simultaneously involved, presenting a clinical picture consistent with that of multicranial neuritis. [1, 3]
The objectives of this manuscript are firstly, to describe the various cranial nerves involvement in RHS and, secondly, to review an adequate treatment protocol for RHS with cranial nerve involvements.
Case Report
Four cases are described in Table 1. Case 1 is a young gentleman with V3, VII and VIII involvement. Case 2 is a paediatric patient with VII and VIII involvement. Case 3 is a middle-aged gentleman with VII, VIII and X involvement. CT reveal fat stranding of the left parapharyngeal space. Case 4 was complicated with facial cellulitis indicating CN V involvement. Informed consent was obtained from all patients for being included in the study.
Discussion
The most commonly affected cranial nerve (CN) involved in RHS is the facial nerve (7th CN). Several theories suggest the pathophysiology of other cranial nerve palsies secondary to a Zosterian infection. Alicandri-Ciufelli M et al. (2012) [4] hypothesized that the VZV infection spreads between adjacent synapses along the brain stem’s reflex pathways. Anatomically, the nucleus of the facial nerve is in the pons alongside the nuclei of cranial nerves VI and VIII. Also, the proximity of the facial nerve (VII) and vestibulocochlear nerve (VIII) at the level of the cerebellopontine angle (CPA) as they enter the internal auditory canal has been thought to facilitate the virus’ transmission.
The specific pathway is believed to be either the vestibulofacial or vestibulocochlear anastomoses. Furthermore, the foramen of Luschka is located inferior-posteriorly to the root entries of CN VII/VIII where the rootlets of origin for CN IX, X, XI lie near to. It is known that anastomoses exist between CN V, VII, IX and X. Inflammation of CN VIII within the internal acoustic meatus may also compress the adjacent CNVIII, resulting in sensorineural hearing loss.
Involvement of the Vagus nerve is rare, but there have been several reports. Postulations include ganglionitis involving adjacent cranial nerves and vascular spread from the infected Carotid sheath/artery. This is in line with the CT findings of the parapharyngeal fat streaking indicating inflammation in case number 3. Another theory is that VZV may cause localized meningitis leading to demyelination in the brainstem [5]. Finally, it is believed that vasculitis-induced infarction of small and large arteries supplying affected cranial nerves may play a role. An example would be a reported case, involving the angiogram findings which revealed occlusion of the ascending pharyngeal artery, which supplies CN IX-XII. The described pathophysiological pathways of RHS form the basic principles of treatment for this condition, which involves the usage of oral antivirals and steroid medications.
Antiviral agents such as Acyclovir, Famiciclovir, Penciclovir, and Valacyclovir belong to a group of medications called “nucleoside analogues” and work by inhibiting the viral replication process directly thereby reducing the severity and subsequent complications of the VZV infection. In fact, post- herpetic neuralgia (PHN) is one of the most common sequelae, and it can be prevented if antiviral therapy is initiated promptly. Furthermore, antiviral therapy may decrease the duration of new vesicle formation and the time for vesicles to become crusted. However, it is worth noting that treatment is most effective if started within the first 72 hours of the onset of rash. According to the European Consensus-based (S2k) Guideline on the Management of Herpes Zoster (2016) [6], there have been a limited number of studies conducted to evaluate the efficacy of treatment 72 hours after onset of rash. However, the panel of experts still suggests to initiate antiviral medications (even after 72 hours of onset of symptoms) in the following cases: the appearance of new vesicles, patients with complications or at risk of developing complications, signs of cutaneous, visceral or neurological dissemination, cases of Herpes Zoster oticus/ opthalmicus and in all immunocompromised patients [6]. In this consensus, the duration of antivirals suggested is as long as no new vesicular skin lesions appear.
The use of corticosteroids in VZV infections is controversial, for there have been studies to suggest that short-term regimens may have benefits such as reducing the incidence of PHN. On the other hand, there are some studies which show steroids have no advantage. Corticosteroids such as Prednisolone and Methylprednisolone have an anti-inflammatory effect, which has been suggested to aid in restoration of facial nerve function. The European Consensus quoted earlier, recommends combined therapy of intravenous Aciclovir and systemic corticosteroids in Herpes Zoster Oticus with facial nerve involvement or with severe pain and other cranial nerve palsies. Steroids play an important role in reducing the viral-induced inflammation of the facial nerve [7].
Combination therapy is more effective in the recovery of facial nerve function and gives a better prognosis. One systematic review revealed that the combination of steroids and Acyclovir reached better recovery rates when compared to monotherapy with steroids only, with a better prognosis of facial nerve palsy on earlier commencement. Various steroid regimens have been proposed, however, the clinician may consider giving an initial loading dose (to gain control of skin condition) eg. 40-60mg daily (0.5-1.0 mg/kg) for 7-10 days with the dose gradually tapered down [8].
Conclusion
Herpes Zoster Oticus most commonly involves cranial nerves VII and VIII, although it may also involve various other cranial nerves simultaneously in complicated cases. We recommend that all patients with Ramsay-Hunt Syndrome should be considered for combination therapy of antiviral-steroid in order to improve the patient’s overall prognosis. As usual, any contraindications must first be excluded to determine patient’s suitability.
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. Gondivkar S, Parikh V, Parikh R. Herpes zoster oticus: A rare clinical entity. J Contemp Clin. 2010;1(2):127-9.
2. Hunt JR. On Herpetic Inflammation of the Geniculate Ganglion. A New Syndrome and its Complications. J Nerv Ment Dis. 1907;34(2):73-96.
3. Kaplama ME. Multiple cranial nerve Injury in Ramsay Hunt Syndrome: A Case Report. J Pak Med Assoc. 2020;70(3):537-8.
4. Alicandri-Ciufelli M, Aggazzotti-Cavazza E, Genovese E, Genovese E, Monzani D, Presutti L. Herpes zoster oticus: a clinical model for a transynaptic, reflex pathways, viral transmission hypotheses. Neurosci Res. 2012;74(1):7-9.
5. Carroll WM, Mastaglia FL. Optic neuropathy and ophthalmoplegia in herpes zoster oticus. Neurology. 1979;29(5):726-9.
6. Werner RN, Nikkels AF, Marinović B, Schäfer M, Czarnecka-Operacz M, Agius AM, et al. European consensus-based (S2k) Guideline on the Management of Herpes Zoster – guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV), Part 2: Treatment. J Eur Acad Dermatol Venereol. 2017;31(1):20-9.
7. Turner JE, Geunes PM, Schuman NJ. Cranial polyneuropathy–Ramsay Hunt’s syndrome: case report and discussion. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997;83(3):354-7.
8. Monsanto RD, Bittencourt AG, Bobato Neto NJ, Almeida Beilke SC, Lorenzetti FTM, Salomone R. Treatment and Prognosis of Facial Palsy on Ramsay Hunt Syndrome: Results Based on a Review of the Literature. Int Arch Otorhinolaryngol. 2016;20(4):394-400.
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Oui Ting Jie, Mawaddah Azman, Balwant Singh Gendeh, Hardip Singh Gendeh. Herpes Zoster oticus with multiple cranial nerves involvement: A case series. Ann Clin Anal Med 2021;12(7):814-818
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The effects of e-cigarette on periodontium: A narrative review
Siraj DAA Khan 1, Musleh Al-Garni 2, Fahad al Gahtani 3, Saad Masood Al-Qahtani 4, Mohannad Al-Wadei 5, Mazen Al-Najrani 5, Ziyad Al-Shahrani 5
1 Pediatric Dentistry, Department of Preventive Dental Sciences, 2 Dental Public Health, Department of Preventive Dental Sciences, 3 Dental Bio-material, Department of Preventive Dental Sciences, 4 Department of Preventive Dental Sciences, 5 Intern, Faculty of Dentistry, Najran University, KSA
DOI: 10.4328/ACAM.20447 Received: 2020-12-22 Accepted: 2021-02-03 Published Online: 2021-02-14 Printed: 2021-07-01 Ann Clin Anal Med 2021;12(7):819-821
Corresponding Author: Siraj DAA Khan, Faculty of Dentistry, Najran University, KSA. E-mail: sdkhan@nu.edu.sa P: +966-17542-7960 Corresponding Author ORCID ID: https://orcid.org/0000-0002-7015-2232
Recently, the popularity of alternative cigarette types, namely electronic nicotine delivery system (ENDS) or electronic cigarettes (e-cigarettes) has increased. E-Cigarettes are electrical devices that vaporize liquid solution based on propylene or polyethylene glycol to form an aerosol mist containing varying levels of nicotine. The effects of smoking on both general and oral health are well-known globally, but the effects of e-cigarettes on periodontium are still uncertain. The aim of the present narrative review is to discuss the effects of e-cigarettes on the periodontium by using different published research papers about e-cigarette, vaping, smoking, oral health, and periodontium. Based on the evidence provided in the present narrative review, it can be concluded that the use of e-cigarettes has a significant impact on oral health. It is also used as a tool for smoking cessation, but there is a lack of evidence on its efficacy.
Keywords: Smoking; E-cigarette; Nicotine; Periodontium
Introduction
Smoking has a negative effect on oral health, including periodontal diseases. Periodontal disease is an inflammation of the supporting tissues of the teeth; it also impaired wound healing and increases the risk of oral and lung cancer [1].
One of the problems of smoking is the addiction to nicotine, which makes it difficult for smokers to quit smoking. However, there is a substitute for nicotine, such as transdermal patches, which may help smokers to quit smoking [2].
Recently, there has been a new popular alternative of cigarettes that simulates conventional smoking, called the E-nicotine delivery system. It is an electrical device, which consists of a metal heating element, solution container and battery. This device vaporizes solutions by heating the metal to give an aerosol, the solution contains diluents like propylene glycol and vegetable or aqueous glycerin, nicotine and flavors to get a better taste [1,3,4].
Smoking is one of the major public health issues and its effects on the periodontium are significant. E-cigarettes are used as a tool for smoking cessation, even though it contains more amount of nicotine. The present review aims to list out the effects of E-cigarette on the periodontium.
Material and Methods
By utilizing the terms electronic cigarettes, vaping, smoking, oral health and periodontium, the data in English-language was extracted from Medline, ScienceDirect and Scopus published from 2014 to 2020. An original research paper with human studies, case reports and the effect of electronic cigarettes on oral health was included; review articles and editorials were excluded for this review. Through the selection procedure, 8 articles were selected and grouped as e-cigarettes and conventional smoking, and e-cigarette and periodontium.
Discussion
E-cigarette and conventional smoking
The differences between E-cigarettes and conventional smoking is that E-cigarette may contain a high amount of nicotine, it does not contain tobacco, and the simplicity of using E-cigarettes make the users vaping more [5].
Worldwide governments are making policies for nicotine control. Regarding the e-cigarette, there still is no regulation of the level of nicotine dose [1,5]. Apart from nicotine, other contaminants and carcinogens are also found in e-cigarettes aerosol.1,5 This raises a question about the safety and purity of ingredients used for the e-cigarette.
E-cigarettes are rapidly spreading among teenagers due to flavoring agents and as a status symbol, which may make them more acceptable to use than conventional smoking. Recent studies (Lauren et al., 2014) [6] have not shown any effect of flavoring agents on the oral cavity, but there is a risk for pulmonary effect.
E-cigarette and periodontium
Studies have scientifically proven that traditional cigarettes affect the health of the surrounding tissue of teeth in terms of disease progression and periodontal healing. However, the data on the effect of E-cigarette are still widely controversial and further research needs to be installed.
One study reported that the bleeding index significantly differed for E-cigarette users, and it gives a wonder because the E-cigarette was thought to be less harmful to the body and an alternative way for smoking quit [1]. Also, Behavioral Risk Factor Surveillance System survey data (2016) suggested that there will be more teeth exfoliation due to dental caries and periodontal disease with the use of E-cigarette.
Moreover, Willershausen et al., (2014) reported that direct exposure to the ingredient of E-cigarette such as the E-liquid will cause a harmful effect on gingival fibroblasts and periodontal ligament. Regarding wound healing, Lei et al., (2017) mentioned that the E-cigarette products affect oral myofibroblast differentiation, which will affect wound healing by reducing wound contraction by these cells.
Cellular apoptosis and permanent DNA damage were found to be associated with the use of E-cigarette [7]. Also, they found a strong relationship between the use of nicotine and healing by reducing the angiogenesis and differentiation of osteoblast. Besides, the use of E-cigarette may affect implant success because the nicotine in E-cigarette may impair the bone formation and healing potential at the implant and bone interface [5].
Regarding microbiology, they found that the use of E-cigarettes will enhance the Candida albicans to evade soft tissue defenses by overgrowth and transition. Also, they revealed an increase in terms of pathogenesis, transition, and virulent genes, such as SAPs of oral microbes due to E-cigarettes [8].
Recently, Javed et al., (2017) revealed that the E-cigarette use not detrimental as a conventional cigarette, in addition, there is no difference between the periodontal status of E-cigarette users and nonsmokers. It also revealed that the E-cigarette induces gingival inflammation similar to the conventional cigarette.7 However, plenty of respectable studies report that the E-cigarette liquid may have a potentially harmful result due to unknown effects of the ingredient [2].
Conclusion
To date, the true effect of E-cigarettes is not completely known, but it has been confirmed that the effect of nicotine, which is involved in E-cigarettes ingredients, deteriorates healing, bone formation and bacterial violence.
In epidemiological studies, the relationship between smoking and the loss of attachment of periodontal tissues has been adduced; these findings revealed that regardless of the type of tobacco used, there is a huge risk for developing periodontitis. The bleeding index was significant for those using E-cigarettes, which gives an idea for unknown risk of this type, nowadays, it is becoming more popular and further studies should be established to detect the true risk, which might be extremely harmful to the general health and the oral cavity.
Programs and further policies are highly recommended to educate the users about the effect of nicotine, which is present in conventional types and E-cigarettes.
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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Siraj DAA Khan, Musleh Al-Garni, Fahad al Gahtani, Saad Masood Al- Qahtani, Mohannad Al-Wadei, Mazen Al-Najrani, Ziyad Al-Shahrani. The effects of e-cigarette on periodontium: A narrative review. Ann Clin Anal Med 2021;12(7):819-821
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Past, present and future of Covid-19 pandemic; review of the pathophysiology and clinical management
Mirza Zeeshan Sikandar 1, Aiman Fatima 1, Syed Imran Ali Shah 2
1 Department of Biochemistry, Central Park Medical College, Lahore, Pakistan, 2 Department of Biochemistry, University of Hafr AlBatin, Saudi Arabia
DOI: 10.4328/ACAM.20457 Received: 2020-12-27 Accepted: 2021-04-18 Published Online: 2021-05-03 Printed: 2021-07-01 Ann Clin Anal Med 2021;12(7):822-828
Corresponding Author: Mirza Zeeshan Sikandar, Department of Biochemistry, Central Park Medical College, 31-km Ferozepur Road (near Kahna Nau), 54600, Lahore, Pakistan. E-mail: m.zee.shan@hotmail.com P: 0336-8656736 Corresponding Author ORCID ID: https://orcid.org/0000- 0002-5499-7884
The coronavirus disease (COVID-19) pandemic has been caused by the worldwide infectious spread of severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2). Its mechanism of action involves RNA virus implantation into the cell’s cytoplasm and the hijack of transcriptional machinery. The infection primarily afflicts the pulmonary system, resulting in multiple complications including, but not limited to, ground glass opacities seen on imaging. Characteristic features of COVID-19 involve pneumonia, shortness of breath, asthma, nasal congestion, sore throat, fever, fatigue, myalgia and it also encompasses a wide variety of other systemic symptoms. Multiple pharmaceutical agents have been tried as a treatment for COVID-19 but the results are inconsistent. With the intention of stopping person- to- person transmission, health measures such as quarantine and social distancing have been adopted, but the implementation was difficult. After the first wave of the pandemic, the second wave surfaced with a clear resurgence of cases followed by a third wave. The present review summarizes what is known about COVID-19 and explores the factors behind the resurgence.
Keywords: COVID-19; RNA Virus; Quarantine; Myalgia; Fever; Fatigue; Anti-inflammatory drugs; Resurgence
Introduction
The novel coronavirus disease (COVID-19) emerged as a public health emergency in China, and in a short span of only a few months, it engulfed the entire world that could not help but suffer the devastating effects of this potentially fatal disease [1]. COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has adapted the features of a pandemic as identified by World Health Organization (WHO) [2-4].
SARS-CoV-2 is a beta coronavirus, similar in genome to the bat virus that is considered to be the natural host [5]. In December 2019, since its beginning in Wuhan, China, it spread worldwide [6]. Historically, coronaviruses have a total of 7 types, two of which are known to be the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), presented in China in 2002, and its animal- to- human transmission was traced to civets. The second severe coronavirus variant transmitted from dromedary camels, was observed in Saudi Arabia in 2012 and termed the Middle-Eastern respiratory syndrome virus (MERS-CoV) [7]. The current outbreak of SARS-CoV-2 originated in a wholesale seafood market of Wuhan city, in the Chinese province of Hubei. The outbreak was aggravated by high human- to- human transmission [8]. Coronavirus encompasses 2 major modes of transmission, including human-to-human transmission (HHT) and animal-to-human (zoonotic transmission) [9].
The virus and its nature
The virus causing COVID-19 has been labeled as SARS-CoV-2 due to its remarkable homology with SARS-CoV, which presented with Acute Respiratory Distress Syndrome (ARDS) and high mortality rates in 2002-2003 [10]. Interestingly, there is a clear similarity between the clinical presentation of COVID-19 and the disease caused by other respiratory viruses. This similarity with SARS-CoV is less than seventy percent, along with a high mutational ability of the SARS-CoV-2, which posed obstacles to the development of an effective vaccine [11]. The main proteins present in and on the surface of the virus include Membrane protein (M), Envelope protein (E), Nucleocapsid protein (N) and Spike protein (S). Mechanisms involving immune targeting of these viral protein epitopes by B and T cells have been employed to develop vaccines, which have been put through clinical trials worldwide [12]. Any stoppage in the transmission chain of COVID-19 through effective vaccinations, social measures and/ or treatment on a larger scale can help inhibit its spread [13]. Mechanism and Infectivity:
COVID-19 is highly infective as the SARS-CoV-2 consists of untranslated RNA regions in the form of 5’UTR, replicase complex, S gene, M gene, E gene, N gene and several other untranslated regions that make it more virulent [14]. SARS- CoV-2 affects helper T cells and results in progressive, severe and systemic inflammation that may even lead to fulminant myocarditis or even disseminated intravascular coagulation (DIC). Inflammatory markers involved in this inflammatory cascade include interleukins like IL-6, inflammatory cytokines, membrane lipopolysaccharides, D-dimers, fibrinogen, angiotensin II release through the renin-angiotensin- aldosterone-system (RAAS), reactive oxygen species (ROS) and pro-inflammatory products released from natural killer (NK) cells (Figure 1) [15].
SARS-CoV-2 is a positively charged and single-stranded RNA virus, which infects by planting itself into the cell’s cytoplasm. The hijacking of the transcriptional machinery involves an intricate initial mechanism involving the angiotensin-converting enzyme 2 (ACE-2), which allows receptors. SARS-CoV-2 interaction with the ACE-2 receptors and transmembrane serine protease 2 to gain entry into the epithelial cells of the lungs, as well as other organs such as the brain, kidneys, lungs, heart, pharynx and liver [16]. ACE-2 and RAAS counter-act each other and downregulation of one system in COVID-19 infection may trigger high immunological response leading to grave complications and organ failure [17].
Global Approaches for Pandemic Management:
Different models and approaches have been used to manage the pandemic around the world in different countries and regions. Important components involve reliable surveillance, news reports, providing detailed patient level data and construction of outbreak management. Surveillance is important as it can unmask and trace down undocumented cases, which have the highest risk of spread. Fatigued and overwhelmed healthcare systems have required encouragement and support of all kinds, which at times have not been forthcoming. [18].
Upper respiratory swab/sputum/aspirates/nasopharyngeal content tested for SARS-CoV-2 Real-time polymerase chain reaction (RT-PCR) test can allow the establishment of effective identification of COVID-19 positive patients and their timely isolation, which can reduce further transmission.
A linear correlation has been observed between the risk of contracting COVID-19 and exposure with a COVID-19 positive patient. Distance and duration of exposure also determined the transmissibility; greater the duration of exposure greater would be transmission and vice versa
The Italian catastrophe was the first major concern arising after the Chinese outbreak of COVID-19. It is widely perceived that the susceptibility of the Italian population to morbidity and mortality from COVID-19 was predominantly due to the large proportion of elderly individuals [19]. It has also been claimed that an earlier mass-scale influenza vaccination drive led to a hyperactive immune response, leading to elevated death rates (available at: https://emedicine.medscape.com/ article/2500139-overview).
In some other parts of Europe, subjecting the susceptible population to safer lockdown arrangements suppressed their chances of getting the virus and reduced deaths. However, this approach eliminated the exposed healthy population, leading to even greater number of victims. Lockdown in developed countries has been shown to be 90 percent effective due to effective implementation, population education and awareness, but the same cannot be said about the developing world [21] After massive endemic in USA, The Tracker of the New York Times Vaccine has listed a number of vaccines for continued clinical trials, as well as approval for full use. A process of investigating number of immunotherapies and treatment combinations is still going on in the United States of America. Following ongoing government struggle in tackling the great percentage of active cases and induced resultant deaths, two mRNA vaccines, including Pfizer and Moderna, have received FDA approval by December 2020. However, vaccines like Johnson and Johnson are nearing their final trials or phase 3 trials and can portray good prospects.
Experience from Pakistan: Pakistan, as a developing country, lacked population awareness and resources for a complete lockdown. Poor socio-economic conditions and the overburdened state systems did not permit the government to provide for a large population that would have undergone unemployment as a result of lockdown. In order to avoid such chaos, only a regional and partial lockdown was observed in Pakistan [22]. The epidemic curve of COVID-19 has been categorized into two distinct waves with an intervening plateau phase after the first wave, followed by an exponential resurgence of cases upon the arrival of the second wave [23]. Immunological responses have been greatly emphasized for the double peak epidemic curve, and both innate and adaptive immunity play a crucial role in responses generated against viral exposure [24]. Innate immunity, if active and efficient, including natural killer cells (NK) cells, interferon, and complement systems of protein and IgA immunoglobulin secreted in body fluids, can inhibit the virus in initial phases. However, the mode of action of adaptive immunity requires the initial viral load and viral replication for presenting its viral particles to CD8+T along with MHC antigens class1 developing memory cells [25].
Clinical Features and Diagnostic Approaches
The incubation period of the SARS-CoV-2 has been averaged as 6.4 days with a range from 0 to 24 days. Symptoms typically appear 5- 7 days after initial exposure to the virus [26]. SARS_ CoV-2 mainly affects the pulmonary system [27] and eventually leads to ground glass opacities and patches in the lungs [28], but every infected person does not develop symptoms [29]. A number of affected individuals developing complications were found to have chronic comorbidities [30] like hypertension, diabetes, coronary heart disease, cerebral infarction, chronic bronchitis, asthma and others [31]. Among adults across all age groups, males are more affected than females. The clinical manifestations observed in patients suffering from COVID-19 include a spectrum of different combinations and intensities of various signs and symptoms, including some major indications like fever and cough in up to 80% of cases with fever of 101oF or above. Shortness of breath has been observed in 31% of clinical cases with the coarseness of breathing sounds upon auscultation.
Physicians experience diagnostic traps in treating COVID-19 patients. One good example is the pneumonia-like appearance on the X-ray that can mask the virus and perplex the physician. In 50 percent of the cases, CT remains normal for 0 to 2 days after the onset of flu-like symptoms [32]. COVID-19 RT-PCR sensitivity is low (60-70 percent). X-ray may show peripheral or multi-focal opacities, but PCR may still be negative [33]. The virus attacks the respiratory system, resulting in severe acute respiratory syndrome characterized by pneumonia, shortness of breath, asthma, nasal congestion, sore throat, fever, fatigue and myalgia [34]. Apart from respiratory involvement, the virus has also been shown to enter and disrupt the gastrointestinal, hepatic and neurological domains [35]. The worst CT findings appear 9- 13 days after contracting SARS-CoV-2, after which CT scan begins to clear and shows a decrease in the ground glass opacities provided no further complications develop [36, 37].
As the world is progressing to the era of molecular mechanics, thus COVID-19 is ideally detected using RT-PCR [38]. As the infection persists, immunoglobulins of IgG and IgM types are produced as a response to control the infection [39]. COVID-19 RT-PCR has a low sensitivity of 60 to 70 percent and mostly depends on the degree of shedding of the virus by the individual in the oropharynx secretions [40]. Complete blood counts giving a viral picture, including leucopenia or decreased lymphocyte count, are also suggestive of COVID-19 in patients with a history of possible exposure. Serum Ferritin, C-reactive protein and D-dimer levels also are useful in the diagnostic and prognostic management of COVID-19 as they reflect inflammatory and immunological responses to the viral invasion [41]. The SARS- Cov2 antibody test is efficient after 1 to 3 weeks following the appearance of symptoms [42].
Radiological aspects such as observance of a pneumonia pattern [43] are important in assessing disease severity, and they are assessed better and earlier on CT-scan rather than on chest X-ray [44]. In 57% of cases, these are referred to as ground- glass opacities or consolidations, or cavitation, depicting airspace disease [45].
Treatment Choices
The search for an absolute treatment of COVID-19 has been going on for the last year, but a single magical therapeutic agent has remained elusive. The combination of anti-influenza agent Oseltamivir and anti-HIV agent Lopinar/Ritonavir has been used together, but no definitive comment can be made on their efficacy [46] Chloroquine/hydroxyl-chloroquine administration in some studies were shown to interfere with the replication cycle, but larger clinical studies have not shown much therapeutic benefit [47]. Immunity boosters such as multi- vitamins and the use of vitamin D may potentially interfere with the intensity of the disease as well as quicker recovery due to their suggested role against aggravated allergic and anti- inflammatory response [48-51]. Antibiotics like azithromycin for bacterial complications has also been used. Anti-inflammatory drugs have been employed to reduce elevated inflammatory and immune responses and extend protection against cytokine strike complications and risks [52].
Nucleoside analog trials such as Remdesvir proved to be useful against a wide range of RNA viruses, but their use in COVID-19 has not yet been established [53-57]. Table 2 lists the various pharmacologic agents that have been tried in the treatment of COVID-19.
Preventive Measures
With the intention of stopping person- to -person transmission, health measures such as Isolation, Quarantine, Social distancing, and Community containment were taken into consideration [77]. The elimination of viruses from the surfaces by chemical means, especially in places with a high risk of contamination, has further reduced their spread. Furthermore, measures at an individual level that include frequent hand washing, use of sanitizer, and wearing of masks have been proven to be beneficial [78-80]. Timely dissemination of information in the media is crucial to effective administration of personal protection, limiting imports, public gatherings and anything aggravating chances of contact and spread. Proper Screening and travel restrictions can potentially withhold the spread of the virus to a great degree. Training of Medical and non-medical teams should avoid reducing the burden on health care professionals [81].
Vaccination
Collaborative initiatives between public and private sectors and facilitated by the World Health Organization (WHO) have allowed for rapid vaccine development programs, which have led to successful production and development of many different vaccines against SARS-CoV-2 involving various mechanisms of action. Pfizer-BioNTech was the first one to gain recognized approval. It has been shown to confer 95% protection against COVID-19 in people older than 16 years of age through a two- shot regimen with the second dose given two weeks after the first. Safety over a median of 2 months has also been demonstrated to be similar to that of other viral vaccines (available at: https://www.biospace.com/article/comparing- covid-19-vaccines-pfizer-biontech-moderna-astrazeneca- oxford-j-and-j-russia-s-sputnik-v/)
Table 3 provides a list of some of the vaccines that are currently being used in the world and their mechanisms of action [84]. Vaccine- induced immunity is considerably different from naturally induced immunity, as the majority of the population (up to 74 percent) who are asymptomatic or have mild symptoms may develop very few antibodies and this may not last long. This seriously changes the dynamics of the possible chances of herd immunity. Keeping tracks of subjects after vaccination is a key feature of any vaccine trial. Making comprehensive data of T-cell and antibody presentation will allow a record of the vaccine- induced protection and its effects later on [83]. Conclusion:
The importance of a well-coordinated approach cannot be denied, and the management of the second wave could be a deciding point in a successfully combating the COVID-19 pandemic. A structured approach is essential for the management of this global crisis. The development of a reliable and effective treatment and fast vaccine deployment are crucial factors. Economic management is required, as well as special attention to patients with other underlying conditions like cancer, renal failure, diabetes and pregnant women [84]. Vaccines are our greatest hope, and transmission prevention should remain a priority to allow for the flattening of the epidemic curve and halt COVID-19 intensity. A better understanding of the disease spread, the initiation of vaccination drives, and adequately equipped healthcare facilities are cause of optimism, but slackness at the government or public levels may lay waste the gains obtained so far.
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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Physical therapy role for COVID 19 patients
Mohamed Ahmed Mohamed 1, Mohamed Farouk Mohamed 2, Hanaa Ali Hafez 3
1 Department of Physical Therapy, Faculty of Physical Therapy, Merit University, 2 Department of Chest Diseases, Faculty of Medicine, Beni Suef University, 3 Department of Physical Therapy, Faculty of Physical Therapy, Nahda University, Egypt
DOI: 10.4328/ACAM.20460 Received: 2020-12-30 Accepted: 2021-03-04 Published Online: 2021-03-25 Printed: 2021-07-01 Ann Clin Anal Med 2021;12(7):829-834
Corresponding Author: Mohamed Ahmed Mohamed, Department of İnternal Physical Therapy, Faculty of Physical Therapy, Merit University, Hassan Abd Elmonem st. El Fashn, Beni suef, Egypt. E-mail: mohamedababa@yahoo.com P: 00201006794075 Corresponding Author ORCID ID: https://orcid.org/0000-0002-4294-9543
Physiotherapy is a longtime profession throughout the globe. Globally, physiotherapists typically work in acute hospital wards and ICUs. Above all, cardiore- spiratory physical therapy focuses on the management of acute and chronic metabolic process conditions and aims to enhance physical recovery following an acute health problem. This study aims to produce info to physiotherapists and acute care aid facilities regarding the potential role of physical therapy within the management of hospital-admitted patients with confirmed or suspected COVID-19. Physiotherapists who add primary aid facilities are possible to play a task within the management of patients admitted to hospital with confirmed or suspected COVID-19.
Keywords: COVID-19; Physical therapy; Chest physical therapy
Introduction
Coronavirus 2019 (COVID-19 or SARS-CoV-2) could be a producing virus of an infectious disease involving severe acute respiratory syndrome. The malady was discovered in December 2019 in Wuhan, the capital of Hubei province in China, and has unfolded everywhere on the planet, inflicting the coronavirus pandemic. Fever, cough, and shortness of breath are commonly present and could embody fatigue, muscle pain, diarrhea, pharyngitis, loss of smell, and abdominal pain [1]. Its incubation period is around 5 days, but could vary from 2 to 14 days, however, nearly 97.5 % of individuals can develop symptoms at intervals of 11.5 days [2]. Most cases are mild but some develop in to respiratory disease “pneumonia” and multi-organ failure [3]. As of the Gregorian calendar, November 30, 2020, has caused over sixty million cases of COVID-19 and claimed the lives of 1.5 million individuals worldwide. Within the US, over thirteen million cases are reported to the Centers for Disease Control and Prevention (CDC), with over 260,000 deaths [4]. Some Chinese cases manifested solely with chest tightness and palpitations. One study stated that about half of the participants developed a fever at the beginning of their hospitalization, and eighty nine developed a fever later on. Fever and chest troubles appeared later in some older adults and people with other medical conditions [5]. Typically, it progressed to respiratory disease, multi-organ failure, and death [3]. With severe symptoms, the time required from onset to mechanical ventilation is often eight days [5].
The virus is primarily unfolded through shut contact typically by respiratory droplets expelled throughout coughing, sneeze and talking. Shut contact is taken into account being at intervals nearly 1–3 m (3–10 ft) from an infected individual. In March 2020, an editorial argued that the reported droplets distance neglected the results of heat wet outbreath close the droplets and that an uncovered cough or sneeze would travel up to 8.2 meters (27 feet). These droplets typically fall to the bottom or on totally different surfaces, instead of remaining within the air over long distances. During this case, infection occurs mainly by touching a contaminated surface followed by touching the eyes, nose, or mouth [6]. This virus remain infective on surfaces for up to seventy two hours. The foremost contagious amount occurs during the first 3 days once the onset of symptoms, however the transmission could occur before symptoms appear and throughout the malady amount [3].
Not all the small print regarding its transmission area unit glorious [6]. Liquid body substance and spit will have oversized microorganism masses [7]. When speaking loudly, many droplets will be released [8]. A study in Singapore expressed that uncovered cough droplets would travel up to 4.5 meters (15 feet) [9].
Physiotherapy is considered a very important as it prevents the adverse effects of prolonged bed rest and mechanical ventilation. Rehabilitation is carried out in accordance with the wishes of the patient and depends on the amount of consciousness, psychological and physical parameters of the patient. It includes any active and passive therapy that promotes movement. The role of the ICU physical therapist can continue throughout the COVID-19 pandemic, so this paper aims to:
– Give information’s on the COVID-19 pandemic and it’s
pathophysiology
– Give an account about the last medical treatment for COVID-19 – Explain the role of physical therapy for the COVID-19 patient – Clarify the benefits of chest physical therapy for the COVID-19 patient [40].
Pathophysiology
The lungs area unit is the foremost target organ as a result of the virus infections of the host cells via the enzyme angiotensin-converting enzyme 2 (ACE2), particularly on type II alveolar cells of the lungs [10]. The density of ACE2 within the tissue matches the severity of its effects, and it was absolutely steered that decreasing ACE2 activity may be protecting [11,12], however this has not tested [13].Thus, with malady progression, respiratory failure and death could occur [12]. Autopsies of infected cases showed diffuse alveolar damage (DAD), and lymphocyte-containing inflammatory infiltrates in the lungs [14].
The virus conjointly affects gastrointestinal organs [15], endothelial tissue cells and enterocytes [16]. ACE2 may be found within the brain, thus infection will cause neurological manifestations like loss of smell, headaches, nausea and vomiting. Encephalopathy can also occur [17]. The virus will harm the circulatory system [5], which has been ascertained in 12% of infected people in Wuhan, China [18], and has been noted in many severe cases [19]. This injury can also be associated with ACE2 receptors within the heart [20]. An increased incidence of thrombosis (31%) and venous thromboembolism (25%) was ascertained in critical care unit patients with the malady [20,21]. The virus conjointly infects kidney cells, causing acute kidney injury, a standard complication and reason for death, particularly in patients with compromised kidney function [22].
There are four forms of pneumonia severity [14]:
• Minor pneumonia: minor serous exudation and minor fibrin exudation.
• Mild pneumonia: pulmonary edema, pneumocyte hyperplasia, large atypical pneumocytes, interstitial inflammation with lymphocytic infiltration and multinucleated giant cell formation. • Severe pneumonia: diffuse alveolar damage (DAD) with diffuse alveolar exudates. DAD causes acute respiratory distress syndrome (ARDS) and severe hypoxemia.
• Healing pneumonia: the formation of exudates in the alveolar cavities and pulmonary interstitial fibrosis.
Not all infected people develop symptoms (asymptomatic carriers). These could contribute to the development of the disease, and their proportion is presently unknown. The Korea Centers for Disease Control and Prevention (KCDC) stated that they represent 20 % of all confirmed cases throughout their hospital stay [23].
Progression
Acute lung injury/acute respiratory distress syndrome (ALI/ ARDS) is detected by Murray score (Table 1), the ultimate score is obtained by dividing the collective score by the quantity of the used elements. Zero indicates no respiratory organ injury, 1 – 2.5 indicates mild to moderate injury, and ≥ 2.5 indicates ARDS [24].
Diagnosis
Real-time reverse transcription-polymerase chain reaction (rRT-PCR) from a nasopharyngeal swab is common. Chest CT might facilitate in people with suspected infection, supported symptoms and risk factors; however, not for routine screening. The World Health Organization (WHO) declared the 2019–2020 coronavirus outbreak a Public Health Emergency of International Concern (PHEIC) on January 30, 2020 and a pandemic on March 11, 2020. Native transmission of the disease has been recorded in most countries across all six WHO regions [25].
Management
1. Prevention
There are several efforts to cut back the number of active cases at any given time, with the infection of “flattening the curve” to permit aid services to rise manage the outbreak. Likewise, increasing aid capability, or “raising the line” will improve management, by increasing bed count, personnel, and instrumentation. Inadequate mitigation may result in a recurrence of the pandemic. Preventive measures embody staying at home, avoiding packed places, washing hands with soap and water for a minimum of twenty seconds, and avoiding touching the eyes, nose or mouth with unwashed hands [26]. The CDC recommends covering the mouth and nose with a tissue or using the inside of the elbow when coughing or sneezing. Correct hand hygiene is needed when coughing or sneezing. In addition, using material protective face covers public places can help, in limiting transmission from symptomless people. Social distancing methods aimed at reducing contact of infected persons with giant teams by closing colleges and workplaces, limiting travel and canceling giant public gatherings. Distancing pointers additionally embody that individuals occupy at least half a dozen feet (1.8 m) apart. Personal hygiene and a healthy lifestyle and diet are counseled to enhance immunity [27].
For medical groups, the CDC recommends using personal protective equipment (PPE): gown, eye protection, respirator or facemask and medical gloves. Once attainable, respirators are most popular. N95 respirators, the sort approved for industrial settings, were approved by the FDA under the Emergency Use Authorization (EUA). Once the masks don’t seem to be out there, the CDC recommends using face shields or, as a final resort, do-it-yourself masks. The use of masks is suggested for those with suspected infection and their caregivers, however recommendation on its use by the overall public varies between required use to recommendations against their use [28]. Reusable non-invasive instrumentation should be decontaminated within the following situation: between and once every patient use, once contaminated by blood and body fluid and regularly as part of equipment cleaning. An increased decontamination frequency is to be considered for reusable non-invasive care instrumentation once employed in isolation/ cohort areas [27].
2. Medications
No specific treatment or vaccine for COVID-19 has been created out there at this stage. However, the analysis is current [6]. Management is restricted to the treatment of symptoms, supportive care, isolation, and experimental measures. No evidence suggests that NSAIDs worsen COVID-19 symptoms. However, there are some recommendations for using paracetamol (acetaminophen) over ibuprofen. No sufficient information has been found to justify stopping ACE inhibitors and angiotensin receptor blockers. Many immune-based therapies that are expected to switch the course of COVID-19, as well as corticosteroids, are currently under investigation or are already in use. These agents might target the virus (e.g., convalescent plasma) or modulate the reaction (e.g., corticosteroids, interleukin [IL]-1 or IL-6 inhibitors) [29].
The Committee has reviewed unpublished section I/II/III safety and effectuality information of the Pfizer BioNTech mRNA vaccine. The vaccine seems to be safe and well-tolerated, and there have been no clinically regarding safety observations. The information indicates a high effectuality in all age groups (2-16 years and over), as well as encouraging older adults. The Committee advises that this vaccine be employed in the primary section of the program, in keeping with the priority order commenced below. Whereas there is some evidence to point high levels of short-run protection from one dose of vaccine, a two-dose vaccine schedule is presently suggested in accordance with restrictive approval [30].
Low molecular weight heparin improves outcomes in severe COVID-19 with signs of coagulopathy (elevated D-dimer). Validation of care will involve fluid medical aid, oxygen support, and support of different very important organs [31]. Extracorporeal membrane oxygenation (ECMO) has been employed in cases of respiratory failure; however, its advantages are underneath analysis [33,34].
Most COVID-19 cases do not need mechanical ventilation or alternatives [35,36], and intubation is often avoided with a high flow nasal cannula or bi-level positive airway pressure [36]. Some doctors like invasive mechanical ventilation because it limits the unfold of aerosol particles compared to a high flow nasal cannula [35]. Severe cases are undoubtedly common in older adults (≥60 years, and particularly ≥80 years) [36]. One study in China showed that 5% of patients were admitted to medical care units, 2.3% required mechanical support of ventilation, and 1.4% died. Roughly 30% of individuals in hospitals in China with COVID-19 are eventually admitted the unit [33].
Also, the absence of major organ system failure should be considered during weaning from MV as [37]:
1. Optimized cardiovascular function (Arrhythmias, Fluid overload, myocardial contractility).
2. Body temperature: 10 degree will increase carbon dioxide production and O2 consumption by 5%
3. Normal electrolytes: potassium, magnesium, phosphate and calcium.
4. Adequate nutritional status: underneath or over feeding. 5. Optimized renal, Acid-base, liver and GI functions.
3. Physiotherapy
Physiotherapy is considering a very important hindrance of the adverse effects of prolonged bed rest and mechanical ventilation. Rehabilitation is performed according to the wishes of the patients and depends on the level of consciousness, psychological and physical parameters of the patient [38]. It includes any active and passive therapy that promotes movement. The role of ICU physical therapist can continue throughout the COVID-19 pandemic, with the utilization of full PPE whereas operating. High-risk patients might also profit. Physiotherapists could give airway clearance techniques for ventilated patients with insufficient airway clearance and position patients with severe respiratory failure related to COVID-19, using a prone position to optimize oxygenation [39]. As with any contagious respiratory condition, physical therapists and people within the immediate atmosphere of the patient must follow strict protocols and make sure the use of PPE while ideally treating the patient during a single space with the door closed, limiting employee’s variety and minimizing entry and exit from the space throughout the treatment. The secretion load of individuals with COVID-19 is low in order that they do not typically need invasive or intensive airway clearance techniques. Physical therapy here is focuses more on non-invasive ventilation support measures than on the rehabilitation section [45].
In the early stages of COVID 19 and respiratory distress, common modalities used are also contraindicated within the acute section (may compromise the high work of breathing). Contraindicated interventions include [40]:
• Diaphragmatic breathing
• Pursed lips breathing
• Bronchial hygiene/ lung re-expansion techniques (PEP Bottle, cough machines, etc.)
• Incentive spirometry
• Manual mobilization techniques or stretching of the skeletal structure
• Nasal washings
• Respiratory muscle training
• Exercise training
• Patient mobilization throughout clinical instability
Goals of physiotherapy in ventilated patients
1- For the acute phase, the program is focused on:
a. Increasing the ventilation and oxygenation:
Positioning techniques: supine, prone and lateral attitude could considerably alter oxygenation. Positioning is significant in the management of the mechanically ventilated COVID-19 patient, with regular turning to optimize ventilation, stop pathology and forestall pressure sores [39]. Positioning includes a lateral positioning and prone positioning, which might be accustomed to treat hypoxemic respiratory failure. Prone ventilation (i.e. ventilation whereas within the prone position) could improve lung mechanics and gas exchange, resulting in enhancements in oxygenation within the majority of patients with ARDS, and might improve outcomes [41]. Prone ventilation has been reported to be effective in hypoxic patients with COVID-19 and will be completed consistent with the hospital pointers that embrace applicable PPE for workers and reduce any adverse events, e.g. accidental extubation and breaking of the circuit.
Prone positioning is usually recommended for a minimum of sixteen hours per day in adults [42].
b. Reduction of the O2 Consumption
In mild to moderate stages of the disease, usual oxygen support (facemask oxygen) is also advantageous. WHO recommends oxygen supplementation like a shot, with a target SpO2 > 94%, for patients with respiratory distress, hypoxemia or shock. Patients should still have accumulated work of breathing or hypoxemia even once whereas employing a mask with reservoir bag (flow rates of 10 – 15 L/min, FiO2 0.60 – 0.95). Nasal cannulas do not seem to be counseled as a they will result in the next spread of droplets [41].
Whereas the use of high-frequency nasal oxygen carries a little risk of aerosol generation, it is a counseled methodology for treatment of hypoxia related to COVID-19, providing the employees are carrying optimum airborne PPE. This may due to the low probability of a transmission mechanism following the use of optimum PPE and different infection management measures. Negative pressure rooms are most well-liked for these patients [41]. Nebulisation is not counseled. If the patient has developed ARDS, noninvasive ventilation (NIV) is generally not recommended and intubation with mechanical ventilation is most preferred, in addition to a prone position to assist ventilation and closed suctioning [39].
2-Early post-acute phase, the rehabilitation program is concentrated on:
a. Reduction of the O Consumption.
Upon stabilization of the patient, the main goal in respiratory physiotherapy is to mobilize secretions and ease the work of breathing. This can be done through the techniques such as positioning, deep breathing exercises, autogenic drainage, active cycle of breathing, breath stacking, mobilization and manual techniques (e.g. percussion, vibrations, assisted cough) to help sputum expectoration [45]. Closed inline suction catheters are recommended and imperative to avoid disconnection of the patient from the ventilator to prevent lung decruitment and aerosolization. If needed, clamp the endotracheal tube and disable the ventilator (to prevent aerosolization). Suctioning is to be used as required, though not on regular basis [43]. 3-Long term rehabilitation, the rehabilitation program is concentrated on:
a. To prevent and/or correct shortening of soft tissues.
b. Mobility and active daily life.
These include passive, active assisted, active, or resisted joint range of motion exercises to maintain or improve the range of motion, joint integrity, and muscle strength. They typically involve mobilization and rehabilitation (e.g. bed mobility, sitting balance, sitting out of bed, sit to stand, standing hoists, walking, tilt table, upper limb or lower limb ergometry, exercise programs) [45].
Conclusion:
Physical therapy is an effective treatment for patients with COVID-19 as it improves secretion clearance, reduces O2 consumption, increase oxygenation, and prevents bed ridden complications.
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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