Incidental dental anomalies and jawbone pathologies in Turkish pediatric patients of the Eastern Mediterranean region
Katibe Tuğçe Temur
Department of Oral and maxillofacial radiology, Niğde Ömer Halisdemir University, Niğde, Turkey
DOI: 10.4328/ACAM.20726 Received: 2021-06-02 Accepted: 2021-08-19 Published Online: 2021-10-28 Printed: 2021-12-01 Ann Clin Anal Med 2021;12(12):1320-1324
Corresponding Author: Katibe Tuğçe Temur, Department of Oral and Maxillofacial Radiology, Faculty of Dentistry, Omer Halisdemir University, Niğde, Turkey. E-mail: email@example.com P: +90 553 161 67 32 Corresponding Author ORCID ID: https://orcid.org/0000-0001-9947-5679
Aim: The present study aimed to examine the prevalence of incidental dental anomalies and jawbone pathologies in a group of pediatric patients from the Eastern Mediterranean region.
Material and Methods: Sociodemographic data of the patients were extracted from digital automation records. Moreover, panoramic radiography archives of pediatric patients, who applied to the School of Dentistry, Sütçü İmam University for examination for any reason, were scanned so that dental anomalies and jawbone pathologies were determined. The study was conducted by an oral and maxillofacial radiologist.
Results: The study examined the panoramic radiographs of 1432 pediatric patients aged 5-17 years. The most prevalent incidental dental anomaly and jawbone pathology were impacted teeth (4.8%) and periapical lesion (21.8%), respectively. Nevertheless, while the least prevalent incidental dental anomalies were ectopic teeth (0.2%), taurodontism, and macrodontia (0.6%), we found the least prevalent pathological finding to be odontoma (0.2%).
Discussion: This retrospective study on a group of pediatric patients from the Eastern Mediterranean region revealed that the most prevalent dental anomaly was impacted teeth, while the most prevalent pathology was periapical lesion. Ultimately, in the early detection of such findings, all regions should be routinely evaluated in panoramic radiographys.
Keywords: Panoramic Radiography, Dental Anomalies, Pathologies, Incidental Findings
In dental practice, radiographs are used in addition to clinical examination to confirm the clinical diagnosis and plan the treatment. In this sense, panoramic radiography is used to visualize the entire maxilla, mandibular, and other surrounding structures with the help of a single image. Its greatest advantage is to offer a straight, single image .
Panoramic radiography is a favored imaging method for pediatric patient groups as most children can tolerate it effortlessly due to its noninvasive features. It also provides comprehensive information on the dentomaxillofacial region, including erupted and unerupted teeth, tooth germ development, and various dental anomalies in the maxilla and mandibula. The information and clinical findings through panoramic radiographs facilitate the diagnosis process .
Dental anomalies are cases of difference in the number (hypodontia and hyperdontia), size (microdontia and macrodontia), shape (taurodontism and dilaceration), structure (amelogenesis imperfecta and dentin dysplasia), and persistence (ectopic and embedded) of teeth and affect both primary and permanent dentition. Dental anomalies may be congenital, developmental, or acquired . Besides, like adults, it is known that lesions such as radicular cyst, odontoma and ameloblastoma develop in pediatric patients as in adults . Lesions and dental anomalies in children’s jawbones may alter tooth eruption, cause abnormal occlusion, and, in advanced cases, affect the aesthetics and their social lives. If such alterations are detected early, they are more likely to be treated surgically and orthodontically; thus, their functional, psychosocial, and financial problems might be reduced .
In the literature, it has been reported that panoramic radiographs of pediatric patients at the first admission could enable the detection of incidental findings other than the findings related to the main complaints, and early treatment of such lesions might help prevent the occurrence of complications .
It is well-known that the incidences of dental anomalies and pathologies vary by society [1,7,8,9,10].
Overall, the present study aimed to examine the prevalence of incidental dental anomalies and jawbone pathologies in a group of pediatric patients from the Eastern Mediterranean region of Turkey.
Material and Methods
In this study, we went through panoramic x-ray archives of pediatric patients, who applied to the School of Dentistry, Sütçü İmam University for examination for any reason. The research was a cross-sectional, retrospective study and granted with ethical permission by the Clinical Research Ethics Committee, School of Medicine, Kahramanmaraş Sütçü İmam University (2020/01).
Panoramic radiographs with the fine image quality of patients under 18 years were included in the study. Radiographs of syndromic patients (Down syndrome, Ectodermal dysplasia, etc.) and patients with cleft lip and palate, radiographs with poor image quality and artifacts affecting the image evaluation, and third molars were excluded from the study.
All radiographs were obtained with the GENDEX, GDP -700 model panoramic X-ray device with 66 kV, 6.3 mA, and 14 seconds exposure time in the pediatric patient module. Sociodemographic data of the patients were extracted from digital automation records. The presence or absence of dental anomalies and jawbone pathologies were determined by examining the panoramic radiographs. Findings were categorized as dental anomalies (supernumerary teeth, hypodontia, impacted teeth, mesiodens, root dilaceration, microdontia, macrodontia, taurodontism, and ectopic teeth), lesions in the jawbones (periapical lesion, odontomas, root resorption), and other (fracture line) (Figure 1, 2, 3, 4). The obtained results were tabulated in the Excel program and then analyzed statistically. The definitions in the book of White and Pharoah  were considered in the diagnoses of anomalies and lesions.
An oral and maxillofacial radiologist evaluated the panoramic radiographs.
In the study, panoramic radiographs of 1,432 pediatric patients aged 5-17 years were evaluated in the study. Of whom, 856 (59.8%) were females and 576 (40.2%) were males. Sociodemographic characteristics of the patients are shown in Table 1.
The incidence of at least one dental anomaly was found to be 16.8%. The most prevalent incidental dental anomaly and jawbone pathology were impacted teeth (4.8%) and periapical lesion (21.8%), respectively. Nevertheless, while the least prevalent incidental dental anomalies were ectopic teeth (0.2%), taurodontism, macrodontia (0,6%) and microdontia (1.3%), we found the least prevalent pathological finding to be odontoma (0.2%). Table 1 demonstrates the descriptive analysis of the incidental findings.
The incidence of impacted teeth was found to be significantly higher in males (p=0.005) and the 12-17 age group (p<0.001). Besides, supernumerary teeth showed themselves significantly more prevalent in the group aged 12-17 years (p<0.001). The males and the group aged 12-17 years had significantly higher incidence of periapical lesions (p <0.005). Finally, we found the incidence of mesiodens to be significantly higher in the group aged 6-12 years (p=0.003).
The incidence of taurodontism was significantly higher in females and the group aged 6-12 years (p <0.005). In addition, we discovered dilaceration to be significantly higher in females and the group aged 12-17 years (p <0.005). There was significantly higher root resorption in the 12-17 age group (p <0.001). While microdontia was significantly more prevalent in the 6-12 age group (p <0.005), the females and the group aged 6-12 years had significantly more macrodontia (p <0.005). Finally, the incidence of fracture lines was significantly higher in males (p = 0.008). Table 2 shows the relationships of the incidental findings by gender and age.
In the literature, there are studies evaluating the incidences of dental anomalies and pathologies in pediatric patient groups in different geographies [1,7,8,9,10,11].
In our study, the incidence of at least one dental anomaly was found to be 16.8%. Previously, Bawazir et al.  found it to be 29.8% in their study with 1,311 Arabic children aged 6-20 years, while Haugland et al.  discovered it to be 28.2% in their study with 500 Norwegian children aged 12 years 11. Also, in their study with Indian students aged 14-17 years, Gupta et al.  reported that 29.8% of the participants had at least one anomaly.
In Turkey, Özveren et al.  revealed that the incidence of dental anomalies was 10% in Thracian child patients, while it was 11.29% in the study of Sümer et al.  conducted with 540 children aged 6-13 years. The differences in the results of the study, the types of dental anomalies included in the study, age group differences in the sample, the sample sizes and the differences in the geographies might be explained. Besides, the diagnostic criteria used in some studies are not clear, which might cause such differences.
In this study, the most prevalent jawbone pathology was found to be periapical lesion (21.8%). In the study conducted by Namdar et al.  on a similar age group, the rate of apical osteitis was reported to be 35.52%. Moreover, in this study, the incidence of periapical lesions was significantly higher in the 12-17 age group and males. Reis et al.  reported that the radiolucent changes in the jawbone could occur in patients aged around ten years but determined no significance by gender. The most prevalent dental anomaly in our study was impacted teeth (4.8%). In addition, we found the incidence of impacted teeth was found to be significantly higher in the 12-17 age group. Unlike this study, Bawazir et al.  reported that impacted teeth (3.2%) were the fourth most prevalent dental anomaly. Nevertheless, similar to this study, Shokri et al.  found that the most prevalent anomaly was impacted teeth (45.5%) among the patients aged 7-35 years. This rate is considerably higher than what was found in this study, which may be due to the high mean age and the inclusion of the third molar teeth in that study .
The incidence of supernumerary teeth (mesiodens and other supernumerary teeth) was 4.6% in our study. Similarly, this incidence was found to be 4.25% in the study of Sümer et al. . In the literature, the incidence of supernumerary teeth was reported to be more in males, but the results were not significant . In this study, no statistical difference was determined according to gender.
In this study, the incidence of mesiodens was 3.6%. In parallel with this study, mesiodens was observed at a rate of 3.94% in the study of Namder et al. . However, the incidence of mesiodens was reported to be 0.1% in the study of Aren et al. with 58,142 pediatric patients . While mesiodens is quite rare in primary dentition, it is considered to be the most prevalent dental anomaly in permanent dentition [15,16]. In parallel with the previous findings, we found the incidence of mesiodens increased significantly in the group aged 12 years, which is likely because the primary dentition period is completed at this age.
In this study, the incidence of hypodontia was 2.8%, and it was determined as the third most prevalent dental anomaly. The incidence of hypodontia was 5.34% in the study of Özveren et al. , while it was 5.37% in the study of Sümer et al. . Bawazir et al.  reported that hypodontia was the most prevalent finding among 1,311 children at the rate of 9.7%. In their study with 13.220 panoramic radiographs, Vibhute et al.  revealed that the most prevalent anomaly in orthodontic patients aged 8-14 years was hypodontia, at the rate of 27.7%. There may be an increase in the incidence of dental anomalies in orthodontic patients.
The incidence of root dilaceration was found to be 1.7% in this study. Unlike this study, Özveren et al.  found root dilaceration in only one lateral tooth among 1,759 children. It was also reported to be 4.3% in a study with a Turkish sample in the 15-65 age group. Although root dilaceration can be observed in all teeth, it is most prevalent in mandibular third molars . The exclusion of third molar teeth may explain the low incidence of this anomaly in this study. Besides, in contrast to this study, Karataş et al.  determined that it was significantly more prevalent in males in an adult patient group. Root dilaceration is rarely seen in the primary dentition; therefore, it was determined to be more prevalent in the patients aged 12-17 years in this study.
In this study, the rate of incidental fractures in the jawbones was 1.7% and significantly more prevalent in males. In parallel to the present research, Tanaka et al.  observed that boys had 2 times more fractures than girls and that the highest incidence was in boys over 13 years of age.
In this study, compared to other anomalies, non-prevalent incidental findings included microdontia (1.3%), root resorption (1.1%), taurodontism (0.6%), ectopic teeth (0.2%), macrodontia (0.6%), and odontoma (0.2%). In parallel with this study, Bawazir et al.  discovered that root resorption (0.2%), taurodontism (0.8%), and macrodontia (0.6) were relatively rare compared to other anomalies. In the study of Özveren et al. , taurodontism (1.56%), ectopic teeth (0.4%), macrodontia (0.45%), and microdontia (0.45%) were found to be other anomalies.
Araz et al.  reported that the prevalences of microdontia and macrodontia were not significantly different between girls and boys. Nevertheless, in this study macrodontia was found to be significantly more prevalent in females and the group aged 6-12 years.
In this study, taurodontism was significantly more prevalent among females, which was also the case in the study of Mac Donald et al. . Yet, some studies could not find a significant difference between children by gender . In addition, the literature generally suggests that taurodontism and the X chromosome are associated, which leads the prevalence to increase in females and permanent dentition to be more affected . This study could also not reach any taurodontism in the primary dentition.
This retrospective study on a group of children from the Eastern Mediterranean region revealed that the most prevalent dental anomaly was impacted teeth, while the most prevalent pathology was periapical lesion. Ultimately, it is recommended to routinely evaluate the other regions as well as the main complaints in the panoramic radiographs of pediatric patients who are first admitted to the clinic. Early detection of such findings may facilitate treatment and prevent possible future complications.
The author thanks Aslı Soğukpınar Önsüren for their support to the study.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Download attachments: 10.4328:ACAM.20726
Katibe Tuğçe Temur. Incidental dental anomalies and jawbone pathologies in Turkish pediatric patients of the Eastern Mediterranean region. Ann Clin Anal Med 2021;12(12):1320-1324
Influence of lumbar intervertebral disc height and geometry of the articular plateau surface on disc pathologies
Volkan Kızılgöz 1, Muhammet Bora Uzuner 2
1 Department of Radiology, Faculty of Medicine, Erzincan Binali Yıldırım University, Erzincan, 2 Department of Anatomy, Faculty of Medicine, Bandırma Onyedi Eylül University, Balıkesir, Turkey
DOI: 10.4328/ACAM.20731 Received: 2021-06-05 Accepted: 2021-08-19 Published Online: 2021-09-05 Printed: 2021-12-01 Ann Clin Anal Med 2021;12(12):1325-1331
Corresponding Author: Volkan Kızılgöz, Department of Radiology, Faculty of Medicine, Erzincan Binali Yıldırım University, Erzincan, Turkey. E-mail: firstname.lastname@example.org P: +90 505 799 40 13 Corresponding Author ORCID ID: https://orcid.org/0000-0003-3450-711X
Aim: This study aimed to investigate the relationship between the height of the intervertebral disc space and disc pathologies and the effect of differences in the vertebral articular surface on disc pathologies with regard to age groups.
Material and Methods: A total of 754 patients examined by magnetic resonance imaging were reassessed in terms of the height of the anterior, middle, and posterior intervertebral disc space and the vertebral articular plateau surface type of the L4–L5 and L5–S1 intervertebral disc levels.
Results: All L4–L5 intervertebral disc heights of all patients with any disc pathology were significantly lower than those in the normal group. For the L5–S1 disc level, anterior, middle, and posterior intervertebral disc heights of all patients with disc pathologies were significantly lower than those of the subjects without any disc pathology. There was a significant difference in the L4–L5 levels in discs with irregular articular plateau surfaces among patients in the age group of 25–40 years and for all patients as compared with normal and pathological discs. At the L5–S1 level, there were more disc pathologies in the flat and irregular articular plateaus in the group of patients older than 40 years.
Discussion: The heights of the intervertebral disc spaces were significantly smaller in patients with disc herniations and in those with any disc pathology at both L4–L5 and L5–S1 levels. The intervertebral disc levels of the L4–L5 and L5–S1 discs with irregular articular plateaus were observed to have significantly more disc herniations among all patients.
Keywords: Intervertebral Disc, Intervertebral Disc Degeneration, Intervertebral Disc Displacement, Magnetic Resonance Imaging, Lumbosacral Region
Lumbar disc degeneration has been described in radiologic terms as decreased signal intensity on T2-weighted magnetic resonance imaging (MRI) with decreased space height . An MRI study with histological correlation also showed that early disc degeneration may occur without any loss of disc height or decreased signal intensity on T2-weighted images . Age is known to be an important factor in radiologically described disc degeneration . The signal intensity, the height of the discs, and the combination of these parameters were found to be related to the disc degeneration [4–8]. Moreover, a relationship between the vertebral articular plateau shape and disc degeneration has been mentioned in the literature . However, there is a lack of studies discussing the effect of the articular plateau surface type on disc degeneration and herniation. Thus, the current study uses the powerful tool of MRI to diagnose lumbar disc pathologies [10, 11], as the value of MRI in the assessment of lumbar discs and detection of disc herniations has been well documented in the literature .
The aim of this study is to reveal the possible association of the height of intervertebral disc spaces and types of vertebral articular surface with disc pathology. We also present the relationship between the level of disc degeneration and disc pathology on MRI. Moreover, all of these results are presented with regard to patient age groups.
Material and Methods
This was a retrospective cross-sectional study approved by the relevant ethics committee. Informed patient consent was waived by our institutional committee because of the study’s retrospective nature. Data from patients admitted to our hospital for lumbar MRI between September 2018 and March 2019 were re-evaluated (n=850). Patients younger than 18 years old (n=11) were not included and only the MRI results of skeletally mature individuals were re-examined. Patients who had congenital pathologies (one patient with diastematomyelia, one patient with dural ectasia, and one patient with a tethered cord), infectious conditions (seven patients with lumbar discitis), or history of trauma (six patients with lumbar vertebra fracture) were excluded from the study. Patients who had undergone a disc operation (n=30) or who had scoliosis (Cobb angle of ≥20°; n=12), or the presence of internal fixation materials due to any kind of previous lumbar surgery (n=22) were also excluded. Patients with any kind of malignant neoplasm or vertebral lesion that affected the vertebral articular surface were also planned to be excluded from the study; however, there were no patients with such conditions among our sample. Moreover, five patients whose MRI results were not appropriate for examination because of motion artifacts were not included. Patients who met these exclusion criteria for any reason according to the MRI results were not included in the study. After exclusions, a total of 754 patients (445 female, 309 male; mean age: 45.66±14.14 years) were enrolled. These patients were divided into three age groups before re-evaluation of MRI results: ≤25 years, between 26 and 40 years, and >40 years. The L4–L5 and L5–S1 intervertebral disc levels were evaluated with regard to anterior, middle, and posterior intervertebral disc spaces; vertebral articular plateau geometry; intervertebral disc degeneration; and disc pathologies of the outer disc margins, representing disc herniation.
MRI Interpretation and Measurements
The heights of the anterior, middle, and posterior intervertebral disc spaces were measured. For each patient, the heights of intervertebral discs were measured as the distance between the anterior edges of the superior and inferior vertebral articular plateau, the distance between the posterior edges of the superior and inferior articular plateau, and the distance between two consecutive vertebral bodies at the midpoint of the anterior and posterior measurements (Figure 1).
The lumbar intervertebral discs were classified as bulging, protruding, or extruding according to the discs’ outer margins. If more than one-quarter of the intervertebral disc circumference was displaced beyond the vertebral body margins, the disc was considered to be bulging. An intervertebral disc was considered to be protruding if the outer edges of the herniated part of the intervertebral disc were smaller than the measured distance at the base of the herniated part of the disc. If the distance measured between the edge of the herniated part of the intervertebral disc and the edge of the nonherniated part of the disc was greater than the length at the base of the herniation in at least one plane of the MRI, it was considered as a case of extrusion . If no continuity was observed between the herniated disc material and the intervertebral disc itself (a sequestration), the disc was also considered to be extruding. Bulging was not accepted as a disc herniation in the current study.
To classify the vertebral body articular surfaces that were adjacent to the intervertebral discs, the terms concave, flat, and irregular were used. If most anterior and posterior edges of the articular plateau were higher than the deepest point of the articular surface for a superior articular plateau and concavity was observed on this surface in three consecutive midsagittal MRIs, the morphology was accepted as concave (the symmetrical shape being accepted as concave for the lower articular surface). If the end plate followed a straight line, the shape was classified as flat. If any surface irregularity was observed (e.g., cortical bumps, pits, or excrescences of the plateau surface), this morphology was classified as irregular. The articular plateau that deviated the most from concave was used for classification as irregular, flat, or concave. For instance, an intervertebral disc level with a concave lower articular surface and flat upper articular surface was considered as flat, whereas a disc level with a flat upper articular surface and irregular lower articular surface was considered as irregular (Figure 2).
The Pfirrmann grading method was used to evaluate lumbar disc degeneration on T2-weighted MRI  (Figure 3). The levels of disc degeneration were analyzed to determine possible relationships with disc space heights for each age group.
All quantitative and qualitative evaluations of MRI results were determined by the consensus of two reviewers, one a radiologist with 15 years of experience and the other an anatomist with 7 years of experience. The level of each lumbar intervertebral disc was evaluated by both observers at the same time.
The Kolmogorov–Smirnov test was used to analyze the homogeneity of data distributions for each dataset. Statistical analysis was performed to determine differences in intervertebral disc space heights between normal and pathological discs (bulging, protruding, and extruding). Moreover, the differences in disc space intervals between normal (nonherniated) discs (including normal and bulging discs) and herniated discs (including those with protrusion and extrusion) were calculated by Mann–Whitney U tests. Chi-square tests were used to compare these groups (normal and pathological, herniated and nonherniated) with regard to the morphological type of the articular plateau (concave, flat, and irregular). The relationship between disc space heights and disc degeneration levels was analyzed using the Kruskal– Wallis test. Detailed analyses (pairwise comparison tests) were conducted to determine the relationship between decreased intervertebral disc space height and each of the degeneration levels (represented by classes). All of the statistical analyses were performed using IBM SPSS 20 for Windows (IBM Corp.). In all statistical analyses, p<0.05 represented a statistically significant difference.
The relationships between the height of the intervertebral disc space of the L4–L5 level and disc pathologies are shown in Table 1. The anterior, middle, and posterior L4–L5 intervertebral disc space heights of normal and pathological discs (including disc bulging, protrusion, or extrusion) were compared for each age group, as also demonstrated in Table 1. The analysis showed that the middle intervertebral disc space height of the age group of 25–40 years, all height measurements of patients older than 40 years, and all L4–L5 intervertebral disc heights of all patients of any age groups with any disc pathology were significantly lower than the values obtained in the normal group. For the L5–S1 disc level, the anterior and middle intervertebral disc space heights of the age group of 25–40 years, all height measurements of patients older than 40 years, and all intervertebral disc heights of patients with disc pathologies were significantly lower than the values obtained for the patients without any disc pathology. The differences in the measurements of the intervertebral disc space height between normal (nonherniated) discs (including normal and bulging discs) and herniated discs were also evaluated. The anterior and middle height measurements of the age group of 25–40 years (p<0.01), all height measurements of patients older than 40 years (for anterior height, p=0.02 for the L4–L5 level and p<0.01 for the L5–S1 level; for middle and posterior heights, p<0.01), and all height values of all patients (p<0.01) were significantly different between normal and herniated discs for both the L4–L5 and L5–S1 disc levels. Herniated discs had significantly lower height values than normal discs in these age groups.
The results of the morphological differences of the articular plateau in normal and pathological discs are shown in Table 2 and Table 3. For the L4–L5 disc level, irregular surfaces of the articular plateau were the cause of the significant differences in the age group of 25–40 years and among all patients as
Table 1. Differences between normal and pathological (including bulging, protruding, and extruding) discs with regard to intervertebral disc space height shown by the chi-square test results of pairs. In the age group of >40 years, there were significantly more pathological discs in the flat and irregular groups than in the concave group. There was no significant difference in the number of pathological discs between the flat and irregular groups, however. At the L5– S1 disc level, there were more disc pathologies observed in the flat and irregular articular plateaus for the group of patients older than 40 years, and the irregular group had significantly more pathological discs than the concave or flat groups for all patients at this disc level.
The effect of articular plateau morphology on disc hernias was also investigated. Patients with flat articular plateaus had significantly more herniated discs than concave end plates among those older than 40 years (p=0.031), and patients with irregular articular plateaus had significantly more herniated discs than the concave group for all patients at the L4–L5 disc level (p<0.01). For the L5–S1 disc level, patients with irregularly shaped end plates had significantly more herniated discs when compared with other morphological types among patients >40 years old and among all patients at the L5–S1 disc level (p<0.01).
As the level of degeneration increased, the presence of disc pathology and herniation also increased significantly for all age groups for both L4–L5 and L5–S1 disc levels (p<0.01). The anterior, middle, and posterior intervertebral disc space heights were significantly lower for those with grade 5 degeneration in comparison with other degeneration classes, and grade 4 discs had significantly lower posterior height values in comparison with grade 1 discs at the L4–L5 level (p<0.01).
This study focused on the L4–L5 and L5–S1 disc levels because disc herniations most often occur in the lumbosacral area. In the literature, it is stated that 75% of lumbar spinal flexion occurs at the lumbosacral joint, while 15% to 20% of lumber flexion occurs at the L4–L5 level . For this reason, the current study was designed to analyze the possible relationships between the intervertebral disc space heights of these levels and disc pathologies, because 90%–95% of clinically significant spinal radiculopathies are known to occur at the L4–L5 and L5–S1 levels .
The sum of the disc heights is generally accepted to be one- quarter of the total height of the vertebral column . We investigated the effect of disc height on disc herniation, and the disc spaces were measured in light of the information provided in previous studies to evaluate these possible relationships. Some researchers have used converted measurements and ratios based on intervertebral disc heights instead of specifically measuring the intervertebral disc spaces in their studies [18, 19]. To determine anomalies in the morphological measurements of intervertebral disc spaces, an understanding of normal morphological values is required. Before discussing the results of the current study, the findings of previous research on the morphological properties of intervertebral disc spaces should be mentioned. Mirab et al. attempted to determine the normal intervertebral disc dimensions of Iranian participants. In their MRI study, they included 14 volunteers with normal intervertebral discs with an age range of 40–59 years and reported mean values of anterior, middle, and posterior intervertebral heights of 18.14, 13.82, and 10.14 mm at the L4–L5 level and 18.71, 12.99, and 8.51 mm at the L5–S1 level, respectively . The study by Hong et al. (n=138, age range of 15–25 years) aimed to reveal the normal intervertebral disc space of the Korean population. The anterior, middle, and posterior intervertebral space distances were 10.83, 10.05, and 7.20 mm at the L4–L5 level and 10.40, 9.58, and 6.02 at the L5–S1 level by MRI . In the study by Kızılgöz and Ulusoy, the researchers used lateral lumbar spine radiography to determine the median anterior, middle, and posterior disc heights, which were 13.26, 11.20, and 8.44 mm for the L4–L5 level and 12.46, 9.50, and 5.89 mm for the L5–S1 level for non- degenerated lumbar discs . In the current study, the median anterior, middle, and posterior intervertebral disc heights were measured as 10.9, 9.5, and 5.1 mm, respectively, for the L4–L5 level and 11.4, 9.1, and 3.9, respectively, for the L5–S1 level. The variations in these measurements might be the result of using different modalities; however, these differences may also reflect genetic variations among populations.
Intervertebral disc space height was another parameter investigated by some researchers as a possible morphological factor contributing to the difference between normal and herniated discs. The results of the research conducted by Kızılgöz and Ulusoy showed that anterior and posterior intervertebral disc space heights were associated with disc degeneration and disc herniation while middle intervertebral disc space height was associated with disc herniation at the L4–L5 level. However, that study was conducted using lateral lumbar radiography . According to the results of Lee et al.’s MRI study, the anterior and middle heights of the intervertebral disc spaces were significantly lower for both degenerated and herniated discs in comparison with normal intervertebral discs at the L4–L5 level. That study was performed with a study population between the ages of 20 and 25 years . In this current research, measurements of the L4–L5 and L5–S1 intervertebral disc space levels indicated a significant difference between those older than 40 years and the group of all patients, and the disc space was narrower for those with disc pathologies and disc herniation among these intervertebral disc levels.
Some other studies have investigated the shape of the end plates to determine their relationship with disc pathologies. In their case-control study, Pouriesa et al. measured the difference of end plates (DEP) . In that study, DEP represented the difference between the anteroposterior diameters of the lower and upper end plates of the vertebral body adjacent to the intervertebral discs. The DEP measurements of herniated discs were significantly higher for the L4–L5 and L5–S1 levels in comparison with normal discs at those levels. Harrington et al. conducted a study among patients younger than 60 years using computed tomography scans and claimed that height, weight, and body mass index were not related to disc herniations at the L4–L5 and L5–S1 levels . However, the shape of the vertebral body was related to disc herniation at these levels, and the authors claimed that more circular vertebral end plates showed a strong correlation with posterior intervertebral disc herniation in both men and women. He et al. measured the concave angle of the vertebral end plate and investigated possible relationships with disc degeneration and disc herniation . This angle was measured by T2 midsagittal MRI. For the superior end plate, the angle was formed by the line passing through the highest anterior point of the vertebral body and the deepest point of the end plate cavity and by the line passing through the highest posterior point of the vertebral body and the deepest point of the end plate cavity. The wider this concave angle, the flatter the vertebral end plate. They claimed that this angle increases with the presence of lumbar disc degeneration and that the degree of widening of this angle is related to the severity of disc degeneration. However, these authors found no relationship between this angle and lumbar intervertebral disc herniation.
The end plate surface is another morphological property that might be related to disc pathologies. Wang et al. classified the surface structure of vertebral end plates as concave, flat, and irregular . According to the results of their study, the shape of the end plate varies considerably between the upper and lower lumbar regions. Moreover, end plates were found to be more concave in the upper lumbar region and more flat in lower lumbar areas. Another significant study by Pappou et al. indicated that intervertebral disc degeneration increased from concave to flat to an irregular end plate morphology. On the other hand, concave levels were associated with fewer degenerated discs and no difference was observed between flat and irregular levels for discs with a herniated nucleus pulposus . In the current study, an irregular articular plateau was observed significantly more often in cases of disc pathologies for the L4–L5 and L5–S1 levels, and more disc herniations were found in the L5–S1 level.
The Pfirrmann grading system  is one of the most popular classifications used in the assessment of disc degeneration. Applying this method, we sought to determine the relationship between age and degeneration levels of intervertebral disks. As the degeneration grade of the discs increased, the presence of disc pathology and herniation also increased significantly for both the L4–L5 and L5–S1 disc levels of all age groups.
This study has some limitations. First, a larger sample size would be beneficial in order to obtain normal morphological values and to determine the differences between patient and control groups. In addition, the current patient sample was obtained from a single center, but multicenter studies might provide more accurate information and more statistical differences of larger populations with variabilities among different populations in terms of normal values, which might be explained by genetic differences. Second, MRI is considered to be the gold standard for the diagnosis of disc pathologies, but this could be considered as another limitation of the present investigation. The results of anatomical studies using cadaveric observations and measurements would provide a better understanding of the morphological differences between patient and control groups. Moreover, measurements and observations could have varied between the reviewers in this study, who investigated the possible anatomical risk factors for disc pathologies. There were few patients with irregularly shaped articular surfaces, and this might have possibly had an effect on the statistical analyses by preventing an accurate comparison of the variations in the articular plateau as a risk factor for disc pathologies in patients in the younger age group. Finally, height, weight, and body mass index are other important parameters that might play roles in intervertebral disc space measurements and disc pathologies. Including these parameters alongside the morphological properties of the intervertebral disc space would provide more impactful results that could contribute to a better understanding of the risk factors of disc pathologies.
In this study, we have presented the normal intervertebral disc height values of a group of patients from a single center. In these patients, measurements of the intervertebral disc space of the L4–L5 and L5–S1 levels showed that among discs with pathologies or herniation, the intervertebral disc levels were narrower in patients older than 40 years as well as for all patients in total. Disc pathologies were more frequently observed in discs with an irregular articular plateau at the L4– L5 and L5–S1 levels, and more disc herniations were found at the L5–S1 level. Among patients of all ages, the presence of disc pathologies and disc herniations was observed much more frequently as the grade of disc degeneration increased.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Volkan Kızılgöz, Muhammet Bora Uzuner. Influence of lumbar intervertebral disc height and geometry of the articular plateau surface on disc pathologies. Ann Clin Anal Med 2021;12(12):1325-1331
Neutrophil/Lymphocyte ratio can distinguish transudate and exudate pericardial effusions
Cemil Zencir 1, Sercan Çayırlı 1, Sevil Gülaştı 2, Ahmet Kenan Türkdoğan 3, Çagdaş Akgüllü 1, Hasan Güngör 1
1 Department of Cardiology, Faculty of Medicine, Adnan Menderes University, Aydın, 2 Department of Cardiology, Bursa Çekirge Publıc Hospital, Bursa, 3 Department of Emergency Medicine, Faculty of Medicine, Adnan Menderes University, Aydın, Turkey
DOI: 10.4328/ACAM.20734 Received: 2021-06-07 Accepted: 2021-08-19 Published Online: 2021-09-06 Printed: 2021-12-01 Ann Clin Anal Med 2021;12(12):1332-1336
Corresponding Author: Sercan Çayırlı, Department Of Cardiology, Faculty Of Medicine, Adnan Menderes University, Aydın, Turkey. E-mail: email@example.com P: +90 506 269 66 78 Corresponding Author ORCID ID: https://orcid.org/0000-0001-9660-9993
Aim: Early and definitive diagnosis is crucial in patients with pericardial effusion. Pericardial effusions can be caused by a variety of disorders and pericardiocentesis is required to identify whether the composition of the fluid is transudate or exudate. In this study, we compare the neutrophil/lymphocyte ratio (NLR) with the pericardial fluid protein/serum protein ratio to discriminate between transudates and exudates in pericardial fluid.
Material and Methods: Seventy-five of 107 consecutive patients who were admitted to a university tertiary-care center with new-onset large pericardial effusions who underwent pericardiocentesis between January 2013 and January 2018 were retrospectively analyzed. Clinical characteristics, final diagnosis, pericardial fluid and serum total protein measurements, and hematological parameters were retrieved from patients’ charts. Patients were divided into two groups with regard to the nature of the pericardial fluid as exudate or transudate according to Light’s criteria.
Results: The pericardial fluid protein/serum protein ratio and NLR were significantly higher in the exudate group than in the transudate group (p<0.001). Receiver operating characteristic curve analysis revealed that the NLR value of 3.93 was able to determine exudate pericardial fluid with 79.3% sensitivity and 82.4% specificity.
Discussion: The NLR might be used to identify the nature of pericardial fluid with high sensitivity and specificity before pericardiocentesis.
Keywords: Pericardial Effusion, Pericardiocentesis, Neutrophil, Lymphocyte, Transudates, Exudates
The pericardium surrounding the heart and great vessels consists of serous visceral and fibrous parietal layers. The pericardial cavity between these two layers contains 15-50 mL of serous fluid, which is essentially a plasma ultrafiltrate, consisting of myocardial interstitial fluid and lymphatic drainage . Pathologies associated with the overproduction of pericardial fluid or obstruction in its drainage may lead to the development of pericardial effusion (PE) . Most cases of PE result from the disruption of the permeability of inflamed pericardium or excessive fluid flow from the visceral pericardium.
Several classifications have been established to address the types of PE. One of the most common classifications involves categorizing the effusions as transudate, exudate, or both according to the composition of the effusion . The distinction between exudate and transudate is helpful in revealing the etiology. Light’s criteria are traditionally used to determine whether a pleural effusion is transudate or exudate in composition . However, fluid aspiration, which exposes the patient to the risks of an invasive procedure, is required to utilize Light’s criteria in the differential diagnosis of the fluid. The neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) are readily available markers of systemic inflammation . Previous studies have demonstrated that the NLR and PLR have diagnostic value in several pathologies characterized by the local or systemic inflammatory response, including coronary artery disease, diabetes mellitus, ulcerative colitis, tuberculosis, sarcoidosis, inflammatory arthritis, and Crimean-Congo hemorrhagic fever [6-9]. A recent study of 465 patients who underwent diagnostic thoracentesis for pleural fluid revealed that the NLR could facilitate the differential diagnosis of pleural effusion .
However, evidence regarding the role of the NLR in the differential diagnosis of the composition of PE is lacking. In this study, we aimed to investigate the role of the NLR in differentiating exudate and transudate PE.
Material and Methods
Seventy-five of 107 consecutive patients presenting to Adnan Menderes University’s Faculty of Medicine with new-onset large pericardial effusions (>2 mm) who underwent pericardiocentesis between January 2013 and January 2018 were included in this cross-sectional descriptive study. Written informed consent for inclusion in the study was obtained from all patients. The study protocol was approved by the Institutional Ethics Committee (protocol no: 2018/1307, date: 18/01/2018).
All patients were imaged in the left lateral decubitus position using the same ultrasound system (VIVID 7, GE Vingmed Ultrasound, Horten, Norway) by two blinded observers. Two- dimensional and M-mode echocardiograms were obtained according to American Society of Echocardiography guidelines. PE was measured from the right ventricle, right atrium, posterior wall, and apex at end-diastole, when it is at its smallest at the fluid-tissue interface. A subxiphoid approach was used in all patients during the pericardiocentesis procedure. Patients’ clinical features, the amount of pericardial fluid, serum levels of total protein, hematological parameters, and final diagnosis were recorded. Patients were divided into two groups according to the composition of the PE as exudate and transudate based on Light’s criteria. The presence of one of the following criteria indicates exudate fluid: pleural fluid protein/serum protein ratio of >0.5, pleural fluid lactate dehydrogenase (LDH)/serum LDH ratio of >0.6, or pleural fluid LDH >2/3 of the serum LDH upper limit of normal . The NLR value was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. The difference in NLR values between subjects with exudate and transudate PE was the primary outcome measure of this study. The predictive role of the NLR and PLR in identifying exudate PE was the secondary outcome measure.
Normality of the continuous variables was evaluated with the Kolmogorov-Smirnov test. Parametric data are expressed as mean±SD and categorical data are expressed as percentages. Nonparametric variables are given as median values and ranges. The optimal cut-off point of the NLR at which the sensitivity and specificity would be maximal for the prediction of exudate was identified using receiver operating characteristic (ROC) curve analysis. Accuracy of the tests was measured using the area under the curve (AUC). Statistical analysis was performed with SPSS 14.0 (SPSS Inc., Chicago, IL, USA). Values of p<0.05 were considered statistically significant.
The mean age of the study population was 61.80±15.90 years and 55% of the patients were male. Demographic characteristics of the study groups are given in Table 1. According to Light’s criteria, 19 of the patients had transudate PE and 56 had exudate PE (Figure 1). The groups were similar with respect to age, diabetes, hypertension, alcohol consumption, smoking, echocardiographic findings, and the etiology of the PE. Laboratory measurements of the study population are presented in Table 2. There were no significant differences between the groups regarding laboratory measurements except for neutrophil and lymphocyte counts. The neutrophil count was significantly higher in the transudate PE group compared to the exudate PE group [4.80 (3.30-8.10)/mm3 vs. 8.50 (5.60-10.80)/ mm3, p=0.004], whereas the lymphocyte count was significantly higher in the transudate PE group than the exudate PE group [1.90 (1.10-2.70)/mm3 vs. 1.30 (0.70-1.70)/mm3, p=0.002]. Total protein levels of serum and pleural fluid, the ratio of pleural fluid protein to serum protein, and NLR values of the transudate and exudate groups are shown in Table 3. Among these parameters, the total protein level of pleural fluid, the ratio of pleural fluid protein to serum protein, and NLR values were significantly higher in the exudate PE group than the transudate PE group (p<0.001 for all). There was a significant correlation between the NLR and the ratio of pleural fluid protein to serum protein (r=0.363, p=0.001).
ROC analysis revealed that a cut-off value of 3.93 for NLR was predictive for exudate PE with 79.3% sensitivity, 82.4% specificity, 93.9% positive predictive value, and 53.8% negative predictive value (AUC: 0.852, 95% confidence interval: 0.762- 0.942, p<0.001) (Figure 2).
This study is the first in the literature to demonstrate that the NLR might be utilized in identifying the composition of the fluid in patients with PE without fluid sampling. The results of this study indicate a strong relationship between the NLR and the pericardial fluid protein/serum protein ratio. Moreover, our findings show that NLR values of ≥3.93 may identify the exudate composition of the PE with high sensitivity and specificity. Inflammation plays a crucial role in many cardiovascular disorders . Growing evidence about the role of inflammation in various cardiovascular diseases has led to studies focusing on high-sensitivity C-reactive protein (hs-CRP) and other inflammatory markers for risk evaluation and the monitoring of disease activity [12, 13]. Total white blood cell count is an easily obtained marker of systemic inflammation. Previous studies have reported a positive correlation between acute phase reactants and proinflammatory proteins such as hs-CRP, tumor necrosis factor-α, interleukin-1 and interleukin-6, and leukocyte subtypes in nonspecific inflammatory conditions [14-16]. Recent trials have shown that increased platelet counts may indicate underlying inflammation as numerous inflammatory mediators stimulate megakaryocytic proliferation and produce relative thrombocytosis. Furthermore, lymphocytopenia is a common finding during inflammation as a consequence of the increased levels of corticosteroid during the stress response . In addition, lymphocytopenia may result from the increased lymphocyte apoptosis in critical inflammatory conditions [18, 19]. Therefore, the NLR represents both the inflammatory status and the stress response of the body.
Recently, the NLR has been found associated with negative outcomes in various cardiovascular diseases [20, 21]. As an inflammatory marker, NLR is associated with negative outcomes in acute coronary syndromes and recurrence of arrhythmias after cryoablation . In addition, the NLR has also been associated with the presence of spontaneous echo contrast in patients with mitral stenosis and increased risk for stroke .
Although the NLR and PLR have been shown to be related to etiologies and outcomes in various clinical settings, their roles in idiopathic pleural effusion need to be clarified. In a previous study in our clinic, we found that the NLR and PLR were significantly higher in patients with PE compared to those without PE and we showed a positive correlation between the NLR and the amount of effusion in patients with idiopathic PE . In a recent trial, Akturk et al. investigated the utility of the NLR in the differential diagnosis of pleural effusion . Those authors found that the mean NLR was significantly higher in cases of malignant, para-pneumonic, and para- malignant pleural effusions compared to tuberculosis-related pleural effusions. They also stated that the role of the NLR in differential diagnosis among malignant, para-pneumonic, and para-malignant effusions was limited due to the close NLR values seen for these conditions.
The present study shows for the first time that the NLR might be utilized in the differentiation of transudate and exudate fluids in patients with PE in a noninvasive manner. Appropriate use of the NLR in cases of PE is likely to tailor the choice of further diagnostic tests. From this point of view, utilization of the NLR for these patients might prevent implementation of invasive diagnostic tests in cases of PE. A possible explanation for our results may be the high number of subjects with idiopathic PE, which has been shown to be associated with viral infections in previous studies . Given that viral infections are associated with the collection of exudative fluid, the high number of patients with idiopathic PE, which is particularly likely to be viral in origin, might have led to the collection of exudative PE in our study population.
This study has some limitations that must be mentioned. The sample size was small and the proinflammatory markers measured in our study population were limited to complete blood count parameters, CRP, and erythrocyte sedimentation rate. Utilization of additional markers of inflammation such as cytokines might help to address the association between the NLR and other inflammatory markers more thoroughly. Conclusion
Discriminating the composition of the fluid before the development of pericardial tamponade is the first step of early diagnosis and treatment of PE. We conclude that the NLR, a readily available and simple measure of inflammatory states, might be helpful in estimating the composition of PE before pericardiocentesis and may consequently prevent the development of the complications related to this procedure.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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17. Onsrud M, Thorsby E. Influence of in vivo hydrocortisone on some human blood lymphocyte subpopulations. I. Effect on natural killer cell activity. Scandinavian journal of immunology 1981; 13(6): 573-9. 1981/01/01. doi: 10.1111/j.1365- 3083.1981.tb00171.x.
18. Gotts JE, Matthay MA. Sepsis: pathophysiology and clinical management. Bmj 2016; 353: i1585. 2016/05/25. doi: 10.1136/bmj.i1585.
19. Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. The New England journal of medicine 2003; 348(2): 138-50. 2003/01/10. doi: 10.1056/ NEJMra021333.
20. Li H, Lu X, Xiong R, Wang S. High Neutrophil-to-Lymphocyte Ratio Predicts Cardiovascular Mortality in Chronic Hemodialysis Patients. Mediators of inflammation 2017; 2017: 9327136. 2017/03/21. doi: 10.1155/2017/9327136.
21. Yanartas M, Kalkan ME, Arslan A, et al. Neutrophil/Lymphocyte Ratio Can Predict Postoperative Mortality in Patients with Chronic Thromboembolic Pulmonary Hypertension. Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia 2015; 21(3): 229-35. 2015/03/11. doi: 10.5761/atcs.oa.14-00190.
22. Akpek M, Kaya MG, Lam YY, et al. Relation of neutrophil/lymphocyte ratio to coronary flow to in-hospital major adverse cardiac events in patients with ST-elevated myocardial infarction undergoing primary coronary intervention. The American journal of cardiology 2012; 110(5): 621-7. 2012/05/23. doi: 10.1016/j. amjcard.2012.04.041.
23. Kaya MG, Akpek M, Elcik D, et al. Relation of left atrial spontaneous echocardiographic contrast in patients with mitral stenosis to inflammatory markers. The American journal of cardiology 2012; 109(6): 851-5. 2011/12/23. doi: 10.1016/j.amjcard.2011.11.010.
24. Zencir C, Akpek M, Selvi M, et al. The Relation of Inflammatory Markers to Idiopathic Pericardial Effusion. Koşuyolu Heart Journal; 20(1): 53-58.
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Download attachments: 10.4328:ACAM.20734
Cemil Zencir, Sercan Çayırlı, Sevil Gülaştı, Ahmet Kenan Türkdoğan, Çagdaş Akgüllü, Hasan Güngör. Neutrophil/Lymphocyte ratio can distinguish transudate and exudate pericardial effusions. Ann Clin Anal Med 2021;12(12):1332-1336
Comparison of balance and coordination abilities between asthmatic patients and healthy subjects
Ayşenur Yılmaz 1, Süleyman Gürsoy 1, Orçin T. Atalay 1, Fatma B. Evyapan 2
1 School of Physical Therapy and Rehabilitation, 2 Department of Chest Diseases, Faculty of Medicine, Pamukkale University, Denizli, Turkey
DOI: 10.4328/ACAM.20741 Received: 2021-06-09 Accepted: 2021-08-19 Published Online: 2021-09-07 Printed: 2021-12-01 Ann Clin Anal Med 2021;12(12):1337-1342
Corresponding Author: Ayşenur Yılmaz, School of Physical Therapy and Rehabilitation, Pamukkale University, Denizli, Turkey. E-mail: firstname.lastname@example.org / email@example.com P: +90 258 296 42 46 / +90 543 283 38 19 F: +90 258 296 44 94 Corresponding Author ORCID ID: https://orcid.org/0000-0002-2357-0351
Aim: Previous studies have shown that structural defects and deformities develop in the chest wall due to decreased thoracal mobility in asthmatic patients. Besides, psychological problems and emotional states play an important role in the pathophysiology of asthma. These conditions may affect balance and coordination. Therefore, the study aimed to compare the balance and coordination capabilities of asthmatic patients with healthy individuals.
Material and Methods: The study included patients diagnosed with asthma by GINA and healthy volunteer subjects. Forty-nine asthma patients aged between 18-50 years and fifty-one healthy subjects were included in the study. Balance was assessed by SportKat Kinesthetic Ability Trainer (SPORTKAT550), Five Times Sit-to-Stand Test (FTSTS), and Timed Up and Go (TUG) test. Coordination ability was assessed by the Finger-to-Nose Test (FNT) and Toe-Tap Test (TTT). In addition, Beck Anxiety Scale (BAS) was used to assess anxiety, and Beck Depression Scale (BDS) was used to assess depression.
Results: The mean age of the asthmatic group was 35,3±10,3 years, and the mean age of the healthy group was 36,17±8,47 years (p>0,05). When the group results were compared, there was a significant difference in SportKAT550 scores, FTSTS, TUG, FNT, TTT, BAS, and BDS (p<0,05).
Discussion: A decrease in the balance and coordination capabilities was found in asthmatic patients. It was observed that asthma patients had high levels of anxiety and depression. Balance and coordination, which are important neuromotor components of most activities of daily living, should be evaluated in asthmatic patients.
Keywords: Asthma, Balance, Postural, Coordination
Asthma is one of the most common chronic diseases in the world (Available at: www.ginasthma.org). Studies have shown that posture and balance changes occur in individuals with asthma [1,2], as well as respiratory symptoms (Available at: www.ginasthma.org). Balance problems in individuals with lung disease may be due to many physiopathological reasons. It has been reported that causes such as hip weakness, poor nutrition or malnutrition, anxiety, depression, cognitive problems, and medicines may increase the risk of falls in patients with lung disease [1,3]. Balance and coordination, which are the basic components of daily activity, are intertwined . Coordinated movements require good balance and posture, as well as correct sequence and timing of synergistic and reciprocal muscle activities . Therefore, impairment in balance can affect coordination.
Accessory inspiratory and expiratory muscles work excessively due to airway obstruction in asthma patients, causing hypertrophy [1,3]. Because of this pressure causing a decrease in muscle length and strength, muscles become shorter and lose their elasticity . As a result, changes occur in the chest biomechanics. These changes are not limited to this region but are reflected on the whole body. Therefore, any changes that occur in the chest will affect whole-body biomechanics . In the study on asthma patients, protrusion of head and shoulders occurred in patients with mild, moderate, and severe persistent asthma and patients with decreased mobility of shoulder internal rotation, chest wall, and thoracic spine. This was found to be related to the onset time of the symptoms .
In addition, a close relationship between anxiety and asthma is frequently described in the literature [8,9]. Anxiety is associated with clinical conditions such as dizziness and balance problems . Dizziness and vestibular dysfunction occur in 90% of patients with anxiety . However, depression and cognitive problems are related to problems such as immobility and balance disorder .
Studies have shown that high anxiety levels , depression , and hypoxia  affect postural control and motor coordination. Therefore, we think coordination may be impaired with anxiety, depression, and hypoxia due to asthma attacks. Unfortunately, there are not many previously published studies that analyzed on coordination of asthma patients.
This study was planned to compare the balance and coordination capabilities of asthmatic patients with healthy individuals.
Material and Methods
This study was carried out with the participation of 49 asthma patients and 51 healthy individuals. Our study was carried out between February 2016 – January 2018. Patients meeting the inclusion criteria were included.
The inclusion criteria for asthma patients: between the ages of 18-50, no heart or other lung disease, no neurological or orthopedic problems, no operations on the upper extremity, lower extremity and/or waist, no ongoing painful musculoskeletal problems, stable symptoms, and medications.
The inclusion criteria for the healthy group: between the ages of 18-50, no heart or lung disease, no smoking, no psychological problems, no drugs or alcohol consumption that may affect balance, no neurological or orthopedic problems, cases who have not undergone an operation in the upper extremity, lower extremity and/or lumbar region, who do not have ongoing painful musculoskeletal problems, who have not had respiratory tract infection in the last three months.
The exclusion criteria for both the groups were as follows: who were treated with psychiatric treatment, were smokers or ex- smokers; had a respiratory infection in the past three months; limited joint movement, chronic musculoskeletal pain, vestibular disorders, or other balance disorders.
Data Collection Tools
1. Respiratory Function Test
Pulmonary function tests were evaluated with the COSMED Pony Fx portable mouth pressure measuring device. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), Tiffeneau index (FEV1 / FVC), Peak expiratory flow (PEF), and Maximal Mid-Expiratory Flow Rate (FEF25-75) values were measured .
2. Beck Anxiety Scale
It is one of several scales aimed at evaluating the anxiety state of the individual. The highest score is 63. The high score obtained from the scale indicates the severity of anxiety experienced by the individual .
3. Beck Depression Scale
It is a self-assessment scale that can be applied to both psychiatric patient groups and healthy people. The higher the total score, the higher the severity of depression .
4. The Evaluation of Balance:
4.1. Kinesthetic ability trainer (SPORTKAT 550): The patients were asked to follow the moving target point circling clockwise for 30 seconds on the monitor (Figure 1). During the test, the subjects received feedback from the monitor, continuously following the position of the sign indicating the displacement of the center of gravity on the platform area with respect to the target point. Low scores in tests indicate that balance performance is good .
4.2. Timed Up and Go (TUG) test: The TUG test was used to measure balance and functional mobility. Scoring is calculated by measuring how many seconds the test took to finish . 4.3.Five Times Sit-to-Stand Test (FTSTS): FTSTS test begins with the participant seated in the middle of the chair (45cm), back straight. The participant is raised to a complete stand and returns to the initial position. The duration was recorded . 5. The evaluation of coordination
5.1.Finger-to-Nose Test: The finger-to-nose test (FNT) was modified from a basic physical therapy neurologic assessment to ensure standardization of the test procedures . The subject was asked to sit on a chair and feet flat on the floor. A target is a black circle that can be moved on a vertical axis according to the subject’s height. The task required the subject to contact both the target and the nose as many times as possible in 20 seconds. The test was performed three times. The best value was noted .
5.2.Toe-Tap Test: The toe-tap test (TTT) was used for the coordination of foot movement. Each subject was asked to move forward in a chair, so the lower legs were not in contact with the chair and the knees and ankles were both at a 90° angle. A circular target (diameter, 5.75 cm) was placed under the subject’s heel, and the second target of equal diameter was placed under the subject’s toes. The task required the subject to contact each of the heel and toe targets as many times as possible in 20 seconds. The test was performed three times. Again, the best value was noted .
As a result of the power analysis, it was calculated that at least 94 people (47 people per group) could get 80% power with 95% confidence . The SPSS package program was analyzing the data. Continuous variables were presented as mean ± standard deviation and categorical variables as number and percentage. The Significance Test of the Difference Between the Two Average in comparing the independent group differences when the parametric test assumptions were provided; If the parametric test assumptions were not provided, the Mann- Whitney U test was be used to compare the independent group differences. Since all data did not show normal distribution, the relationship between the two variables was analyzed by Spearman correlation analysis. A correlation coefficient between 0 and 0.3 was considered a weak relationship, between 0.3 and 0.6 as a moderate relationship, and between 0.7 and 1.00 as a strong relationship. Statistical significance level was accepted as p < 0.05.
Ethical considerations: The study was approved by the Ethics Board Committee of Pamukkale University Medical Faculty (Ref No:60116787-020/71601 Date:17/11/2016)), and ethical principles laid down in the Declaration of Helsinki have been followed.
When the groups were compared, there was no significant difference between the two groups regarding the mean age and weight (p> 0.05). A statistical difference was found between the two groups in terms of the mean height and BMI (p<0.05). When the groups were compared in terms of FEV1, FVC, FEV1 / FVC, and PEF were significantly different (p<0.05). A statistical difference was found when the anxiety and depression results of the groups were compared. (p<0.05) (Table 1). The mean duration of disease in asthma patients was determined as 17,59 ± 9,16 years.
Comparison of balance and coordination tests
When the groups were compared in terms of SportKAT dynamic balance total score and subcategories (Front, Back, Right, Left), TUG, FTSTS, FNT, and Toe-tap test were found a significant difference in favor of Healthy Group (p<0.05) (Table 2).
The relationship emotional state, age, duration of disease, respiratory parameters balance and coordination tests in the asthmatic group
A moderate correlation was found between Dynamic balance total score, Beck anxiety and Beck depression scores (r = 0.621, p = 0.000, r = 0.618, p = 0.000 respectively). A moderate correlation was found between TUG, FTST, Beck anxiety (r = 0,496, p = 0.000, r = 0.478, p = 0.001 respectively). A moderate correlation was found between TUG, FTST, Beck depression scores (r = 0.557, p = 0.000, r = 0.483, p = 0.000, respectively) A moderate negative correlation was found between FNT, Toe-tap test, Beck anxiety (r = -0.465, p = 0.001, r = -0.391, p = 0.005, respectively). A moderate negative correlation was found between FNT, Toe-tap test, Beck depression scores (r = -0.354, p = 0.013, r = -0.378, p = 0.007) (Table 3).
A moderate correlation was found between age, dynamic balance test, TUG, (r = 0.601, p = 0.000, r = 0.441 p = 0.002, respectively). A moderate negative correlation was found between age, FTST, FNT and TTT (r = -0.392, p = 0.005, r = -0.495, p = 0.000, r = -0.491, p = 0.000, respectively). A moderate negative correlation was found between duration of disease, FNT and FTST (r = -0.312, p = 0.029, r = -0.311, p = 0.029, respectively). A moderate correlation was found between duration of disease, dynamic balance total score, TUG (r = 0.389, p = 0.006, r = 0.335, p = 0.018, respectively). A moderate negative correlation was found between dynamic balance total score, FEV1, FVC and PEF (r = -0.502, p = 0.000, r = -0.528, p = 0.000, r = -0.365, p = 0.010, respectively). A weak correlation was found between TUG, FVC and PEF (r = -0.292, p = 0.042, r = -0.219, p = 0.042, respectively). A moderate correlation was found between FNT, FEV1, FVC and PEF (r = 0.310, p = 0.030, r = 0.318, p = 0.026; r = 0.319, p=0.026, respectively). A weak correlation was found between TTT, FVC and PEF (r = 0.285, p = 0.047, r = 0.295, p = 0.040, respectively) (Table 3).
In this study, which was conducted to investigate balance and coordination disorders in asthmatic patients and to compare them with healthy individuals, it was found that asthma patients have worse balance and coordination.
Our results obtained from this study indicate that asthmatic patients demonstrated poorer balance and coordination compared with healthy subjects. Balance and coordination problems in lung problems may occur due to several reasons. They stated that a significant difference in dynamic balance with open eyes might be associated with postural disorders . Asthmatic patients had biomechanical changes. This condition may also cause postural control alterations. In asthmatic patients, heads and shoulders are further forward with an increased internal rotation of the shoulder, lowered chest wall expansion, reduced flexibility of the thoracic spine are seen . Posturography results were affected due to these alterations because the body’s center of gravity displaces. Asthmatic patients may not have been able to achieve the appropriate integration of vision and vestibular information. Therefore, asthmatic patients have larger and faster CoP displacement in conditions with the mobile platform. In addition, asthmatic patients may not be able to accomplish a better motor response to the challenge of balancing on a mobile platform because asthmatic patients have postural alterations of the chest, shoulder, and spine [1,2].
Cunha et al. (2013) stated that balance disorders are anxiety and vestibular problem origin , Almeida et al. (2013) stated that the mediolateral balance disorders are postural disorder origin . We found that asthma patients were worse than healthy people in balance in the antero-posterior and medio- lateral. They are worse in antero-posterior dynamic balance tests because of fear of falling. We think that the difference in the medio-lateral balance in dynamic balance tests will be related to the presence of postural alterations.
In this study, It was observed that our asthma patients had high levels of anxiety and depression. Psychological problems and emotional states play an important role in the pathophysiology of asthma. Studies have shown a strong relationship between anxiety and asthma [8,9]. It is reported that the balance will be disturbed by anxiety [2,10,11]. In addition, in depressive patients, deceleration in movements is common. In the study, a relationship was found between depression, immobility, and balance disorders . In our study, similar to the literature, we found a moderate relationship between balance and emotional states.
FNT and TTT results were worse in asthma patients. Kertzman et. (2010) performed FNT and cognitive control tests on the subjects with depression. They found significant differences in these tests. It is reported that there is a slower reaction time in the elongation movements in the presence of depression . Butcher et al. (2004) reported that the coordination of patients with COPD is impaired in their study. Similarly, asthma is also an obstructive disease; therefore, the coordination capabilities of asthma patients may be impaired . In addition, various pathophysiological and environmental conditions, such as sleep apnea and chronic obstructive pulmonary disease temporarily high altitude, are among the conditions that cause intermittent hypoxia. It has been shown that intermittent hypoxia affects balance and coordination in studies performed at high altitudes. Intermittent hypoxia is an effective stimulus in the human body that elicits compliance responses at various levels in the circulatory, respiratory, sleep systems, and other organ systems. Studies have shown that this stimulus causes neurocognitive disorders as well as myocardial ischemia, cerebral ischemia, hypertension, balance disorder, coordination, and oxidative damage [21,22]. Hypoxia during acute attacks is observed in asthma (Available at: www.ginasthma.org).
There are studies showing that there was a decrease in motor performance and coordination capabilities in children with high anxiety levels. Anxiety and depression have been shown to be associated with prolongation of reaction times and deceleration in movements [13,14]. In our study, the movements of asthma patients were slower.
Patients with COPD using oxygen were found that the finger- nose test, TTT, and the TUG test had a moderate relationship with FEV1, FVC, and PEF . In our study, we found a moderate relationship between respiratory parameters, balance, and coordination. However, balance and coordination disorders may be due to different reasons, such as drug use. Therefore, other reasons should be investigated.
The limitation of our study is that our patients do not have homogeneous distribution in terms of sex. Also, the effect of drugs has not been examined. On the other hand, the strengths of our study are having a control group, a large sample size, and evaluate anxiety, depression and coordination.
Asthmatic patients demonstrated poorer balance and coordination performances as compared to healthy subjects. Therefore, we suggest that the balance and coordination of the asthmatic patients should be evaluated. It would be useful to identify these neuromotor components and add them to rehabilitation programs. So that balance and coordination abilities can be improved.
The authors would like to thank people for participating in this study.
Scientific Responsibility Statement
Animal and human rights statement
Conflict of interest
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Download attachments: 10.4328:ACAM.20741
Ayşenur Yılmaz, Süleyman Gürsoy, Orçin T. Atalay, Fatma B. Evyapan. Comparison of balance and coordination abilities between asthmatic patients and healthy subjects. Ann Clin Anal Med 2021;12(12):1337-1342
Evaluation of the Free Triiodothyronine/Free Thyroxine ratio and Euthyroid Sick Syndrome in patients with COVID-19: A cross-sectional study
Durmuş Ayan 1, Tevfik Balcı 1, Sercan Ünal 2, Haydar Ulucan 3, Cevdet Türkyürek 1, Ergül Bayram 1
1 Department of Medical Biochemistry, Niğde Research and Training Hospital, Niğde, 2 Department of Internal Medicine, Niğde Research and Training Hospital, Niğde, 3 Department of Radiology, Health Sciences University Samsun Research and Training Hospital, Samsun, Turkey
DOI: 10.4328/ACAM.20743 Received: 2021-06-11 Accepted: 2021-08-15 Published Online: 2021-08-27 Printed: 2021-12-01 Ann Clin Anal Med 2021;12(12):1343-1347
Corresponding Author: Durmuş Ayan, Aşağıkayabaşı mahallesi, Hastaneler caddesi, Niğde Research and Training Hospital, Department of Medical Biochemistry, 5100, Niğde, Turkey. E-mail: firstname.lastname@example.org P: +90 553 633 81 85 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2615-8474
Aim: In our study, we aimed to evaluate the prevalence of euthyroid sick syndrome among patients with COVID-19, and the relationship between the possible change in free-triiodothyronine/free-thyroxine (fT3/fT4) ratio and the biochemical parameters used during the follow-up of COVID-19.
Material and Methods: A total of 114 sequential patients between 18-65 years of age, who were treated in the internal medicine service allocated to patients with COVID-19, were included in the study. fT3, fT4, thyroid-stimulating hormone (TSH), thyroid peroxidase antibodies, and thyroglobulin antibodies antibody levels were analyzed. fT3/fT4 ratio was calculated.
Results: According to the results, only isolated low fT3 levels were found in 39.5% (45/114) of the patients, while 25.4% (29/114) had both low TSH and fT3 levels, 31.6% (36/114) had autoimmune thyroid disease, and 3.5% (4/114) had normal results in the thyroid function tests. The fT3/fT4 ratio was also determined to be low in all groups. However, no significant correlation was found between the low fT3/fT4 ratio and the parameters used in monitoring COVID-19.
Discussion: We believe that studies with a wider scope of participants are needed for testing the reduction in fT3/fT4 ratio with other biochemical parameters in patients with COVID-19 and without known thyroid disease.
Keywords: SARS-CoV-2, Thyroid Disease, Thyroid Hormones, ESS, COVID-19
The novel type of coronavirus, which is known as severe acute respiratory syndrome coronavirus-2 (SARS-COV-2), is responsible for the Coronavirus 19 (COVID-19) global pandemic that started in late 2019. COVID-19 can range from a very mild or asymptomatic clinical picture to critical illness and death . The data obtained indicated that the severity of COVID-19 was associated with the interleukin (IL)-2, IL-7, IL-10, tumor necrosis factor (TNF), The fatal COVID-19 has been characterized as a cytokine release syndrome (CRS) induced by the cytokine storm with a high mortality rate .
One of the systems that may be affected by COVID-19 is the thyroid gland. Specifically, thyroid disorders associated with COVID-19 include thyrotoxicosis, hypothyroidism, and non-thyroidal illness syndrome . Changes in thyroid function parameters, commonly referred to as “non-thyroidal illness syndrome” (or euthyroid sick syndrome (ESS) or low triiodothyronine (T3) syndrome), can be detected in many serious clinical acute and chronic conditions. The most typical change is a decrease in serum T3 level. This may or may not be accompanied by a slight decrease in the level of thyroid- stimulating hormone (TSH) . As the severity and duration of non-thyroidal illness syndrome (NTIS) increases, levels of total tetraiodothyronine (T4) will also increase. The magnitude of TSH and thyroid hormone changes is proportional to the severity of the underlying condition of NTIS, and the changes usually regress once the cause of the disease is eliminated . NTIS has been considered as an adaptation mechanism in reduced tissue metabolism in order to conserve energy during systemic diseases. The conversion of the T4 prohormone to the biologically active hormone T3 is catalyzed by type 1 (DIO1) and type 2 (DIO2) deiodinases . In contrast, type 3 deiodinase (DIO3) catalyzes the inactivation of both T4 and T3. DIO3 creates two biologically inactive forms, by regulating the conversion of T4 to reverse T3 and the conversion of T3 to 3.3-T2.
Decreased conversion of T4 to T3 and increased activity of DIO3 are typically observed in NTIS. NTIS is common in patients treated in intensive care units (ICU) for sepsis, trauma, acute myocardial infarction, and patients with pneumonia [6, 7].
The cytokine storm associated with SARS-CoV-2 contributes to non-thyroid illness syndrome with three different mechanisms in patients with COVID-19. First of all, it causes negative feedback on TRH and NTIS secretion as it increases the conversion of T4 to T3 by decreasing the secretion and release of the thyroid releasing hormone (TRH) and NTSI and increasing the DIO2 activity. Secondly, it is thought to reduce the expression of DIO1 and DIO2 by reducing iodine uptake, T3 secretion, and mRNA expressions of thyroid-specific genes in the thyroid gland. Therefore, the conversion of T4 to T3 is decreased. It is stated that the conversion of T3 to reverse T3 will increase as DIO3 activity and expression increase. Thirdly, cytokine storm associated with SARS-CoV-2 leads to a decrease in the secretion of proteins carrying thyroid hormones (thyroxine- binding globulin, thyroxine-binding prealbumin or transthyretin, albumin, and lipoproteins) in the liver .
Recently, the fT3/ fT4 ratio has been used to obtain information about the status of the enzyme activity of 5-deiodinase [8-10].
In our study, we aimed to determine the frequency of ESS in patients who were hospitalized after the diagnosis of COVID-19 and to compare the possible change in the fT3/fT4 ratio with the biochemical parameters used in the follow-up of COVID-19.
Material and Methods
Study Design, Participants, and Collection of Blood Samples
This study is a prospective, analytical and cross-sectional study. The study was approved by the Non-Interventional Clinical Research Ethics Committee of Niğde Ömer Halisdemir University (No.2021/51). A total of 144 patients between 18 and 65 years of age, who were confirmed to have COVID-19 with the PCR (polymerase chain reaction) test in the laboratory and were treated in the internal medicine clinic allocated to the patients with COVID-19 at Nigde Training and Research Hospital, were sequentially and randomly included in our study. Blood samples were obtained from these patients in the mornings on an empty stomach. Serums were obtained after the blood samples were centrifuged at 4000 rpm for 10 minutes. In addition to the routine tests performed during the follow-up of COVID-19 (CRP, troponin T, procalcitonin, D-dimer, leukocyte, ferritin), thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb), TSH, fT3, and fT4 levels were determined in the sera obtained. The ratio of fT3/fT4 was calculated according to the results of the analysis on fT3 and fT4 tests. After the analyses, patients were classified as patients with autoimmune thyroid disease (Group I), patients with ESS and only isolated low fT3 levels (Group II), and patients with both isolated low fT3 and low TSH levels (Group III). Patients with normal thyroid function tests (n= 4) were not classified in a group, as their quantity was statistically small. In addition, the findings of the patients in the lung tomography were evaluated together with the test results. Patients with a history of thyroid disease other than autoimmune thyroid disease, who had undergone thyroid surgery, who had used medication for thyroid, who had a known history of coronary heart disease, who had liver disease or failure, who had known chronic inflammatory disease (FMF, rheumatoid arthritis, tuberculosis, etc.), who received chemotherapy and radiotherapy, and who had pituitary and hypothalamic diseases within the last 6 months, were excluded from the study.
Measurement of Parameters
TPOAb, TgAb, TSH, fT3, fT4, and the levels of troponin T, procalcitonin, and ferritin from the tests in the routine test panel were measured through the ECLIA (electrochemiluminescence assay) method on a Roche Cobas 8000 (Roche Diagnostics GmbH, Mannheim; Germany) hormone analyzer. CRP levels were measured using the immunoturbidimetry method on a Roche Cobas c701 (Roche Diagnostics GmbH, Mannheim; Germany) biochemistry analyzer, D-dimer levels were measured using the coagulometric method on ACL-TOP 700 (Instrumentation Laboratory) coagulation analyzer, and the leukocyte levels were measured using the fluorescence flow cytometry method on the Sysmex XN-1000 (Sysmex Corporation, Kobe, Japan) hematology analyzer. Normal reference ranges for thyroid function tests and thyroid antibodies were accepted as 0-34 U/ml for TPOAb, 0-115 U/ml for TgAb, 1.95-5.85 ng/L for fT3, 0.9-1.7 ng/dl for fT4, and0.27-4.2 mIU/L for TSH.
The SPSS 15.0 software for Windows was used for statistical analysis. Descriptive statistics were presented as numbers and percentages for categorical variables, and as interquartile range (IQR) and median for the numerical variables. Normal distribution was determined by skewness, kurtosis, Kolmogorov- Smirnov (Lilliefors Significance Correction), Shapiro-Wilk tests, and examination of the distribution of histogram graphics. After the Kruskal-Wallis analysis was performed for comparing multiple independent groups without normal distribution, the non-parametric Mann-Whitney U test was used as a verification test for the comparison of two independent groups. In addition, the relationship between biochemical parameters used in the follow-up of patients with COVID-19 and the fT3/fT4 ratio was determined through correlation analysis. Since the parametric test condition could not be achieved, relationships between the numerical variables were analyzed using the Spearman Correlation test. The statistical alpha significance level was accepted as p<0.05.
Demographic information and results of the lung tomography belonging to the patient groups participating in the study are presented in Table 1. Among the 114 patients, 64 (56.1%) were males, and 50 (43.9%) were females. We concluded that only isolated low fT3 levels were detected in 39.5% (45/114) of the patients, while 25.4% (29/114) had both isolated low TSH and fT3 levels, 31.6% (36/114) had autoimmune thyroid disease, and 3.5% (4/114) had normal results in the thyroid function tests. When grouping the patients, patients with normal thyroid function tests were not included in any groups as they were quantitatively insufficient. In addition, 102 (89.5%) of 114 patients had ground-glass opacity on lung tomography, while 12 (10.5%) patients had no ground-glass opacity on lung tomography.
The median, interquartile range of the tests belonging to all groups and p-values obtained according to the comparison results of the 3 groups are presented in Table 2. According to the results of the comparison performed within the group, a statistical difference was obtained when fT3/fT4 ratio, TgAb, TPOAb, and fT3 values of Group I and Group II were compared among themselves (p<0.01, p0.01, p0.01, p0.01, respectively); however, no statistical difference was obtained among fT4, TSH, procalcitonin, D-dimer, troponin T, CRP, leukocyte and ferritin levels (p= 0.220, p= 0.488, p= 0.079, p= 0.642, p= 0.347, p= 0.229, p= 0.168, p= 0.197, respectively). A statistical difference was obtained when the fT3/fT4 ratio, TgAb, TPOAb and fT3, TSH, procalcitonin, CRP and ferritin levels of Group I and Group III were compared among themselves (p<0.01, p0.01, p0.01, p0.01, p0.01, p0.01, p=0.027, p0.01, respectively); however, there was no statistical difference in terms of D-dimer, troponin T and leukocyte values (p= 0.227, p= 0.303, p= 0.225, p= 0.828, respectively). A statistically significant difference was obtained when fT3, TSH and ferritin levels of Group II and Group III were compared (p= 0.047, p<0.01, p= 0.018, respectively); however, no statistically significant difference was obtained when the procalcitonin, D-dimer, troponin T, CRP and leukocyte values were compared (p= 0.510, p= 0.472, p= 0.779, p= 0.122, p= 0.234, p= 0.640, p= 0.698, p= 0.485, p= 0.457, respectively). The boxplot belonging to the fT3/fT4 ratios is displayed in Figure 1.
According to the correlation results, when the data obtained as a result of the analysis for Group I were compared within themselves, the fT3/fT4 ratio was found to have no statistically significant correlation with TgAb (r= 0.3, p= 0.076), procalcitonin (r= -0.014, p= 0.935), D-dimer (r= 0.058, p= 0.735), troponin T (r= 0.157, p= 0.735), C-reactive protein (r= -0.21, p= 0.218), leukocyte (r= 0.030, p= 0.860), ferritin (r= -0.279, p= 0.099) (p>0.05); however, a statistically significant correlation was found with TPOAb (r= 0.65, p= 0.001) and TSH (r= 0.397, p= 0.010) (p<0.05). According to the correlation results of Group II, the fT3/fT4 ratio was found to have no statistically significant correlation with TgAb (r= 0.073, p= 0.632), TPOAB (r= 0.124, p= 0.415), TSH (r= 0.213, p= 0.159), procalcitonin (r= 0.289) , p= 0.054), D-dimer (r= -0.192, p= 0.213), Troponin T (r= -0.002, p= 0.992), C-reactive protein (r= 0.087, p= 0.576), Leukocyte (r= 0.058, p= 0.710), and ferritin (r = 0.249, p = 0.103) values (p>0.05). Looking at the correlation results of Group III, the fT3/fT4 ratio was found to have no statistically significant correlation with TgAb (r= -0.146, p= 0.451), TPOAb (r= -0.237, p= 0.216), TSH (r= 0.091, p= 0.640), D-dimer (r= -0.021, p= 0.916), troponin T (r= -0.049, p= 0.805), C-reactive protein (r= 0.007, p= 0.971), procalcitonin (r= 0.330, p= 0.080), leukocyte (r= 0.185, p= 0.337), ferritin (r= 0.185, p= 0.337) (p>0.05).
This study investigated the change in thyroid hormones in randomly selected patients, who were hospitalized due to COVID-19, and the possible relationship between this change and other biochemical markers used for COVID-19. In the light of the results we obtained, our first notable finding was that 64.9% of these patients had ESS. Our second notable finding was that 35.1% of the patients had autoimmune thyroid disease. It was also noteworthy that the ratio of fT3/T4 was at the lowest value in all groups, especially in Group III, which contained patients with increased severity of thyroid disease. Recent studies have revealed that COVID-19 causes changes in thyroid hormone levels [11-14]. According to data obtained by Lui et al. on 191 patients with COVID-19, they found that it was accompanied by abnormal thyroid function, especially in 25 (13.1%) patients. They reported that 10 of these patients with abnormal thyroid function had isolated low TSH levels, and 10 had isolated low fT3 levels, which they thought were caused by non-thyroid illness syndrome. In addition, they stated in their studies that patients with isolated low fT3 levels had worse outcomes and systemic infection associated with COVID-19 and that isolated low fT3 levels and fT3/ fT4 ratio could be a prognostic marker . In another study, 62 sequential patients, who were treated in the hospital during the COVID-19 pandemic, were included in the study, and the patients were divided into two groups as patients with low serum fT3 levels (n= 38 patients) and patients with normal serum fT3 levels (n= 24 patients). As a result of their examination, they found that the severity of COVID-19 was higher in the group with low fT3 levels, and that serum fT3 levels were associated with the severity of the disease . In the study conducted by Zou et al., it was found that 41 (27.52%) of 149 patients with COVID-19 had ESS. They reported later in the study that, when patients with COVID-19 who did not have ESS were compared with the patients with ESS, they reported that ESS was significantly associated with inflammation parameters and the severity of the disease in patients with COVID-19 .
In the study by Wang et al., which included 84 patients with COVID-19, 91 patients with non-COVID-19 pneumonia, and 807 healthy participants, they found that serum TSH levels were significantly lower in patients with COVID-19 compared to the other groups. They also reported that this change in patients with COVID-19 may be partly due to ESS . Serum fT4 levels also increase over time as the severity of ESS increases. In our study, the severity of the disease was higher at both central (isolated low TSH) and thyroid hormone (isolated low fT3) levels, especially in Group III patients, the fT4 levels were higher in Group III compared to the serum fT4 levels of Group I and Group II. However, these high serum fT4 levels belonging to Group III were not statistically significant when compared to the other groups. In addition, the statistically significantly higher ferritin levels obtained in Group III compared to other groups were the reflection of the increased acute phase response; therefore, the increase in acute phase response may have caused the suppression of central TSH and 5-deiodinase activity. Our study is a cross-sectional study conducted in a specific region in the Turkish population. The regional and social variability of SARS- CoV-2 strains causes the achievement of different results in previous studies. In addition, regional differences play a large role in immune defense due to genetic features. Accordingly, studies conducted in different populations and different regions become important for understanding the disease mechanisms caused by the SARS-CoV-2 infection in the body. Finally, there is a need for comparative studies, where the changes in different variants of SARS-CoV-2 are examined in patients infected with SARS-CoV-2.
As a result, there was a high prevalence of ESS in patients treated for COVID-19. In addition, we believe that studies with a wider scope of participants are needed for testing the reduction in fT3/fT4 ratio with other biochemical parameters in patients with COVID-19 without known thyroid disease.
Scientific Responsibility Statement
Animal and human rights statement
Conflict of interest
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Download attachments: 10.4328:ACAM.20743
Durmuş Ayan, Tevfik Balcı, Sercan Ünal, Haydar Ulucan, Cevdet Türkyürek, Ergül Bayram. Evaluation of the fT3/fT4 ratio and prevalence of Euthyroid Sick Syndrome among patients with COVID-19: A cross-sectional study. Ann Clin Anal Med 2021; DOI:12(12):1343-1347
The effect of the Coronavirus 2019 pandemic on the mental health of healthcare workers
Serdar Özdemir 1, Hatice Şeyma Akça 1, Abdullah Algın 1, Abuzer Özkan 1, Serkan Emre Eroğlu 1, Sümeyra Acar Kurtuluş 1 Habib Sevimli 1, Zeliha Dönmez 2
1 Department of Emergency Medicine, 2 Department of Psychiatry, University of Health Sciences, Umraniye Training and Research Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.20745 Received: 2021-06-12 Accepted: 2021-08-09 Published Online: 2021-08-20 Printed: 2021-12-01 Ann Clin Anal Med 2021;12(12):1348-1352
Corresponding Author: Serdar Özdemir, Department of Emergency Medicine, University of Health Sciences, Umraniye Training and Research Hospital, Istanbul, Turkey. E-mail: email@example.com P: +90 (505) 2673292 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6186-6110
Aim: The riskiest working group in pandemics is healthcare workers. This study sought to determine the effect of the coronavirus 2019 pandemic on the mental health of healthcare workers.
Material and Methods: The study, designed as a case-control, clinical observation study, was conducted on healthcare workers working in pandemic clinics during the pandemic period. One hundred fifty-three healthcare workers included. The study form included demographic data, marital status, working hours, job, Insomnia Severity Index, Patient Health Questionnaire-9 and Beck’s Depression Inventory, and clinical questions. Turkish-adapted versions of all scales were applied.
Results: In our clinical observation study, 26.2% of healthcare professionals working in pandemic clinics during the pandemic period were depressed (according to Beck’s Depression Inventory), 39.8% had moderate and severe depression (according to the Patient Health Questionnaire-9), and 58.6% had insomnia (according to the Insomnia Severity Index). However, there was no significant difference between the subgroups of health workers in terms of depression and insomnia.
Discussion: All medical and non-medical healthcare workers working in COVID 19 clinics during the pandemic have been widely adversely affected by the process.
Keywords: Sleep Wake Disorders, Depression, Health Personnel, Anxiety Disorders, COVID-19
Coronavirus 2019 disease has caused social, economic, and cultural changes in the world since it was first identified in December 2019 . In times of global pandemics, the capacities of the service providers of the health system are exceeded, and health institutions are at the forefront of the institutions that work the most. During pandemic periods, individuals are affected socioeconomically and spiritually, and health personnel, whose work responsibilities and obligations increase in this process, are also affected psychologically . The riskiest working group in pandemics is healthcare workers . Health workers are affected psychologically because of the increase in working hours during these periods and the feeling of insecurity due to intense virus load [2,3].
Pandemics are a trauma that poses a risk to people’s lives and existence, and that is distressing for society . Mental trauma has been reported as abnormal events in which death, serious injury, a threat to physical or vital integrity occur and people learn that an individual they live, see or love is living . Psychiatric disorders caused by mental traumas include alcohol and substance addiction, suicide, depression-anxiety symptoms, and sleep disorders . Sleep disorders are among the psychiatric disorders that cause the most serious functional impairment along with depression . The risk of mental trauma is higher in health personnel, especially in pandemic service workers, compared to other occupational groups.
We speculated that the detection of risk groups in terms of psychological stress during the pandemic process will lead to the introduction of early psychological support programs and reduce burnout. In this study, it was aimed to compare the scores obtained from the Insomnia Severity Index, Patient Health Questionnaire-9 and Beck’s Depression Inventory scales in people working in pandemic services during the pandemic period. In addition, it was aimed to compare the demographic characteristics of the individuals in the case group and the scores they got from the roots.
Material and Methods
The study designed as a case-control, clinical observation study, was conducted on healthcare workers working in pandemic clinics during the pandemic period. The hospital where this study was conducted was declared a pandemic hospital, and it was a tertiary public hospital serving approximately 3.4 million population.
During the working period, emergency room staff, thoracic surgery staff, cardiovascular surgery staff worked in the outpatient clinics. Other services staff worked in intensive care units and inpatient clinics. Our study population is healthcare professionals working in pandemic clinics during the pandemic period. Clinical support staff (non-medical healthcare workers), nurses, and doctors were included.
The study was carried out using a study form prepared with the Google® forms application in a digital environment. The study form included demographic data, marital status, working hours, job, Insomnia Severity Index, Patient Health Questionnaire-9 and Beck’s Depression Inventory, and clinical questions. Turkish- adapted versions of all scales were applied in Turkish. The clinical questions were “Have you had been diagnosed with COVID- 19 “, “Have you been tested for COVID- 19 because of symptoms”, “Have your relatives been diagnosed with COVID -19”.
Beck’s Depression Inventory was created by Aaron Beck et al. in 1961 and revised in 1978 [6,7]. The original version consists of 21 questions about how the person has been feeling in the last week. No special training is required for the use of the scale. The person to whom the scale was applied is asked to choose the sentence that best expresses how he or she felt during the past week, including the day of scale implementation. The scale includes a total of 21 self-evaluation sentences that are numbered as 0, 1, 2, 3 and provide a four-point Likert- type measurement. The sentence with the number “0” is in such a way as to indicate that there is no depressive feeling or situation specified in that item, and that it is experienced more intensely as the number increases . The Turkish version of the depression scale (Beck Depresyon Ölçeği) was tested for validity and reliability by Hisli .
The Insomnia Severity Index, developed to determine the degree of insomnia symptoms, can be used in normal population screenings and clinical evaluation of insomnia . The scale is both a self-report tool and a tool that can be used by a caregiver (spouse/parent) or clinician for evaluation. It is a five- point Likert-type scale consisting of seven items. Each item is scored between 0 and 4, and the total score is between 0 and 28. A score of 0-7 on the scale indicates clinically insignificant insomnia, 8-14: insomnia sub-threshold, 15-21: clinical insomnia (moderate), 22-28: clinical insomnia (severe). Turkish validity and reliability of index (Uykusuzlık Şiddet İndeksi) study was performed by Boysan et al. in 2010 .
Patient Health Questionnaire-9 is a depression module consisting of nine items. Each item has a four-point Likert scale. “Never”, “Some days”, “More than half of the days” and “Almost every day” are options. The Patient Health Questionnaire-9 can be scored from 0 to 27. The answers given to the items included in the scoring are scored with 0 as the lowest and 3 as the highest. A score of 1-4 is the minimum score, 5-9 is mild depression, 10-14 is moderate depression, 15-19 is moderately severe depression, and 20-27 is severe depression. The Turkish validity and reliability study of the test (Hasta Sağlığı Anketi) was carried out by Sarı et al. in 2016 .
IBM SPSS Statistics for Mac, Version 27.0. Armonk, NY, IBM Corp was used to perform statistical analyses. The Kolmogorov-Smirnov test was conducted for the evaluation of the conformance of variables with a normal distribution. The remaining data were expressed as interquartile range (IQR) and median values. Categorical data were presented with the number of cases and percentages. For the comparison of quantitative and qualitative data between two groups, the chi- square and Mann-Whitney U tests were used.
The ethical committee approval for our study was obtained from the local ethics committee of clinic research (approval number: B. 10.1. TKH.4.34.H.GP. 0.01 /112). Before filling out the study form, participants were offered to participate in the study digitally. Participants who agreed to participate in the study signed an informed consent form in a digital environment containing the demographic data of the participants. The study form included demographic data, marital status, working hours, job, Insomnia Severity Index, Patient Health Questionnaire-9 and Beck’s Depression Inventory, and clinical questions.
A total of 153 participants were included in the study. Ninety- two (60.1%) of the participants included in the study were males and 61 (39.9%) were females. Eighty-seven (56.9%) participants were single, 24 (15.7%) were married, and 42 (27.5%) were married and had children. Twenty (13.1%) participants were high school graduates, 54 (35.3%) were university graduates, 79 (51.6%) were postgraduates. Twenty-one (13.7) participants had comorbidity and 132 (86.3%) participants did not have comorbidity. The median of the participants’ weekly working hours was 48 (IQR: 40-56). One hundred ten (71.9%) of the participants were doctors, 21 (13.7%) were nurses, 22 (14.4%) were clinical support personnel. Sixty-four (41.8%) participants tested at least once for SARS-CoV-2, and 9 (5.9%) participants have a positive test for SARS-CoV-2. Seventy-eight (51%) participants had a relative who tested positive for SARS-CoV-2. The study population was evaluated by Beck’s Depression Inventory, and 38 (26.2%) of them were evaluated as depression with a score of 17 and above. According to the Patient Health Questionnaire-9, 30 (20.4%) of the study population were none- minimal depression, 60 (40.8%) of them were mild depression, 30 (20.4%) of them were moderate depression, 21 (14.3%) of them were moderately severe depression, 6 (14.3%) of them were severe moderate depression. On the other hand, according to the Insomnia Severity Index, 63 (41.4%) of them were diagnosed with no clinically significant insomnia, 69 (45.4) of them were diagnosed with subthreshold insomnia, 15 (9.9%) of them were diagnosed with moderate clinical insomnia and 5 (3.3%) of them were diagnosed with were severe clinical insomnia. The distribution of participants in terms of Insomnia Severity Index, Patient Health Questionnaire-9 and Beck’s Depression Inventory are shown in Figures 1-3. Comparisons of the participants in terms of Insomnia Severity Index, Patient Health Questionnaire-9 and Beck’s Depression Inventory are shown in Tables 1-3.
Eight (5.2%) of the participants had been diagnosed with COVID 19 by the study date. There was no statistically significant difference in terms of Insomnia Severity Index, Patient Health Questionnaire-9 and Beck’s Depression Inventory between the COVID-19 group and the non-COVID-19 group (p = 0.939, p = 0.845, and p = 0.936, respectively). Sixty-four (41.8%) participants had been tested for COVID-19 at least once. There was no statistically significant difference in terms of Insomnia Severity Index, Patient Health Questionnaire-9 and Beck’s Depression Inventory between group tested for COVID -19 and the group not tested for COVID- 19 (p = 0.613, p = 0.831, and p = 0.818, respectively). Seventy-eight (50.9%) participants had at least one relative diagnosed with COVID-19. There was no statistically significant difference in terms of Insomnia Severity Index, Patient Health Questionnaire-9 and Beck’s Depression Inventory between the group that had at least one relative diagnosed with COVID-19 and the group that did not (p = 0.536, p = 0.586, and p = 0.512, respectively).
In our clinical observation study, 26.2% of healthcare professionals working in pandemic clinics during the pandemic period were depressed (according to Beck’s Depression Inventory), 39.8% had moderate and severe depression (according to Patient Health Questionnaire-9), and 58.6% had insomnia (according to Insomnia Severity Index). However, there was no significant difference between the subgroups of health workers in terms of depression and insomnia. We can say that all health workers are psychologically affected by the pandemic process.
Pandemics are traumas that threaten people’s lives and identities and are distressing for all individuals. The severity of psychiatric trauma symptoms that can be seen in individuals may differ due to factors such as socioeconomic status, cultural characteristics, class status in society, personal characteristics, and mental states . Working with COVID-19 positive individuals or being infected with this virus is a situation that increases mental effects. Healthcare workers face such risk factors as infection, exposure to radiation, physical and mental fatigue, exposure to violence . Health workers are the group with the highest risk of encountering the virus among workers . During this period, employees face a heavy virus load, and the fact that they must work in an insecure environment without adequate rest due to high working hours causes them to experience serious mental effects. In addition, the inability to clearly reveal the transmission routes in the early period of the pandemic and the lack of proven drugs in the treatment yet bring an additional psychological burden [2,3-5]. Healthcare workers have been affected by infectious diseases that have been seen so far, and they are among the groups with the highest risk of being affected by future epidemics . It is well known that healthcare workers experience significant stress during infectious epidemics. Among the causes of stress, there are thoughts such as the worry of getting sick due to the virus, the anxiety that it will infect relatives .
In our study, no difference was observed between age, marital status, and working groups. An explanation for this might be that all healthcare workers are equally adversely affected by the mental burden of the pandemic [12-14]. Another plausible explanation for similar mental exposure may include similar access to formal psychological support, more first-hand medical information about the pandemic and COVID-19, and more intensive training in personal protective equipment and infection control measures [12-14]. Another interesting result of our study was that increased scale scores were not observed in those who had COVID- 19 and those whose relatives had COVID-19 and were tested. These data confirms that mental impact in healthcare workers is cumulative.
In the literature, it has been reported that sleep disorders increased, and existing sleep disorders worsened in healthcare workers during the pandemic process [15-17]. Our study showed that 58.6% of healthcare workers had insomnia. Insomnia in healthcare workers may be due to long working hours and disruption of circadian rhythm. Sleep disorders and psychiatric disorders and anxiety are interrelated. Sleep disorders have been associated with chronic inflammatory processes, as well as neuroendocrine and immune system effects . Coping with sleep disorders should focus on individual emotional control and emotional stability, which includes efforts to maintain hope, deal with a stressful situation through emotional regulation, sleep hygiene, and psychoeducation techniques, and engaging in pleasurable activities that bring mindfulness and a sense of accomplishment [15-17].
This study has several limitations. Firstly, this study was a single-center study. Secondly, the cases were not examined by a psychiatrist, and the data obtained from self-reported questionnaires were not verified with medical records. The patients were evaluated only with psychiatric evaluation scales. Scales were used in the evaluation of mental status; thus, we were able to show the symptom level rather than the diagnosis of the disease. Another limitation of this study is the low number of participants. More precise data can be obtained with studies to be conducted in many centers with different characteristics, with larger samples and accompanied by a psychiatric examination.
As a conclusion, this study demonstrated that 26.2% of healthcare professionals working in pandemic clinics during the pandemic period were depressed (according to Beck’s Depression Inventory), 39.8% had moderate and severe depression (according to Patient Health Questionnaire-9), and 58.6% had insomnia (according to Insomnia Severity Index). However, there was no significant difference between the subgroups of health workers in terms of depression and insomnia. No difference was observed between age, marital status, and working groups. However, the data of our study should be validated in multi-center and larger cohorts.
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1. Özdemir S, Algın A. How will the Health Literacy and Crowded Emergency Room Be Affected After the COVID-19 Pandemic? Phnx Med J. 2021; 3(1):50.
2. Lenzo V, Quattropani MC, Sardella A, Martino G, Bonanno GA. Depression, Anxiety, and Stress Among Healthcare Workers During the COVID-19 Outbreak and Relationships with Expressive Flexibility and Context Sensitivity. Front Psychol. 2021; 12:623033. DOI:10.3389/fpsyg.2021.623033
3. Khunti K, Griffiths A, Majeed A, Nagpaul C, Rao M. Assessing risk for healthcare workers during the COVID-19 pandemic BMJ. 2021; 372:n602 DOI:10.1136/bmj. n602
4. Di Tella M, Romeo A, Benfante A, Castelli L. Mental health of healthcare workers during the COVID-19 pandemic in Italy. J Eval Clin Pract. 2020; 26(6):1583-7. DOI: 10.1111/jep.13444.
5. Avcı S, Yağcı İ. COVID-19 Pandemisi Döneminde Acil Servis Çalişanlarinin Psikolojik Durumlari. Bozok Tıp Dergisi. 2021; 11(1):49-55.
6. Şahiner Önal G, Hisar K. Üniversite Öğrencilerinde Uykusuzluk Şiddeti ve Depresyon Semptomları İlişkisi ve Depresyon Tedavisinin Uykusuzluk Şiddetine Etkisi (The Relationship Between Insomnia Severity and Depression Symptoms in University Students and the Effect of Depression Treatment on Insomnia Severity). Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi/ Gumushane University Journal of Health Sciences.. 2018; 7(1):125-30.
7. Beck AT, Ward CH, Mendelson M. An invertory for measuring depression. Arch Gen Psychiatry. 1961; 4:561-71.
8. Hisli N. Beck Depresyon Envanterinin geçerliği üzerine bir çalışma (A study on the validity of the Beck Depression Inventory). Türk Psikoloji Dergisi/ Turkish Journal of Psychology. 1988; 6:118-26.
9. Boysan M, Güleç M, Beşiroğlu. Uykusuzluk şiddeti indeksinin Türk örneklemindeki psikometrik özellikleri (Psychometric properties of insomnia severity index in Turkish sample). Anadolu Psikiyatri Derg. 2000; 11:248-52.
10. Sarı YE, Kökoğlu B, Balcıoğlu H, Bilge U, Çolak E, Ünlüoğlu İ. Turkish Reliability of The Patient Health Questionnaire-9. Biomedical Research -India. 2016; 27:460-2.
11. Saladino V, Algeri D, Auriemma V. The Psychological and Social Impact of Covid-19: New Perspectives of Well-Being. Front Psychol. 2020; 11:577684. DOI: 10.3389/fpsyg.2020.577684.
12. Tan BYQ, Chew NWS, Lee GKH, Jing M, Goh Y, Yeo LLL, et al. Psychological Impact of the COVID-19 Pandemic on Health Care Workers in Singapore. Ann Intern Med. 2020; 173(4):317-20. DOI: 10.7326/M20-1083.
13. Underner M, Perriot J, Peiffer G, Jaafari N. COVID-19 et trouble de stress post-traumatique (TSPT) chez les professionnels de santé [COVID-19 and post- traumatic stress disorder (PTSD) among health care professionals]. Rev Mal Respir. 2021; 38(2):216-19. French. DOI: 10.1016/j.rmr.2020.11.014.
14. Jemal K, Deriba BS, Geleta TA. Psychological Distress, Early Behavioral Response, and Perception Toward the COVID-19 Pandemic Among Health Care Workers in North Shoa Zone, Oromiya Region. Front Psychiatry. 2021; 12:628898. DOI: 10.3389/fpsyt.2021.628898.
15. de Almondes KM, Marín Agudelo HA, Jiménez-Correa U. Impact of Sleep Deprivation on Emotional Regulation and the Immune System of Healthcare Workers as a Risk Factor for COVID 19: Practical Recommendations from a Task Force of the Latin American Association of Sleep Psychology. Front Psychol. 2021; 12:564227. DOI:10.3389/fpsyg.2021.564227
16. Conroy DA, Hadler NL, Cho E, Moreira A, MacKenzie C, Swanson LM, et al. The effects of COVID-19 stay-at-home order on sleep, health, and working patterns: a survey study of US health care workers. J Clin Sleep Med. 2021; 17(2):185-91. DOI: 10.5664/jcsm.8808.
17. Richards A, Kanady JC, Neylan TC. Sleep disturbance in PTSD and other anxiety-related disorders: an updated review of clinical features, physiological characteristics, and psychological and neurobiological mechanisms. Neuropsychopharmacology. 2020; 45(1):55-73. DOI: 10.1038/s41386-019-0486- 5.
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Serdar Özdemir, Hatice Şeyma Akça, Abdullah Algın, Abuzer Özkan, Serkan Emre Eroğlu, Sümeyra Acar Kurtuluş, Habib Sevimli, Zeliha Dönmez. Analysis of laboratory parameters in patients with COVID-19: Experiences from a pandemic hospital. Ann Clin Anal Med 2021;12(12):1348-1352
Serum albumin level in critically ill pediatric patients
Gurkan Atay, Seher Erdoğan
Department of Pediatric Critical Care, Health Science University, Umraniye Research and Training Hospital, İstanbul, Turkey
DOI: 10.4328/ACAM.20746 Received: 2021-06-14 Accepted: 2021-08-19 Published Online: 2021-10-28 Printed: 2021-12-01 Ann Clin Anal Med 2021;12(12):1353-1356
Corresponding Author: Seher Erdoğan, Department of Pediatric Critical Care, Health Science University, Umraniye Research and Training Hospital, İstanbul, Turkey. E-mail: firstname.lastname@example.org P: +90 532 667 83 70 Corresponding Author ORCID ID: https://orcid.org/0000-0002-3393-3363
Aim: Hypoalbuminemia is a frequent condition among patients admitted to the pediatric intensive care unit (PICU). The aims of the present study were to determine the prevalence of hypoalbuminemia among critically ill pediatric patients and assess its relationship with prognosis.
Material and Methods: This was a retrospective observational study evaluating the albumin levels and prognoses recorded among patients admitted to the PICU between May 2017 and December 2018. The patients were categorized into two groups; those with hypoalbuminemia were assigned to Group 1.
Results: The study enrolled a total of 126 pediatric patients, of whom 64 (50.8%) were female. One hundred and five (83.3%) patients survived and 21 (16.7%) died. Forty-six (36.5%) patients had hypoalbuminemia. Among the patients assigned to Group 1, the need for mechanical ventilation (MV) was significantly greater (p=0.007), but there was no significant difference between the number of days of MV (p=0.64). Group 1 had significantly greater PRISM scores, significantly longer hospital stays, and a significantly higher mortality rate (p=0.000, p=0.013, and p=0.000, respectively). No significant difference was seen for the number of days spent in the PICU. Prognosis analysis revealed that surviving patients had a higher mean age, less need for MV, shorter hospitalization and MV times, and lower serum total protein and albumin levels.
Discussion: We suggest that serum albumin level is an important prognostic marker as it is a simple, specific, and low-cost parameter that is routinely used in most PICUs.
Keywords: Hypoalbuminemia, Pediatric, Intensive Care, Mortality
Albumin has a long half-life of 15-19 days. Among critically ill patients, however, serum albumin levels may rapidly drop within 3-5 days. Albumin plays many physiological roles including the regulation of colloid osmotic pressure; binding and transport of various substances in the blood, such as drugs and hormones; contributions of antioxidant properties; and nitric oxide modulation . Inflammatory processes increase albumin catabolism and may reduce its production. During critical illnesses, capillary permeability is dramatically reduced, leading to albumin exchange between the intravascular and extravascular compartments [2-4]. Previous studies have shown a hypoalbuminemia prevalence of 21-76% among critically ill children [5-7]. The aim of the present study was to determine the prevalence of hypoalbuminemia and its relationship with prognosis among children admitted to a pediatric intensive care unit (PICU).
Material and Methods
This study was approved by the local ethics committee of Ümraniye Training and Research Hospital. It was conducted retrospectively in a 10-bed PICU. Age, sex, admission diagnosis, Pediatric Risk of Mortality (PRISM) score, serum total protein and albumin levels, mechanical ventilation (MV) need, number of days on MV, number of days in the PICU, number of days in the hospital, and prognosis were recorded for all patients admitted to the PICU between May 2017 and May 2018. Patients with nephrotic syndrome, liver cirrhosis, protein energy malnutrition, burns, recent cardiovascular surgery, and various disorders that might potentially affect serum albumin level were excluded in addition to those who received parenteral nutrition and albumin infusion prior to admission. Hypoalbuminemia was defined as a serum albumin level of ≤2.5 g/dL among patients younger than 7 months and ≤3.4 g/dL among older ones. The patients were assigned to two separate groups, Group 1 and Group 2, indicating hypoalbuminemia and normal serum albumin levels, respectively. Written informed consent was not obtained from the parents and guardians of the patients included in this study since the study is a retrospective study and data were obtained by the screening of patient files.
The study data were analyzed using the IBM SPSS Statistics 22 software package (IBM SPSS, Turkey). The normality of data distribution was tested with the Shapiro-Wilk test; the descriptive statistics included mean, standard deviation, and frequency. The Student t-test was used for comparison of normally distributed quantitative data and the Mann-Whitney U test for non-normally distributed data. Qualitative data were compared with Yates continuity correction. Statistical significance was set at p<0.05.
During the study period 154 patients were admitted; 28 patients not meeting the inclusion criteria were excluded. There were 64 (50.8%) female and 62 (49.2%) male patients, with a total of 126 pediatric patients included in the study. The mean age was 64.66±71.28 months. The mean serum total protein level was 5.84±1.11 (min-max: 3.4-8), while mean albumin level was 3.63±0.59 (min-max: 2.1-4.9). Fifty-three (42.1%) patients received respiratory support via MV. The mean PRISM score was 11.8±10.3, the mean number of days on MV was 25.6±30.9, the mean duration of PICU stay was 17.6±24.0 days, and the mean duration of hospital stay was 23.5±25.9 days. While 105 (83.3%) patients survived, 21 (16.7%) patients died. Forty-six (36.5%) patients had hypoalbuminemia (Table 1).
The female patients had a higher rate of hypoalbuminemia (p=0.03), and the mean age of patients in Group 1 was younger, but that difference did not reach statistical significance. Among patients in Group 1, the need for MV was significantly greater although the numbers of days on MV were similar. The patients in Group 1 had higher PRISM scores, longer hospital stays, and higher mortality rate (p=0.000, p=0.013, and p=0.000, respectively). The numbers of days spent in the PICU were similar (Table 2).
As for prognosis, the surviving patients had higher mean age, less need for MV, shorter durations of PICU stay and MV use, and higher serum total protein and albumin levels (Table 3).
Our study showed a hypoalbuminemia prevalence of 36% at admission among patients admitted to the PICU. Like previous studies, patients with hypoalbuminemia had greater need for MV, higher PRISM scores, longer hospital stays, and higher mortality rates than those with normal albumin levels [7-10]. In a study from 2016 involving 202 critically ill children, the prevalence of hypoalbuminemia was found to be 57.9%. Those patients had longer PICU stays and MV requirements as well as a mortality rate four times higher than that of children with normal albumin levels. Likewise, our study demonstrated greater mortality among patients with hypoalbuminemia. Although there was a greater need for MV, the duration of MV use was not significantly different between the study groups, but the duration of hospital stay was prolonged in Group 1. Patients in that group were younger, but the age difference did not reach statistical significance .
Durward et al. , in a similar study, reported a hypoalbuminemia prevalence of 57% at admission, which rose to 76% after 24 hours. They suggested that that increase may have been due to a decrease in albumin synthesis capacity and the very low rate of use of albumin as a volume expander in their unit. There was no correlation between mortality and hypoalbuminemia at admission or the 24th hour, but they reported that PICU stays were longer in patients with hypoalbuminemia (4.9 vs. 3.6 days). They suggested that patients with extreme hypoalbuminemia constituting a minority resulted in that finding.
Tiwari et al.  reported that 21% of 435 critically ill children had hypoalbuminemia at admission, with that rate rising to 34% by the end of the first week and 37% during the whole period of PICU follow-up. Those patients had higher PRISM scores (12.9 vs. 7.5), longer PICU stays (13.8 vs. 6.7 days), greater MV needs, longer MV usage (p<0.001), and a higher mortality rate (87.8% vs. 16.2%). This effect of albumin on mortality does not solely depend on its regulatory effect on colloid osmotic pressure and capillary permeability, but also on binding lipids and drugs as well as providing a means for transport of trace elements such as copper and zinc in the circulation .
The indications for albumin treatment include hypovolemia, shock, burns, hypoalbuminemia, surgery and trauma, acute respiratory distress syndrome, plasmapheresis, and hemodialysis. In critically ill patients who may have endothelial injury, treatment with colloids and crystalloids may increase interstitial fluid volume [12, 13]. In the SAFE (Saline versus Albumin Fluid Evaluation) study  comprising 6997 patients, 4% albumin or saline was administered when there was a need for fluids. That study demonstrated no significant difference between the mortality rates of the groups. A subgroup analysis revealed that albumin was beneficial in severe sepsis but detrimental in traumatic brain injury. The EARSS study , a randomized and controlled multicenter study, compared patients with early severe sepsis who were administered normal saline or 100 mL of 20% albumin, finding no significant difference between the two groups with respect to mortality. In 2015, the ALBIOS study  compared patient groups administered crystalloids alone and crystalloids plus 20% albumin and found no significant mortality difference.
A metanalysis comprising 90 studies involving adult patients revealed that every 1 g/dL decrease in serum albumin led to a 137% increase in mortality as well as a 28% and 71% increase in the durations of ICU and hospital stay, respectively .
The limitations of the present study include having a single- center and retrospective design and involving a heterogeneous patient population.
Serum albumin level is a simple, sensitive, specific, and low- cost marker used in most PICUs; we therefore suggest that it has an important prognostic value in this setting.
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1. Vincent JL. relevance of albumin in modern critical care medicine. Best Pract Res Clin Anaesthesiol 2009;23:183-191.
2. Nicholson JP, Wolmaratis MR, Park GR. The role of albumin in critical illness. Br J Anaesth 2000;85:599-610.
3. Vincent JL, Russel JA, Jacob M, Martin G, Guidet B, Wernerman J, et al. Albumin administration in the acutely ill; what is new and where next? Crit Care 2014;18:231-241.
4. Rodoman GV, Shalaeva TI, Dobretsov GE, Naumov EK, Obelenskii VN. Serum albumin in systemic inflammatory reaction syndrome. Anesteziol Reanimatol 2006;2;62-4.
5. Kumar S, Aroor S, Kini GP, Mundkur S, Moideen A. Hypoalbuminemia aş a marker of adverse outcome in children admitted to pediatric intensive care unit. Indian J Child Heal 2018;5(1); 6-10.
6. Leite HP, Rodrigues da Silva AV, de Oliveira Iglesias SB, Koch Nogueira PC. Serum albumin is an independent predictor of clinical outcomes in critically ill children. Pediatr Crit Care Med 2016;17(2)e50-70.
7. Horowitz IN, Tai K: Hypoalbuminemia in Critically ill children. Arch Pediatr Adolesc Med 2007;161: 1048−1052.
8. Kittisakmontri K, Reungrongrat S, Lao-araya M. Hypoalbuminaemia at admission predicts the poor outcomes in critically ill children. Anaesthesiol Intensive Ther 2016;48:158-161.
9. Durward A, Mayer A, Skellett S, Taylor D, Hanna S, Tibby SM, et al. Hypoalbuminemia in critically ill children: incidence, prognosis and influence on the anion gap. Arch Dis Child 2003; 88: 419−422.
10. Tiwari LK, Singhi S, Jayashree M, Baranwal AK, Bansal A: Hypoalbuminemia in critically sick children. Indian J Crit Care Med 2014; 18: 565−569. doi: 10.4103/0972-5229.140143.
11. Fanali G, di Masi A, Trezza V, Marino M, Fasano M, Ascenzi P. Human serum albumin: From bench to bedside. Mol Aspects Med 2012;33:209-290.
12. Martin GS, Mangialardi RJ, Wheeler AP, Dupont WD, Morris JA, Bernard GR. Albumin and furasemide therapy in hypoproteinemic patients with acute lung injury. Crit Care Med 202;30:2175-2182.
13. American Thoracic Society. Evidence-based colloid use in the critically ill: American Thoracic Society Consensus Statment. Am J Respir Crit Care Med 220;170:1247-1259.
14. Finfer S, Bellomo R, Boyce N, French J, Myburgh J, Norton R:SAFE Study Investigators. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Eng J Med, 2004;350:2247-2256.
15. Charpenter J, Mira JP. EARSS study group:Effeciency and tolerance of hyperoncotic albumin administration in septic shock patients: the EARSS study. Intensive Care Med 2011;37(Suppl 2)S115-0438.
16. Caironi P, Tognoni G, Massion S, Fumagalli R, Pesenti A, Romero M, et al. Albumin replacement in patients with severe sepsis or septic shock. N Eng J Med 2014;370:1412-1421.
17. Vincent JL, Dubois MJ, Navickis RJ, Wilkes MM: Hypoalbuminemia in acute illness: is there a rationale for intervention? A meta-analysis of cohort studies and controlled trials. Ann Surg 2003; 237: 319−334.
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Gurkan Atay, Seher Erdoğan. Serum albumin level in critically ill pediatric patients. Ann Clin Anal Med 2021;12(12):1353-1356
In-hospital mortality prediction using dual antiplatelet therapy score in coronavirus disease 2019
Department of Cardiology, Faculty of Medicine, Çanakkale Onsekiz Mart University, Çanakkale, Turkey
DOI: 10.4328/ACAM.20747 Received: 2021-06-15 Accepted: 2021-08-19 Published Online: 2021-09-21 Printed: 2021-12-01 Ann Clin Anal Med 2021;12(12):1357-1361
Corresponding Author: Uğur Küçük, Barbaros Street, Terzioglu Campus, B Block, No: 4, Onsekiz Mart University, Faculty of Medicine, Department of Cardiology, Canakkale, Turkey. E-mail: email@example.com P: +90 534 591 19 02 Corresponding Author ORCID ID: https://orcid.org/0000-0003-4669-7387
Aim: Mortality rates are high in cases of coronavirus disease 19 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) despite the advances in treatment regimens. The Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score, an up-to-date scoring system, is frequently used in cardiology practice after stent implantation.
This study aimed to investigate the use of the PRECISE-DAPT score to predict in-hospital mortality in patients with COVID-19.
Material and Methods: A total of 264 consecutive patients with positive COVID-19 polymerase chain reaction (PCR) tests were enrolled in this study. Patients were divided into three groups according to PRECISE-DAPT scores: low-, intermediate-, and high-score groups (PRECISE-DAPT scores of <17, 17–24, and ≥25; n=170, 57, and 37, respectively). Those who died in the hospital and those discharged after recovery were noted.
Results: Among 120 women and 144 men with positive PCR test results, a total of 40 patients (low-score, n=16; intermediate-score, n=11; and high-score, n=13) died in the hospital. Prolonged hospital stay was observed in the high-score group compared with the low-score group (p=0.011). In multivariate analysis, the PRECISE-DAPT score (hazard ratio: 0.962, 95% confidence interval: 0.943–0.982, p<0.001) significantly correlated with in-hospital mortality.
Discussion: PRECISE-DAPT scores are associated with mortality in patients with COVID-19. The PRECISE-DAPT scoring system may be useful for predicting in-hospital mortality.
Keywords: COVID-19, Mortality, Survival, Poor Prognosis
In the last year, a factor of unknown origin in Wuhan of Hubei Province in the People’s Republic of China caused severe respiratory failure and affected the entire world in a short time with a serious increase in deaths . The factor that left all humanity desperate was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the World Health Organization (WHO) on February 11, 2020, and the disease that emerged was added to the medical literature as coronavirus disease 2019 (COVID-19) .
The disease became better known; however, it continued to spread across the continents. In addition to pulmonary involvement, COVID-19 presents with cardiac, renal, and central nervous system involvements, and it can cause increased mortality and morbidity . There is no simple and widely accepted scoring system that can be used to reduce the short- term and long-term mortality associated with the disease, but studies have shown that low platelet counts and acute renal failure during hospitalization are associated with increased mortality [4,5]. In one study, older age and female gender were associated with more arrhythmic events .
The Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score, which has recently been used especially in cardiology practice, is useful in patients with ST-elevation myocardial infarction (STEMI) in terms of determining for which individuals and how long dual antiplatelet therapy should continue after the invasive procedure . The PRECISE- DAPT score is simply calculated by using five components (age, hemoglobin level, white blood cell count, creatinine clearance, and bleeding history of the patient) . In addition to the information provided about the optimal duration of dual antiaggregant therapy in patients with STEMI, recent studies have shown that it can be a useful score in predicting the short-term and long-term mortality of patients with STEMI. Furthermore, another study showed that it can be used to predict contrast nephropathy that may develop after coronary angiography in patients with STEMI . Although studies have been conducted to evaluate individual risk factors in COVID-19, the use of a scoring system to be obtained with a combination of various parameters remains unclear. The aim of our study was to investigate the use of the PRECISE-DAPT score, which plays a role in the understanding of various issues from the treatment process to mortality studies in cardiology practice, in predicting in-hospital deaths in patients diagnosed with COVID-19.
Material and Methods
Patient group and study protocol
This single-center retrospective observational study comprised 264 consecutive patients whose polymerase chain reaction (PCR) tests were positive for COVID-19 according to the diagnostic guidance of the WHO. Patients who applied to our tertiary university hospital between April and December 2020 and were found to have RNA for SARS-CoV-2 in samples taken from combined throat and nasal swabs were included in the study.
Patient data such as demographic characteristics, comorbidities, and laboratory results were obtained from electronic medical records. The background information of the patients was collected from medical records for comorbidities including hypertension, diabetes, cardiovascular disease, chronic kidney disease, and malignancy. Laboratory values and PCR test results obtained from peripheral venous blood samples taken during hospitalization were recorded.
The PRECISE-DAPT score for all patients was calculated using the website of the PRECISE-DAPT Score Working Group Executive Committee (http://www.precisedaptscore.com). This score evaluates age, hemoglobin level, white blood cell count, creatinine clearance, and bleeding history . The patients were divided into three groups according to their scores as low- , intermediate-, and high-score groups (PRECISE-DAPT scores of <17, 17–24, and ≥25; n=170, 57, and 37, respectively) as defined in the literature. Those who died in the hospital and those discharged after recovery were noted (Figure 1).
The following patients were excluded from the study: those who underwent an intervention in the hospital due to newly diagnosed coronary artery disease, stage 5 chronic kidney disease or dialysis, or an active infection other than COVID-19; those with an acute cerebrovascular disease or active bleeding that may cause anemia; those receiving plasma therapy, those with a history of bleeding diathesis or known coagulopathy, and those receiving immunosuppressive therapy; and all patients younger than 18 years of age. The study was approved by the COVID-19 Science Committee of the Ministry of Health and our university’s ethics committee and was conducted in accordance with the Declaration of Helsinki (Decision No: 23-2011-KAEK- 27/2020-E.200018129).
Hypertension was defined as systolic blood pressure of >140 mmHg and/or diastolic blood pressure of >90 mmHg or the use of antihypertensive drugs. Diabetes mellitus was defined as fasting blood glucose of >126 mg/dL or the use of antidiabetic medication. Chronic kidney disease was defined as a glomerular filtration rate of <60 mL/min/1.73 cm2. Anemia was defined as the presence of hemoglobin values of <12.0 g/dL in women and <13.0 g/dL in men. Bleeding history was defined as active pathological bleeding or major bleeding within the previous 3 months.
Statistical data were analyzed using SPSS 20.0 (IBM Corp., Armonk, NY, USA). The Kolmogorov–Smirnov test was used to evaluate the distribution of continuous variables. Data that did not conform to normal distribution are expressed as median and interquartile range. Categorical variables are expressed as percentages and numbers. The chi-square test was used when comparing the probability ratios of categorical variables. For the comparison of continuous variables between groups, the Kruskal–Wallis test was used. In addition, Bonferroni’s post hoc test was used. Univariate and multivariate Cox proportional hazard analyses were performed to determine the relation of the PRECISE-DAPT score and its components with mortality. Receiver operating characteristic (ROC) curves were used for in-hospital mortality predictions of the PRECISE-DAPT score and its components in patients with COVID-19. Values of p<0.05 were considered statistically significant.
The demographic results of the patients are shown in Table 1. We included 264 PCR-positive patients with COVID-19 (144 men and 120 women). There were 170 (103 men and 67 women), 57 (30 men and 27 women), and 37 (11 men and 26 women) patients in the low-, intermediate-, and high-score groups, respectively. The high-score group comprised older patients. There was no difference between the groups in terms of diabetes mellitus, previous cardiovascular disease, heart failure, chronic kidney disease, or previous malignancy.
At the time of first diagnosis, oxygen therapy in room air was begun by looking at oxygen saturation and respiratory support. Considering the length of hospitalization between the groups, longer hospitalization was observed in patients with high scores. When the groups were compared in terms of mortality and complications related to COVID-19 pneumonia, 16 patients in the low-, 11 in the intermediate-, and 13 patients in the high- score groups died during the in-hospital period. The laboratory results of the patients are shown in Table 2.
In univariate and multivariate Cox proportional hazard analyses, in-hospital mortality, diabetes mellitus, hypertension, age, and the PRECISE-DAPT score and its components were analyzed. In univariate analysis, hypertension, white blood cell count, hemoglobin, and PRECISE-DAPT score were associated with mortality (p=0.005, p<0.022, p=0.004, and p<0.001, respectively). In multivariate analysis, there was a relationship between the PRECISE-DAPT score and mortality (hazard ratio [HR]: 0.962, 95% confidence interval [CI]: 0.943–0.982, p<0.001; Table 3).
The area under the curve value of the PRECISE-DAPT score and its components (hemoglobin, white blood cell count, creatinine clearance, and age) was 0.752 (95% CI: 0.681–0.823, p<0.001) for all-cause mortality (Figure 2). The predictive value of the PRECISE-DAPT score for in-hospital death in patients with COVID-19 was superior to that of three components of the score (white blood cell count 0.618, 95% CI: 0.514–0.722, p=0.018; hemoglobin 0.368, 95% CI: 0.267–0.469, p=0.008; age 0.651, 95% CI: 0.564–0.738, p=0.002). No statistical difference was observed when it was compared with creatinine clearance (0.429, 95% CI: 0.333–0.525, p=0.155).
To the best of our knowledge, there are no simple scoring algorithms that can be used routinely to predict in-hospital mortality according to the current guidelines for patients with COVID-19. This is the first study to show the relationship between the PRECISE-DAPT scoring system and in-hospital mortality in patients with COVID-19.
Advanced age, diabetes, hypertension, congestive heart failure, and chronic renal failure are well-known prognostic factors in patients with COVID-19. Systemic diseases were observed at varying rates between patient groups, and the effects of hypertension on mortality in univariate regression analysis were similar to the results in the literature .
Our present information about the PRECISE-DAPT score comes from patients with coronary artery disease. It is a useful score to obtain information about the duration of the use of antiplatelet drugs following invasive procedures, especially in patients with STEMI . In addition to its routine use, in a study in which Tanik et al. examined the PRECISE-DAPT score in two groups of patients with STEMI with scores of ≥25 and <25, they demonstrated the use of the score to predict in-hospital mortality . In addition to such studies, as seen in our study, both prolonged hospitalization and mortality rate were associated with increased scores in patients with COVID-19, which were examined here among three groups according to PRECISE-DAPT scores.
Disruptions in oxygen and carbon dioxide exchange as a result of secretion and infiltration in the lungs in patients with COVID-19 cause hypoxia. Changes in iron metabolism because of hypoxia result in a decrease in hemoglobin levels. The decrease in hemoglobin, which is the main determinant of blood oxygen concentration, may cause adverse events that can result in multiple organ failure and death by worsening the clinical picture . Recent studies have shown that comorbid conditions such as cardiovascular diseases and chronic obstructive diseases are associated with increased mortality in patients with advanced age hospitalized for COVID-19; however, there were no differences in hemoglobin levels between survivors and nonsurvivors [15,16]. Another study showed that decreased hemoglobin levels were associated with increased mortality in individuals aged <60 years . In our study, decreased hemoglobin levels were associated with increased mortality in univariate regression analysis. Despite this, hemoglobin was not associated with mortality in multivariate regression analysis, and in our ROC analysis, the PRECISE-DAPT score was superior to the hemoglobin variable.
Inflammatory markers may vary in blood serum levels depending on the severity of the disease and other accompanying comorbid conditions. According to the information obtained from studies conducted among patients with COVID-19, inflammatory markers vary according to the course of the disease . White blood cell count was analyzed in our study; however, it was not statistically useful for predicting mortality and it was not superior to the PRECISE-DAPT score.
In recent studies, in addition to many clinical conditions such as acute coronary syndrome and pulmonary embolism, troponin and D-dimer values have been found useful as prognostic tools in patients with COVID-19 . In our study, high-sensitivity troponin T and D-dimer values could not be shown to be associated with mortality, but the PRECISE-DAPT score was superior to D-dimer and troponin T for mortality.
When the results of the studies in the literature are evaluated, it seems more logical to use combinations instead of single parameters in various clinical situations. As seen in our study, the PRECISE-DAPT score can be used to predict in-hospital mortality in patients with COVID-19.
Our study had some limitations. First, the study comprised a single center and a small number of patients. Second, the use of the PRECISE-DAPT score was examined in the in-hospital period and we could not obtain data about its usability after discharge. Considering the study dates, the score should be reconsidered with patients who have received the full vaccination protocol. Therefore, larger multicenter studies are needed.
The PRECISE-DAPT score is a simple scoring system that uses the patient’s clinical and complete blood count parameters, and increased PRECISE-DAPT scores are associated with mortality in patients with COVID-19. Therefore, we think that the PRECISE-DAPT score can be useful in various applications beyond patients with STEMI.
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1. Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med. 2020; 382(13): 1199-207.
2. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020; 395(10224): 565574.
3. Madjid M, Safavi-Naeini P, Solomon SD, Vardeny O. Potential Effects of Coronaviruses on the Cardiovascular System: A Review. JAMA Cardiol. 2020; 5(7): 831-40.
4. Yang X, Yang Q, Wang Y, Wu Y, Xu J, Yu Y, et al. Thrombocytopenia and its association with mortality in patients with COVID-19. J Thromb Haemost. 2020; 18(6): 1469-72.
5. Cheng Y, Luo R, Wang K, Zhang M, Wang Z, Dong L, et al. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020; 97(5): 829-38.
6. Nabors C, Sridhar A, Hooda U, Lobo SA, Levine A, Frishman WH, et al. Characteristics and Outcomes of Patients 80 Years and Older Hospitalized With Coronavirus Disease 2019 (COVID-19). Cardiol Rev. 2021; 29(1): 39-42.
7. Choi KH, Song YB, Lee JM, Park TK, Yang JH, Choi JH, et al. Clinical Usefulness of PRECISE-DAPT Score for Predicting Bleeding Events in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: An Analysis From the SMART-DATE Randomized Trial. Circ Cardiovasc Interv. 2020; 13(5): e008530.
8. Morici N, Tavecchia GA, Antolini L, Caporale MR, Cantoni S, Bertuccio P, et al. Use of PRECISE-DAPT Score and Admission Platelet Count to Predict Mortality Risk in Patients With Acute Coronary Syndrome. Angiology. 2019; 70(9): 867-77.
9. Çınar T, Tanık VO, Aruğaslan E, Karabağ Y, Çağdaş M, Rencüzoğulları İ, et al. The association of PRECISE-DAPT score with development of contrast-induced nephropathy in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Cardiovasc Interv Ther. 2019; 34(3): 207-15.
10. Costa F, van Klaveren D, James S, Heg D, Räber L, Feres F, et al. Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials. Lancet. 2017; 389(10073): 1025-34.
11. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020; 395(10229): 1054-62.
12. Sharma R, Kumar P, Prashanth SP, Belagali Y. Dual Antiplatelet Therapy in Coronary Artery Disease. Cardiol Ther. 2020; 9(2): 349-61.
13. Tanik VO, Cinar T, Arugaslan E, Karabag Y, Hayiroglu MI, Cagdas M, et al. The Predictive Value of PRECISE-DAPT Score for In-Hospital Mortality in Patients With ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention. Angiology. 2019; 70(5): 440-47.
14. Taneri PE, Gómez-Ochoa SA, Llanaj E, Raguindin PF, Rojas LZ, Roa-Díaz ZM, et al. Anemia and iron metabolism in COVID-19: a systematic review and meta- analysis. Eur J Epidemiol. 2020; 35(8): 763-73.
15. Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020; 323(13): 1239-42.
16. Liu Y, Du X, Chen J, Jin Y, Peng L, Wang HHX, et al. Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19. J Infect. 2020; 81(1) :e6–12.
17. Sayad B, Afshar ZM, Mansouri F, Rahimi Z. Leukocytosis and alteration of hemoglobin level in patients with severe COVID-19: Association of leukocytosis with mortality. Health Sci Rep. 2020; 3(4): e194.
18. Guan X, Zhang B, Fu M, Li M, Yuan X, Zhu Y, et al. Clinical and inflammatory features based machine learning model for fatal risk prediction of hospitalized COVID-19 patients: results from a retrospective cohort study. Ann Med. 2021; 53(1): 257-66.
19. Hachim MY, Hachim IY, Naeem KB, Hannawi H, Salmi IA, Hannawi S. D-dimer, Troponin, and Urea Level at Presentation With COVID-19 can Predict ICU Admission: A Single Centered Study. Front Med (Lausanne). 2020; 7: 585003.
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Uğur Küçük. In-hospital mortality prediction using dual antiplatelet therapy score in coronavirus disease 2019. Ann Clin Anal Med 2021;12(12):1357-1361
Patients with intracardiac masses: 12-year observation from a tertiary referral hospital
Omer Tasbulak 1, Arda Guler 1, Mustafa Duran 2, Ahmet Anil Sahin 3, Begum Uygur 1, Umit Bulut 1, Yalcin Avci 1, Ali Riza Demir 1, Serkan Kahraman 1 Unal Aydin 4, Mehmet Erturk 1
1 Department of Cardiology, University of Health Sciences, Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, 2 Department of Cardiology, University of Health Sciences, Konya Training and Research Hospital, Konya, 3 Department of Cardiology, School of Medicine, Istinye University, Istanbul, 4 Department of Cardiovascular Surgery, University of Health Sciences, Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.20748 Received: 2021-06-15 Accepted: 2021-08-19 Published Online: 2021-09-08 Printed: 2021-12-01 Ann Clin Anal Med 2021;12(12):1362-1366
Corresponding Author: Omer Tasbulak, Istasyon Mahallesi, Turgut Ozal Bulvarı No: 11 Kücükcekmece, Istanbul, Turkey. E-mail: firstname.lastname@example.org P: +90 507 293 61 70 F: +90 212 471 94 94 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6307-5136
Aim: Intracardiac masses are extremely rare and challenging to manage. Due to the rarity of the disease and the absence of data from large randomized clinical trials, recommendations for the diagnosis and management of intracardiac masses are still derived from expert opinion and observational cohort studies. In this study we aim to describe the epidemiological features, clinical characteristics, and prevalence of intracardiac masses.
Material and Methods: The records of 133 patients aged >18 who underwent open surgery due to confirmed intracardiac masses were investigated retrospectively. Demographic and clinical characteristics of the patients, the indication for the procedure, and postoperative outcomes were retrospectively analyzed. For isolated intracardiac masses, the mass location, final histopathologic diagnosis, concomitant clinical conditions, and preferred surgical approach were analyzed.
Results: The most common histopathologic diagnosis was atrial myxoma (n=62, 46.6%), followed by cardiac thrombus (n=33, 24.8%), and the most common location of the intracardiac masses was the left interatrial septum (n=48, 36.1%). The composite of all-cause mortality was the most common early outcome (n=11, 8.3%) while tumor-related mortality was the most common late outcome (n=15, 11.3%).
Discussion: Our data show that intracardiac masses have diverse etiology and various clinical manifestations, and they often require cardiac surgery. In order to prevent complications, careful assessment and optimal timing of surgery is mandatory.
Keywords: Intracardiac Masses, Myxoma, Thrombus
Intracardiac masses are seen extremely rarely and they are challenging to manage. The associated disease states may be congenital, infectious, thrombotic, reactive, iatrogenic, or neoplastic lesions [1, 2]. Depending on the cardiac location and size, patients with intracardiac masses present with various symptoms including congestive heart failure, dyspnea, embolic events, and rhythm disturbances [3-5]. In addition, patients with cardiac metastasis experience constitutional symptoms such as fever, weight loss, fatigue, myalgia, night sweats, coughing, or leukocytosis . Due to the extensive use of cardiac imaging modalities such as echocardiography, computed tomography (CT), and magnetic resonance imaging (MRI), patients may also present with no symptoms . With respect to neoplastic lesions, the incidence of primary cardiac tumors is 0.02% with atrial myxomas accounting for the majority of cases. On the other hand, cardiac metastases are the most frequently observed type of cardiac neoplasms in the adult population [8, 9]. Owing to the increased risk of secondary complications, cardiac surgery is generally the preferred therapeutic approach for malignant cardiac neoplasms. On the other hand, patients with cardiac metastases predominantly originating from lymphomas may undergo systemic chemotherapy [10, 11].
Due to the rarity of the disease and the lack of data from large randomized clinical trials, recommendations for the diagnosis and management of intracardiac masses are still derived from expert opinion and observational cohort studies. Therefore, in this study we aim to describe the epidemiological features, clinical characteristics, and prevalence of intracardiac masses in a single tertiary-care hospital in Turkey while also focusing on the postoperative outcomes.
Material and Methods
In this retrospective study, data were retrieved from cardiac surgical cases reported in the medical records and the electronic database of our hospital. The search for intracardiac masses within the electronic database was based on the Systematized Nomenclature of Medicine (SNOMED) codes routinely given to each patient. Data were available from January 1, 2009 through December 31, 2020, during which 133 consecutive patients aged >18 underwent cardiac surgery due to confirmed intracardiac masses. Demographic and clinical characteristics of the patients and the indication for the procedure were retrospectively analyzed. For isolated intracardiac masses, mass location, final histopathologic diagnosis, concomitant clinical conditions, and preferred surgical approach were analyzed. The obtained data pool was statistically analyzed. With respect to postoperative variables, early and late outcomes were also identified. In this study, early outcomes are defined as the development of atrial fibrillation (AF), stroke, cardiac tamponade, pulmonary complications, sternal wound infection, incomplete resection of intracardiac mass, and the composite of all-cause mortality, occurring less than one month after surgery. Late outcomes are defined as development of AF, infective endocarditis (IE), congestive heart failure, recurrence of intracardiac mass, tumor-related mortality, and the composite of all-cause mortality, occurring one month or more after surgery.
The study was approved by the Ethics Committee of the İstanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital.
Statistical analysis was performed using IBM SPSS Statistics for Windows (IBM Corp., Armonk, NY, USA). Conformity to normal distribution was analyzed with the Kolmogorov-Smirnov test. Data were expressed as mean±standard deviation (SD) for data with normal distribution, as median (25th-75th percentiles) for data with non-normal distribution, and as number (%) for categorical variables. The effects of different variables on mortality were calculated by univariate analysis for each. The variables for which the unadjusted p-value was <0.05 in univariate regression analysis were identified as potential risk markers and included in the multivariate regression model to detect independent predictors of mortality. Values of p<0.05 were considered statistically significant.
The baseline demographic and clinical characteristics of the study population are summarized in Table 1. The mean age of patients at the time of surgery was 46.88±20.4 years and 56.4% were female. All patients had ejection fraction of >50%. The majority of the patients presented with obstructive symptoms (n=79, 59.4%) and mitral valve insufficiency (n=86, 64.7%) was found to be more prevalent than other valvular conditions. Diagnostic and histopathologic information about the patients is also provided in Table 1. All patients underwent transthoracic echocardiographic assessment of the cardiac masses before the planned procedures. Among all cases, 99 patients (74.4%) underwent transesophageal echocardiography assessment, 28 patients (21.1%) underwent CT evaluation, and 24 patients (18%) underwent MRI evaluation for detection of intracardiac masses. The most common histopathologic diagnosis was atrial myxoma (n=62, 46.6%), followed by cardiac thrombus (n=33, 24.8%), and the most common location for the intracardiac mass was the left atrial septum (n=48, 36.1%). Figure 1 shows the localizations and etiologies of the intracardiac masses in all patients. Figure 2 demonstrates the localizations of the benign (A) and malignant (B) masses of the heart. Regarding malignant neoplasms, the incidence of leiomyosarcomas was higher than that of other malignant neoplasms (n=2, 1.5%). Locations of the masses and information about surgical procedures are provided in Table 2. Among the preferred surgical techniques, the superior transseptal approach was the most commonly applied method (n=77, 57.9%). Robotically assisted surgery was performed for 14 patients (10.5%) and right anterior mini- thoracotomy surgery was conducted for 2 patients (1.5%). With respect to postoperative outcomes, the composite of all-cause mortality was the most common early outcome (n=11, 8.3%), while all-cause mortality was the most common late outcome (n=15, 11.3%). The mean time for mortality was 9.5 (0-23.75) months (Table 2). According to our data, development of cerebrovascular accident and presence of malignant neoplasm were found to be independent predictors of mortality (Table 3).
This study represents the largest report from Turkey to investigate patients undergoing cardiac surgery due to confirmed intracardiac masses and it is also the largest study to evaluate the utility of contemporary surgical techniques for the treatment of intracardiac masses. According to our data, primary intracardiac masses were most commonly atrial myxomas and were mostly benign. Of the total 62 patients with atrial myxomas, the most common location was the left atrial septum (n=42, 67.7%). After myxomas, the most common etiology among cardiac masses was observed to be thrombus, and thrombi were most often located in the left atrial wall. Among malignant masses, leiomyosarcomas were the most common, and malignant masses were most frequently localized in the right atrial septum. As a result of our study, it was found that intracardiac masses most frequently caused obstruction symptoms. However, malignancy was the most important indicator of mortality in these patients.
Although patients with intracardiac masses present with diverse symptoms, the most common symptoms observed in the patient population in our study were associated with obstruction. These symptoms were mainly characterized by dyspnea and peripheral edema, together with nonspecific symptoms such as weakness and fatigue. Apart from this, in these patients, embolism and conduction anomalies could be seen, as also shown in previous studies [12-14]. Even when cardiac masses are detected in these patients, patients may be asymptomatic, a situation that may cause some difficulties for diagnosis.
Regarding the incidence and characteristics of the intracardiac masses, our findings were comparable with the results of previous reports. In a recently published multicenter study, Tasdemir et al. evaluated 40 patients who underwent surgery for intracardiac masses. Similar to our data in this study, they reported that intracardiac masses were frequently detected in left atrial locations and that myxomas were the most common type . In previous studies, it has also been reported that leiomyosarcomas and osteosarcomas are the most common malignant masses [16, 17]. Our study thus seems to be compatible with the literature, with similar results. In a study by Isogai et al. evaluating 1317 patients, the most important predictor of mortality in patients with cardiac masses was found to be malignancy, as in our study .
In our study, 4.5% of the cardiac masses (6/133) were malignant and the most common location among those malignant masses was the right atrial septum (n=3, 50%). The incidence of malignant cardiac masses was significantly lower compared to previous studies and the most plausible explanation for this outcome lies in the characteristics of our institution .
Patients with cardiac metastases for whom the treatment of choice was complete resection in combination with systemic chemo- or radiotherapy were referred to our hospital. On the other hand, patients with cardiac metastases predominantly originating from peripheral solid tumors or lymphomas who were not eligible for cardiac surgery due to the course of the disease were not referred to our hospital.
Despite the long follow-up period, this was a single-center, retrospective study with a relatively small number of patients due to the rarity of the disease. Thus, prospective multicenter studies with larger patient populations will provide additional information for understanding the clinical characteristics and prevalence of intracardiac masses and therapeutic approaches. Finally, this study was designed for evaluating patients who underwent cardiac surgery due to confirmed intracardiac masses. We did not investigate patients with suspected intracardiac masses. Although cardiac thrombus was the second-most common benign intracardiac mass with a relatively low prevalence, we only evaluated patients for whom cardiac surgery was the only treatment option for cardiac thrombus.
Intracardiac masses have diverse pathological features, are associated with adverse clinical manifestations, and often require cardiac surgery. Despite the identification of various intracardiac masses, atrial myxomas are found to be the most common primary intracardiac masses in adults. In addition, the development of cerebrovascular accident following surgery and the presence of malignant neoplasms are significantly associated with postoperative mortality.
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1. Karnik AA, Awtry EH. Management of Inflammatory Cardiac Masses. Cardiol Res. 2018;9(6):400-406. doi:10.14740/cr801.
2. Asa SL, Ezzat S, Mete O. The Diagnosis and Clinical Significance of Paragangliomas in Unusual Locations. J Clin Med. 2018;7(9):280. Published 2018 Sep 13. doi:10.3390/jcm7090280.
3. Hoffmeier A, Sindermann JR, Scheld HH, Martens S. Cardiac tumors–diagnosis and surgical treatment. Dtsch Arztebl Int. 2014;111(12):205-211. doi:10.3238/ arztebl.2014.0205.
4. Just S, Schubel B, Minden HH. herzchirurgisches Handbuch. Berlin: Verlag HJB; 2002. Tumoren des Herzens.
5. Strotmann J. Kardiale Tumoren – Klinik, Diagnostik und Therapie. [Cardiac tumors—clinical symptoms, diagnostic approaches, and therapeutic aspects] Med Klin. 2008;103:175–180. doi: 10.1007/s00063-008-1025-2.
6. Joshi M, Kumar S, Noshirwani A, Harky A. The Current Management of Cardiac Tumours: a Comprehensive Literature Review. Braz J Cardiovasc Surg. 2020;35(5):770-780. Published 2020 Oct 1. doi:10.21470/1678-9741-2019- 0199.
7. Goldberg AD, Blankstein R, Padera RF. Tumors metastatic to the heart. Circulation. 2013;128:1790–94. doi: 10.1161/CIRCULATIONAHA.112.000790.
8. Patel P, Karch J. Regulation of cell death in the cardiovascular system. Int Rev Cell Mol Biol. 2020;353:153-209. doi:10.1016/bs.ircmb.2019.11.005.
9. Yanagawa B, Mazine A, Chan EY, et al. Surgery for Tumors of the Heart. Semin Thorac Cardiovasc Surg. 2018;30(4):385-397. doi:10.1053/j. semtcvs.2018.09.001.
10. Hosoda T, Katayama M. Epidemiology and prognosis of ommaya reservoir- related bacterial meningitis in adult patients with leptomeningeal metastases from solid tumors: A 10-year retrospective single-center study in Japan. J Infect Chemother. 2021;27(3):486-491. doi:10.1016/j.jiac.2020.10.025.
11. Reardon MJ, Walkes JC, Benjamin R. Therapy insight: Malignant primary cardiac tumors. Nat Clin Pract Cardiovasc Med. 2006;3(10):548–53. doi: 10.1038/ ncpcardio0653.
12. Maraj S, Pressman GS, Figueredo VM. Primary cardiac tumors. Int J Cardiol. 2009;133:152–6.
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19. Bruce CJ. Cardiac tumours: diagnosis and management. Heart. 2011;97(2):151–160.
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Omer Tasbulak, Arda Guler, Mustafa Duran, Ahmet Anil Sahin, Begum Uygur, Umit Bulut, Yalcin Avci, Ali Riza Demir, Serkan Kahraman, Unal Aydin, Mehmet Erturk. Patients with intracardiac masses: 12-year observation from a tertiary referral hospital. Ann Clin Anal Med 2021;12(12):1362-1366
Relationship between androgen levels and neutrophil/lymphocyte ratio in patients diagnosed with hirsutism
Samet Sayılan 1, Meral Mert 2, Nursen Kulakac 3
1 Department of Internal Medicine, Medicine Faculty, Kirklareli University, Kirklareli, 2 Department of Endocrinology, Istanbul Cam and Sakura City Hospital, Istanbul, 3 Health Faculty, Gumushane University, Gumushane, Turkey
DOI: 10.4328/ACAM.20752 Received: 2021-06-17 Accepted: 2021-08-19 Published Online: 2021-09-09 Printed: 2021-12-01 Ann Clin Anal Med 2021;12(12):1367-1371
Corresponding Author: Samet Sayılan, Yayla mah. Çamlık cad. No: 49, 39060, Kırklareli, Turkey. E-mail: email@example.com P: +90 288 214 10 43 F: +90 288 214 29 42 Corresponding Author ORCID ID: https://orcid.org/0000-0002-8959-8381
Aim: Hirsutism is a disease involving increased terminal hair growth in women with a male-type distribution pattern in androgen-sensitive areas such as the chin, upper lip, chest, abdomen, back, and thighs. Our review of the available literature revealed no previous studies concerning the role of the peripheral blood neutrophil/lymphocyte ratio (NLR), an easily calculated and noninvasive marker, in hirsutism. The purpose of this research was to determine the relationship between androgen levels and NLR in female patients diagnosed with hirsutism.
Material and Methods: The files of 392 patients presenting to the Bakırköy Dr. Sadi Konuk Education and Research Hospital due to hirsutism between 2018 and 2020 were included in this cross-sectional, retrospective study. Patients’ hirsutism and menstrual cycles, age at menarche, number of pregnancies in the case of married women, number of living children, and history of infertility were investigated. Hyperandrogenemia findings, such as hair loss and acne, were also recorded. Patients’ biochemical and complete blood count parameters were evaluated.
Results: The mean age of the participants was 26.27±6.37 years (min-max: 16-48), and their androgen levels were statistically significantly associated with high-density lipoprotein, hemoglobin, hematocrit, 17-hydroxyprogesterone, and HbA1c levels (p<0.05). However, no significant relationship was found between patients’ androgen levels and NLR values (p>0.05).
Discussion: No significant relationship was determined in this study between androgen levels and NLR values in women diagnosed with hirsutism. Due to the limited numbers of previous similar studies, further research with larger patient numbers is now needed.
Keywords: Androgen, Hirsutism, Neutrophil/Lymphocyte Ratio
Hirsutism is a disease involving increased terminal hair growth in women with a male-type distribution pattern in androgen- sensitive areas such as the chin, upper lip, chest, abdomen, back, and thighs . It affects approximately 10-15% of women of reproductive age [2,5]. Various diseases including polycystic ovary syndrome (PCOS), non-classic adrenal hyperplasia (NCAH), Cushing’s syndrome, and acromegaly as well as certain drugs may be involved in the etiology. PCOS and idiopathic hirsutism have frequently been identified as etiological causes . The blood neutrophil/lymphocyte ratio (NLR) has recently come to prominence as an easily measured and practical method providing valuable information in the diagnosis and prognosis of various diseases . The principal causes implicated in the emergence of the manifestation of hirsutism are increased androgen secretion, a decrease in sex hormone- binding globulin concentrations, and a resulting increase in free androgen levels. The most important androgens in this context are androstenedione, testosterone, and dihydrotestosterone . Adrenal diseases are a rarer cause of hirsutism. One of the most common causes of adrenal hirsutism is NCAH. This can develop in association with deficiencies of 21-α hydroxylase, 11-β hydroxylase, or 11-β hydroxysteroid dehydrogenase enzymes . The patient’s history and physical examination findings yield important clues in the determination of virilizing diseases, PCOS or other endocrinopathies, and androgenic drug use. The investigation of PCOS findings, one of the most frequent causes of hirsutism, is important in the approach to the condition. Examination of anovulation, one of the important findings of PCOS and frequently manifesting with menstrual cycle irregularity, is also important in terms of the investigation of insulin resistance findings such as obesity, metabolic syndrome, acanthosis nigricans, or familial type 2 diabetes mellitus. Investigation of androgenic drug use is also important in the differential diagnosis . Hyperprolactinemia-related hirsutism should be considered during examination in the event of thyroid dysfunction symptoms together with galactorrhea, since hyperprolactinemia can result in increased adrenal androgen secretion . Comorbidity of hyperprolactinemia and polycystic ovaries is also frequently seen, and hirsutism is detected in 59% of these patients . Moon face, muscular atrophy, stria, and thinning of the skin with easy bruising are suggestive of the presence of Cushing’s syndrome. The upper total plasma testosterone limit in women is 70-90 ng/dL. Dehydroepiandrosterone sulfate (DHEA) elevations may be observed in approximately 15% of women with normal total and free testosterone levels. Idiopathic hirsutism may be determined in women with normal total testosterone levels or levels above the threshold and no other findings. Laboratory findings in cases of PCOS include high luteinizing hormone (LH) in blood collected on the third day of the menstrual cycle, normal or low follicle- stimulating hormone (FSH) levels, and moderately increased testosterone, androsterone, and DHEA levels with polycystic ovaries upon pelvic ultrasound. A significantly increased 17-hydroxyprogesterone (17-OHP) and 11-deoxycorticosterone (11-DOC) response to the adrenocorticotropic hormone (ACTH) stimulation test is diagnostically important in cases of NCAH .
Since the physiological response to the stress of circulating leukocytes causes an increase in neutrophil numbers and a decreased leukocyte count, the ratio between these two subgroups is employed as an inflammatory marker [9, 10]. Neutrophils activated with tissue destruction release enzymes such as myeloperoxidase, acid phosphatase, and elastase [11, 12]. Changes in leukocyte rates occur during inflammatory responses. Relative lymphopenia accompanies neutrophilia. The NLR has been proposed as a simple inflammatory response marker and has been used as an inflammatory marker in several cardiac and noncardiac diseases . An increased mortality rate in cases of acute coronary syndromes has been recently shown with elevation in the NLR [14, 15]. Higher NLR compared to the attack-free period has also been reported during attacks in patients with familial Mediterranean fever .
The presence of T lymphocytes in a tumor indicates a significant immune response to the lesion. Recent data have shown that a low lymphocyte count in colorectal tumors is associated with poor prognosis. The NLR has been identified as a prognostic factor for survival in colorectal and ovarian cancers [17, 18]. It has also been suggested that preoperative NLR may be a simple tool for identifying colorectal cancer patients with poor prognosis .
An increased inflammatory response and oxidative stress are also thought to occur in patients with hirsutism. The NLR in peripheral blood is also used as a parameter providing information about the relationship between the inflammatory environment and physiological stress. Our review of the available literature revealed no previous studies concerning the role of the peripheral blood NLR, an easily calculated and noninvasive marker, in hirsutism. The purpose of this research was therefore to determine the relationship between androgen levels and the NLR in female patients diagnosed with hirsutism.
Material and Methods
The files of 458 female patients presenting to the Bakırköy Dr. Sadi Konuk Education and Research Hospital’s Internal Diseases Clinic in İstanbul, Turkey, due to hirsutism in 2018- 2020 were examined retrospectively. Women with missing sociodemographic data and test results, women using drugs such as antidepressants, and pregnant and menopausal women were excluded from the study. Patients’ Ferriman- Gallwey scores were not available. The files of 392 (85.5%) women containing full data were included in the study. Women’s hirsutism and menstrual histories, age at menarche, number of pregnancies in the case of married women, number of living children, and infertility history were investigated. Hyperandrogenemia findings such as loss of hair and acne were also recorded. Results for hormone analysis performed in the follicular phase (days 2-5 of the menstrual cycle) were recorded. Evaluations were performed for FSH, LH, estradiol (E2), prolactin (PRL), dehydroepiandrosterone sulfate (DHEA-S), 17-OHP, androstenedione, total testosterone, free testosterone, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, uric acid, ferritin, glucose, insulin, and HbA1c levels and all complete blood count parameters. The research commenced following receipt of approval from the Gümüşhane University Education and Research Hospital Ethics Committee (Date: 04.02.2021, No: E-95674917-108.99-8026) and the study complied with the principles of the Declaration of Helsinki.
Statistical analyses were performed with SPSS 23.0 for Windows (IBM Corp., Armonk, NY, USA). Descriptive methods (mean, standard deviation, median, frequency, and percentage) were applied in the evaluation of the study data. The Mann- Whitney U test and Spearman correlation analysis were employed in the evaluation of nonnormally distributed data. Correlation coefficients (r) were regarded as weak correlations at 0.00-0.24, moderate at 0.25-0.49, powerful at 0.50-0.74, and very powerful at 0.75-1.00. Results were expressed at 95% confidence intervals with significance set at p<0.05.
The mean age of the patients in this study was 26.27±6.37 years (min-max: 16-48). Complete blood count and biochemistry findings are shown in Table 1.
Lymphocyte, glucose, HbA1c, and 17-OHP levels were found to be significantly higher in patients with high s-testosterone levels (p<0.05). Hemoglobin (Hb), hematocrit (HTC), triglycerides, glucose, HbA1c, and 17-OHP levels were found to be significantly higher in patients with high t-testosterone levels. HDL levels were found to be significantly higher in patients with normal s-testosterone and t-testosterone levels (Table 2).
The correlations between the androgen levels of the patients and some other parameters are shown in Table 3. There was a positive correlation between DHEA-S levels and s-testosterone and t-testosterone levels in these patients, while a weak but significant negative correlation was found with the level of HbA1c. There was a positive correlation between the patients’ t-testosterone levels and their s-testosterone, Hb, and HCT levels while a significant negative correlation was found with HDL level. There was a positive correlation between the patients’ s-testosterone levels and triglyceride, Hb, HCT, HbA1c, and 17-OHP levels while a significant negative correlation was found with HDL level.
Levels of inflammatory markers are known to increase in patients with PCOS. Several studies have suggested an increased inflammatory response in patients hospitalized due to PCOS . Some of these studies have employed high- sensitivity C-reactive protein (hs-CRP), mean platelet volume (MPV), and NLR as inflammatory markers . For example, Yılmaz et al. reported higher NLR and MPV values in patients with PCOS compared to healthy controls, although hs-CRP levels were similar between the two groups .
No significant difference was observed in NLR values in idiopathic hirsutism patients in the present study. Meanwhile, lymphocyte, glucose, HbA1c, and 17-OHP values were significantly higher in patients with elevated free testosterone levels. These findings show that there is no correlation between NLR and clinical or laboratory parameters.
Zhao et al. compared androgen and lipid levels in PCOS patients with high LH/FSH ratios and determined increased LDL and triglyceride levels and decreased HDL levels compared to a control group . In the present study, Hb, HTC, triglyceride, glucose, HbA1c, and 17-OHP levels were significantly higher in patients with total testosterone elevation.
Salman et al. compared fasting blood sugar, insulin, total cholesterol, LDL, HDL, and triglyceride levels between a patient and a control group, but only fasting blood sugar levels in the patient group were higher than those in the control group. This difference was statistically significant, although values in both groups were within normal limits . In the present study, fasting blood sugar levels were significantly higher among patients with total testosterone elevation.
Celikbilek et al. reported higher neutrophil and lymphocyte counts and NLR values in a patient group with Behçet disease compared to a control group. Neutrophil counts and NLR values during attack periods were significantly higher than post-attack values .
Walsh et al. determined significant NLR elevation in the preoperative period in a study of colorectal cancer patients . In their study of acute coronary syndrome patients, Öztürk et al. reported no significant difference in NLR values between stable and unstable angina pectoris groups . In the present study, no statistically significant difference was determined in NLR values according to androgen levels.
This study was conducted in a single center and involved a single diagnosis. Therefore, as a limitation of this study, the results cannot be generalized.
Our study results revealed no statistically significant association between androgen levels in hirsutism patients and NLR and MPV values or leukocyte counts. On the basis of these findings, we conclude that a diagnosis of idiopathic hirsutism has no significant impact on these biomarkers. However, we also think that further studies on this subject will provide sounder evidence and will enhance our current levels of understanding.
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4. Keleştimur F. Hirsutism of adrenal origin in adolescents: Consequences in adults. J Ped Endocrinol Metabol 2001; 14: 1309-1315.
5. Azziz R, Carmina E, Sawaya ME. İdiopathic hirsutizm. Endocr Rev 2000; 21: 347-362.
6. Nelson-DeGrave VL, Wickenheisser JK, Coc-krell JE, Wood JR, Legro RS, Strauss JF, et al. Valproate potentiates androgen biosynthesis in human ovarian theca cells. Endocrinology 2004; 145:799-808.
7. Yıldız BO. Diagnosis of hyperandrogenism: clinical criteria. Best Pract Res Clin Endocrinol Metab 2006; 20: 167-176.
8. Rosenfield RL. Hirsutism. N Engl J Med 2005; 353: 2578- 2588.
9. Jilma B, Blann A, Pernerstorfer T, Stohlawetz P, Eichler HG, Vondrovec B, et al. Regulation of adhesion molecules during human endotoxemia. No acute effects of aspirin. Am J Respir Crit Care Med 1999; 159: 857-63.
10. Zahorec R. Ratio of neutrophil to lymphocyte counts Rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy 2001; 102:5-14.
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13. Demirkol S, Balta S, Kucuk U, Kucuk HO. The neutrophil lymphocyte ratio may be useful inflammatory indicator before applying other expensive and invasive procedures. Indian J Nephrol. 2014; 24(1): 65-6.
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16. Celikbilek M, Dogan S, Akyol L, Borekci E, Zararsiz G, Kozan M, et al. NeutrophilLymphocyte Ratio in Patients with Familial Mediterranean Fever. J Clin Lab Anal. 2014 Mar 28. Doi: 10.1002/jcla.21732. [Epub ahead of print]
17. Tsujimura A, Kawamura N, Ichimura T, Honda KI, Ishiko O, Ogita S. Telomerase activity in needle biopsied uterine myoma-like tumors: differential diagnosis between uterine sarcomas and leiomyomas. Int J Oncol 2002; 20:361-5.
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20. Randeva HS, Tan BK, Weickert MO, Lois K, Nestler JE, Sattar N, et al. Cardiometabolic aspects of the polycystic ovary syndrome. Endocr Rev 2012;33(5):812e41.
21. Kahal H, Aburima A, Ungvari T, Rigby AS, Dawson AJ, Coady AM, et al. Poly-cystic ovary syndrome has no independent effect on vascular, inflammatory orthrombotic markers when matched for obesity. Clin Endocrinol 2013;79(2):252e8.
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Samet Sayılan, Meral Mert, Nursen Kulakac. Relationship between androgen levels and neutrophil/lymphocyte ratio in patients diagnosed with hirsutism. Ann Clin Anal Med 2021;12(12):1367-1371
Is magnetic resonance imaging necessary for every patient with low back pain?
Neslihan Soran 1, Serap Satis 2
1 Department of Physical Medicine and Rehabilitation, Beyhekim Training and Research Hospital, Konya, 2 Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Harran University, Sanliurfa, Turkey
DOI: 10.4328/ACAM.20754 Received: 2021-06-18 Accepted: 2021-08-19 Published Online: 2021-09-08 Printed: 2021-12-01 Ann Clin Anal Med 2021;12(12):1372-1375
Corresponding Author: Serap Satis, Department of Physical Medicine and Rehabilitation, Harran University, Faculty of Medicine, Osmanbey Campus, 63300, Sanliurfa, Turkey. E-mail: firstname.lastname@example.org P: +90 506 976 57 61 Corresponding Author ORCID ID: https://orcid.org/0000-0002-5496-197X
Aim: The aim of this study is to evaluate lumbar magnetic resonance imaging findings in patients with low back pain to reveal the relationship between clinical pain and magnetic resonance imaging findings.
Material and Methods: This was a retrospective study. For all participants, age, gender, visual analog scale (VAS) score, and magnetic resonance imaging findings were recorded. Participants were divided into 2 groups according to magnetic resonance imaging results, with normal magnetic resonance imaging findings in Group 1 and pathological findings in Group 2. Gender, age, and visual analog scale scores were compared between groups. In addition, magnetic resonance imaging pathologies were grouped by number of patients, age, gender, and visual analog scale score. The most common magnetic resonance imaging findings and accompanying clinical data were reviewed.
Results: Mean visual analog scale scores were found to be 5.5±1.70 and 7±1.56 with no statistically significant difference between Group 1 and Group 2, respectively (p=0.055). The number of patients with a single magnetic resonance imaging finding was 90. Among these, bulging was the most common with 54 patients; among these patients, the mean age and visual analog scale scores were lower. Patients with canal stenosis and spondylosis had higher ages and visual analog scale scores. Coexistence of flattening and bulging in 20 (8.3%) patients and the association of protrusion, flattening, and spondylosis in 20 (8.3%) patients represented the most common combinations of multiple magnetic resonance imaging findings.
Discussion: Magnetic resonance imaging does not usually alter clinical results in cases of low back pain without serious underlying symptoms. Routine lumbar magnetic resonance imaging should be avoided in patients with acute or subacute low back pain without symptoms suggestive of a serious underlying condition.
Keywords: Low Back Pain, Magnetic Resonance Imaging, Lumbar
Low back pain (LBP) is a common health problem in society and can occur at any age, causing serious socioeconomic losses [1, 2]. Epidemiological studies evaluating the prevalence of LBP in adulthood throughout the world are available, revealing that the prevalence is 12% instantaneously, 23% monthly, 38% annually, and approximately 40% throughout life, while the lifetime prevalence in Turkey is 50% in urban areas and 80% in rural areas [3-5].
It is not easy to determine the specific etiology of LBP. It may occur as a result of a specific pathophysiological mechanism such as lumbar disc herniation, infection, inflammation, osteoporosis, rheumatoid arthritis, fracture, or neoplastic, or it can be observed to be nonspecific .
The majority (97%) of cases of LBP are mechanical. This can be defined as a clinical picture that develops as a result of excessive use, strain, traumatization, or deformation of the structures that constitute the spine [7, 8].
It should be kept in mind that radiological evidence has revealed that spine pathologies may not be associated with nonspecific LBP and that radiological changes can be seen at a substantial rate in society without any symptoms . It should also be noted that performing many imaging studies without indication will not change the clinical results .
Radiological imaging methods are used in the evaluation of patients with LBP to examine the lumbar spine and its components. All imaging modalities can be used in the diagnosis of cases of LBP with the correct clinical indication. However, it is very important to use imaging methods according to a certain algorithm. Direct radiography before further imaging should be used for patients with neurological deficits, pain that does not go away despite all treatment and preventive measures, and urinary and/or stool incontinence.
Today, magnetic resonance imaging (MRI) is the most frequently requested imaging method for LBP patients. In a systematic review, eight studies investigating whether MRI findings identified patients with LBP and/or sciatica were examined, and two studies yielded statistically significant results between specific MRI findings and response to treatment, while the other studies showed discordance . Degenerative findings and anatomical abnormalities may appear with MRI but their clinical significance is uncertain and controversial.
The aim of this study is to evaluate lumbar MRI findings in patients with LBP to reveal the relationship between clinical pain and MRI findings.
Material and Methods
The patients who applied to our clinics with LBP complaints between January 1 and December 31, 2019, and who underwent lumbar MRI were reviewed retrospectively. Patient data were obtained from the hospital records system and age, gender, visual analog scale (VAS) score, and MRI findings were recorded. Individuals who had previously undergone back surgery and those who had received treatment in the last three months (medical or physical therapy, etc.) were excluded from the study. Participants were divided into two groups according to MRI findings, with normal MRI results in Group 1 and pathological results in Group 2. Gender, age, and VAS scores were compared between groups. In addition, MRI pathologies were grouped by number of patients, age, gender, and visual analog scale (VAS) score. The most common MRI findings and accompanying clinical data were reviewed.
The SPSS 20.0 software program (IBM Corp., Armonk, NY, USA) was used for statistical analysis. Numerical data were presented as mean±standard deviations. The Kolmogorov-Smirnov test was applied for evaluating the distribution of numerical data. The independent samples t-test was used when the distribution of numerical data was normal, whereas the Mann-Whitney U test was used for abnormal distribution. In addition, the Kruskal- Wallis H test was used for comparison when the distribution was abnormal, whereas the Mann-Whitney U test was used for paired comparisons if the results were significant. The chi- square test was used for the comparison of nonnumerical data. Values of p<0.05 were considered statistically significant.
A total of 242 patients with mean age of 41.89±17.21 years were evaluated, 139 (57.43%) of whom were women while 103 (42.57%) were men. Eighteen had complaints of LBP but no findings on MRI, while 242 had MRI findings. Mean ages were 28.55±11.19 and 39.00±17.18 years in Group 1 (normal MRI results) and Group 2 (pathological MRI results), respectively, and the difference between the groups was statistically significant (p=0.001). VAS scores were 5.5±1.70 and 7±1.56 in Groups 1 and 2 and there was no statistically significant difference (p=0.055) (Table 1).
The number of patients with a single MRI finding was 90. Among these, bulging was the most common, observed for 54 patients. This subgroup also had a higher percentage of women, a lower mean age, and lower mean VAS score. Patients with canal stenosis and spondylosis had higher ages and VAS scores. All relevant data are given in Table 2.
Data for patients with multiple MRI findings are presented in Table 3. Coexistence of flattening and bulging in 20 (8.3%) cases and the association of protrusion, flattening, and spondylosis in 20 (8.3%) cases were the most commonly seen multiple MRI findings. The percentage of women was higher in this subgroup and patients with signs of spondylosis were older.
In the present study, no correlation was observed between MRI findings and VAS scores. This suggests that the patients’ clinical complaints are not correlated with MRI findings. Bulging was the most common MRI finding. Flattening and bulging was the most common combination observed in patients with multiple pathologies on MRI, followed by the combination of protrusion, flattening, and spondylosis.
Treatment decisions in cases of LBP depend on the results of physical examination and, if necessary, medical imaging. MRI is the most common method that specialist doctors apply for the detection of disorders in the lumbar vertebrae and attached discs. MRI also plays an important role in the detection of soft tissue disorders. Currently, however, the importance of identifying the source of LBP is unclear and controversial, with MRI findings such as disc herniation, facet joint arthropathy, and Modic changes (bone marrow and endplate lesions) being reported. Studies have presented conflicting results regarding the possible relationships between LBP and MRI findings in symptomatic patients [9, 12]. While MRI is outstanding at imaging the spine, the causes of LBP are very diverse and few are detectable on MRI. The cause of LBP is often muscular in nature, including postural muscle tension or protective muscle spasms. MRI does not detect these causes or pain reflected from the internal organs .
Kjaer et al.’s study of 412 patients aged 40 years reported abnormal MRI findings, usually encountered in the lower lumbar region (L4-S1). In that study, reduced disc height in more than 50% of cases, 25-50% hypointense disc signals, annular tears, “endplate” changes, facet joint degeneration, asymmetry, and foraminal stenosis were detected . In our study, 92% of the patients had abnormal MRI findings. The reason for this high rate is that the study enrolled only patients presenting with LBP. Another study found that disc degeneration was associated with pain in 164 men reporting LBP for 12 months. However, no relationship was found between pain and the number of degenerated discs . In our study, no correlation was found between VAS scores and MRI findings such as spinal stenosis and spondylosis. Bulging on MRI was most common in our younger patients. These results show that routine lumbar MRI in patients with LBP without any serious underlying condition is a waste of time for both the patient and the doctor. Many studies have shown that the reason for application of MRI is often patient demand or the fear of litigation among healthcare professionals [16, 17]. Nevertheless, unnecessary imaging should be avoided to reduce exposure to unnecessary procedures.
The significance of MRI findings such as disc herniation, facet joint arthropathy, and spondylosis is unclear and controversial in identifying the source of LBP. Many MRI findings are also common in people without LBP, but they are usually more common in people with LBP [18, 19]. Research on the significance of MRI findings has been disappointing due to the lack of a widely accepted gold standard . Whether or not MRI findings predict differential response to medical interventions should be investigated further .
MRI does not usually alter clinical results in cases of LBP without serious underlying symptoms. Therefore, routine lumbar MRI should be avoided in patients with acute or subacute LBP without features suggestive of a serious underlying condition.
The authors thanks Mustafa Soran for his support of this study.
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Animal and human rights statement
Conflict of interest
1. Buchbinder R, Blyth FM, March LM, Brooks P, Woolf AD, Hoy DG. Placing the global burden of low back pain in context. Best Pract Res Clin Rheumatol 2013;27:575–589.
2. Hoy D, Brooks P, Blyth F, Buchbinder R. The epidemiology of low back pain. Best Pract Res Clin Rheumatol 2010;24:769–781.
3. Manchikanti L, Singh V, Falco FJ, Benyamin RM, Hirsch JA. Epidemiology of low back pain in adults. Neuromodulation 2014;17 Suppl 2:3–10. CrossRef
4. Gilgil E, Kaçar C, Bütün B, Tuncer T, Urhan S, Yildirim C, Sünbüloglu G, Arikan V, Tekeoglu I, Oksüz MC, Dündar U. Prevalence of low back pain in a developing urban setting. Spine (Phila Pa 1976) 2005;30(9):1093–1098.
5. Şenköylü A. Bel ağrısında kırmızı bayraklar. Türk Fiz Tıp Rehab Derg 2011;57:0– 0.
6. Deyo RA, Rainville J, Kent DL. What can the history and physical examination tell us about low back pain? JAMA 1992;268(6):760–765.
7. Kinkade S. Evaluation and treatment of acute law back pain. Am Fam Physician 2007;75: 1181-1188.
8. Borenstein DG. Law back pain. In: Rheumatology, Klippel JH, Dieppe P (Eds), Mosby Ltd., London . p. 41,1994.
9. van Tulder MW, Assendelft WJ, Koes BW, Bouter LM. Spinal radiographic findings and nonspecific low back pain. A systematic review of observational studies. Spine (Phila Pa 1976) 1997;22(4):427–434.
10. Chou R, Fu R, Carrino JA, Deyo RA. Imaging strategies for low-back pain: systematic review and meta-analysis. Lancet 2009;373(9662):463–472.
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12. Symmons DP, van Hemert AM, Vandenbroucke JP, Valkenburg HA. A longitudinal study of back pain and radiological changes in the lumbar spines of middle aged women. I. Clinical findings. Ann Rheum Dis. 1991;50(3):158-161.
13. Okada E, Matsumoto M, Fujiwara H, Toyama Y. Disc degeneration of cervical spine on MRI in patients with lumbar disc herniation: comparison study with asymptomatic volunteers. Eur Spine J. 2011; 20(4):585-591.
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19. Steffens D, Hancock MJ, Maher CG, Williams C, Jensen TS, Latimer J. Does magnetic resonance imaging predict future low back pain? A systematic review. Eur J Pain. 2014; 18(6):755-765.
20. Hancock M, Maher C, Macaskill P, Latimer J, Kos W, Pik J: MRI findings are more common in selected patients with acute low back pain than controls? Eur Spine J 2012:21:240–246.
Download attachments: 10.4328:ACAM.20754
Neslihan Soran, Serap Satis. Is magnetic resonance imaging necessary for every patient with low back pain? Ann Clin Anal Med 2021;12(12):1372-1375
Analysis of factors affecting adolescent patients’ demands for orthodontic treatment
Gokhan Coban 1, Taner Ozturk 1, Gokhan Turker 2
1 Department of Orthodontics, Faculty of Dentistry, Erciyes University, Kayseri, 2 Department of Orthodontics, Faculty of Dentistry, Mersin University, Mersin, Turkey
DOI: 10.4328/ACAM.20757 Received: 2021-06-22 Accepted: 2021-08-19 Published Online: 2021-09-09 Printed: 2021-12-01 Ann Clin Anal Med 2021;12(12):1376-1382
Corresponding Author: Taner Ozturk, Department of Orthodontics, Faculty of Dentistry, Erciyes University, Kayseri, Turkey. E-mail: email@example.com P: +90 533 168 04 66 F: +90 352 438 07 56 Corresponding Author ORCID ID: https://orcid.org/0000-0003-1670-286X
Aim: This study aimed to evaluate the factors that affect adolescent patients’ treatment requests and determine their main reasons for demanding orthodontic treatment.
Material and Methods: This cross-sectional retrospective study included 360 (189 female and 171 male) adolescents (mean age: 15.49±2.28 years) who demanded orthodontic treatment. Face-to-face interviews were conducted by an orthodontist using a specially structured questionnaire to determine the reasons for these demands. Pearson’s chi-square test and Fisher’s exact test were used to analyze the relationships between dental malocclusion groups and reasons for demanding treatment. Statistical significance was set at p<0.05.
Results: The demands for orthodontic treatment did not differ between male and female patients but were significantly affected by malocclusion type. Patients concerned with dental crowding (DC) demanded orthodontic treatment the most (50.6%), regardless of DC severity, followed by patients (30.6%) concerned with dental esthetics (30.6%). Overall, 57.8% of patients who demanded orthodontic treatment reported a problem in the maxillary anterior teeth. Regarding the relationship between demanding orthodontic treatment and patients’ problematic areas, no relationship was observed for class I and II malocclusions but a relationship was observed for class III malocclusions.
Discussion: It is necessary to identify adolescent patients’ reasons for demanding orthodontic treatment and establish what would represent a successful treatment outcome. Regardless of DC severity, irregularity in the upper anterior region was the most common reason for patients to demand treatment.
Keywords: Demand for Treatment, Dental Malocclusion, Dental Crowding, Orthodontic Treatment
Dental malocclusion can be considered a public health problem due to its high prevalence (39-93%) in the population and the need for prevention and treatment possibilities . Several studies have reported the effects of malocclusion on the quality of life , and malocclusion has been recognized by the World Health Organization as the third-highest priority for oral health .
The main goal of orthodontics is to improve dental occlusion and eliminate malocclusion, one of the etiological factors of periodontal disease, dental caries, and temporomandibular joint disorders. In addition, the esthetic improvement that is obtained as a result of orthodontic treatment helps develop the individual’s sense of self and is highly gratifying . Patients’ and parents’ expectations regarding orthodontic treatment include the improvement of dentofacial esthetics, oral health, and self-esteem .
Many previously published studies have reported various reasons for and factors affecting patients’ demands for orthodontic treatment [4-6]. These factors include self-esteem, facial esthetics, self-image, dentofacial appearance, status, pride, discomfort, concerns for future oral health, parents’ and friends’ influences, referrals by dentists, gender, age, and severity of malocclusion and dental crowding. The effects of these factors depend on the sociocultural characteristics of each subgroup of the population [7, 8].
Identifying the factors involved in the requests for orthodontic treatment in a population enables better planning of resources and better assessment of treatment needs and priorities . Understanding this situation is extremely important for public health.
It remains unclear which concerns are most common in adolescent patients demanding orthodontic treatment. In other words, it is not well documented which dental or visual traits predominantly motivate or affect patients demanding orthodontic treatment. Thus, this study aimed to determine the reasons and motivating factors that affect patients’ demands for orthodontic treatment at orthodontic clinics.
Material and Methods
This cross-sectional retrospective study was conducted using a specially structured questionnaire and dental cast models of 360 patients who presented to the Department of Orthodontics of the Faculty of Dentistry of Erciyes University between 2017 and 2019. This study was approved by the Erciyes University Clinical Research Ethics Committee (Approval Code: 2020/333). The determination of patients to be included in the study was performed by random selection (coin-toss method) according to the inclusion criteria during the first examination performed immediately after patients underwent consultation regarding their orthodontic treatment demands. The authors obtained informed consent from all patients and their parents before beginning treatment and before administering the questionnaire. These 360 patients (mean age: 15.49±2.28 years) were divided into 3 groups as dental class I (Cl-I; mean age: 15.25±2.23 years), dental class II (Cl-II; mean age: 15.27±2.09 years), and dental class III (Cl-III; mean age: 15.97±2.48 years) according to Angle’s dental malocclusion classification, with an equal number of individuals in each group .
Aside from administering the questionnaire, a complete clinical examination was performed for all included patients by the same orthodontist (G.C.) using a mouth mirror under natural lighting. For each patient, following the clinical examination, the orthodontist took an alginate impression for a dental cast. The inclusion criteria for participation were defined as follows: patients undergoing orthodontic examination for the first time; patients aged 13-18 years; patients who had not received orthodontic treatment before; patients whose orthodontic treatment started in our orthodontic department; and patients for whom the main demands for requesting treatment and the amount of dental crowding in millimeters for the upper and lower jaw were clearly recorded on questionnaire forms. Exclusion criteria were as follows: patients with a syndromic disease, congenital anomaly, or craniofacial deformity; those with prosthetic restoration; and those with a history of severe trauma.
The modified questionnaire included the following components [11, 12]:
1. Demographic data (sex and age) obtained directly from the patients and their parents.
2. Self-satisfaction with their teeth, which patients subjectively assessed.
3. Awareness of their teeth and mandibular position, which patients subjectively assessed.
4. Motivation for demanding orthodontic treatment (e.g., to improve esthetics, dental appearance), which was determined through questions asked by one of the investigators.
The responses of the patients about their demands for orthodontic treatment were evaluated. For this purpose, patients was asked two questions: to select one of five items regarding the reason for demanding treatment and one of six items regarding which teeth they wanted to have treated (Figure 1) . The same orthodontist who administered the survey during the first examination collected the questionnaire answers while parents were not present. No orthodontic data were obtained from the patients’ parents because it was the opinion/self-assessment of the adolescent patients demanding orthodontic treatment that was evaluated.
Dental Model Analysis
The amount of crowding was determined using dental casts to evaluate the effects of dental crowding in the maxilla and mandible on the patients’ orthodontic treatment demands. During the initial orthodontic examination before treatment, dental models of the maxilla and mandible were obtained with alginate impression material (Tropicalgin, Zhermack, Badia Polesine, Italy). These casts were scanned with a 3Shape dental model scanner (3Shape R700 3D Scanner, 3 Shape A/S, Copenhagen, Denmark) and transferred to digital media. Hayes- Nance analysis was performed using OrthoAnalyzer software (3Shape A/S, Copenhagen, Denmark) on the scanned models, and the amounts of dental crowding in the upper and lower jaws of the patients were classified as mild, moderate, and severe where mild crowding was defined as arch length-tooth length discrepancy of up to 3 mm, moderate crowding as discrepancy of 3-6 mm, and severe crowding as discrepancy over 6 mm . These dental crowding values were divided into subgroups for the lower and upper jaws.
orthodontic treatment (p>0.05). Unlike other malocclusion classes, it was found that “my lower jaw is behind compared with my upper jaw” was the reason for demanding orthodontic treatment in only 6.6% (8 patients) in this group. While 47.5% of Cl-II patients (57 patients) had mild crowding, 67.5% of Cl-II patients (81 patients) thought that the problem area was the maxillary anterior teeth.
In patients with dental Cl-III malocclusion, no significant relationship was found between dental crowding and the reason for demanding orthodontic treatment (p>0.05, Table 2). Only “my lower jaw is ahead compared with my upper jaw” was observed among the reasons for demanding orthodontic treatment in this group. There was a significant relationship between the reason for demanding orthodontic treatment and the noticed problem area (p<0.05, Table 3). Unlike the other malocclusion groups, there was a significant relationship (p<0.05) between mandibular prognathism and the fact that there were more people who thought that there was a problem in the mandibular anterior (64.3%) and the overall (72.7%) region in patients (Figure 2) included in this dental malocclusion class.
It is necessary to identify adolescent patients’ reasons for demanding orthodontic treatment and establish what would represent a successful treatment outcome. These concerns need to be recorded and focused on throughout treatment to avoid patient disappointment. A common cause of medicolegal problems after treatment is failure to resolve patients’ complaints . However, we could not find any study in the literature that focused on reasons for demanding orthodontic treatment among Turkish adolescents. Therefore, this study was conducted to identify the most relevant demands for orthodontic treatment and their possible relationships with treatment decisions.
One of the most significant factors in adolescents’ demands for orthodontic care is whether they have malocclusion . Lindegård et al. reported that in planning orthodontic care, it is necessary to consider not only the status of the teeth; the care needs expressed by specialists and the demands for treatment as expressed by patients must also be taken into account . Other consumer factors include wishes to improve in appearance, gender and age, peer group norms, and social levels . Similarly, the decisions of orthodontic care providers are affected by the dentist’s and orthodontist’s perceptions of the need for treatment, recognition of malocclusion features, availability of services, and costs of treatment [14, 19].
The demand for orthodontic treatment can be considered as a way to improve the dentofacial appearance and gain self- confidence [8, 11, 12]. The requirements for orthodontic treatment are increasing in most countries. The literature shows the demand for treatment by the number of patients who have made appointments and are seeking care . Orthodontic precautions must be planned rationally for the society in question to evaluate the necessary resources for providing such services. This information reveals the prevalence of different types of malocclusions based on epidemiological studies, the factors affecting patient demands, and the need for orthodontic treatment .
There is a consensus among orthodontists that they are motivated to demand orthodontic treatment due to the malocclusion’s unfavorable physical, psychological, and social consequences [2, 18]. However, it has been reported that malocclusion affects the quality of life in less than 50% of adolescents who need orthodontic treatment .
The growth and development in female adolescents may be slightly ahead of that of males, with a higher percentage of girls being ready to start treatment while boys may need further development . Data for children in different populations revealed that females are more interested in orthodontic correction than males because of esthetics . In all five main categories of secondary motivation, dental crowding, esthetic reasons, mandibular prognathism, and retrognathism, the demand for treatment was observed similarly among boys and girls , in contrast to other reports . Our findings may be due to the fact that males in Turkish society care about physical appearance as much as females. Oliveira determined that adult patients complained of bad esthetics most frequently before treatment . In contrast to our study, they found that a small number of adult patients complained of mastication and gum problems, cavities, and speech problems. Their study had a small sample size and provided pre- and posttreatment evaluations, but it did not fully reflect the determination of the patients’ pretreatment concerns. In addition, considering that most of the population seeking orthodontic treatment comprises adolescents, their findings are difficult to generalize. The most common complaint of patients who applied to our clinic (50.6%) was that their teeth were crowded, regardless of the severity of crowding . Shaw et al. reported a positive relationship between patients’ demands for orthodontic treatment and visible irregularity in their teeth . In our study, it was determined that the primary demand for orthodontic treatment was dental crowding. Similarly, Wędrychowska-Szulc and Syryńska reported that the main reason for the orthodontic treatment demands of adolescent patients and their parents or guardians was dental crowding leading to poor esthetic appearance . However, they did not state which region dental crowding occurred in more frequently or where the patients noticed problems.
It has also been reported that 48% of individuals with moderate or severe visible irregularities stated that they were very or quite satisfied with their dental appearance, while those with minor or no abnormalities stated that they were dissatisfied with their appearance at a similar rate [15, 23]. It was further reported that these individuals were disturbed by the appearance of their teeth, which were thought to be seriously affected by dental crowding or tooth morphology, multiple diastemata, or congenitally missing teeth. However, some studies have reported that dentofacial esthetics is the most influential factor in demands for treatment [10, 22]. Dissimilarity among these findings may be due to material differences.
When the relationship between dental malocclusion type and the reason for demanding orthodontic treatment was evaluated, a statistically significant difference was observed; thus, we evaluated the dental malocclusion classes separately. Among patients of all dental malocclusion classes, no significant relationship was found between the severity of dental crowding and the reason for demanding orthodontic treatment; however, when the relationships between noticed problem areas and reasons for demanding treatment were evaluated, a significant difference was observed only for dental class III malocclusions. Hence, patients with class III problems were more likely to demand evaluations than those with other malocclusions . To report overall rates, we present them all in Table 3. Accordingly, 57.7% of patients were concerned about problems in the maxillary anterior teeth and 45% had mild dental crowding in both jaws.
Regarding dentofacial appearance, cultural factors also have powerful effects. An abnormality such as dental crowding or malocclusion such as Cl-II or Cl-III type evaluated as esthetically unacceptable in one population may be acceptable or even a marker of attractiveness in another .
Although this study has limitations such as limited sample selection and its single-center nature, along with the need to consider other factors affecting orthodontic treatment demands and more objective assessments of orthodontic treatment needs such as the Index of Orthodontic Treatment Need, it can be predicted that this work will serve as a guide for further studies. With both objective and subjective evaluations, it will be possible to reveal the orthodontic treatment needs of Turkish adolescents from a different perspective and provide better guidance to orthodontists in this respect. One of the limitations of our study is that our questions were limited in number, but we still aimed to obtain accurate information using this questionnaire to achieve the purposes of our study. In addition, as our questionnaire was written using short and clear phrasing to achieve the desired results, the individuals being tested were not confused.
The results of this study have revealed the demands of patients requesting orthodontic treatment. These results can be summarized as follows:
• The main factor affecting the demand for orthodontic treatment is dental crowding, regardless of its severity.
• Patients who demand orthodontic treatment are most often dissatisfied with their upper anterior teeth.
• Significant differences were observed between the reasons for demanding orthodontic treatment and dental malocclusion classes.
• No difference was observed in reasons for requesting treatment between genders.
We would like to express our thanks to Associate Professor Dr Nisa Gul Amuk from the Department of Orthodontics, Faculty of Dentistry, Erciyes University for her valuable contribution and insights in presenting our study.
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Animal and human rights statement
Conflict of interest
1. Thilander B, Pena L, Infante C, Parada SS, de Mayorga C. Prevalence of malocclusion and orthodontic treatment need in children and adolescents in Bogota, Colombia. An epidemiological study related to different stages of dental development. Eur J Orthod. 2001;23(2):153-68.
2. Bernabé E, Tsakos G, Messias de Oliveira C, Sheiham A. Impacts on daily performances attributed to malocclusions using the condition-specific feature of the Oral Impacts on Daily Performances Index. Angle Orthod. 2008;78(2):241-7.
3. Marques LS, Pordeus IA, Ramos-Jorge ML, Filogônio CA, Filogônio CB, Pereira LJ, et al. Factors associated with the demand for orthodontic treatment among Brazilian adolescents and their parents. BMC Oral Health. 2009 Dec 18;9:34.
4. Tayer BH, Burek MJ. A survey of adults’ attitudes toward orthodontic therapy. Am J Orthod. 1981;79(3):305-15.
5. Kazancı F, Aydoğan C, Alkan Ö. Patients’ and parents’ concerns and decisions about orthodontic treatment. Korean J Orthod. 2016;46(1):20-6.
6. Bos A, Hoogstraten J, Prahl-Andersen B. Expectations of treatment and satisfaction with dentofacial appearance in orthodontic patients. Am J Orthod Dentofacial Orthop. 2003;123(2):127-32.
7. Kiyak HA. Comparison of esthetic values among Caucasians and Pacific- Asians. Community Dent Oral Epidemiol. 1981;9(5):219-23.
8. Oliveira PGSA, Tavares RR, Freitas JC. Assessment of motivation, expectations and satisfaction of adult patients submitted to orthodontic treatment. Dental Press J Orthod. 2013;18(2):81-7.
9. De Oliveira C, Sheiham A. Orthodontic treatment and its impact on oral health- related quality of life in Brazilian adolescents. J Orthod. 2004;31(1):20-7.
10. Sayin M, Türkkahraman H. Malocclusion and crowding in an orthodontically referred Turkish population. Angle Orthod. 2004;74(5):635-9.
11. Jayachandar D, Dinesh SS. Factors affecting patient’s demand for seeking orthodontic treatment. Int J Orthod Rehabil. 2016;7(3):89-91
12. Li XT, Tang Y, Huang Xl, Wan H, Chen YX. Factors influencing subjective orthodontic treatment need and culture-related differences among Chinese natives and foreign inhabitants. Int J Oral Sci. 2010;2(3):149-57.
13. Arnett GW, McLaughlin RP. Facial and dental planning for orthodontists and oral surgeons. Mosby; 2004.
14. O’Brien K, McComb J, Fox N, Wright J. Factors Influencing the Uptakes of Orthodontic Treatment. Br J Orthod. 1996;23(4):331-4.
15. Lindegård B, Lindegård L, Carlson M, Larsson S. Need and demand for orthodontic treatment. Tandlaegebladet. 1971;75(12):1198-210.
16. Shaw W, O’brien K, Richmond S. Quality control in orthodontics: factors influencing the receipt of orthodontic treatment. Br Dent J. 1991;170(2):66-8.
17. Oshagh M, Salehi P, Pakshir H, Bazyar L, Rakhshan V. Associations between normative and self-perceived orthodontic treatment needs in young-adult dental patients. Korean J Orthod. 2011;41(6):440-6.
18. Birkeland K, Katle A, Løvgreen S, Bøe OE, Wisth PJ. Factors influencing the decision about orthodontic treatment. A longitudinal study among 11- and 15-year-olds and their parents. J Orofac Orthop. 1999;60(5):292-307.
19. Wheeler TT, McGorray SP, Yurkiewicz L, Keeling SD, King GJ. Orthodontic treatment demand and need in third and fourth grade schoolchildren. Am J Orthod Dentofacial Orthop. 1994;106(1):22-33.
20. Ng’ang’a PM, Stenvik A, Ohito F, Ögaard B. The need and demand for orthodontic treatment in 13-to 15-year-olds in Nairobi, Kenya. Acta Odont Scan. 1997;55(5):325-8.
21. Burden D. The influence of social class, gender, and peers on the uptake of orthodontic treatment. Eur J Orthod. 1995;17(3):199-203.
22. Abdullah A, Yassin ZM, Zamzam N. Reasons For Seeking Orthodontic Treatment A Pilot Study. Ann Dent Univ Malaya. 2001;8:13-9.
23. Shaw W. Factors influencing the desire for orthodontic treatment. Eur J Orthod. 1981;3(3):151-62.
24. Wędrychowska-Szulc B, Syryńska M. Patient and parent motivation for orthodontic treatment—a questionnaire study. Eur J Orthod. 2010;32(4): 447-52.
25. Proffit W, Phillips C, Dann C. Who seeks surgical-orthodontic treatment? Int J Adult Orthodon Orthognath Surg. 1990;5(3):153-60.
As a result of power analysis, it was determined that 120 patients in each group would be sufficient with 5% error, 95% power, and 0.59 effect size. Questionnaire answers obtained from the patients were recorded as categorical data and processed with Microsoft Office Excel (Office 365, Microsoft Corporation, Redmond, WA, USA). Pearson’s chi-square test and Fisher’s exact test were used to evaluate the relationship between dental crowding groups, the area where the patient noticed a problem, dental malocclusion groups, and the reasons for orthodontic treatment demands. The data obtained are presented as sample counts and percentage values. In addition, while one-way ANOVA was used to evaluate relationships with age between dental malocclusion classes, the independent samples t-test was used to assess relationships with age
between male and female patients. Statistical evaluations were conducted using Stata/ICC Statistical Software (Version 15.1, StataCorp LLC, College Station, TX, USA). Statistical significance was set at p<0.05.
Fifty patients’ dental models were reexamined 1 month after their first measurements by the same investigator (T.O.). Intraclass correlation coefficients for dental crowding measurements were 0.81 and 0.89 for the maxilla and mandible, respectively, indicating sufficient reliability.
According to Angle’s dental malocclusion classification, there was no significant difference between male and female respondents in the evaluations (Table 1).
According to the data obtained, there was a statistically significant relationship between the reasons for patients to demand orthodontic treatment and dental malocclusion type (p<0.05, Table 1). The main concerns of the patients were crowding of the teeth and esthetic reasons for all types of dental malocclusions. Patients with Cl-II malocclusion complained that “my lower jaw is behind compared with my upper jaw,” whereas patients with Cl-III malocclusion complained that “my lower jaw is ahead compared to my upper jaw.” There were no significant differences in reasons for demanding orthodontic treatment between genders.
The total distribution of dental crowding groups according to the reasons for demanding treatment is presented in Tables 2 and 3. It was determined that the vast majority of patients had mild crowding in the upper and lower dental arch (n=162, 45.0%), and the area that patients noticed to be problematic was mostly the maxillary anterior region (n=208, 57.8%). The general reasons for these patients to demand orthodontic treatment were dental crowding and esthetics.
In patients with dental Cl-I malocclusion, a significant relationship could not be established between dental crowding (Table 2), the noticed problem area (Table 3), and the reasons for demanding orthodontic treatment (p>0.05). No complaints of mandibular retrognathism and/or prognathism were observed in dental Cl-I malocclusion patients. It was found that the vast majority of patients had mild crowding and the noticed problem area was the maxillary anterior teeth (n=50, 41.7%).
In patients with dental Cl-II malocclusion, no significant relationship was found between dental crowding (Table 2), the noticed problem area (Table 3), and the reasons for demanding
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Gokhan Coban, Taner Ozturk, Gokhan Turker. Analysis of factors affecting adolescent patients’ demands for orthodontic treatment. Ann Clin Anal Med 2021;12(12):1376-1382
Impact of leg wrapping in combination with leg elevation on postspinal hypotension in subjects undergoing elective cesarean section under spinal anesthesia
Osman Esen 1, Canan Balcı 2, Mehmet Akif Sargın 3, Başar Erdivanlı 4
1 Department of Anesthesiology And Reanimation, Vocational School of Health, Istinye University, Istanbul, 2 Department of Anesthesiology And Reanimation, Faculty of Medicine, Kütahya Health Sciences University, Kütahya, 3 Department of Obstetrics and Gynecology, Medical Park Hospital, Istanbul, 4 Department of Anesthesiology and Reanimation, Faculty of Medicine, Recep Tayyip Erdogan University, Rize, Turkey
DOI: 10.4328/ACAM.20759 Received: 2021-06-25 Accepted: 2021-08-20 Published Online: 2021-09-10 Printed: 2021-12-01 Ann Clin Anal Med 2021;12(12):1383-1387
Corresponding Author: Osman Esen, Zümrütevler Mah. Handegül Sokak, No: 98/16, Maltepe, Istanbul, Turkey. E-mail: firstname.lastname@example.org P: +90 505 677 13 85 F: +90 216 457 38 00 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6280-5064
Aim: This study aimed to compare the efficacy of lower extremity wrapping with elastic bandages in conjunction with leg elevation to leg elevation alone in terms of maternal systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, and SaO2 in term mothers undergoing elective cesarean section (CS) with spinal anesthesia.
Material and Methods: A series of 62 term mothers aged between 20 and 45 years who were scheduled for elective CS under spinal anesthesia were enrolled in the study. Using sealed envelopes, participants were allocated to one of two study groups: the wrapping group (n=30) or the control group (n=32). All subjects received volume administration of lactated Ringer’s solution of 10 mL/kg over the 15 min prior to the administration of the spinal block. Subjects allocated to the wrapping group received lower extremity wrapping with 10-cm Esmarch elastic bandages applied from the ankle to the mid-thigh immediately before the administration of the subarachnoid block. Following intrathecal injection, lower limbs were elevated 20° in subjects allocated to the wrapping group by tilting the foot-end of the operating table. Systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, and SaO2 were monitored intraoperatively.
Results: Systolic, diastolic, and mean blood pressures were significantly higher in the wrapping group compared to the control subjects beginning from the 2nd minute of the intrathecal injection to the 20th-30th minute of the intrathecal injection. The median ephedrine dose was significantly higher in the control group than the wrapping group [15 (0-40) mg vs. 5 (0-30) mg, p=0.007]. Vomiting was also more frequent in control subjects compared to those receiving lower extremity wrapping and leg elevation (18% vs. 0%, p=0.024).
Discussion: Lower extremity wrapping in combination with leg elevation provides a better hemodynamic profile than volume administration alone in subjects undergoing elective CS under spinal anesthesia. Subjects receiving lower extremity wrapping and leg elevation require less vasopressors and experience less vomiting compared to subjects receiving only volume administration.
Keywords: Cesarean Section, Spinal Anesthesia, Hypotension
Spinal anesthesia is frequently employed in the anesthesia of healthy pregnant women undergoing elective cesarean section (CS). However, spinal anesthesia may cause hypotension in about 70% of the subjects undergoing CS depending on the presence of preoperative hypertension, age, the type of anesthesia used, and the weight of the newborn infant . Increased sympathetic activity compared to the parasympathetic activity in addition to increased susceptibility to the effects of sympathetic block exposes pregnant women to increased vasodilatation . Prolonged hypotension can not only lead to harmful effects in mothers but may also cause uteroplacental hypoperfusion. Several measures have been introduced to prevent maternal hypotension occurring after spinal anesthesia for CS. Intravenous fluid therapy including crystalloid prehydration, administration of colloids, transcutaneous electrical nerve stimulation to augment sympathetic tone, and administration of vasopressors such as ephedrine and phenylephrine have been used to prevent maternal hypotension in subjects undergoing elective CS with spinal anesthesia [3-7]. These methods have been shown to improve maternal hemodynamics to some degree.
Wrapping the lower extremity with tight elastic bandages has also been studied for the prevention of maternal hypotension in subjects undergoing elective CS [8-10]. This technique theoretically improves autotransfusion from the lower extremity to the central veins. However, there are controversial results regarding the utility of lower extremity wrapping in subjects undergoing elective CS with spinal anesthesia.
This study aimed to compare the efficacy of lower extremity wrapping with elastic bandages in conjunction with leg elevation to leg elevation alone in terms of maternal systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, and SaO2 in term mothers undergoing elective CS with spinal anesthesia.
Material and Methods
A series of 62 term mothers aged between 20 and 45 years who were scheduled for elective CS under spinal anesthesia were enrolled in the study. Written informed consent was obtained from all participants. The study was approved by the institutional review board and was conducted in accordance with the Declaration of Helsinki. Subjects with severe mental illness or retardation, preoperative hypovolemia, more than mild-degree valvular disease, and coagulation disorders were excluded from the study. Using sealed envelopes, participants were allocated to one of two study groups: the wrapping group (n=30) or the control group (n=32).
All subjects received volume administration of lactated Ringer’s solution at 10 mL/kg over the 15 min prior to the administration of the spinal block. Subjects allocated to the wrapping group received lower extremity wrapping with 10-cm Esmarch elastic bandages applied from the ankle to the mid-thigh immediately before the administration of the subarachnoid block. Each leg was wrapped in turn and the presence of adequate capillary pulsation in the toes was confirmed to ensure that arterial pressure had not been exceeded. Leg wrapping was completed within 3 min. Lower extremities were lifted at an angle of 45° during the application of the Esmarch elastic bandages.
All intrathecal injections were performed by the same anesthesiologist while the patient was sitting with legs extended on the horizontal operating table. A standard of 12 mg of hyperbaric 0.5% bupivacaine was injected through a 25-gauge Quincke-type spinal needle at the L3-4 interspace using the midline approach. Following intrathecal injection, lower limbs were elevated 20° in subjects allocated to the wrapping group by tilting the foot-end of the operating table. Systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, and SaO2 were monitored non-invasively using the same dedicated intraoperative monitoring system at baseline (prior to fluid infusion), immediately after intrathecal injection, at 2-min intervals for the first 10 min subsequent to intrathecal injection, and every 5 min thereafter until completion of surgery. Elastic bandages were removed slowly within 5 min following the surgery.
The difference in intraoperative hemodynamic measurements between the groups was the primary outcome measure of this study. Intraoperative ephedrine and atropine requirements and intraoperative nausea and vomiting were the secondary outcome measures.
All analyses were performed with SPSS 21 (IBM Corp., Armonk, NY, USA). To check the normality of the data, the Shapiro-Wilk test was used. Data are presented as mean±standard deviation and median (minimum-maximum) for continuous variables and as frequency and percentage for categorical variables. Normally distributed variables were analyzed using Student’s t-test. Non-normally distributed variables were analyzed with the Mann-Whitney U test. Pearson’s chi-square test was used for comparison of the categorical variables. Two-tailed p-values of less than 0.05 were considered statistically significant.
A total of 62 term mothers undergoing elective CS with spinal anesthesia were enrolled in the study (mean age: 28.5±5.1 years). The groups were similar with respect to age, ASA class, anesthetic agent dose, and level of spinal block. The values of the study subjects are presented in Table 1. Systolic blood pressure was significantly higher in the wrapping group compared to the control subjects beginning from the 2nd minute of the intrathecal injection to the 20th minute of the intrathecal injection (Figure 1). Diastolic blood pressure was also significantly higher in the wrapping group compared to the control subjects beginning from the 2nd minute of the intrathecal injection to the 30th minute of the intrathecal injection (Figure 2). Consistent with systolic and diastolic blood pressure, mean blood pressure was significantly higher in the wrapping group compared to the control subjects beginning from the 2nd minute of the intrathecal injection to the 20th minute of the intrathecal injection (Figure 3). There were no significant differences between the groups in terms of heart rate or SaO2 in any of the recordings.
The median ephedrine dose was significantly higher in the control group than the wrapping group [15 (0-40) mg vs. 5 (0- 30) mg, p=0.007]. Atropine requirement was similar among the groups. There were no significant differences in the rate of intraoperative nausea and tremor. However, vomiting was more frequent in control subjects compared to those receiving lower extremity wrapping (18% vs. 0%, p=0.024).
The present study hypothesized that lower extremity wrapping with elastic bandages in combination with leg elevation would provide better intra- and postoperative hemodynamic profiles compared to leg elevation alone in subjects undergoing elective CS with spinal anesthesia. Our findings demonstrate that lower extremity wrapping in combination with leg elevation provides significant hemodynamic improvement in subjects undergoing elective CS with spinal anesthesia. Subjects receiving wrapping and leg elevation required less vasopressors compared to controls. Moreover, subjects receiving wrapping and leg elevation experienced less vomiting during the surgery compared to subjects not receiving wrapping and leg elevation. Hypotension occurring following the intrathecal injection of the anesthetic agents in subjects undergoing elective CS is the major drawback of spinal anesthesia in this patient group. The reduction in blood pressure not only exposes the mother to the detrimental effects of hypotension but also leads to placental hypoperfusion, which may cause fetal acidosis and in severe cases fetal bradycardia and cardiovascular collapse. Reduced arterial and venous tonus resulting from the sympathetic block is the main cause of the hypotension occurring after spinal anesthesia. Moreover, increased sensitivity to local anesthetics in pregnant women leads to a more extensive spinal block compared to non-pregnant women.
Several preventative measures have been investigated in previous studies to overcome the hypotension occurring with spinal block. Intravenous fluid administration before spinal anesthesia is one of the most studied strategies aiming to prevent hypotension. Despite questionable efficacy, a recent survey on the management of spinal-induced hypotension in subjects scheduled for cesarean delivery revealed that fluid management is still popular in obstetric anesthesia . However, a recent Cochrane review indicated that crystalloids alone may be insufficient to prevent hypotension during spinal anesthesia . On the other hand, several studies have shown that fewer women receiving colloids experience hypotension compared to those receiving crystalloids.
Autotransfusion by leg elevation or compression of the leg has also been subject to several studies investigating preventative measures against spinal hypotension. An early study revealed that 16% to 20% of the blood volume is accumulated in the legs during the spinal blockade . The volume of the blood pooled in the legs is estimated to be 150 mL . There are also studies demonstrating increased vascular distensibility of the calf vessels during spinal anesthesia . This evidence led to the conduction of studies investigating the impact of passive leg elevation and leg compression techniques on blood pressure and heart rate in subjects undergoing CS with spinal anesthesia. One of the earliest reports documenting the efficacy of leg elevation was written by Assali and Prystowsky. These authors showed in their study on subjects undergoing CS with spinal anesthesia that leg elevation by 90° or exclusion of the legs from the systemic circulation by cuffs could prevent hypotension related to spinal blockade . Pernoll et al. reported that simultaneous elevation of the legs to the straight-up position and left uterine displacement was the most efficient method to prevent hypotension . However, some authors asserted that the volume subject to autotransfusion is limited and thus cannot provide a remarkable change in blood pressure .
Compression of the legs has also provided conflicting results. James et al. studied the impact of inflatable boots covering the legs from the toes to the upper part of the thighs in 83 women undergoing CS with spinal anesthesia . They reported that inflatable boots did not add any benefit to standard care in prevention of spinal hypotension. Opposite results were derived from the study of Goudie et al., in which the authors used inflatable splints to prevent hypotension during spinal anesthesia. They reported that hypotension was less common and less severe in subjects receiving inflatable splints; moreover, the incidence of hypotension was significantly lower in splint-treated patients compared to controls . Rout et al. used Esmarch bandages for lower extremity wrapping and found that lower extremity wrapping in combination with 30° leg elevation provided a fivefold reduction in the likelihood of postspinal hypotension compared to leg elevation alone . Similar to the findings of Rout et al., Bhagwanjee et al. showed in subjects undergoing CS with spinal anesthesia that lower extremity wrapping immediately after spinal injection resulted in reduced incidence of hypotension and vasopressor agent requirement compared to conventional care . Similarly to the findings of the earlier trials, the study by van Bogaert reported reduced incidence of postspinal hypotension with lower extremity wrapping compared to leg elevation alone in subjects undergoing elective CS .
Consistent with the previous data reported by Rout et al. , we found that lower extremity wrapping in combination with leg elevation provides favorable hemodynamic profile, less vasopressor requirement, and less vomiting in subjects undergoing elective CS under spinal anesthesia. Our results indicate that autotransfusion obtained with the implementation of leg wrapping and leg elevation is likely sufficient to prevent spinal hypotension. In contrast to the study of Rout et al., we did not enroll a group of subjects receiving only leg elevation; thus, we cannot comment on whether leg elevation itself could also prove successful in prevention of spinal hypotension. This can be regarded as a major limitation of this study. Nevertheless, we suggest that leg wrapping along with leg elevation can prevent the development of hypotension in subjects undergoing elective CS under spinal anesthesia.
Our findings indicate that lower extremity wrapping in combination with leg elevation provides a better hemodynamic profile than volume administration alone in subjects undergoing elective CS under spinal anesthesia. Subjects receiving lower extremity wrapping and leg elevation required less vasopressors and experienced less vomiting compared to subjects receiving only volume administration. These findings indicate that the combination of lower extremity wrapping with leg elevation may improve the hemodynamic profile and prevent spinal hypotension in elective CS.
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Conflict of interest
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12. Asmussen E, Christensen EH, Nielsen M. The regulation of circulation in different postures. Surgery. 1940;8(4):604-16.
13. Rutlen DL, Wackers F, Zaret B. Radionuclide assessment of peripheral intravascular capacity: a technique to measure intravascular volume changes in the capacitance circulation in man. Circulation. 1981;64(1):146-52.
14. Shimosato S, Etsten B. The role of the venous system in cardiocirculatory dynamics during spinal and epidural anesthesia in man. Anesthesiology. 1969;30(6):619-28.
15. Assali N, Prystowsky H. Studies on autonomic blockade. II. Observations on the nature of blood pressure fall with high selective spinal anesthesia in pregnant women. The Journal of clinical investigation. 1950;29(10):1367-75.
16. Thomas, D. G., Robson, S. C., Redfern, N., Hughes, D., & Boys, R. J. Randomized trial of bolus phenylephrine or ephedrine for maintenance of arterial pressure during spinal anaesthesia for Caesarean section. British journal of anaesthesia, 1996. 76(1), 61-5.
17. Bhagwanjee S, Rocke D, Rout C, Koovarjee R, Brijball R. Prevention of hypotension following spinal anaesthesia for elective caesarean section by wrapping of the legs. BJA: British Journal of Anaesthesia. 1990;65(6):819-22.
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Osman Esen, Canan Balcı, Mehmet Akif Sargın, Başar Erdivanlı. Impact of leg wrapping in combination with leg elevation on postspinal hypotension in subjects undergoing elective cesarean section under spinal anesthesia. Ann Clin Anal Med 2021;12(12):1383-1387
Is malignancy effective in the healing time of pressure ulcers in intensive care patients?
Guldeniz Argun 1, Murat Aydın 2, Gülyaşar Ketenci İncel 3, Eda Karaismailoğlu 4
1 Department of Anesthesiology and Algology, Ankara Oncology Training and Research Hospital, Ankara, 2 Department of Orthopedics and Traumatology, Medical School, Nigde Omer Halis Demir University, Nigde, 3 Department of Intensive care, Ankara Oncology Training and Research Hospital, Ankara, 4 Department of Medical Informatics, University of Health Sciences, Ankara, Turkey
DOI: 10.4328/ACAM.20763 Received: 2021-06-28 Accepted: 2021-08-10 Published Online: 2021-08-24 Printed: 2021-12-01 Ann Clin Anal Med 2021;12(12):1388-1392
Corresponding Author: Murat Aydin, Department of Orthopedics and Traumatology, Nigde Omer Halis Demir University Medical School, Nigde, Turkey. E-mail: email@example.com P: +90 532 452 85 59 Corresponding Author ORCID ID: https://orcid.org/0000-0003-4098-0907
Aim: In this study, we aimed to investigate the duration of wound healing and an effective treatment management approach to patients with or without ma- lignancy receiving wound care to provide effective wound care and to accelerate discharge.
Material and Methods: Three hundred and forty-five patients who were treated in our clinic were included in the study. Records of patients with pressure ulcers among those who stayed in the Surgical Intensive Care Unit between January 1, 2018 and January 1, 2020 were accessed. Patients’ pressure ulcers were graded on the Waterlow scale and standardized therapies were applied according to the grades. Dates of admission to the Intensive Care Unit (ICU), the pressure ulcers grades, comorbidities, laboratory values, administered treatment protocols and treatment response times were retrieved from the records and evaluated.
Results: The patients were divided into two groups: patients with malignancy (Group M, n = 78) and those without malignancy (Group NM, n = 73). Comparison of all parameters according to pressure ulcer stages revealed a significantly low albumin level in malignant patients with Stage 2 and 3 pressure ulcers when compared to the non-malignant patients (Group M / Group NM, Stage 2 p<.01 and stage 3 p = 0.015). In malignant patients with low albumin levels and Stage 2 pressure ulcers, the wound healing time was prolonged statistically significant (Group M/Group NM, 13.28±5.64/11.50±6.34 days, p = 0.047). No significant difference was established in the mean duration of wound healing between patients with and without malignancy when groups were taken up in general (Group M/Group NM: 8.00±6.49 / 6.67±6.35 days, p = 0.52).
Discussion: Malignancy does not play a role in the duration of wound healing in malignant and non-malignant patients treated in the intensive care unit at stage 1 pressure wounds. Furthermore, there is a difference in the duration of wound healing between malignant and non-malignant patients, even for Stage 2 and 3 pressure ulcers on the Waterlow scale.
Keywords: Critical Care, Pressure Ulcer, Neoplasms, Wounds and Injuries
Pressure ulcers are a syndrome that can cause significant morbidity and mortality, but can be prevented when the necessary precautions are taken. Pressure ulcers are a common complaint in geriatric patients due to pathological changes resulting from comorbidities. Selecting an appropriate approach to the treatment of pressure ulcers requires knowledge of the pathophysiology of the event. Pressure ulcers increase the length of hospital stays, morbidity and mortality, contributing therefore to increased healthcare costs [1–5].
Both intrinsic and extrinsic factors are involved in pressure ulcer formation, with the main pathology being interrupted blood flow and hypoxia due to pressure in the affected area [6, 7]. The pressure gradient at the arterial and venous ends of capillaries supports tissue perfusion. The disruption of capillary circulation due to pressure leads to hypoxia, triggering wound formation. With advanced age, the amount of collagen and elastin in the dermis decreases, and skin perfusion decreases .
Previous studies have reported that age is not a cause of pressure ulcer formation, but should be considered as a significant risk factor in the presence of other accompanying risk factors and chronic diseases, among which, malignancy is one such risk factor . There is a chronic catabolic process. Low blood counts, and neutrophils, in particular, predispose patients undergoing malignancy treatment to infections. Different products are available for wound care that are selected depending on the characteristics of the wounds in question . The main principle behind the prevention of pressure ulcers is to identify at-risk patients in advance, and take e appropriate measures to relieve pressure. The best-known scales for grading pressure ulcers are the Norton Scale (1962), the Gosnell Scale (1973), the Knoll Scale (1985), the Waterlow Scale (1985) and the Braden Scale (1987) . The Braden Scale assesses six parameters, including sensory perception, activity, mobility, moisture, nutrition and friction-shear, and produces a maximum score of 23. A score of 15–18 indicates mild risk, 13–14 moderate risk, 10–12 high risk and 0–9 very high risk. Patient risk assessments require an assessment of all patient data. Factors that should not be ignored when managing wound care include treatment of existing systemic diseases, treatments for changes in laboratory values, general condition, drug interactions and side effects experienced by the patient.
For Stage 1 pressure ulcers, it will be sufficient to prevent the progression of the lesion by relieving pressure. For Stage 2 pressure ulcers, no debridement is required, although it is important to keep the wound area non-infected and to provide a suitable moist environment. Stage 3 and 4 pressure ulcers often require debridement. Selection of products suitable for the characteristics of the wound, antibiotic treatment if infection is present, a combination of passive and active closure products when necessary, and surgical treatments may be required.
No previous studies related to wound healing in intensive care patients with malignancy were identified in the literature. We believe that such a study on wound healing would serve to guide the treatment of patients in the future due to the large malignant patient population in our oncological hospital. The present study investigates whether malignancy has an effect on the healing of pressure ulcers in intensive care patients, and is conducted based on our belief that such a study of wound healing could serve as a guide in the treatment of patients in the future, due to the large malignant patient population of our oncological hospital.
Material and Methods
Following approval from the local ethics committee and informed consent from the patients, the records of patients with pressure ulcers among those who stayed in the Surgical Intensive Care Unit between January 1, 2018 and January 1, 2020 were accessed. Three hundred and forty-five patients who were treated in our clinic were included in the study. A further 126 patients with pressure ulcers who needed surgical debridement, mechanical ventilation and/or vacuum-assisted closure (VAC) were also excluded. The remaining patients were examined in 2 groups: those with malignancy (Group M, n = 108) and those without malignancy (Group NM, n = 111). Patients with diabetic wounds and those who died during treatment (30 patients in group M, 38 patients in group NM) were excluded from the study. Therefore, 78 patients in group M and 73 patients in group NM were included in the study. Patients’ pressure ulcers were graded using the Waterlow scale, and standard treatment methods were applied according to the grades . Dates of admission to the Intensive Care Unit (ICU), the pressure ulcers grades, comorbidities, laboratory values, administered treatment protocols and treatment response times were retrieved from the records and evaluated.
For Stage 1 pressure ulcers, the pressure was relieved by changing the position every two hours, and transparent film dressings and barrier cream were applied. (Figure-1)
For Stage 2 pressure ulcers, if the wound was exuding, hydrofiber + hydrocolloid dressings were applied and changed every other day. If the wound was moist, a hydrocolloid dressing was applied for 3–5 days.
For Stage 3 pressure ulcers, if the wound was necrotic and non- exuding, the dressing was changed after autolytic debridement or surgical debridement with a hydrogel dressing, and hydro- fiber + hydrocolloid dressings were applied every 2–3 days. If the wound was exuding, hydro-fiber + hydrocolloid dressings were applied for 2–3 days and changed every day as needed. If the wound was moist, hydro-fiber + hydrocolloid dressings were applied, and changed every 2–3 days as needed.
For Stage 4 pressure ulcers, negative pressure therapy (VAC) was administered after surgical debridement.
The study included cases with Stage 1, 2 and 3 pressure ulcers according to the Waterlow scale. Cases requiring surgical debridement (stage 4) were not included in the study. The healing time was counted from the day of initial diagnosis. The time taken for the wound to heal and regress to a lower Waterlow scale stage with appropriate treatment was compared (Stage 3 to 2, Stage 2 to 1, Stage 1 to 0).
For both groups of patients, laboratory values, treatment protocols and healing processes of pressure ulcers during treatment were retrieved from available intensive care records and evaluated retrospectively.
For statistical analysis, IBM SPSS Statistics for Windows (Version 25.0. Armonk, NY: IBM Corp.) was used. Prior to the analysis, the assumption of normality for all data was assessed with the Shapiro-Wilk test. Numerical data were expressed in median and minimum-maximum values, and categorical data in numbers (percentage). The Chi-square test was used to compare categorical variables, and the Mann-Whitney U test to compare numerical data between the two groups. The study was conducted at a 95% confidence interval.
The distribution of age, gender and the ASA (American Society of Anesthesiologists) scores was statistically similar in the malignant and non-malignant patient groups (p = 0.67; p = 0.11, p = 0.18, respectively, Table 1). Likewise, there was no statistically significant difference in healing, leukocyte, CRP, albumin, pressure ulcer stage and ASA score between the two groups (Table 1). Comparison of all parameters according to pressure ulcer stages revealed a significantly low albumin level in malignant patients with Stage 2 and 3 pressure ulcers when compared to the non-malignant patients (Group M / Group NM, Stage 2 p<.01 and stage 3 p = 0.015, Table 2).
In malignant patients with low albumin levels and Stage 2 pressure ulcers, the wound healing time was statistically significantly increased (Group M / Group NM, 13.28±5.64 / 11.50±6.34 days, p = 0.047, Table 2). CRP levels were lower in the NM Group than in the M Group (p=0.018).
Albumin levels were lower in malignant patients with Stage 3 pressure ulcers than in the non-malignant group (Group A / Group B: 2.18 ±0.23/ 1.05±1.20 g/dl, p =0.01, Table 2). This finding was statistically significant (p<0.05).
Furthermore, in patients with malignancy, the healing time of Stage 3 pressure ulcers was statistically significant (Group M/ Group NM: 13.75±5.79/7.90±6.31 days, p=0.009, Table 2).
No significant difference was established in mean duration of wound healing between patients with and without malignancy when groups were taken up in general (Group M / Group NM: 8.00±6.49 / 6.67±6.35 days, p = 0.52, Table 1).
In the present study, the wound healing time was similar in both the malignant and non-malignant patient groups. When the groups were compared separately according to the pressure ulcer stages, albumin levels were found to be low in malignant patients with Stage 2 and 3 pressure ulcers. The healing time of Stage 2 and 3 pressure ulcers was statistically significantly delayed in malignant patients with low albumin levels.
Ricci et al. discussed the significance of having an albumin level of >3 g/dl and a prealbumin level of >20 mg/dl in wound treatment . In the present study, when the groups were compared separately according to the pressure ulcer stages, albumin levels were found to be low in malignant patients with stage 2 and 3 pressure ulcers. Although the healing time of Stage 2 pressure ulcers was statistically insignificant in malignant patients with low albumin, it was observed to be delayed numerically. In addition, malignant patients with stage 3 pressure ulcers had low albumin levels along with a statistically prolonged healing time.
They recommend the optimization of protein, vitamin and mineral intake, and correction of albumin and prealbumin levels, and stress the necessity of reaching target nutritional values through calorie calculations, high-protein diets and, if necessary, tube gastrostomy and jejunostomy . This is also important for the success of treatment in patients treated with a turning flap. In the present study, the albumin value was <3 g/dl in malignant patients with stage 2 pressure ulcers, and wound healing time was prolonged, although not significantly. This absence of a significant prolongation in wound healing may suggest the effectivity of the applied wound care, even in malignant patients with low albumin levels.
Reed et al. investigated the factors affecting the formation of pressure ulcers in hospitalized patients with a randomized, prospective study of 2,771 patients from 47 centers . The authors identified confusion and low albumin to be risk factors for the development of pressure ulcers. The stage of pressure ulcers, presence of indications for resuscitation, presence of malnutrition, body mass index, albumin level, mental state, presence of urinary or fecal incontinence, and presence of pneumonia on chest radiography were considered risk factors. In the absence of fecal incontinence, an albumin level of <3 g/ dl and the presence of confusion were found to be statistically significant in the formation of pressure ulcers. In the present study, we found no difference in ASA scores, pressure ulcer stages, leukocyte counts, CRP or healing times between the malignant and non-malignant patients, while a low albumin level in malignant patients with Stage 2 pressure ulcers was noted.
In a multicenter randomized controlled study, the etiology of pressure ulcers was examined in 6,155 patients, of whom 97% had stage 2 and eight patients had stage 3 pressure ulcers . More pressure sores were observed in acute patients, the elderly, and patients undergoing orthopedic and vascular surgeries.
The risk factors for pressure ulcer formation were investigated in a prospective cohort study of 213 in patients over the age of 65 years. In this population, appetite, continence, skin condition and age, all of which are among the Waterlow risk factors, were considered more important in risk identification than the other Waterlow risk factors . Cancer diagnosis was found to be positively associated with pressure ulcer formation, while the presence of Parkinson’s disease had the opposite effect. In the present study, no difference was found in the healing times of the pressure ulcers of the malignant and non-malignant groups. The limitations of this study include the fact that the general condition of the majority of malignant patients admitted to the postoperative surgical intensive care unit worsened, and they underwent mechanical ventilation or died. The number of patients who were discharged or transferred to inpatient service upon improvement in their general condition, and the number of patients meeting our criteria were not high, resulting in a small number of patients with wound healing. When patients were classified according to pressure ulcer stage, the number of patients per group was not equal and also low. However, there was no statistically significant difference in healing times in stage 1 and 2 pressure wounds. Therefore, there was a statistically significant difference in healing times in stage 3 pressure wounds.
Malignancy does not play a role in the duration of wound healing in malignant and non-malignant patients treated in the intensive care unit for pressure wounds. Therefore, malignancy no longer plays a role in the duration of wound healing in malignant and non-malignant patients treated in the intensive care unit at stage 1 pressure wounds. However, there is a difference in the duration of wound healing between malignant and non-malignant patients, even for stage 2 and 3 pressure ulcers on the Waterlow scale. The healing time of stage 2 and 3 pressure ulcers was statistically significantly in malignant patients with low albumin. We believe that optimizing albumin levels in patients with malignancies is essential for the effective advanced pressure wound care.
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6. Brown G. Long-term outcomes of full-thickness pressure ulcers: Healing and mortality. Ostomy Wound Manage. 2003; 49(10):42-50.
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8. Allman RM. Pressure ulcers among the elderly. N Engl J Med. 1989; 320(13):850- 3. DOI:10.1056/NEJM198903303201307
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Download attachments: 10.4328:ACAM.20763
Guldeniz Argun, Murat Aydın, Gülyaşar Ketenci İncel, Eda Karaismailoğlu. Is malignancy effective in the healing time of pressure ulcers in intensive care patients? Ann Clin Anal Med 2021;12(12):1388-1392
The relationship between IL-16 and Foxp3 expression in Treg cells of healthy individuals
Durmus Burgucu 1, Levent Undar 2
1 Teknokent Babylife Cord Blood Bank and Human Cell-Tissue Production Center, 2 Department of Hematology, Faculty of Medicine, Akdeniz University, Antalya, Turkey
DOI: 10.4328/ACAM.20770 Received: 2021-08-23 Accepted: 2021-09-28 Published Online: 2021-10-06 Printed: 2021-12-01 Ann Clin Anal Med 2021;12(12):1393-1396
Corresponding Author: Levent Undar, Akdeniz University, Faculty of Medicine, Department of Hematology, Campus, 07070, Antalya, Turkey. E-mail: firstname.lastname@example.org P: +90 242 226 16 80 F: +90 242 226 16 79 Corresponding Author ORCID ID: https://orcid.org/0000-0002-9853-5075
Aim: It has been demonstrated that Interleukin-16 (IL-16) is a protein that has specific effects on CD4+ T lymphocytes and is secreted from many immune and non-immune cells. Regulatory T cells (Tregs) are cells that prevent the development of autoimmune diseases and transplant rejections. It is thought that Tregs may also play an important role in the development of allergy and asthma. Tregs can control the immune response by inhibiting the function of other cells involved in the immune response. FoxP3 is a transcription factor that regulates the activation of Tregs. In this study, we aim to determine whether there is a correlation between serum IL-16 levels and FoxP3 expression in CD4+CD25+ mononuclear cells in healthy individuals.
Material and Methods: While IL-16 levels were analyzed with the ELISA method, FoxP3 levels were measured by flow cytometry in peripheral mononuclear cells, in serum samples obtained from 30 healthy volunteers. The Spearman correlation test and the SPSS 15.0 statistical program were used to evaluate the relationship between serum IL-16 and FoxP3 Expression MFI.
Results: The average serum IL-16 levels were 151.9 pg/ml (89.4-230.6). A positive correlation was observed between serum IL-16 and FoxP3 expression. To the best of our knowledge, the in-vivo relationship between IL-16 and the Treg cells was demonstrated in this study.
Discussion: High serum levels of IL-16 are observed in the disease groups with atopy, allergy, and autoimmunity, where the immune system is deficient or malfunctioning, which may contribute to the comprehensibility of the IL-16-disease relationship and may clarify the relationship between Treg-IL-16.
Keywords: Treg, FoxP3, IL-16, CD4
Interleukin-16 (IL-16) was first described in 1982 as the result of increasing chemotactic activity of T lymphocytes by stimulating peripheral blood mononuclear cells with mitogens. During the inflammatory response, IL-16 is released from mast cells, eosinophils, dendritic cells, T lymphocytes, and certain stromal cells. While IL-16 was previously known as a lymphocyte chemotactic factor, today, it has been proven to be a cytokine with specific effects on CD4+ T lymphocytes, specifically, it has been shown to be a cytokine released from CD8+ T lymphocytes as a result of stimulation of histamine and serotonin. IL-16 has two primary functions in the immune system. Its first function is that it is a chemoattractant factor of CD4+ cells. The other important task of IL-16 is to suppress the release of Th2 type cytokines (IL-4, IL-5, IL-13) as a result of antigenic stimulation and to increase the production of interferon-gamma (IFN- gamma) [1, 2]. In addition, IL-16 plays a role in the expression of IL-2R and MHC class-II of resting CD4+ T cells and selectively inhibits chemokine stimulation. In asthma patients, IL-16 has been shown to play a role in reducing or preventing the inflammatory response. It was observed that, while IL-16 knockout mice showed to be hyperresponsive to experimental lung changes and increased inflammation, parenteral or aerosol administration of IL-16 to normal mice inhibited lung hyperresponsiveness, goblet cell hyperplasia, and inflammation . IL-16 is associated with the inflammatory response observed in asthma, rheumatoid arthritis, systemic lupus, erythematous, colitis, atopic dermatitis, and multiple sclerosis [4, 5]. The fact that IL-16 affects the functions of CD4+ T cells and causes IL-2R expression in these cells suggests that it is a pro-inflammatory immune-regulatory cytokine. Regulatory T cells (Tregs) are cells that prevent the development of autoimmune diseases and transplant rejections. Tregs are able to control the immune response by inhibiting the function of other cells involved in the immune response. Specific markers of CD4+ CD25+ Treg cells were detected. These are the glucocorticoid-induced tumor necrosis factor (TNF) receptor and the FoxP3 . This study aims to examine the relationship between the expression of IL-16, which plays an important role in the immune system and acts through CD4+, and FoxP3, which plays a role in Treg cell functions. For this purpose, the serum IL-16 levels and the FoxP3 expression levels in CD4+CD25+ mononuclear cells of volunteer participants were evaluated.
Material and Methods
Study Groups and Blood Samples:
The study included a total of 30 healthy individuals, 17 males and 13 females aged between 19 and 35 years . Participants were carefully evaluated for any history of allergy and autoimmunity and whether they had any infections in the last 10 days. Complete blood counts of all participants were normal. Before participating in the project, all participants were informed in detail, and they all signed an informed consent form (a master thesis project by the Health Sciences Institute Board Date and No: 2006.02.0122). The blood sample was taken in a sterile environment by entering a vein of suitable diameter on the forearm, in a vacutainer 2 ml straight tube, in a vacutainer 10 ml heparin tube, and in a vacutainer 3 ml
EDTA tube. A complete blood count was performed on blood samples taken into tubes containing EDTA, mononuclear cells were prepared from the heparinized blood samples. Serum was separated from the blood that was drawn into straight tubes and subsequently stored at -800 C to check the IL-16 level. Peripheral Blood Mononuclear Cell Preparation
Blood samples from 30 healthy adult volunteers, 10 ml each, collected in vacutainer heparin tubes, were assayed in a sterile environment. Mononuclear cells were added to sterile 15 ml tubes on 3 ml of ficoll-isopaque (specific gravity 1.077 g/ml) by slowly adding 5 ml of peripheral blood (careful not to mix the Ficoll with the blood). This was obtained after centrifugation for 30 min at 400 G. Obtained cells were washed 2 times with sterile PBS and prepared for immunophenotypic analysis. Determination of the Serum IL-16 Levels
After the serums that were stored in -800 C were thawed at room temperature, the following steps were followed using the IL-16 ELISA Kit (BioSource Human IL-16 ELISA). In summary, 100 μL of standard serum controls were added to the wells. Antigen-specific Biotin Conjugate (50 μL) was added onto it. The wells were incubated at 25°C for 3 hours. At the end of incubation, the wells were emptied and washed 4 times with wash buffer. Streptavidin-HRP conjugate (100 μL) was added to each well. It was incubated at 25°C for 30 minutes. The liquid in the wells was drained and washed 4 times with wash buffer. Stabilized chromogen (100 μL) was added to each well. The liquid in the wells was drained and washed 4 times with wash buffer. It was incubated at 25°C for 30 minutes, and100 μL of stop solution was added. The absorbance was read at 450 nm. Measuring of the FoxP3 Expression Level
FoxP3 expression was measured with the flow cytometric method. Before the analysis, mononuclear cells were immunophenotyped using the following antibodies. Antibodies used for isotype control: anti-IgG1-FITC, anti-IgG2-PE, anti- IgG1-APC; antibodies used to detect Treg cells: anti-CD4- FITC, anti-CD25-PE, anti-FoxP3-APC. Flow cytometry analysis was performed after the immunophenotyping. Analyzes were performed at Akdeniz University Central Laboratory, using the Becton Dickinson (FACS Calibur) flow cytometry device. Fragmented cell debris and electronic contamination were removed by adjustment via forward scatter. First of all, the distribution of cells according to their size and granularity is shown, mononuclear cells were covered with the forward and 90 0 side scatter histogram, and analyzes were performed on this region. To detect the expression of the monoclonal antibody of interest, regions showing more intense fluorescence than the fluorescence of the negative isotypic control were determined from the particles in the analysis region. The percentage of the entire population of the target cells and the mean fluorescence intensity were evaluated separately when performing the analysis. Analyzes were performed with the CellQuest software.
1. CD4+ CD25+ FoxP3+ Cell Ratios
After the mononuclear cells were isolated from the blood samples of 30 healthy volunteers, CD4+CD25+ FoxP3+ cells were evaluated flow cytometrically (Figure 1). The mean was found to be 1.1% (0.9-1.3).
2. Comparison of Serum IL-16 Levels and FoxP3 Mean Fluorescence Intensity (MFI) of CD4+ CD25+ FoxP3+ Cell Population
Serum IL-16 levels were found to be 151.9 pg/ml (89.4-230.6) on average, when measured for the first time, a statistically significant correlation was found between the FoxP3 mean fluorescence intensity (MFI) of the CD4+ CD25+ FoxP3+ cell population (p< 0.05, Figure 2). This result shows us that the CD4+ CD25+ FoxP3+ cell population and the mean fluorescence intensity of FoxP3 expression are high in individuals with high serum IL-16 levels.
Interleukin-16 (IL-16) is a cytokine that is a natural ligand of CD4. Sites of allergic inflammation have been identified in both the animal and human airway epithelium and bronchoalveolar lavage specimens. It is a known chemoattractant factor for CD4+ lymphocytes, monocytes, eosinophils, and dendritic cells, and it exhibits selective chemoattractant activity for the Th1 subgroup of CD4+ cells. It also increases the expression of CD25 (IL-2R) on CD4+ cells. In vivo studies suggest that administration of IL-16 results in a reduction in inflammation and airway hyperreactivity. The mechanism of this regulatory effect on inflammation has not yet been fully explained . There are also studies showing that IL-16 plays a vital role through its effect on the pathogenesis of CD4+ T cells in the immune/inflammatory diseases such as allergic rhinitis . Some researchers have reported that IL-16 may also accompany the pathogenesis of diseases such as asthma , rheumatoid arthritis, systemic lupus erythematosus, colitis, atopic dermatitis, and multiple sclerosis [8,9]. Regulatory T cells (Tregs) control the immune response by inhibiting the function of other cells involved in the immune response. They are divided into two main groups. The first group was named natural CD4+ CD25+ regulatory T (n Treg). The other group is the cell type called adaptive Treg, these cells form under certain conditions in the periphery . FoxP3 is the specific marker of Tregs. Studies in both human and FoxP3-deficient mice indicate that this transcription factor plays an important role in the regulation of T cell function .
In this study, the chemotaxis effect of IL-16 on the CD4+ T cells, which is also an activation marker of CD4+ CD25+ T cells on the FoxP3 expression, was examined. In our study, conducted with 30 healthy individuals, the mean serum IL-16 level was found to be 151.9 pg/ml (SD: 33.4 Min: 89.4 Max: 230), and there was a statistically significant relationship (p< 0.05) between FoxP3 MFI in the first CD4+ CD25+ FoxP3+ cells. FoxP3 MFI was found to be high in individuals with high serum IL-16 levels. To our knowledge, this is the first in vivo report showing that IL-16 has a positive effect on FoxP3, which is the activation marker of Tregs. As a result, there is a positive correlation between serum IL-16 and FoxP3 expression. We believe that our study may contribute to the pathophysiology of diseases such as atopy, allergy, and autoimmunity, in which the immune system is deficient or malfunctioning, and to understanding the unclarified mechanism of IL-16 in the immune response.
This article is based on the master’s thesis of Durmus Burgucu.
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Animal and human rights statement
Funding: This study was supported by Akdeniz University Research Fund (Project No: 2006.02.0122.012)
Conflict of interest
1. Pinsonneault S, El Bassam S, Mazer B, Cruikshank WW, Laberge S. IL-16 inhibits IL-5 production by antigen-stimulated T cells in atopic subjects. J Allergy Clin Immunol. 2001; 107(3): 477-82.
2. Gantner F, Sakai K, Tusche MW, Cruikshank WW, Center DM, Bacon KB. Histamine h(4) and h(2) receptors control histamine-induced interleukin-16 release from human CD8(+) T cells. J Pharmacol Exp Ther. 2002; 303(1): 300-7.
3. De Bie JJ, Jonker EH, Henricks PA, Hoevenaars J, Little FF, Cruikshank WW, et al. Exogenous interleukin-16 inhibits antigen-induced airway hyper-reactivity, eosinophilia and Th2-type cytokine production in mice. Clin Exp Allergy. 2002; 32(11): 1651-8.
4. Bellini A, Yoshimura H, Vittori E, Marini M, Mattoli S. Bronchial epithelial cells of patients with asthma release chemoattractant factors for T lymphocytes. J Allergy Clin Immunol. 1993; 92(3): 412-24.
5. Biddison WE, Taub DD, Cruikshank WW, Center DM, Connor EW, Honma K. Chemokine and matrix metalloproteinase secretion by myelin proteolipid protein- specific CD8+ T cells: potential roles in inflammation. J Immunol. 1997; 158(7): 3046-53.
6. Walker MR, Kasprowicz DJ, Gersuk VH, Benard A, Van Landeghen M, Buckner JH, et al. Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T cells. J Clin Invest. 2003; 112(9): 1437-43.
7. McFadden C, Morgan R, Rahangdale S, Green D, Yamasaki H, Center D, et al. Preferential migration of T regulatory cells induced by IL-16. J Immunol. 2007; 179(10): 6439-45.
8. Conti P, Kempuraj D, Kandere K, Di Gioacchino M, Reale M, Barbacane RC, et al. Interleukin-16 network in inflammation and allergy. Allergy Asthma Proc. 2002; 23(2): 103-8.
9. Pullerits T, Lindén A, Malmhäll C, Lötvall J. Effect of seasonal allergen exposure on mucosal IL-16 and CD4+ cells in patients with allergic rhinitis. Allergy. 2001; 56(9): 871-87
10. Kramer MF, Ostertag P, Pfrogner E, Rasp G. Nasal IL-16 and MIP-1 alpha in late-phase allergic response. Allergy Asthma Proc. 2001; 22(3): 127-32.
11. Laberge S, Durham SR, Ghaffar O, Rak S, Center DM, Jacobson M, et al. Expression of IL-16 in allergen-induced late-phase nasal responses and relation to topical glucocorticosteroid treatment. J Allergy Clin Immunol. 1997; 100(4): 569-74.
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13. Deng G, Song X, Fujimoto S, Piccirillo CA, Nagai Y, Greene MI. Foxp3 Post- translational Modifications and Treg Suppressive Activity. Front Immunol. 2019; 10: 2486.
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Durmus Burgucu, Levent Undar. The relationship between IL-16 and Foxp3 expression in Treg cells of healthy individuals. Ann Clin Anal Med 2021;12(12):1393-1396
The role of monocyte to HDL-cholesterol ratio and neutrophil to lymphocyte ratio in metabolic syndrome
Serkan Karahan, Ertugrul Okuyan
Department of Cardiology, Health Sciences University, Bağcılar Training and Research Hospital, İstanbul, Turkey
DOI: 10.4328/ACAM.20776 Received: 2021-07-08 Accepted: 2021-08-20 Published Online: 2021-09-07 Printed: 2021-12-01 Ann Clin Anal Med 2021;12(12):1397-1400
Corresponding Author: Serkan Karahan, Department of Cardiology, Health Sciences University, Bağcılar Training and Research Hospital, 34200, İstanbul, Turkey. E-mail: email@example.com P: +90 532 159 44 01 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1203-7615
Aim: Metabolic syndrome (MetS) is characterized by a low-grade inflammatory condition that causes changes in noninvasive indices, namely the monocyte-to- high-density lipoprotein (HDL) ratio (MHR) and neutrophil-to-lymphocyte ratio (NLR), from which blood counts are derived. In our study, we aimed to evaluate systemic inflammatory markers in cases of MetS.
Material and Methods: A retrospective analysis of a population of 156 subjects (88 control subjects and 68 MetS patients) was performed in this study. Patients followed in our hospital with the diagnosis of MetS between June 2018 and June 2021 were included in the study. Demographic data of the patients, such as age and gender, and vital signs, lipid profiles, and complete blood count results at admission were recorded and analyzed.
Results: There were statistically significant differences between the MetS group and the control group in terms of age, gender, fasting blood glucose, hemoglobin, HDL, low-density lipoprotein (LDL), total cholesterol, triglycerides, white blood cell count, lymphocytes, and monocytes (p=0.008, p=0.024, p=0.001, p=0.022, p=0.034, p=0.001, p=0.001, p=0.001, p=0.001, and p=0.001, respectively). While the NLR was statistically significantly lower in the MetS group compared to the control group (p=0.001), the MHR was statistically significantly higher in the MetS group (p=0.001). There was a significant positive correlation between MetS and male gender, age, fasting blood glucose, white blood cell count, lymphocytes, monocytes, HDL, LDL, total cholesterol, triglycerides, MHR, and survival status. There was a significant negative correlation between MetS and NLR. There was a statistically significant difference in survival between the MetS group and the control group (p=0.019). Of all the patients included in this study, 16 (30.2%) patients in the MetS group and 9 (12.3%) in the control group died. The MHR was higher among deceased patients than survivors (p=0.001).
Discussion: The MHR and NLR, which are inexpensive markers that can be calculated easily in all centers, can be used in the evaluation of MetS and mortality.
Keywords: Metabolic Syndrome, Monocyte-to-HDL Ratio, Neutrophil-to-Lymphocyte Ratio, Mortality
Metabolic syndrome (MetS) is a systemic condition characterized by a wide range of clinical features such as central obesity, hypertension, and impaired glucose and lipid homeostasis . Various changes have been made to the definition of MetS over the last 20 years. In 2006, the International Diabetes Federation established some criteria to define MetS. These are fasting plasma glucose of ≥100 mg/dL (or drug therapy for high glucose), high-density lipoprotein (HDL) concentration of <40 mg/dL in men or <50 mg/dL in women (or drug therapy for dyslipidemia), triglycerides of ≥150 mg/dL (or drug therapy for high triglycerides), waist circumference of >94 cm in men or >80 cm in women, and systolic arterial pressure of ≥130 mmHg or diastolic blood pressure of ≥85 mmHg (or antihypertensive therapy) .
MetS is characterized by a low-grade inflammatory state caused by increased cytokine, chemokine, and adipokine production and abnormal activation of immune cells that collectively contribute to atherosclerotic plaque formation and non-alcoholic fatty liver disease [3, 4].
Recently, subtypes of leukocyte ratios (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to- monocyte ratio (LMR), and monocyte-to-HDL ratio (MHR)) have been recognized as markers of systemic inflammation . In addition, various studies have stated that there are relationships between NLR, PLR, LMR, MHR, and cardiovascular diseases such as peripheral arterial occlusive disease, coronary artery diseases (including myocardial infarction), atrial fibrillation, and aortic changes, but the relationship with MetS is still not fully established [6-8]. HDL cholesterol, on the other hand, abolishes the proinflammatory and pro-oxidant effects of monocytes by inhibiting the migration of macrophages. Therefore, MHR may indicate a patient’s inflammatory state . Previous studies have indicated that MHR may be a new cardiovascular prognostic marker [1-4, 10].
In our study, we aimed to evaluate systemic inflammatory markers in cases of MetS.
Material and Methods
This study was designed as a retrospective cohort study. Before the start of the study, the study protocol was approved by the local ethics committee of Medipol University hospital and the study was conducted in accordance with the ethical principles of the Declaration of Helsinki. A retrospective analysis of a population of 156 subjects (88 control subjects and 68 MetS patients) was performed. Patients followed in our hospital with the diagnosis of MetS between June 2018 and June 2021 were included in the study. Patient files were scanned through the hospital registry system, and patient data were retrospectively scanned and recorded.
Demographic data such as age and gender, vital signs, complete blood count results at admission (hemoglobin, neutrophils, platelets, lymphocytes, monocytes), lipid profiles (triglycerides, HDL, LDL), and smoking status were recorded and analyzed. Correlations of the NLR and the MHR with MetS were analyzed. Statistical Analysis
The data obtained in this study were analyzed using the statistical program SPSS 25 (IBM Corp., Armonk, NY, USA).
Descriptive statistics such as frequency distribution, mean, and standard deviation were used to evaluate the data. The difference between the means of two independent groups was compared with the Student t-test. The Mann-Whitney U test, which is a nonparametric alternative to that test, was used when parametric test assumptions were not met. Descriptive statistics were expressed with odds ratios and 95% confidence intervals (Cis). Receiver operating characteristic (ROC) curve analysis was used to determine the cut-off point, the area under the curve (AUC), the sensitivity, and the specificity of the data. Categorical data were analyzed with chi-square or Fisher exact tests. Values of p<0.05 were considered statistically significant at the 95% CI.
There were statistically significant differences between the MetS group and the control group in terms of age, gender, fasting blood glucose, hemoglobin, HDL, LDL, total cholesterol, triglycerides, white blood cell count, lymphocytes, and monocytes (p=0.008, p=0.024, p=0.001, p=0.022, p=0.034, p=0.001, p=0.001, p=0.001, p=0.001, and p=0.001, respectively) (Table 1). While the NLR was statistically significantly lower in the MetS group compared to the control group (p=0.001), the MHR was statistically significantly higher in the MetS group (p=0.001) (Table 1).
There was a statistically significant difference in survival between the MetS group and the control group (p=0.019) (Table 1). Of all patients included in this study, 16 (30.2%) patients in the MetS group and 9 (12.3%) in the control group died. The MHR was higher among deceased patients than survivors (p=0.001) (Table 1).
There was a significant positive correlation between MetS and male gender, age, fasting blood glucose, leukocytes, lymphocytes, monocytes, HDL, LDL, total cholesterol, triglycerides, MHR, and survival status. There was a significant negative correlation between MetS and NLR (Table 2). According to ROC analysis, MHR (AUC: 0.746, 95% CI: 0.655- 0.836, p=0.001) and NLR (AUC: 0.23, 95% CI: 0.138-0.333, p=0.001) were prognostic factors for MetS (Figure 1).
Of all patients included in this study, 16 (30.2%) patients in the MetS group and 9 (12.3%) in the control group died. The MHR was higher among deceased patients (0.041±0.01) than survivors (0.023±0.07) (p=0.001) (Figure 2).
In this study, we investigated the relationships of the obtained laboratory markers of MHR and NLR with MetS. MetS is a disease with significant morbidity and mortality, characterized by various risk factors such as central obesity, dyslipidemia, hypertension, hyperglycemia, and low-grade inflammatory state. Several studies have highlighted the role of inflammation in the development of MetS and atherosclerosis. The literature also suggests that the analysis of parameters that can be easily measured from peripheral complete blood count, such as NLR and MHR, could be useful in evaluating the chronic inflammatory state seen in MetS patients.
Inflammation is the most commonly suggested mechanism to explain the relationship between MetS and hematological parameters. Inflammation plays a primary role in the pathophysiology of MetS. In inflammatory diseases, the number of monocytes increases and HDL cholesterol levels decrease. Monocytes are a different type of leukocytes and they migrate to tissue macrophages and initiate inflammation. In previous studies, it was reported that the number of monocytes was associated with the prediction of coronary artery disease . On the other hand, HDL cholesterol inhibits the activation of monocytes, inhibits the conversion of monocytes into macrophages, and reduces inflammation. Thus, the combination of these two parameters in the MHR is thought to represent inflammatory processes. This relationship between monocytes and HDL cholesterol has prompted researchers to investigate whether MHR is more effective than monocyte count or HDL cholesterol alone in predicting cardiovascular events. Kanbay et al. reported that MHR acts as an independent predictor for cardiovascular events and increases in parallel with the decrease in estimated glomerular filtration rate in patients with chronic kidney disease . It has been suggested that MHR is associated with systemic infection and endothelial dysfunction and can be used as a new inflammation-based diagnostic and prognostic marker in cardiovascular diseases. In the study by Pamukcu and Aker, the MHR was associated with calcification of the mitral annulus . Yilmaz et al. reported that in the follow-up of patients with angina pectoris who had undergone percutaneous coronary bare-metal stent implantation, high values of preintervention MHR were found to be closely associated with in-stent restenosis . In addition, another recent study demonstrated a significant and independent association between MHR and saphenous vein graft disease in patients undergoing coronary bypass graft surgery . In our study, the MHR was found to be statistically significantly higher in the MetS group compared to the control group and significant positive correlations were found between MetS and male gender, age, fasting blood glucose, leukocytes, lymphocytes, monocytes, HDL, LDL, total cholesterol, triglycerides, MHR, and survival status. In ROC analysis, MHR was found to be a prognostic factor for MetS. In addition, 16 patients (30.2%) in the MetS group and 9 (12.3%) in the control group died among all patients included in this study. The MHR was higher among the deceased patients (0.041±0.01) than the survivors (0.023±0.07).
The NLR has also been proposed as a surrogate marker for inflammation in different populations and it has prognostic and predictive value [1, 4, 10, 16]. Yue et al. reported the predictive value of the NLR in cases of diabetic retinopathy . Additionally, in a study involving cases of acute pulmonary embolism, low NLR was found to be an independent predictor of in-hospital and short-term mortality . NLR was also observed to be associated with vascular pathologies such as coronary artery and peripheral vascular diseases . In another study, it was demonstrated that there was a significant negative correlation between coronary slow flow and NLR value . In our study, the NLR was statistically significantly lower in the MetS group compared to the control group while there was a significant negative correlation between MetS and NLR. In ROC analysis, the NLR was found to be a prognostic factor for MetS.
This study has some limitations. It was designed as an observational, retrospective, and single-center study. In addition, repeating the MHR and NLR measurements at regular intervals would likely affect the results. We were unable to compare the MHR and NLR with other markers used in cases of MetS. More extensive studies are needed to further elucidate these relationships.
We suggest that the MHR and NLR, as inexpensive markers that can be easily calculated in all centers, can be used in the evaluation of MetS and mortality. The results of our study should be supported by multicenter and larger patient groups.
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Conflict of interest
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2. Abaci A, Kilickap M, Goksuluk H, Karaaslan D, Barcin C, Kayikcioglu M, et al. [Data on prevalence of metabolic syndrome in Turkey: Systematic review, meta- analysis and meta-regression of epidemiological studies on cardiovascular risk factors]. Turk Kardiyol Dern Ars. 2018;46(7):591-601.
3. Al Saudi RM, Kasabri V, Naffa R, Bulatova N, Bustanji Y. Glycated LDL-C and glycated HDL-C in association with adiposity, blood and atherogenicity indices in metabolic syndrome patients with and without prediabetes. Ther Adv Endocrinol Metab. 2018;9(10):311-23.
4. Battaglia S, Scialpi N, Berardi E, Antonica G, Suppressa P, Diella FA, et al. Gender, BMI and fasting hyperglycaemia influence Monocyte to-HDL ratio (MHR) index in metabolic subjects. PLoS One. 2020;15(4):e0231927.
5. Karahan S, Okuyan E. Systemic Inflammatory Index and Platelet-to- Lymphocyte Ratio Predicted Mortality in patients with Acute Myocardial Infarction. Experimental Applied Medical Science. 2021;2(2):146-53.
6. Konstantinides SV, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D, Galie N, et al. 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J. 2014;35(43):3033-69, 69a-69k.
7. Alper S, Ulu MS, Kazan S, Tunca O, Kazan ED. Comparison Of Monocyte/HDL Ratio In Routine Hemodialysis And Peritoneal Dialysis Patients. Dicle Tıp Dergisi. 2020;47(1):139-7.
8. Marongiu F, Mameli A, Grandone E, Barcellona D. Pulmonary Thrombosis: A Clinical Pathological Entity Distinct from Pulmonary Embolism? Semin Thromb Hemost. 2019;45(8):778-83.
9. Varol S, Karahan S, Okuyan E. Monocyte High-Density Lipoprotein cholesterol Ratio and coronary collateral circulation development in patients with stable coronary artery disease and no history of revascularization. The Medical Journal Of Haydarpaşa Numune Training Research Hospital. 2021;63(2):0-.
10. Jialal I, Jialal G, Adams-Huet B, Ramakrishnan N. Neutrophil and monocyte ratios to high-density lipoprotein-cholesterol and adiponectin as biomarkers of nascent metabolic syndrome. Horm Mol Biol Clin Investig. 2020;41(2).
11. Zeynalova S, Bucksch K, Scholz M, Yahiaoui-Doktor M, Gross M, Loffler M, et al. Monocyte subtype counts are associated with 10-year cardiovascular disease risk as determined by the Framingham Risk Score among subjects of the LIFE- Adult study. PLoS One. 2021;16(3):e0247480.
12. Kanbay M, Solak Y, Unal HU, Kurt YG, Gok M, Cetinkaya H, et al. Monocyte count/HDL cholesterol ratio and cardiovascular events in patients with chronic kidney disease. Int Urol Nephrol. 2014;46(8):1619-25.
13. Pamukcu HE, Aker M. Association between monocyte to HDL cholesterol ratio and mitral annulus calcification. Journal of Surgery Medicine. 2019;3(1):44-8.
14. Yilmaz S, Akboga MK, Sen F, Balci KG, Aras D, Temizhan A, et al. Usefulness of the monocyte-to-high-density lipoprotein cholesterol ratio to predict bare metal stent restenosis. Biomark Med. 2016;10(9):959-66.
15. Akboga MK, Yayla C, Balci KG, Ozeke O, Maden O, Kisacik H, et al. Relationship between Serum Albumin Level and Monocyte-to-High-Density Lipoprotein Cholesterol Ratio with Saphenous Vein Graft Disease in Coronary Bypass. Thorac Cardiovasc Surg. 2017;65(4):315-21.
16. Sefil F, Ulutas KT, Dokuyucu R, Sumbul AT, Yengil E, Yagiz AE, et al. Investigation of neutrophil lymphocyte ratio and blood glucose regulation in patients with type 2 diabetes mellitus. J Int Med Res. 2014;42(2):581-8.
17. Yue S, Zhang J, Wu J, Teng W, Liu L, Chen L. Use of the Monocyte-to- Lymphocyte Ratio to Predict Diabetic Retinopathy. Int J Environ Res Public Health. 2015;12(8):10009-19.
18. Ertem AG, Yayla C, Acar B, Kirbas O, Unal S, Uzel Sener M, et al. Relation between lymphocyte to monocyte ratio and short-term mortality in patients with acute pulmonary embolism. Clin Respir J. 2018;12(2):580-6.
19. Gary T, Pichler M, Belaj K, Eller P, Hafner F, Gerger A, et al. Lymphocyte-to- monocyte ratio: a novel marker for critical limb ischemia in PAOD patients. Int J Clin Pract. 2014;68(12):1483-7.
20. Yayla C, Akboga MK, Gayretli Yayla K, Ertem AG, Efe TH, Sen F, et al. A novel marker of inflammation in patients with slow coronary flow: lymphocyte-to- monocyte ratio. Biomark Med. 2016;10(5):485-93.
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Serkan Karahan, Ertugrul Okuyan. Evaluation of systemic inflammatory markers in metabolic syndrome. Ann Clin Anal Med 2021;12(12):1397-1400
Pathological factors affecting morbidity in breast cancer with modified radical mastectomy after neoadjuvant therapy
Murat Kartal 1, Tolga Kalaycı 1, Ahmet Erkan Bilici 2
1 Department of General Surgery, 2 Department of Pathology, Erzurum Regional Education and Research Hospital, Erzurum, Turkey
DOI: 10.4328/ACAM.20780 Received: 2021-07-11 Accepted: 2021-08-20 Published Online: 2021-09-14 Printed: 2021-12-01 Ann Clin Anal Med 2021;12(12):1401-1405
Corresponding Author: Murat Kartal, Erzurum Regional Education and Research Hospital, Erzurum, Turkey. E-mail: firstname.lastname@example.org P: +90 507 191 96 09 Corresponding Author ORCID ID: https://orcid.org/0000-0003-1396-5365
Aim: The aim of this study is to investigate the pathological factors causing postoperative complications in breast cancer patients who underwent modified radical mastectomy (MRM) after neoadjuvant therapy.
Material and Methods: Breast cancer patients who underwent MRM after neoadjuvant therapy in our clinic between 2015 and 2020 were retrospectively included in the study. The relationship between pathological parameters and postoperative complications was evaluated using Mann-Whitney U tests, independent sample t-tests, and chi-square tests and p<0.05 was considered significant.
Results: There were 21 patients meeting the study criteria. The mean age of all patients was 48.76±13.98 years (range: 29-88). Morbidity developed in 7 cases (33.3%) and the average length of stay in the hospital was 11.90±4.49 days (range: 6-20). Morbidity increased in patients with advanced age (p=0.003) and cases with microcalcification (p=0.026) and neural invasion (p=0.017) in pathological evaluation, while morbidity decreased in cases with a high mean number of reactive lymph nodes (p=0.05). In addition, seroma formation was increased in patients with advanced age and microcalcification. None of the pathological factors affected hematoma formation or surgical site infection.
Discussion: According to the results of our study, we recommend harvesting reactive axillary lymph nodes as much as possible to reduce morbidity. In addition, it should be kept in mind that morbidity may increase in patients with microcalcification and neural invasion in preoperative imaging and at advanced ages.
Keywords: Advanced Age, Microcalcification, Modified Radical Mastectomy, Morbidity, Reactive Lymph Node
Carcinoma of the breast is one of the most common malignancies. In light of the Cancer Statistics 2021 report of Siegel et al., 284,200 new breast cancer cases were expected to be seen in the United States. The same report also predicted that approximately 44,130 people would die due to breast cancer in the United States . The treatment of breast cancer is managed with multidisciplinary approaches. These approaches include surgery, radiotherapy, chemotherapy, hormone therapy, immunotherapy, and their combinations.
Preoperative tumor staging is the most important factor in deciding on treatment. Diagnostic imaging work-up and mass biopsy play important roles in establishing a diagnosis and informing surgical decisions on the management of the primary tumor, staging of the axilla, and the sequence of therapy . Once a diagnosis of breast cancer is established, the extent of disease is assessed, which, for the most part, determines whether or not preoperative (neoadjuvant) systemic therapy is indicated. For advanced-stage tumors, systemic therapy, also known as neoadjuvant treatment, is administered as the initial treatment to reduce tumor volume and will render approximately 80% of patients operable . Based on the evaluation after neoadjuvant treatment, modified radical mastectomy (MRM) is one of the surgical options.
Seroma, hematoma, wound infection, flap necrosis, pain, and edema of the hand are the main complications of MRM. Post- mastectomy complication rates are variable. In the study of Browne et al., the overall complication rate was 10.1% for patients undergoing mastectomy without reconstruction . On the other hand, in the study by Berry et al., the total complication rate after mastectomy was 32.5% .
The aim of this study is to investigate the possible pathological factors increasing postoperative complications in breast cancer patients who underwent MRM after neoadjuvant therapy.
Material and Methods
Patients undergoing MRM for breast cancer after neoadjuvant therapy between 2015 and 2020 at Erzurum Regional Education and Research Hospital, Erzurum, Turkey were included in the study. Patients who were diagnosed and treated at external centers before admission to our center and patients who underwent bilateral MRM were excluded from the study. Patients’ hospital records, consultation and operation notes, pathology reports, and clinical charts were used. Each patient’s demographical data (gender, age), tumor localization, pathology reports, and postoperative complications were examined. In pathology reports, hormone receptor status, lymphatic and vascular invasion status, presence of microcalcification, presence of axillary lymph nodes (reactive, metastatic, total), and lymph node ratio were investigated. The TNM stage was defined according to the American Joint Committee on Cancer (Version 8) guidelines for breast cancer. The relationships between pathological parameters and postoperative complications and their subgroups were evaluated.
Statistical evaluations were carried out using SPSS 22.0 (IBM Corp., Armonk, NY, USA). The normality distributions of quantitative variables were checked using the Shapiro-Wilk test.
Either an independent t-test or Mann-Whitney U test was used according to the results of the Shapiro-Wilk test. The chi-square test was used to compare qualitative variables. Differences with p-values below 0.05 were considered statistically significant. Ethical approval was obtained from the Noninvasive Clinical Research Ethics Committee of Erzurum Regional Education and Research Hospital, Erzurum, Turkey (Decision Number: 2021/12-206).
There were 21 patients meeting the study criteria. The mean age of all patients was 48.76±13.98 years (range: 29- 88). Thirteen (61.9%) had a tumor located in the left breast. Complications in the first 30 days after surgery were defined as morbidity. Morbidity developed in 7 patients (33.3%) (seroma in 5 patients, hematoma in the axillary region in 1 patient, and wound infection in 1 patient), and the average length of stay in the hospital was 11.90±4.49 days (range: 6-20).
In the pathological examination of the patients, the mean tumor diameter was 31.23±13.04 mm (range: 10-65). The most common pathological T stage was T2 at 81%, while the most common pathological N stage was N0 at 47.6%. On the other hand, in the evaluation of patients with advanced imaging tools, 6 patients had distant metastasis (M1 stage). There were axillary metastatic lymph nodes in 11 cases (52.4%) with a mean diameter of 2.85±3.53 mm (range: 0-12). The pathological data of the patients are shown in Table 1.
Morbidity increased in patients with advanced age (p=0.003) and those with microcalcification (p=0.026) and neural invasion (p=0.017) in pathological evaluation, while morbidity decreased in cases of a high mean number of reactive lymph nodes (p=0.05). In addition, postoperative seroma after MRM affected advanced age (p=0.019) and presence of microcalcification in the pathology specimen. Neither postoperative hematoma nor surgical site infection was affected by the parameters investigated. The comparison of the patients according to the presence of morbidity is shown in Table 2 and the comparison according to seroma is shown in Table 3.
Breast cancer is a global health problem all over the world. In suitable cases, the main treatment is mastectomy with or without axillary lymph node dissection. However, for advanced- stage diseases, the first step of treatment is chemotherapy. After the chemotherapy process, patients are mostly scheduled for MRM .
The rate of postoperative complications after mastectomy ranges widely from 8% to 26% . The most common complications following MRM are seroma, lymphedema, infection, and wound necrosis . Postoperative complications cause a prolonged hospital stay and add psychological and economic burdens for the patient. Therefore, it is important to know the factors that prevent complications. In this study, we have evaluated morbidity in a different way, aiming to show the pathological factors that prevent morbidity.
Seroma is one of the most common complications after mastectomy with an incidence of 3% to 85% . The seroma prevalence in this study was 23.8%. Some authors believe that seroma occurs due to acute inflammatory exudates in response to surgical trauma and the acute phase of wound healing . During dissection, some lymph pathways are opened and lymph fluid leaks out. The leaking lymph fluid accumulates in the spaces where the adhesion of the skin flaps is difficult, especially in the axilla. Generally, seroma accumulates in the first 2 weeks postoperatively and then begins to resorb after being stable in the next 2-3 weeks. The controllable predictive factors for seroma formation are still unknown. Although the results are inconsistent, some factors affecting seroma formation have been reported. Can-Özkan et al. showed in their study that no statistical correlation was found between age, tumor diameter, or number of lymph nodes removed and seroma development . However, in this study, seroma after mastectomy was mostly seen at older ages and the prevalence of seroma was in keeping with the literature range.
The roles of preoperative factors like age, obesity, and hypertension in seroma formation were studied with conflicting results. In the study of Garzali and El-Yakub, patients with higher body mass index had higher risk of seroma . Intraoperative factors studied include the extent of dissection and the choice of dissector. Extensive axillary dissection and the use of electrocautery for dissection have been found to be significant in the development of seroma. Postoperative factors like short duration of drainage less than 10 days and early shoulder exercise have been associated with postmastectomy seroma. On the other hand, Pan et al. showed that neither tumor diameter nor presence of axillary lymph node metastasis affected postoperative seroma, as was seen in our study . Suresh et al. showed that patients older than 40 years, those with tumor sizes above 30 mm, patients with more than 5 metastatic lymph nodes harvested, and those with total lymph node count above 20 had a higher probability of seroma in their study . Petrek et al. found that the number and extent of axillary lymph node involvement were the most significant factors in the causation of seroma . Unlike previous studies, neither tumor size nor lymph node parameters were seen to affect seroma formation in the present report. In contrast to other studies in the English-language literature, we found that the presence of microcalcification in pathological specimens was a poor prognosis factor for seroma development after mastectomy.
Hematoma after mastectomy occurs in 2% to 10% of all mastectomy cases. Our study’s hematoma rate was 4.76%. The widespread use of electronic devices has reduced the incidence of hematoma formation . Seth et al. found that age difference, tumor size, tumor localization, and lymph node number had no effects on postoperative hematoma, as did the present study.
Breast surgeries are considered essentially clean surgeries and do not require antibiotic treatment. Incidence rates for postoperative wound infections are variable and range from 3% to 19% . Our study’s surgical site infection rate was 4.76%. Predisposing factors for infection include seroma, separation in the wound, thin skin flaps that may have limited nutrition, impaired lymphatic drainage around the axilla, advanced age, diabetes, malnutrition, and possible host defense mechanisms [18-20]. In the study conducted by Nieto et el., patients with advanced age had a higher rate of surgical site infections . However, age was not a factor affecting the surgical site infection rate in our sample.
Complications after mastectomy are problems that every surgeon may encounter. As in our study, seroma is the most common morbidity following mastectomy. Advanced age is a poor prognosis factor for both overall morbidity and seroma formation. The presence of neural invasion and microcalcification had negative effects on overall morbidity, while the presence of microcalcification alone had a negative effect on seroma formation. However, the number of reactive lymph nodes harvested showed a protective effect on morbidity. None of the pathological factors affected hematoma formation or surgical site infection. To date, there has not been a study evaluating the relationship between pathological factors and morbidity and morbidity subgroups, and further studies with larger numbers of cases are needed.
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Conflict of interest
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4. Browne JP, Jeevan R, Gulliver-Clarke C, Pereira J, Caddy CM, van der Meulen JH. The association between complications and quality of life after mastectomy and breast reconstruction for breast cancer. Cancer. 2017;123(18):3460-7.
5. Berry T, Brooks S, Sydow N, Djohan R, Nutter B, Lyons J, et al. Complication rates of radiation on tissue expander and autologous tissue breast reconstruction. Annals of surgical oncology. 2010;17(3):202-10.
6. Staradub VL, Morrow M. Modified radical mastectomy with knife technique. Archives of Surgery. 2002;137(1):105-10.
7. Chandrakar N, Shinde RK. Study the early complications of modified radical mastectomy performed. International Surgery Journal. 2018;6(1):239-43.
8. Obadiel YA. Early Complications Following Modified Radical Mastectomy— Among Breast Cancer Patients Admitted to AL Gomhory Teaching Hospital, Sana’a, Yemen between Jan. 2019-Jan. 2020. Open Access Library Journal. 2020;7(12):1.
9. Kumar S, Lal B, Misra M. Post-mastectomy seroma: a new look into the aetiology of an old problem. Journal of the Royal College of Surgeons of Edinburgh. 1995;40(5):292-4.
10. AboAmra M. Seroma formation after modified radical mastectomy. Al-Azhar Assiut Medical Journal. 2017;15(4):168.
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12. Garzali IU, El-Yakub AI. Factors affecting seroma formation after mastectomy among West African patients: a single center experience in North West Nigeria. PAMJ-Clinical Medicine. 2020;3(174):1-6.
13. Pan X-F, Huan J-L, Qin X-J. Potential risk factors for the development of seroma following mastectomy with axillary dissection. Molecular and clinical oncology. 2015;3(1):222-6.
14. Suresh B, Sachin H, Naidu M, Gopalkrishna V. A study to evaluate the factors influencing seroma formation after breast cancer surgery at tertiary care centre. International Surgery Journal. 2018;6(1):278-82.
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Download attachments: 10.4328:ACAM.20780
Murat Kartal, Tolga Kalaycı, Ahmet Erkan Bilici. Pathological factors affecting morbidity in breast cancer with modified radical mastectomy after neoadjuvant therapy. Ann Clin Anal Med 2021;12(12):1401-1405
Endovascular treatment of central thoracic venous stenosis and occlusion in hemodialysis patients
Erdem Birgi, Onur Ergun, Hasanali Durmaz, Azad Hekimoğlu, Işık Conkbayır, Baki Hekimoğlu
Department of Radiology, University of Health Sciences, Diskapi Yildirim Beyazit Training and Research Hospital, Ankara, Turkey
DOI: 10.4328/ACAM.20781 Received: 2021-07 Accepted: 2021-08-20 Published Online: 2021-09-12 Printed: 2021-12-01 Ann Clin Anal Med 2021;12(12):1406-1410
Corresponding Author: Erdem Birgi, University of Health Sciences, Diskapi Yildirim Beyazit Training and Research Hospital, Department of Radiology, Şehit Ömer Halisdemir Street, No: 20, 06110, Ankara, Turkey. E-mail: email@example.com P: +90 536 574 43 22 Corresponding Author ORCID ID: https://orcid.org/0000-0001-7808-7300
Aim: This study aims to present the endovascular treatment of symptomatic central venous stenosis or occlusion in patients with ipsilateral native arteriovenous fistula or graft.
Material and methods: A total of 21 patients with central venous disease were reviewed retrospectively. The patients were referred with swelling in the arm, neck, or both and inadequate or unsuccessful dialysis sessions. The location, length, and extension of the stenosis/occlusion were evaluated by diagnostic venography and angioplasty with or without stenting was performed. The patients were monitored until the termination of follow-up, renal transplantation, complete loss of ipsilateral vascular access, or death.
Results: The technical success rate was 90.5%. The mean follow-up period for the patients who received successful treatment was 12.53 months. The primary patency rates at 3, 6, and 12 months were 89.4%, 61.1%, and 50%, respectively.
Discussion: Endovascular interventions performed in cases of central venous occlusion and stenosis are technically successful, safe, and effective in terms of short-term results. However, patients should be under close follow-up and be prepared for repetitive interventions due to low patency rates in the long term. To prevent the emergence of central venous pathologies, unnecessary, prolonged, and repetitive central venous catheterizations should be avoided.
Keywords: Arteriovenous Fistulas, Balloon Angioplasty, Endovascular Procedures, Stents, Veins
Central venous stenosis and occlusion, defined as central venous disease (CVD), occurs as a result of venous intimal hyperplasia of over 50% in the superior and inferior vena cava, internal jugular, subclavian, or brachiocephalic veins and is one of the most important causes of vascular access dysfunction in patients undergoing hemodialysis via arteriovenous fistula or graft (AVF/AVG) for a prolonged duration [1, 2]. Although CVD can be seen at rates between 1.5% and 17% in patients undergoing dialysis, rates as high as 40% have been reported in some series [3-5].
The most important causes include central venous damage resulting from long-term catheterization and hemodynamic stress secondary to the high flow caused by AVF/AVG . Today, the first choice in the treatment of central venous pathologies is the endovascular method, which includes percutaneous transluminal angioplasty (PTA), bare stents, and covered stents . However, there is no consensus on which option is optimal.
This study aims to share our experience in the endovascular treatment of central venous disease in patients with ipsilateral native AVF suffering arm or neck swelling accompanying dialysis difficulty.
Material and Methods
This retrospective study was approved by the ethics committee of our hospital. All patients included in the study were informed verbally and in writing before the procedure was commenced, and their consent was obtained. The study was conducted in accordance with the Declaration of Helsinki.
In this study, patients who underwent endovascular treatment due to central venous stenosis or occlusion in our interventional radiology unit between 2012 and 2020 were reviewed.
The patients were referred to us from in-hospital and less commonly out-of-hospital dialysis centers after experiencing severe swelling in the relevant arm, neck, or both and inadequate or unsuccessful dialysis sessions.
The inclusion criteria were undergoing dialysis via AVF/AVG due to CKD and the presence of symptomatic central venous stenosis or occlusion. Patients who did not have AVF/AVG but developed central venous stenosis secondary to central venous catheterization and dialysis patients with fistula dysfunction but no central venous pathology were excluded from the study. A total of 21 patients, of whom 16 were men (76.2%) and five were women (23.8%), were included in the study based on the aforesaid inclusion criteria, and their mean age was 60.29 years (range: 35-86 years, SD: 13.39).
Diagnosis and treatment
Before the procedure, arteriovenous Doppler US examination of the upper extremity with AVF was carried out for all patients. Patients with no fistula-level or peripheral vascular pathology but suspected of central venous pathology were referred for venography for further examination.
For venography, images were obtained under fluoroscopy (Siemens Artis Zee, Erlangen, Germany) with the manual injection of 20 mL of contrast agent after achieving appropriate venous cannulation from the relevant extremity.
Venous access was performed under US and local anesthesia (5-10 mL, 2% lidocaine) with a single puncture. A 5-French (F) or 6-F vascular sheath (Cordis Corp., Switzerland) was initially placed for diagnostic venography. The location, length, and extension of the stenosis/occlusion were evaluated in diagnostic venography. While upper extremity access was sufficient in patients with stenosis, femoral venous access was also used to show the length and extension of the occlusion in cases of occluded lesions. The stenotic or occluded segment was first attempted to be passed primarily through a 5-F vertebral catheter (Penty, Barty Medical, China) or a 0.035-inch support catheter (Rubicon 35, Boston Scientific, USA) using a 0.035- inch straight-tipped hydrophilic coated guidewire (Glidewire®, Terumo, Japan). A 0.035-inch, stiff-body occlusion wire (Roadrunner® PC Hydrophilic Wire Guide, Cook Medical, USA) with hydrophilic and stiff features was used for patients with failed attempts and chronic occlusion. In cases where this wire- catheter combination failed, the combination of a 0.018-inch support catheter (CXI Support Catheter, 2.6 F, Cook Medical, USA) and a 0.018-inch straight-tipped wire (V-18 Control Wire, Boston Scientific, USA) was used. In cases where the proximal or distal part of the occlusion could not be passed, another attempt was always made on the other side. After ensuring that the correct lumen was accessed based on the contrast agent upon the passage of the lesion, the access was secured with a 0.035-inch exchange stiff guidewire (Amplatz Super Stiff, Boston Scientific, USA). At this stage, a vascular sheath of 7-10 F was placed over the existing stiff wire in accordance with the diameter of the balloon, stent, or both to be used. To facilitate the passage of large-diameter balloons through occlusions, first, pre-dilatation was performed using small-diameter (4-6 mm) balloons. Then the PTA (XXLTM, Boston Scientific, USA/Armada 35, Abbott, USA) was applied 2 or 3 consecutive times, each lasting at least 2 minutes, using balloon catheters of 1-2 mm wider than the adjacent patent vessel (8-18 mm, most often 12 mm). The patency degree and possible complications such as extravasation were checked in angiograms after PTA (Figures 1). In patients found to have residual stenosis of >50% in the lumen, a self-expandable bare stent of the same diameter or 2 mm wider than the first balloon catheter was placed (EpicTM Vascular, Boston Scientific, USA/Venous WallstentTM, Boston Scientific, USA), depending on the location and extension of the lesion. During the procedures, 3000 units of intravenous unfractionated heparin were administered. Anticoagulant or antiplatelet therapy was not given to the patients after the procedure.
The patients were monitored until the termination of their follow-up by our hospital, renal transplantation, complete loss of ipsilateral vascular access, or death.
No significant residual stenosis (>30%) after the procedure and completion of the treatment without complications were defined as technical success, non-passable lesions as technical failure, and primary patency as the continuous patency interval from the first procedure to the next endovascular intervention. The classification system of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) was used to assess the complications .
Numerical data were presented as average, standard deviation, median, maximum, and minimum, while categorical data were pre¬sented as number and percentage. Editing and analysis of statistical data were per¬formed using SPSS 25.0 (IBM Corp., USA).
All 21 patients included in the study presented with AVF/AVG; upper extremity, neck, or chest swelling; and difficulty in dialysis. The right side was affected in seven patients (33.3%) and the left in 14 patients (66.7%). The brachiocephalic vein was the most affected vein, either alone or in combination with other veins in 76.2% of the patients (16/21). In 23.8% of the patients (5/21), the subclavian vein was involved alone. After diagnostic venography, 61.9% of the patients had occlusion (13/21) and 38.1% had stenosis (8/21). Stenoses were in one segment in six patients (75%) and were multiple in two patients (25%). In- stent stenosis was observed in five of the previously treated patients (Figures 2 and 3). The mean occlusion segment length was found to be 3.31 cm in patients with occlusion (range: 2-8 cm, SD: 1.75).
Five (26.3%) of the 19 patients who were successfully treated within the scope of the study received more than one intervention in different sessions. The vast majority (80%) of those who underwent more than one procedure consisted of patients who were stented previously. In two patients with central venous occlusion, although attempts were made to pass through the occluded segments using combinations of the upper extremity and femoral venous access, the procedure was unsuccessful because the occlusion could not be passed through. A total of 30 procedures performed in the remaining 19 patients were successful. Based on the initial procedure performed, the technical success rate was calculated to be 90.5% (19/21).
Before the first session treatments, only PTA was applied in seven of the eight stenoses detected by venography, and PTA with stent was applied in the remaining one stenosis. Only PTA was applied in seven of the 11 occlusions, and PTA with stent was applied in the remaining four occlusions. When repeated attempts were also considered, of all the 30 procedures, only PTA was applied in 19 and PTA with stent in 11.
In addition to being treated for central venous stenosis or occlusion, during the repeated attempts made before or after the first session, a total of three different patients also underwent thrombolytic therapy along with PTA for a thrombus in the fistula efferent vein.
The mean follow-up period for the 19 patients who received successful treatment was 12.53 months (range: 4-29 months, SD: 6.69), and the primary patency rates of the patients who received endovascular treatment (only PTA and PTA + stent) at 3, 6, and 12 months were 89.4%, 61.1%, and 50%, respectively, according to short-term follow-up results.
No minor or major complications were encountered during the endovascular treatment or follow-up of the patients included in the study. The demographic information of the patients and the data concerning their central venous lesions and the procedure are summarized in Table 1.
CVD often occurs as a complication of central venous catheterization and interrupts dialysis sessions from the ipsilateral upper extremity AVG/AVF . Central venous damage secondary to venous catheterization and the subsequent inflammatory response trigger intimal hyperplasia, resulting in central venous pathology .
Cannulation of the subclavian veins results in 50% stenosis, and the right internal jugular vein has the lowest rate among the central veins. Therefore, it is necessary to avoid subclavian vein catheterization in patients with AVF/AVG or those that are likely to be accessed through AVF/AVG in the future [9-11]. In our study, it was found that subclavian vein involvement was less common than involvement of other central thoracic veins, which might be because more attention is recently being paid to this issue during central venous catheterization. In their study, Nael et al. encountered central venous occlusion at a rate of 11% in venography performed for patients with dialysis dysfunction and reported that they reached this low rate by preventing subclavian vein catheterization .
Primary patency rates after surgical reconstruction of mediastinal veins in hemodialysis patients are better than those of endovascular treatments; they are reported to be 80- 90% for one year. However, these major surgical interventions are often difficult to apply in this group of patients who already suffer from many comorbid diseases .
Today, endovascular treatments have satisfactory results in addition to being less invasive and having high rates of technical success. Although there is no clear consensus on the optimal option in the treatment of central venous pathologies, the primary treatment method recommended for central venous lesions is percutaneous angioplasty [6, 13]. Inadequate flow during the post-PTA procedure or early postop period is a valid indication for stent placement .
PTA and stenting paradoxically cause venous neointimal hyperplasia in the long term. Efforts to prevent this are increasing in interventional treatments, and the use of covered stents and paclitaxel-coated balloons has gained prominence with the aim of improving long-term patency .
There are many studies in the literature comparing PTA and stenting retrospectively. In these studies, the primary patency rates of the different techniques were compared and there was no consensus on which method was better due to the lack of randomized controlled studies on this subject. The primary patency rates of only PTA were reported to be 58%, 23-63%, and 12-53% at 3, 6, and 12 months, respectively, while the primary patency rates of bare stents were 63-100%, 42-89%, and 14-73% at 3, 6, and 12 months, respectively [15-17]. Among the reasons for the difference in the patency rates in different studies is that the protocols applied, stent types used, study populations, and the treated veins differ . Based on these results, we agree that it would be better to consider endovascular treatment as a complete therapy where ballooning, bare stenting, and covered stenting are used. The treatment decision should be made on a case-by-case basis by considering the patient’s previous intervention history, the location and extension of the existing lesion, the presence of residue after the procedure, and the clinical state of the patient. Following the successful endovascular treatments in our study, the 3-month, 6-month, and 12-month primary patency rates were calculated to be 89.4%, 61.1%, and 50%, respectively. The National Kidney Foundation Disease Outcomes Initiative (KDOQI) guidelines published in 2006 recommend PTA as the preferred method regardless of whether a stent is subsequently placed . While deciding on the endovascular treatment in central venous lesions, as recommended by most authors and guidelines and in line with the principle of “leave nothing behind,” we believe that the primary treatment should always be PTA. Ozyer et al. reported that the number of repeated attempts was higher in stenting than in ballooning and that stenting should be used not as a primary treatment method but only in resistant or recurrent lesions after PTA . Similarly, in our study, the number of repeated attempts was higher in patients who underwent stenting. However, this difference could be attributed to the fact that stenoses that require stents tend to be more resistant.
Technical success in the recanalization of central veins has been reported to be over 90% in most studies . We found a similarly high rate of 90.5% in our study.
The self-expandable stent options used in our treatment were first-generation wall stents and second-generation nitinol stents. Nitinol stents have high flexibility and are resistant to kink development. In two different studies, it was reported that there was no significant difference between wall stents and nitinol stents [20, 21].
In some studies, it has been shown that nitinol stents have better patency rates than wall stents [8, 22]. In a recent study, Gür et al. showed that when compared with steel stents, nitinol stents have significantly longer primary and secondary patency results . On the other hand, it has been reported that covered stents potentially reduce the intimal hyperplastic response, but there are not enough studies in the literature regarding their efficacy .
Extravasation of the contrast agent while trying to pass through the segment in the occlusion with the guidewire by resorting to difficult manipulations is a pathology in favor of local venous rupture, and it regresses spontaneously in most patients without the need for additional intervention. Late complications include stent fracture, which occurs mainly when the stent is inserted to the subclavian vein at the level of the clavicle, and stent migration due to stenting with inappropriate sizes. Stent fracture can be prevented by preferring self-expandable nitinol stents with high radial strength, while stent migration can be prevented by adequately oversizing the measured vein diameter [2-6].
One limitation of our study is that the number of patients for whom only PTA was applied and the number of patients who were stented along with PTA were insufficient for comparison. Also, due to the lack of long-term follow-up data, only short- term patency rates of the patients could be calculated. Conclusion
Endovascular interventions performed in cases of central venous occlusion and stenosis are technically successful, safe in terms of complications, and effective in terms of short-term results. These patients should be under close follow-up and be prepared for repetitive interventions due to low patency rates in the long term. Additionally, to prevent the emergence of central venous pathologies, unnecessary, prolonged, and repetitive central venous catheterizations should be avoided.
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Conflict of interest
1. Modabber M, Kundu S. Central venous disease in hemodialysis patients: an update. Cardiovasc Intervent Radiol 2013; 36(4): 898-903.
2. Yadav MK, Sharma M, Lal A, Gupta V, Sharma A, Khandelwal N. Endovascular treatment of central venous obstruction as a complication of prolonged hemodialysis – Preliminary experience in a tertiary care center. Indian J Radiol Imaging 2015; 25(4): 368-74.
3. Hernandez D, Diaz F, Rufino M, Lorenzo V, Rodriguez A, De Bonis E, et al. Subclavian vascular access stenosis in dialysis patients: natural history and risk factors. J Am Soc Nephrol 1998; 9: 1507-10.
4. Lumsden AB, MacDonald MJ, Isiklar H, Martin LG, Kikeri D, Harker LA, et al. Central venous stenosis in the hemodialysis patient: incidence and efficacy of endovascular treatment. Cardiovasc Surg 1997; 5: 504-9.
5. Schillinger F, Schillinger D, Montagnac R, Milcent T. Central venous stenosis in hemodialysis: comparative angiographic study of subclavian and internal jugular access. Nephrologie 1994; 15: 129-31.
6. Aj A, Razak Uk A, R P, Pai U, M S. Percutaneous intervention for symptomatic central vein stenosis in patients with upper limb arteriovenous dialysis access. Indian Heart J 2018; 70(5): 690-8.
7. Filippiadis DK, Binkert C, Pellerin O, Hoffmann RT, Krajina A, Pereira PL. Cirse Quality Assurance Document and Standards for Classification of Complications: The Cirse Classification System. Cardiovasc Interv Radiol 2017; 40(8): 1141-6.
8. Gür S, Oğuzkurt L, Gedikoğlu M. Central venous occlusion in hemodialysis access: Comparison between percutaneous transluminal angioplasty alone and nitinol or stainless-steel stent placement. Diagn Interv Imaging 2019; 100(9): 485-92.
9. Glanz S, Gordon DH, Lipkowitz GS, Butt KM, Hong J, Sclafani SJ. Axillary and subclavian stenosis: Percutaneous angioplasty. Radiology 1988; 168: 371-3.
10. Morosetti M, Meloni C, Gandini R, Galderisi C, Pampana E, Nicoletti M, et al. Late symptomatic venous stenosis in three hemodialysis patients without previous central venous catheters. Artif Organs 2000; 24: 929-31.
11. Nael K, Kee ST, Solomon H, Katz SG. Endovascular management of central thoracic veno-occlusive diseases in hemodialysis patients: a single institutional experience in 69 consecutive patients. J Vasc Interv Radiol 2009; 20(1): 46-51. 12. Mickley V. Central Vein Obstruction in Vascular Access. Eur J Vasc Endovasc Surg. 2006;32(4):439-44.
13. Kundu S. Central Venous Obstruction Management. J Vasc Surg 2009; 26: 115-21.
14. Gilmore J. KDOQI clinical practice guidelines and clinical practice recommendations-2006 updates. Nephrol Nurs J 2006; 33: 487-9.
15. Bakken AM, Protack CD, Saad WE, Lee DE, Waldman DL, Davies MG. Long- term outcomes of primary angioplasty and primary stenting of central venous stenosis in hemodialysis patients. J Vasc Surg 2007; 45: 776-83.
16. National Kidney Foundation. NKF-K/DOQI clinical practice guidelines for vascular access. Am J Kidney Dis 2001; 37(1): 137-81.
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18. Ozyer U, Harman A, Yildirim E, Aytekin C, Karakayali F, Boyvat F. Long-term results of angioplasty and stent placement for treatment of central venous obstruction in 126 hemodialysis patients: a 10-year single-center experience. AJR Am J Roentgenol 2009; 193(6): 1672-9.
19. Kim YC, Won JY, Choi SY, Ko H, Lee K, Lee DY, et al. Percutaneous treatment of central venous stenosis in hemodialysis patients: long-term outcomes. Cardiovasc Intervent Radiol 2009;32(2):271-8.
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Download attachments: 10.4328:ACAM.20781
Erdem Birgi, Onur Ergun, Hasanali Durmaz, Azad Hekimoğlu, Işık Conkbayır, Baki Hekimoğlu. Endovascular treatment of central thoracic venous stenosis and occlusion in hemodialysis patients. Ann Clin Anal Med 2021;12(12):1406-1410
Predictive significance of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in patients undergoing stereotactic breast marking
Mehmet Ali Çaparlar, Özhan Çetindağ, Aydan Eroğlu
Department of Surgical Oncology, Medical Faculty, Ankara University, Ankara, Turkey
DOI: 10.4328/ACAM.20785 Received: 2021-07-13 Accepted: 2021-08-19 Published Online: 2021-09-16 Printed: 2021-12-01 Ann Clin Anal Med 2021;12(12):1411-1414
Corresponding Author: Mehmet Ali Çaparlar, Department of Surgical Oncology, Ankara University, Medical Faculty, Balkiraz, 21, Tıp Fakültesi Cd., 06620 Mamak, Ankara, Turkey. E-mail: firstname.lastname@example.org P: +90 0312 595 60 00 / +90 506 543 76 99 F: +90 312 319 11 91 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6466-0348
Aim: In recent years, parallel to the progress in breast screening programs and radiological examinations, many breast abnormalities have been detected in radiological images of the breast that cannot be distinguished from malignancy and therefore require histopathological evaluation. With the advances in interventional radiology and stereotactic marking methods, histopathological evaluation has become common. It is now widely accepted that inflammation plays an effective role in cancer development and spread. This study aimed to demonstrate the predictive value of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) values obtained from a cheap and simple peripheral venous blood analysis that is easily accessible in every clinic.
Material and Methods: The retrospective database of 76 female patients who underwent excisional biopsy with mammography using the stereotactic technique in the Clinic of Surgical Oncology of the Ankara University Faculty of Medicine was examined. All blood test results and histopathology reports of the patients were examined retrospectively. The demographic and clinicopathological characteristics of the patients were found. NLR and PLR values were calculated from the number of peripheral blood cells. The data were presented as mean±standard deviation (SD) and minimum-maximum values and were statistically analyzed.
Results: Significant differentiation was observed in the statistical analysis of patients’ NLR values between the patient group diagnosed with benign findings and the group of patients with invasive tumor diagnosis (p=0.01, <0.05). Patients with malignant tumors had high NLR values. Patients with axillary lymph node involvement also had high PLR values compared to patients in this group without involvement (p=0.028, <0.05).
Discussion: NLR values were high in cases of invasive malignant breast masses. PLR values were found to be high in the group with invaded lymph nodes among these patients. Further randomized prospective studies are needed for the improvement of clinical practice.
Keywords: Breast Mass, Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, Stereotactic Biopsy
Benign breast diseases represent a broad spectrum. Sometimes they appear with abnormalities only in imaging methods without any clinical symptoms. Most clinical breast changes in women are benign, and only 3% to 6% of cases are related to breast cancer . Therefore, management of benign breast changes requires clinical, radiological, and histological diagnostic studies to exclude malignancy if necessary. Some changes increase the risk of cancer in the affected breast, while some increase the risk of breast cancer in both breasts. Breast cancer poses an increasing threat to women in proportion to their advancing age, but mortality rates have decreased due to improvements in early diagnosis and treatment modalities. Most governments have made breast cancer screenings a part of their health policy. Nearly 25-35% of breast cancers are diagnosed without palpation due to the widespread application of breast screening programs and improvements in diagnostic imaging [2, 3]. Screening by mammography increases breast cancer incidence, shifts the mean of stage distribution to earlier stages, and is associated with better survival in developed countries . However, numerous breast abnormalities that cannot be distinguished from malignancy and therefore require a histological evaluation are also detected during screening. Approximately 20% of suspicious lesions are proven to be malignant after histological evaluation [5, 6].
Diagnostic methods include breast examination, imaging, and biopsy methods. One of the early diagnostic modalities of biopsy methods is excisional biopsy by stereotactic marking. When a suspicious breast finding is detected, the separation of benign and malignant tissue can only be determined by biopsy. During stereotactic breast marking, mammography, ultrasound, and sometimes magnetic resonance imaging are used to guide the placement of the biopsy needle into the breast. This method has been considered the gold standard for unpalpable lesions for the last 30 years . Inflammatory markers (procalcitonin, C-reactive protein, white blood cell count, etc.) have been investigated for many solid tumors, especially gastrointestinal system malignancies , and these markers are accepted to have predictive value in the early diagnosis of complications in cancer patients . This method has both diagnostic and therapeutic significance in 21% of patients. It is now widely recognized that chronic inflammation is closely related to the cancer development process and hematological parameters in simple, noninvasive routine blood tests are considered as inflammation markers . These parameters can be obtained simply and inexpensively in all hospitals. They are requested for all patients as part of routine blood tests.
In this study, we aimed to reveal the predictive value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to- lymphocyte ratio (PLR) values among these markers in patients who underwent excisional biopsy of the breast by marking with the stereotactic method.
Material and Methods
In our study, the retrospective database of 76 consecutive female breast patients who were marked with mammography by the stereotactic method and for whom excisional biopsy was performed in Ankara University’s Surgical Oncology Clinic between January 2017 and December 2021 was examined. Predictive data were preoperational. Patients who used steroids that could affect the peripheral blood picture, had hematological disorders, were previously diagnosed with malignancy, or had acute or chronic inflammation during the procedure were not included in the study. Clinical properties were collected including age, diagnosis, clinical TNM stage, blood test results, pathological type, and results. Cases diagnosed as malignant were staged according to the American Cancer Joint Committee’s TNM staging system (AJCC 7th edition, 2010). The counts of neutrophils, thrombocytes, and lymphocytes was obtained from medical records a week before treatment. NLR was calculated by dividing the absolute count of neutrophils by the absolute count of lymphocytes. In the same manner, PLR was defined by dividing the absolute count of platelets by the absolute count of lymphocytes.
The study included female patients with nonpalpable breast masses with mammographic findings who were examined in our clinic or referred from external centers between January 2017 and December 2021. Mammographic findings were classified according to the Breast Imaging Reporting and Data System (BIRADS). BIRADS 3 and 4 lesions were marked with mammography.
Wire localization method
This procedure was supposed to be performed on the same day as the surgery. After local anesthesia was administered, a marking needle with a thin wire was placed in the suspicious area under the guidance of mammography imaging. The needle was then withdrawn and the wire was left inside. Part of the wire was in the breast and part was outside. The part that was left out was taped onto the breast and a plain radiograph was taken to show the location of the wire.
The procedure was performed in the radiology department, and the patient went from there to the operating room. The tip of the wire was hook-shaped, so it was clinging to the tissue and did not slip. However, it was necessary to take care not to pull the wire accidentally and not to move the arm too much. The surgeon first found the wire during surgery and then removed the tissue around it within safe limits. All samples were sent back to the radiology unit, and radiography was performed to verify the margins. The samples were then sent to the pathology laboratory for histopathological examination in storage containers containing formaldehyde.
The mean age of the patients included in the study was 51.1±8.4 years. All of the patients were female. While 45.5% of patients (n=30) had disease in the right breast, 54.5% (n=36) had disease in the left breast. Furthermore, 72% of cases (n=55) were diagnosed as benign and 28% (n=21) were diagnosed as malignant. Among the malignant cases, 57% (n=12) of the patients had in situ tumors and 43% (n=9) had invasive ductal carcinoma. Four of the patients with invasive ductal carcinoma had axillary lymph node involvement and the others had clean axilla. The mean NLR value was 2.23±1.80 (1.05-8.11) and the mean PLR value was 136.16±59.46 (47.30-356.50). The mean neutrophil count was 4.46±1.45 (1.96-7.40), mean lymphocyte count was 2.20±0.61 (0.69-4.34), and mean platelet count was 267.70±66.75 (92-483) (Tables 1 and 2).
The Ankara University Faculty of Medicine’s Hospital Ethics Committee approved this study (Decision Number: İ10-628-20). Statistical analysis
All data were presented as mean±standard deviation (SD) and minimum-maximum values, and parametric test assumptions were reviewed before differential analysis was performed. Normality was checked by the Shapiro-Wilk test, skewness, and kurtosis. Since the assumption of normality was not provided, difference analysis was performed by Mann-Whitney U test. Statistical analyses were conducted within the confidence range of 95% and values of p<0.05 were considered statistically significant.
The demographic characteristics and blood test results of the patients included in this study are presented in Table 1 and histopathological characteristics of excised breast tissues are shown in Table 2.
In the statistical analysis performed, the PLR values of the patients did not differ statistically significantly according to the pathological diagnosis (p>0.05). However, a statistically significant difference was found in NLR rates between patients with a benign diagnosis and patients with an invasive tumor (p=0.01, <0.05). NLR ratios of patients diagnosed with invasive tumors were significantly higher than those with a benign diagnosis. PLR values of patients with axillary lymph node involvement were statistically higher in patients with a malignant diagnosis than patients with non-pathological axilla (p=0.028, <0.05).
In this study, we aimed to reveal the predictive importance of NLR and PLR values in patients who underwent mammography- guided marking and then an excisional breast biopsy. Our study showed that there was a significant difference in NLR values between the patient group with benign diagnoses and the patient group with invasive carcinoma. That is, the NLR values of patients diagnosed with invasive carcinoma were significantly higher than those of patients with a benign diagnosis. This differentiation was not observed in PLR values, however. In subgroup analysis, the PLR values of the patients with lymphatic metastasis in the patient group with invasive carcinoma were again found to be higher than those of patients without metastasis.
Breast cancers are often detected before they are palpated and without invasive pathological features by screening mammograms. This has significantly increased the number of breast cancers diagnosed. It also provides improvement in survival by creating a decrease in the size and stage of breast cancers during the first application. Nonpalpable breast cancers may present radiographically as masses, calcifications, masses with calcification, or changes in breast density. This radiographic appearance also depends on the age of the patient, the density of the breast, and the biology of the tumor . Correct localization of these radiological changes before surgery is a great necessity. There are various methods in which wire-guided marking in association with radiology is considered as the gold standard .
In the early days, surgical excisional biopsy was the only option and could only be performed for masses large enough to be localized by palpation during surgery. From the mid to late 1980s, a new and rapid series of practical advances occurred in minimally invasive procedures. Initially, three hands were required for ultrasound-guided biopsy, but Lindgreen, a radiologist who was disturbed by the difficulty of this method, developed a one-handed biopsy system that included springs and buttons. Later, mammography and magnetic resonance were integrated into this stereotactic biopsy system and modified. Thus, the system was developed to perform both marking and biopsy . Today, the increasing use of mammography and the initiation of breast screening programs have clinically led to an increase in occult breast cancer, enabling the diagnosis of one-third of all breast cancers without palpation. Cancers diagnosed in this way also have a different natural history and biology compared to others .
Many recent studies have revealed the relationship between cancer development and inflammation and demonstrated that neutrophils, lymphocytes, and platelets, which are components of peripheral blood-based inflammation, manage this process with the cytokines and chemokines they secrete [14, 15]. In this process, although the cytokine microenvironment generated by neutrophils and thrombocytes is mostly associated with tumor growth and metastasis, it has been observed that lymphocytes represent the host immune response against cancer with the cytotoxic activities of cytokines and T cells [16, 17]. Scoring systems for breast cancer have been developed using NLR and PLR values derived from these inflammation components . Many researchers have studied the prognostic and predictive significance of NLR and PLR values in many solid tumors and breast cancer patients [19-21]. As a result, the numerators of NLR and PLR values (neutrophil and thrombocyte counts) are poor, while the denominators (lymphocyte count) are good result markers.
Indeed, NLR values were found to be higher in the patient group diagnosed with invasive tumors than the patient group with a benign diagnosis in our study. The PLR values of the subgroups with axillary lymph node metastasis were also high in patients with an invasive cancer diagnosis. In a controlled retrospective study by Okuturlar et al., leukocyte, lymphocyte, and NLR values were found to be high in the breast cancer patient group , while in the study of Sun et al., both NLR and PLR values were found to be high in the patient group . In a study conducted in our clinic in 2013, a high NLR was found in breast cancer patients with lymph node involvement, albeit it without statistical significance .
In the study of Koh et al., including 2059 breast cancer patients, high NLR values were significantly correlated with tumor size, lymph node involvement, and metastasis . In the study of Yersal et al., no such relationship was found for the NLR value, but they found the PLR value to be higher in patients with lymph node metastasis .
Studies have shown that the NLR value is a sensitive prognostic marker and that inflammation components and the scoring systems derived from them are important factors in tumor growth and progression, but further prospective studies are still needed to reflect these findings in clinical practice.
The authors thank Birhan Özhan from the Hacettepe University Faculty of Sciences for professional assistance with biostatistics.
Scientific Responsibility Statement
Animal and human rights statement
Conflict of interest
1. Stachs A, Stubert J, Reimer T, Hartmann S. Benign breast disease in women. Dtsch Arztebl Int. 2019;116(33–34):565–73.
2. Skinner KA, Silberman H, Sposto R, Silverstein MJ. Palpable breast cancers are inherently different from nonpalpable breast cancers. Ann Surg Oncol. 2001;8(9):705–10.
3. Lovrics PJ, Cornacchi SD, Vora R, Goldsmith CH, Kahnamoui K. Systematic review of radioguided surgery for non-palpable breast cancer. Eur J Surg Oncol. 2011;37(5):388–97.
4. Verdial FC, Etzioni R, Duggan C, Anderson BO. Demographic changes in breast cancer incidence, stage at diagnosis and age associated with population-based mammographic screening. J Surg Oncol. 2017;115(5):517–22.
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6. Kopans DB. The positive predictive value of mammography. Am J Roentgenol. 1992;158(3):521–6.
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8. Çaparlar MA, Uçar Y, Dokcu Ş, Hasirci I, Ulutaş ME, Erşen O. The Relationship between Procalcitonin with Morbidity, Mortality and Survival in Gastric Cancer. J Adv Med Med Res. 2021;33(6):80–91.
9. Çaparlar MA, Uçar Y, Dokcu Ş, Hasırcı İ, Ulutaş ME, Erşen O. Procalcitonin: the ideal predictor of anastomotic leakage. But, when? Int Surg J. 2021;8(5):1418.
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11. Gajdos C, Ian Tartter P, Bleiweiss IJ, Hermann G, De Csepel J, Estabrook A, et al. Mammographic appearance of nonpalpable breast cancer reflects pathologic characteristics. Ann Surg. 2002;235(2):246–51.
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13. Ahmed M, Douek M. The management of screen-detected breast cancer. Anticancer Res. 2014;34(3):1141–6.
14. McMillan DC. Systemic inflammation, nutritional status and survival in patients with cancer. Curr Opin Clin Nutr Metab Care. 2009;12(3):223–6.
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16. Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A. Cancer-related inflammation, the seventh hallmark of cancer: Links to genetic instability. Carcinogenesis. 2009;30(7):1073–81.
17. Denkert C, Loibl S, Noske A, Roller M, Müller BM, Komor M, et al. Tumor- associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol. 2010;28(1):105–13.
18. Koh CH, Bhoo-Pathy N, Ng KL, Jabir RS, Tan GH, See MH, et al. Utility of pre-treatment neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as prognostic factors in breast cancer. Br J Cancer. 2015;113(1):150–8.
19. Templeton AJ, Ace O, McNamara MG, Al-Mubarak M, Vera-Badillo FE, Hermanns T, et al. Prognostic role of platelet to lymphocyte ratio in solid tumors: A systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2014;23(7):1204–12.
20. Azab B, Shah N, Radbel J, Tan P, Bhatt V, Vonfrolio S, et al. Pretreatment neutrophil/lymphocyte ratio is superior to platelet/lymphocyte ratio as a predictor of long-term mortality in breast cancer patients. Med Oncol. 2013;30(1).
21. Okuturlar Y, Gunaldi M, Tiken EE, Oztosun B, Inan YO, Ercan T, et al. Utility of peripheral blood parameters in predicting breast cancer risk. Asian Pacific J Cancer Prev. 2015;16(6):2409–12.
22. Eroglu A. AS. The Role of Pretreatment Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio in the Diagnosis of Breast Cancer: Predicting Lymph Node Metastasis. World J Oncol. 2013;4(6):262–3.
23. Yersal Ö, Çetinkünar S, Aktimur R, Aziret M, Özdas S, Erdem H, et al. Neutrophil/lymphocyte and platelet/lymphocyte ratios are not different among breast cancer subtypes. Asian Pacific J Cancer Prev. 2017;18(8):2227–31.
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Mehmet Ali Çaparlar, Özhan Çetindağ, Aydan Eroğlu. Predictive significance of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in patients undergoing stereotactic breast marking. Ann Clin Anal Med 2021;12(12):1411-1414
Investigation of S100A12 levels in children with community-acquired pneumonia
Uğur Fahri Yürekli, Faruk Günak
Department of Biochemistry, Sanliurfa Mehmet Akif Inan Education and Research Hospital, Sanliurfa, Turkey
DOI: 10.4328/ACAM.20786 Received: 2021-07-14 Accepted: 2021-09-22 Published Online: 2021-09-28 Printed: 2021-12-01 Ann Clin Anal Med 2021;12(12):1415-1418
Corresponding Author: Uğur Fahri Yürekli, Sanliurfa Mehmet Akif Inan Education and Research Hospital, Şanlıurfa, Turkey. E-mail: email@example.com P: +90 532 777 93 99 Corresponding Author ORCID ID: https://orcid.org/0000-0002-7969-5196
Aim: Community-acquired pneumonia is an important cause of morbidity and mortality in the world. Prompt diagnosis and appropriate treatment are essential. The efficiency of existing biomarkers alone is not sufficient for diagnosis, so the search for new biomarkers continues. S100A12 is involved in innate immune responses against microorganisms and parasites. The aim of this study is to investigate the relationship between S100A12 levels and routine inflammation markers and disease activity in children diagnosed with community-acquired pneumonia.
Material and Methods: Serum S100A12 (by ELISA method) and C-reactive protein (CRP; by immunonephelometric method) levels were measured for both patients (n=60) and a control group (n=50).
Results: Levels of CRP and S100A12 were found to be significantly higher in patients with community-acquired pneumonia compared to the control group. CRP and S100A12 levels were also significantly higher in the subgroup of patients with severe disease activity.
Discussion: S100A12 levels were found to be significantly higher in children with community-acquired pneumonia in our study, and a significant relationship was found between the severity of the disease and S100A12. These findings indicate that S100A12 may be a new marker that has a place in prognostic evaluation, in addition to its similar properties to other inflammation markers in the evaluation of community-acquired pneumonia.
Keywords: S100A12, C-Reactive Protein, Community-Acquired Pneumonia
Clinical and radiological findings in community-acquired pneumonia (CAP) patients are not reliable in determining the etiological factor. Among the general parameters associated with the presence of infection, white blood cell (WBC) count, neutrophil count, erythrocyte sedimentation rate, C-reactive protein (CRP), and procalcitonin are commonly used markers . However, to date, the efficiency of these biomarkers alone is not high enough and the search for new biomarkers continues. S100A12 is thought to be an important marker for many inflammatory diseases in humans . However, there is no study in the literature investigating S100A12 levels in children with CAP. Only Hou et al. examined S100A12 levels in adults with bacterial pneumonia . Considering the results in diseases with inflammation, CAP may be suggested as a candidate for application of this biomarker in diagnosis and monitoring.
Our aim is to evaluate levels of S100A12 in children diagnosed with CAP and to investigate its relationship with routine inflammation markers and disease activity.
Material and Methods
Fifty patients who applied to the University of Health Sciences Mehmet Akif İnan Training and Research Hospital’s Pediatric Outpatient Clinic and were diagnosed with CAP were included in this study. The control group comprised 50 healthy children. CAP patients were divided into subgroups of patients with mild to moderate pneumonia (n=31) and severe pneumonia (n=29) according to disease activity .
Serum samples were obtained by taking 2 mL of blood and were stored in a freezer at -86 °C. The S100A12 levels of these samples were studied by ELISA method (Bioassay Technology Laboratory Human S100 A12 ELISA Kit No. E3074) for both patients and the control group. Serum CRP levels were also measured with a Cobas c501 biochemistry device (Roche Diagnostics, Turkey) by immunonephelometric method. Blood was taken into EDTA tubes for complete blood count analysis performed with a Penta DX-Nexus device.
Evaluation of the data was conducted using SPSS 21.00 (IBM Corp., Armonk, NY, USA). Descriptive statistics were used.
Maternal age, CRP, and S100A12 were found to be significantly higher in CAP patients compared to the control group. WBC and neutrophil counts were also significantly higher in CAP patients compared to the control group (Table 1). CRP and S100A12 levels were significantly higher in the subgroup of patients with severe disease activity (Table 2). As a result of the correlation analysis, a negative, weak relationship was found between CRP and S100A12, while a positive, weak, and significant relationship was found between WBC count and S100A12 (Table 3). As a result of the analysis performed to determine the correlation between S100A12 and the considered variables, no significant relationship was found in the control group (Table 3). In stepwise regression analysis, significant relationships were found between S100A12 and CRP (p=0.003) and age (p=0.046). Receiver operating characteristic (ROC) curve analysis was performed for CRP, S100A12, neutrophils, WBC count, and neutrophil/lymphocyte ratio in the prediction of the efficacy of these biomarkers in patients with pneumonia. As a result of this analysis, CRP (AUC=0.84, 95% CI=0.752-0.939), S100A12 (AUC=0.71, 95% CI=0.58-0.84), neutrophils (AUC=0.67, 95% CI=0.55-0.79), WBC count (AUC=0.696, 95% CI=0.579-0.813), and neutrophil/lymphocyte ratio (AUC=0.61, 95% CI=0.48- 0.73) were found to have diagnostic value (Figure 1). However, the AUC values for neutrophils, WBC count, and neutrophil/ lymphocyte ratio were found to be below the acceptance value of 0.70 for areas under the ROC curve.
In our study, the CRP values and WBC and neutrophil counts of the patients with CAP were found to be significantly higher than those of the control group. These results confirm that acute phase response is increased in patients with CAP. The neutrophil count was similarly found to be significantly higher in other research , although Chalupa et al.  could not find a significant difference in neutrophil levels in 21 adult patients with bacterial CAP compared to a control group. At the same time, CRP values are found to be higher in cases of invasive acute bacterial infections but lower in viral infections . The analysis of CRP and WBC count is cheap, simple, and widely used, but CRP is not specific in patients with CAP because it is a general acute phase protein .
In our study, the S100A12 levels of CAP patients were found to be significantly higher than those of the control group. There is no other study examining S100A12 levels in childhood cases of CAP in the literature. However, Hou et al.  found increased S100A12 levels in 12 of 46 adult patients with bacterial pneumonia. Again supporting our findings, Achouiti et al.  found that S100A12 levels were significantly higher among 29 severe sepsis pneumonia patients compared to 31 healthy controls. High concentrations of S100A12 were also found in bronchial alveolar lavage fluid in cases of acute lung inflammation characterized by diffuse alveolar damage . Since S100A12 is a small protein weighing 9-14 kDa, it can easily diffuse into the blood .
In our study, S100A12 levels were significantly higher in patients with severe pneumonia than patients with mild to moderate pneumonia. No study in the literature to date has investigated the relationship between S100A12 levels and disease activity in patients with pneumonia. However, results showing that S100A12 is associated with disease activity in other diseases with chronic inflammation have been reported .
In our study, only CRP levels in children with severe CAP were found to be significantly higher compared to the group with mild to moderate CAP. Although WBC count, neutrophil count, lymphocyte count, and neutrophil/lymphocyte ratio were high in patients with severe CAP, these results did not reach statistical significance. In other studies, CRP levels were found to be significantly higher in children with severe CAP, similar to our findings .
In our group of patients with CAP, positive correlations were found between serum S100A12 and CRP and WBC count. Supporting our findings, Heu et al. found positive correlations between S100A12 and WBC count and CRP in patients with bacterial pneumonia . High correlations of traditional inflammatory markers with S100A12 levels clearly reveal that S100A12 can be used as a biomarker. This also suggests that the level of S100A12 may reflect the severity and presence of inflammation in CAP.
In our study, positive correlations were found between S100A12 and CRP and disease activity. However, no correlation was found between WBC count and disease activity. Contrary to these findings, Kim et al.  found low correlations between CRP and WBC count and CAP severity in their study with 155 elderly CAP patients. Liu et al.  found only a positive correlation between disease activity and CRP. Kao et al.  did not show a significant correlation between disease activity and CRP in their study with 61 CAP patients, similarly to the findings of Hedlund and Hansson  in a study conducted with 96 CAP patients. All these findings demonstrate that the disease activity-related results of CRP and WBC are contradictory and do not reflect the severity of the disease alone.
The results of the linear regression analysis performed to determine the independent factors affecting S100A12 levels as a continuous variable in patients with CAP are shown in Table 1. In this model, age and CRP levels were found to be independent factors affecting S100A12 levels. This relationship between S100A12 and CRP is an important result that supports the relationship of S100A12 with inflammation in patients with CAP.
The possibility of the serum S100A12 level of a randomly selected patient among individuals with CAP being higher than the serum S100A12 level of a randomly selected individual from among the controls without CAP was investigated by ROC analysis in our study. The area under the ROC curve showed that our results, which were 0.846 (p=0.000) for CRP and 0.713 (p=0.003) for S100A12, were acceptable. Reviewing the literature, AUC values of >0.70 for CRP were found to be significant in studies of patients with CAP . These results support the usability of S100A12 in the diagnosis of CAP, but also show that its effectiveness is lower than that of CRP. However, the measurement of S100A12 can be especially useful in patients with negative CRP results in the first 12 hours or in the presence of other inflammatory conditions that cause increases in CRP.
WBC counts and CRP values are often obtained in hospitalized children with pneumonia. However, the potential role of WBC count and CRP in predicting disease courses and clinical outcomes remains unclear. Although the results of various pneumonia studies indicate that CRP values are useful in predicting clinical outcomes, it has also been reported that acute phase inflammation is a non-specific marker . As a result, new markers are being investigated due to the lack of available markers in the diagnosis and treatment of this disease. We therefore tried to show that S100A12, a new marker in the diagnosis of inflammatory diseases, can be used in the diagnosis of patients with CAP, and we also sought to explain its relationship with CRP, an inflammatory marker.
As a result, S100A12 levels were found to be significantly higher in children with CAP in our study, and a significant relationship was found between the severity of the disease and S100A12 levels. These findings indicate that S100A12 may be a new marker that has a place in prognostic evaluation, in addition to having properties similar to those of other inflammation markers in the evaluation of CAP. However, we are of the opinion that the course and prognostic value of S100A12 in cases of CAP, a disease with highly variable pathogenesis and prognosis, should be studied in larger series of patients with similar phenotypes.
Scientific Responsibility Statement
Animal and human rights statement
Conflict of interest
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14. Kim JH, Seo JW, Mok JH, Kim MH, Cho WH, Lee K, et al. Usefulness of plasma procalcitonin to predict severity in elderly patients with community-acquired pneumonia. Tuberc Respir Dis. 2013;74(5):207.
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Uğur Fahri Yürekli, Faruk Günak. Investigation of S100A12 levels in children with community-acquired pneumonia. Ann Clin Anal Med 2021;12(12):1415-1418
De ritis ratio and neutrophil-to-lymphocyte ratio in the diagnosis of COVID-19
Yusuf Uzum 1, Zeynep Zehra Gumus 1, Orhan Balıkcı 1, Ugur Bayram Korkmaz 1, Mehmet Sonbahar 1, Servet Akar 2
1 Department of Internal Medicine, 2 Department of Rheumatology, Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey
DOI: 10.4328/ACAM.20791 Received: 2021-07-17 Accepted: 2021-09-22 Published Online: 2021-10-05 Printed: 2021-12-01 Ann Clin Anal Med 2021;12(12):1419-1422
Corresponding Author: Yusuf Uzum, Department of Internal Medicine, Katip Celebi University, Ataturk Training, and Research Hospital, Izmir, Turkey. E-mail: firstname.lastname@example.org P: +90 232 244 44 44 / +90 536 665 87 86 Corresponding Author ORCID ID: https://orcid.org/0000-0001-5027-1827
Aim: The outbreak of the novel coronavirus disease (COVID-19) has been affecting the world day by day. The definitive diagnosis of COVID-19 is made using the real-time polymerase chain reaction (RT-PCR) method. Although the RT-PCR method is the gold standard for confirming infection, it requires a specialized laboratory, expensive equipment, and trained personnel. Thus, simple and alternative laboratory tests are needed to predict PCR positivity and disease.
Material and Methods: We analyzed laboratory parameters of 147 patients who were hospitalized with a pre-diagnosis of COVID-19 and sent RT-PCR samples. Of these, 76 tests were positive and 71 were negative. In addition to routine laboratory parameters, we also examined ratios derived from them, such as the De Ritis ratio (AST to ALT ratio) and Neutrophil- to- Lymphocyte Ratio (NLR). We investigated whether these parameters can predict the positivity or negativity of the PCR test.
Results: CRP, D-dimer, Ferritin, AST values, NLR, and De Ritis ratio were found to be significantly higher in the PCR- positive group. It was observed that the lymphocyte count was lower in the positive group.
Discussion: Our results suggest that routine laboratory tests that can be performed easily may also have the potential to predict COVID-19 positivity and negativity. These parameters can especially be used as an alternative in areas with a shortage of laboratories, equipment and personnel for PCR testing. Combining some hematological parameters and specific ratios derived from hematological parameters can help in identifying false positive/negative RT-PCR tests.
Keywords: De Ritis Ratio, Neutrophil-to-Lymphocyte Ratio, COVID-19
Coronavirus Disease-2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was first seen in December 2019 in Wuhan, China, and affects the world every day . The definitive diagnosis of COVID-19 is made using the real-time polymerase chain reaction (RT-PCR) method, which is performed by amplifying viral RNA. Due to the rapid increase in the number of cases and their worldwide spread, it has been difficult to rapidly perform RT-PCR for every patient with symptoms or contact. To be able to apply the RT- PCR method, a specialized laboratory, expensive equipment, and trained personnel are required. It is a known fact that in some parts of the world, especially in developing countries, specialized laboratory facilities are limited. Even if the PCR test is performed in these specialized laboratories, the false negative rate is still around 20-30% [2-5]. Additionally, the PCR method is costly and takes 4 to 6 hours to obtain, process, and study a blood sample.
Major symptoms of SARS-CoV-2 include fever, dry cough, weakness, fatigue, and dyspnea [6,7]. Since the symptoms of COVID-19 are similar to those of other respiratory viral diseases, there has been an increased need for laboratory parameters that can predict a positive PCR result. Although there are many publications on the effects of laboratory parameters, especially acute phase reactants, on clinical outcomes in COVID-19 patients, studies on their value in predicting PCR positivity are limited .
In our study, we aimed to analyze laboratory parameters of 147 patients who were hospitalized with a pre-diagnosis of COVID-19 and sent RT-PCR samples. Of these, 76 tests were positive and 71 were negative. In addition to routine laboratory parameters, we also examined ratios derived from them, such as the De Ritis ratio (AST to ALT ratio) and Neutrophil- to- Lymphocyte Ratio (NLR). We investigated whether these parameters can predict a positive or negative PCR test result.
Material and Methods
Ethical approval for this stuy was obtained from the local ethics committee (No: 2020/770). Patients, who were admitted to our clinic with a pre-diagnosis of COVID-19 between March 1, 2020, and August 31, 2020, who had complete clinical data and over 18 years of age, who had at least one of the symptoms such as fatigue, fever, cough, and dyspnea were included in the study. An RT-PCR sample for COVID-19 was taken from each patient. Patients with any infection other than SARS- CoV-2 that could affect neutrophil and lymphocyte counts, and patients with any disease that might affect AST, ALT levels, and thus AST/ALT ratio, were not included in the study. As a result of screening based on the above criteria, 31 out of 178 patients were excluded from the study. Of those, 28 had deficiencies in laboratory parameters and medical history, and one of them was under 18 years of age. Two patients were transferred to the intensive care unit due to a deterioration of their general condition on the day of hospitalization. The study included 147 patients (Figure 1).
Data collection and assessments:
The data were scanned retrospectively. Age, gender, symptoms, and findings of the patients at the time of diagnosis were recorded. The levels of neutrophils, lymphocytes, AST, ALT, C-reactive protein (CRP), ferritin, D-Dimer, lactate dehydrogenase (LDH), hemoglobin, platelets, monocytes were examined simultaneously with the RT-PCR sample taken for the diagnosis of COVID-19. The NLR and De Ritis ratios were calculated. Laboratory data of 76 patients with positive RT-PCR results and 71 patients with negative results were compared in terms of assessing the positivity or negativity of the PCR test. Statistical Analysis:
Discrete variables, numbers and ratios were used for descriptive statistics. For continuous variables with normal distribution, standard deviation was preferred. The Chi-square test was used to compare groups involving discrete variables. P<0.05 was accepted as statistically significant. All statistical analyzes were performed using SPSS (Statistical Packages for the Social Sciences) software version 22.0 (Chicago, IL, USA).
The study included 147 cases, 76 of which tested positive for COVID-19 whereas 71 were negative. It was observed that the mean age of the positive group (59.96 years) was higher than that of the negative group. When patients’ complaints upon presentation to the hospital were questioned, the most common symptoms and signs were cough and fatigue in the positive group, and fatigue, cough, and fever in the negative group, respectively. Gastrointestinal symptoms were least common in both groups (Table 1).
The AST value was found to be significantly higher in the PCR- positive group (p=0.013). On the other hand, ALT values did not differ significantly between the two groups. Whereas, the De Ritis ratio was higher in the PCR-positive group (p=0.002). When the neutrophil and lymphocyte counts of the cases were examined, it was observed that the lymphocyte count was lower in the positive group, and there was a significant difference between the groups (p=0.002). Lymphopenia was seen in 73.6% (n=56) of positive cases. This rate was 47.8% (n=34) in negative cases. There was no significant difference between neutrophil values. The NLR value was higher in the positive group (p=0.035). CRP (p<0.001) and D-dimer (p <0.001) values were also statistically significantly higher in the positive group. The mean of ferritin values of COVID-19 positive cases was found to be close to 2 times the average of the negative group, and a significant difference was observed (p=0.005). There was no significant difference between the groups for LDH, platelet, monocyte, and hemoglobin values, respectively (p=0.662, p=0.084, p=0.318, p=0.955).
Of the 147 patients included in our study, more than half of all cases were males. More than half of the cases in the PCR (+) group were also males. In the descriptive studies by Chen et al. with 99 patients and Wang et al. with 138 patients, the number of male patients was found to be higher than that of females [1,8]. In our study, the median age of all patients was 57.1 years old, which is close to the data reported by Chen et al (55.5 years) and Zhang et al (57 years) [1,6]. Fever, cough, and fatigue were the dominant symptoms of the RT-PCR- positive group in our study. In a study by Liu et al. with 245 patients, the most common symptoms and signs were fever, cough, and fatigue .
In our study, a significant and strong relationship was found between AST, one of the transaminases, and PCR positivity (p=0.013). In a study by Ferrari et al., it was found that there is a strong relationship between the elevation of serum transaminases (AST and ALT) and the presence of COVID-19 . However, in our study, no significant relationship was observed between the ALT elevation and PCR positivity (p=0.780). AST values were found to be significantly higher in the COVID-19 group in the study by Zhang et al., in which they examined 115 patients and compared COVID-19 with community-acquired pneumonia . In a review by Feng et al., it was stated that the
AST value was more affected and increased by liver damage and dysfunction due to COVID-19. Although the pathophysiological mechanisms of this increase have not been fully clarified, it has been suggested that the possible mechanisms may be systemic inflammatory response, multiple organ dysfunction, and hypoxia caused by respiratory distress syndrome, which can be seen in the course of the disease . The De Ritis ratio, known as an AST to ALT ratio, has been studied in many clinical conditions since it was defined by Fernando De Ritis in 1957 and has been shown in some studies to be an indicator of the inflammatory process and a parameter that affects survival in malignant processes [13,14]. In our study, the De Ritis ratio was found to be significantly higher in the PCR positive group (p=0.002). This result suggested that the De Ritis ratio may have the potential to predict PCR positivity of cases at the time of their first admission.
In the studies by Zhang et al. with 140 patients and Shi et al. with 90 patients, severe and non-severe patient groups were compared and it was found that the severity of the disease was associated with the low lymphocyte count (p=0.048, p<0.001) [6,15]. Ferrari et al. found that lymphocyte counts were lower in patients who presented with COVID-19 symptoms and tested positive with reverse RT-PCR than in the negative group (p=0.01) . In our study, the results were consistent with the literature. Lymphocyte counts in the PCR-positive group were numerically lower than in the negative group and a statistically significant difference was found (p=0.002). However, the neutrophil counts of the patients were similar in both groups (p=0.684). Ferrari et al. found that the neutrophil count was lower in the PCR- positive group . In the study by Cheng et al., it was observed that the average number of neutrophils in the COVID-19 and non-COVID-19 groups were similar to each other as in our study (p = 0.14) .
In the study by Yormaz et al., it was observed that more than half of PCR- positive patients (53%) had a high NLR . In a study conducted by Shi et al., NLR was examined between the severe and non-severe groups and was found to be higher in the severe group (p<0.001) [15.] In our study, the NLR rates in the PCR-positive group were found to be significantly higher than in the negative group (p=0.035). There are publications in the literature showing that NLR and neutrophil counts were detected to be higher and lymphocyte count to be lower in severe disease, but there are no publications directly investigating that these parameters can be used as markers to predict PCR- positive cases.
We observed no association between hemoglobin, platelet, monocyte levels, and PCR positivity (Table 2). Ferrari et al. found that there was a strong relationship between COVID-19 and low monocyte levels (p=0.001), but not with platelets . Cheng et al. observed that platelet counts were lower in the COVID-19 group compared to the non-COVID-19 group (p = 0.00) .
When we examined the levels of CRP, D-dimer, and ferritin in our study, all of these parameters were found to be statistically significantly higher in the PCR-positive group compared to the negative group (p<0.001, p<0.001, and p=0.005). In the study by Ferrari et al., a significant difference was found between the groups with and without COVID-19 when CRP values were examined (p=0.034) . In the study conducted by Zhang et al., it was found that the high CRP and D-dimer levels were associated with the severity of the disease (p<0.001 and p<0.001) . Also, in another study conducted by Shi et al. comparing laboratory parameters between severe and non- severe groups, a relationship was found between high CRP and D-dimer levels and severe disease (p<0.001 and p<0.001) . Ferritin, which is a positive acute-phase reactant, increases in COVID-19, as in other inflammatory diseases. Studies have stated that ferritin may reach very high levels during COVID-19. In the study by Liu et al., the protein structure of SARS-CoV-2 was examined and it was observed that ORF1ab, ORF10, and ORF3a proteins attacked the heme part of the beta-1 chain of hemoglobin. As a result, it was observed that iron was dissociated from porphyrin. In light of these data, it was thought that ferritin values increased more during COVID-19 than during a normal inflammation . There is no publication in the literature on the predictive value of ferritin levels for PCR positivity. In a retrospective cohort study conducted by Guan et al. with 1270 COVID-19 patients, the relationship between ferritin and mortality was examined, and ferritin was accepted as a significant predictor . In another study examining 100 COVID-19 patients followed in the intensive care unit, ferritin levels were compared between the survivor and non-survivor groups, and the median ferritin concentration was about three times higher in the non-survivor group than the survival group (1722.25μg / L vs. 501.90μg / L, p <0.01) .
The most striking limitation of our study is the number of patients. Considering the increasing number of positive COVID-19 cases all over the world, the number of our patients is low. More cases and multi-center studies are needed to support our findings.
In our study, we examined the predictability of laboratory parameters and some specific ratios for the RT-PCR result. We suggest that high AST, CRP, ferritin, D-dimer values, NLR, De Ritis ratio, and low lymphocyte counts at the time of admission could predict PCR positivity. Although the RT-PCR test is the gold standard, routine laboratory tests that can be easily performed may also have the potential to predict COVID-19 positivity and negativity. These parameters can especially be used as an alternative in areas with a shortage of laboratories, equipment, and personnel for PCR testing.
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Animal and human rights statement
Conflict of interest
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Download attachments: 10.4328:ACAM.20791
Yusuf Uzum, Zeynep Zehra Gumus, Orhan Balıkcı, Ugur Bayram Korkmaz, Mehmet Sonbahar, Servet Akar. De ritis ratio and neutrophil-to-lymphocyte ratio in the diagnosis of COVID-19. Ann Clin Anal Med 2021;12(12):1419-1422
Are shock index, modified shock index, NLR and qSOFA useful in making COVID-19 intensive care follow-up decisions?
Fulya Çiyiltepe 1, Ayten Saraçoğlu 2, Özge Yıldız 1, Yeliz Bilir 1, Elif Bombacı 1, Kemal Tolga Saraçoğlu 1
1 Department of Anesthesiology and Reanimation, University of Health Sciences, Istanbul Kartal Dr. Lütfi Kırdar City Hospital, 2 Department of Anesthesiology and Reanimation, University of Marmara, Istanbul, Turkey
DOI: 10.4328/ACAM.20796 Received: 2021-07-21 Accepted: 2021-10-05 Published Online: 2021-10-09 Printed: 2021-12-01 Ann Clin Anal Med 2021;12(12):1423-1426
Corresponding Author: Fulya Çiyiltepe, D-100 South Side, No: 47, Cevizli Location 34865 Kartal, Istanbul, Turkey. E-mail: email@example.com P: +90 505 510 14 36 Corresponding Author ORCID ID: https://orcid.org/0000-0002-0959-5202
Aim: To meet the increasing intensive care and mechanical ventilator needs during the COVID-19 pandemic process, parameters that will enable rapid assessment and decision-making at the bedside are required in emergency services. The aim is to provide rational use of intensive care units by determining appropriate parameters that can be used to evaluate the intensive care follow-up indication.
Material and Methods: Demographic data,vital signs, and hemogram results were recorded during the consultation in terms of intensive care follow-up requirements of the patients. The qSOFA, shock index, modified shock index, and the neutrophil-lymphocyte ratio were calculated.
Results: Three hundred patients were included in the study.The median age was 69.2 years, 88% of the patients had at least one comorbid disease. The neutrophil-lymphocyte ratio was significant in predicting the need for intubation, but is not an independent risk factor. Male gender, qSOFA scores and need for intubation were predictors of intensive care mortality.
Discussion: We found out that no scoring system can predict the requirement of intubation, but qSOFA is effective in showing mortality when making intensive care follow-up decisions for COVID-19 patients consulted in emergency departments.
Keywords: Coronavirus, Intensive Care Units, Modified Shock Index, Neutrophil-to-Lymphocyte Ratio, QSOFA, Shock Index
Having broken out in Wuhan province of China in December 2019 and being caused by acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), Coronavirus Disease 2019 (COVID-19) rapidly spread around the world and caused a pandemic . In a report of 72.314 cases, 14% of the patients were reported to be severely ill, including dyspnoea, low blood oxygen saturation ≤93%, increased respiratory rate and increased oxygen demand . Moreover, 5% were critically ill accompanied by respiratory failure, septic shock and/or multi-organ dysfunction. As the COVID-19 outbreak spread, the need for intensive care units and the increasing number of patients during the pandemic process necessitated the determination of criteria for identifying patients requiring intensive care follow-up . Since the first patient was diagnosed in our country, algorithms and guidelines aimed at guidance strategies in patient follow-up have been prepared and updated by expert scientific committee members . However, for patients who are treated in the emergency service, there are no definitive criteria to predict cases that will develop a need for intubation or have a critical course in the decision-making process of COVID-19-related intensive care follow-up.
Shock index (SI), modified shock index (MSI), quick sequential organ failure assessment (qSOFA) and neutrophil-lymphocyte ratio (NLR) were the parameters used to diagnose patients in shock [5-8]. In patients suffering from severe COVID-19, the clinical course is acute and aggressive, following a course similar to shock . However, their role in determining critically ill patients with COVID-19 is not clear.
In order to determine the Intensive Care Unit (ICU) follow-up process of COVID-19 patients and to identify patients’ invasive mechanical ventilation (IMV) requirement early, parameters are necessary for rapid evaluation. Therefore, in this study, the success rate of the scoring systems was evaluated in patients consulted for an indication of ICU follow-up. Our primary study has focused on identifying appropriate parameters for the early diagnosis of critically ill patients.
Material and Methods
Following the approval of the Institutional Ethics Committee [Protocol number: 2020/514/179/13, date: 11/06/2020], informed consent was obtained from the relatives of all COVID-19 patients who were treated in the intensive care unit between March 23 and September 30, 2020. The data were retrospectively analyzed. The study was carried out in accordance with the ethical principles stated in the guides of “Good Medical Practices” and “Good Clinical Practices” of the Declaration of Helsinki. The primary endpoint of the study was determined as the development of intubation and the need for IMV, and the secondary as the presence of mortality in the ICU. COVID-19 diagnosis:
Nasal and oral swab samples were taken from the patients who applied to the emergency department with complaints of fever, weakness, cough, shortness of breath, chest or headache, abdominal pain, or diarrhea. The diagnosis of COVID-19 followed a positive Real-Time Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) result.
The demographic data including age, gender, comorbid diseases, number of days of treatment before the ICU admission, chest tomography involvement weight (Mild = less than 50% involvement, Moderate-Severe = more than 50% involvement), tracheal intubation requirement, and ICU mortality were recorded. The examined comorbid diseases were hypertension (HT), diabetes mellitus (DM), coronary artery disease (CAD), cerebrovascular disease (CVD), chronic obstructive pulmonary disease (COPD), asthma, and malignancy (CA). During the consultation, vital parameters such as respiratory rate (RR), Glasgow Coma Score (GCS), heart rate (HR), systolic (SBP) and diastolic blood pressures (DBP), calculated mean arterial pressure (MAP) and NLR were recorded. SI, MSI, qSOFA, and NLR were calculated and the relationship between these parameters and ICU survival and the need for tracheal intubation were determined. The data of the patients were evaluated according to intubation and mortality and were interpreted under two main tables.
SI was calculated with the formula ‘’ [SpO 2 / FiO 2] / RR ‘’ . MSI was calculated with the formula ‘’ [SpO 2 / FiO 2] / RR ‘’ . The qSOFA score included 3 clinical criteria that assign 1 point for blood pressure (SBP ≤ 100 mmHg), respiratory rate (>22 breaths / minute) and consciousness (GCS score <15). The score ranges from 0 to 3 points. A score of 2 or more was considered positive . The NLR value was calculated using a hemogram test, which is routinely performed during the admission of patients to the emergency department. The study included all adult patients whose necessary data were available and who were consulted with the diagnosis of COVID-19 because of the necessity of follow-up in the ICU.
Statistical analyzes were performed with the SPSS 21 program. Quantitative variables, expressed as mean ± Standard deviation, were compared using the Oneway Anova test. Qualitative variables were expressed as percentages and compared using either the chi-square test or Fisher’s exact test. A multivariate analysis was performed to evaluate the significant variables associated with intubation and mortality. A p < 0.05 was considered significant.
The data of 300 patients who were followed up in the ICU due to COVID-19 were evaluated. The median age of the patients was 69.2 years, 63.7% of them were males. In 88% of the patients, at least one comorbid disease was present, and the most common accompanying disease was hypertension with a rate of 52.2%. While 66 patients were followed without intubation, 234 patients constituted the intubated group. There was no difference between the groups in terms of age and comorbid diseases, but the male gender ratio was higher in the intubated group . The average number of treatment days the patients received before ICU admission was 1.98 ± 3.1 days, and there was no difference between the two groups according to the tracheal intubation requirement. Computed Tomography (CT) evaluation of 232 patients revealed moderate to severe involvement, and both groups were similar. To determine the need for intubation, no difference was observed between the two groups in terms of qSOFA, SI, and MSI calculated during admission to ICU. A higher NLR was found in the intubated group (9.4 vs 17.2; p <0.05, Table 1) in univariate analysis, but it is not an independent risk factor for intubation.
Table 2 shows the relationship between patient demographics and mortality. The two groups were similar in terms of age and presence of comorbidity. Male patients had a significantly higher mortality rate (69.7%). No significant difference was observed between the CT classification of the patients and the treatment day before ICU and the presence of mortality (Table3). Table 3 also examines the criteria that can be used to predict mortality during admission of patients to ICU. There was no difference between the two groups in terms of SI and MSI during ICU admission. While 29.9% of patients with mortality were Qsofa-positive, this rate was 17.2% in patients who did not develop, and the difference was statistically significant. While the mean NLR value of 201 patients in the mortality group was 18.1, it was 10.2 in 99 patients who did not die, but it is not an independent risk factor for mortality (p=0,100). Besides, there was a significant correlation between intubation and mortality.
In this study, we investigated the possibility of using SI, MSI, NLR and qSOFA scores to be indicators of mortality . Mortality was higher in cases with a high intubation ratio and positive qSOFA. In our study, male gender and the need for mechanical ventilation were associated with a high mortality rate. Our results were similar with a study conducted in Italy . The mortality rate was higher in patients requiring IMV. However, mortality was not observed in a small group of extubated patients in the intensive care unit. All these patients were discharged to the ward.
Studies have shown that clinical signs of shock are present in critical COVID-19 patients, even in the absence of hypotension . This has revealed the presence of a viral sepsis mechanism in COVID-19. According to the Chinese data, the prevalence of shock reported in adult patients with COVID-19 varies greatly depending on the patient population studied and the definition of shock (1% to 35%) . In another analysis, acute respiratory distress syndrome (ARDS), septic shock, and acute renal failure were identified as possible clinical manifestations associated with critically ill COVID-19 patients [11, 12]. Therefore, early diagnosis of COVID-19 patients also suffering from shock may prove effective in early ICU follow-up and intubation decisions. There are some markers used to detect early shock, such as qSOFA, SI, MSI, and NLR values.
After the new definition of sepsis  was published, the qSOFA score was recommended for pre-evaluation in intensive care admissions with a diagnosis of septic shock . We also found that qSOFA is a practical and useful indicator of COVID-19- related ICU mortality in emergency patient evaluation.
Another sepsis marker is NLR. Previous studies have shown that NLR during hospitalization was an independent predictor of in-hospital mortality in COVID-19 patients with sepsis who were admitted to the emergency service. In a retrospective analysis of 63 patients in China, NLR was found to be an independent risk factor for severe COVID-19 . In a meta- analysis involving 1579 patients, NLR was found to be an acceptable predictor of disease severity and mortality in COVID 19 patients. It is stated that it can contribute to reducing the overall mortality rate of COVID 19 by helping clinicians to detect serious cases early, triage them quickly, and start their treatment effectively . In this review, NLR> 9.11 has been associated with mortality in critically ill patients. In our study, we found that NLR is significantly higher in the mortality group, but is not an independent risk factor.
It has been reported that SI is a useful parameter for early diagnosis of sepsis, acute critical illness, unplanned ICU transfers, risk stratification for pulmonary embolism, acute myocardial infarction, and death [5, 15, 16]. Besides, the conducted studies have indicated that high shock index values are associated with death from critical illnesses . In addition to similar benefits, mean blood pressure values are taken into account in MSI, and guidelines recommend the initiation and titration of vasopressor treatments based on MAP. The Surviving Sepsis Campaign guidelines on the management of adults with COVID-19 in the ICU are based on MAP monitoring, not vital signs such as SBP, to guide both fluid and vasoactive requirements . Additionally, Nathan J. et al.  showed that there is a significant risk of death in critically ill patients with high MSI within the first 24 hours after admission to the ICU. Considering that MSI can be easily calculated at the bedside, it is stated that its use in practice may be beneficial for clinicians to initiate interventions earlier that may increase survival. Based on the fact that COVID-19 is a newly-recognized disease and progresses in combination with shock in critically ill patients, we retrospectively evaluated SI and MSI to determine the ICU follow-up indication, and found that they could not predict ICU mortality. There are also studies in the literature using similar markers to predict the need for early diagnosis of intubation in septic shock. Most COVID-19 patients with severe respiratory failure should be followed up in the ICU due to the need for intubation and IMV. However, while making this decision, it is necessary to consider a number of factors, including timing. There are also views opposing the idea that early intubation may be beneficial [19-22].
In the study by Sangita Trivedi et al. , pre-intubation SI and MSI were addressed as easily accessible, non-invasive, bedside clinical tools to identify patients with high complication risk. While a pre-intubation SI value of ≥ 0.90 was defined as an important predictor of post-intubation hypotension and ICU mortality, MSI was stated to be useless in predicting any outcome. Although deciding on the necessity of tracheal intubation in COVID-19 intensive care follow-up is of significance in terms of survival, we could not find any significant contribution of qSOFA, MSI, SI or NLR values in predicting intubation.
In this study, we found out that no scoring system can predict the requirement of intubation, but qSOFA is effective in showing mortality when making ICU follow-up decisions in COVID-19 patients consulted in the emergency department. We concluded that we still need parameters and studies in larger series that will guide us in making this critical decision.
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Animal and human rights statement
Conflict of interest
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16. Toosi MS, Merlino JD, Leeper KV. Prognostic value of the shock index along with transthoracic echocardiography in risk stratification of patients with acute pulmonary embolism. Am J Cardiol. 2008;101(5):700-5.
17. Sloan EP, Koenigsberg M, Clark JM, Weir WB, Philbin N. Shock index and prediction of traumatic hemorrhagic shock 28-day mortality: data from the DCLHb resuscitation clinical trials. West J Emerg Med. 2014;15(7):795-802.
18. Alhazzani W, Møller MH, Arabi YM, Loeb M, Gong MN, Fan E, et al. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19). Intensive Care Med. 2020;46(5):854-87.
19. Tobin MJ. Principles and practice of mechanical ventilation. 3rd ed. New York: Mc Graw-Hill; 2013.
20. Slutsky AS, Ranieri VM. Ventilator-induced lung injury. N Engl J Med. 2013;369(22):2126-36.
21. Marini JJ, Gattinoni L. Management of COVID-19 respiratorydistress. Jama. 2020;323(22):2329-30.
22. Gattinoni L, Chiumello D, Caironi P, Busana M, Romitti F, Brazzi L, et al. COVID-19 pneumonia: different respiratory treatments for different phenotypes? Intensive Care Med. 2020;46(6):1099-102
23. Trivedi S, Demirci O, Arteaga G, Kashyap R, Smischney NJ. Evaluation of preintubation shock index and modified shock index as predictors of postintubation hypotension and other short-term outcomes. J CritCare. 2015;30(4):861.
Download attachments: 10.4328:ACAM.20796
Fulya Çiyiltepe, Ayten Saraçoğlu, Özge Yıldız, Yeliz Bilir, Elif Bombacı, Kemal Tolga Saraçoğlu. Are shock index, modified shock index, NLR and qSOFA useful in making COVID-19 intensive care follow-up decisions? Ann Clin Anal Med 2021;12(12):1423-1426
A case-control study to evaluate awareness level of human papillomavirus among women healthcare professionals in tertiary health care facility
Seren Ermiş Güven 1, Zuhal Aydan Sağlam 2, Ayşe İnci 3
1 Family Medicine Specialist, Samsun Asarcik District State Hospital, Samsun, 2 Department of Family Medicine, Health Sciences University, Istanbul Training and Research Hospital, Istanbul, 3 Department of Infectious Diseases and Clinical Microbiology, Health Sciences University, Istanbul Training and Research Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.20901 Received: 2021-10-11 Accepted: 2021-10-25 Published Online: 2021-11-07 Printed: 2021-12-01 Ann Clin Anal Med 2021;12(12):1427-1431
Corresponding Author: Seren Ermiş Güven, Family Medicine Specialist, Samsun Asarcik District State Hospital, Samsun, Turkey. E-mail: firstname.lastname@example.org P: +90 533 350 91 26 Corresponding Author ORCID ID: https://orcid.org/0000-0001-8788-9890
Aim: Human Papilloma Virus ranks first in the etiology of sexually transmitted diseases. In this study, it was aimed to determine factors affecting the knowledge and attitudes of female health care professionals about Human Papillomavirus (HPV) infection and vaccine.
Material and Methods: Between February and June 2020, 245 female healthcare professionals working in Health Sciences University Istanbul Training and Research Hospital, including doctors, nurses and midwives, participated in this observational, analytical and case-control study. The case group included 90 participants, and the control group included 155 participants. In the online questionnaire, socio-demographic and gynecological characteristics were evaluated using 21 questions, and awareness of HPV infection and vaccination using 49 questions.
Results: Physicians accounted for 71.1% in the case group and 49.7% in the control group. The median age was 28 (min.23-max.51) years in the case group and 28 (min.21-max.59) years in the control group, and there was no significant difference between the two groups (p=0.189); 90.2% of the participants knew about HPV and 87.2% about the HPV vaccine. One hundred ninety-one participants answered all questions about HPV and its vaccine. The reason for those who did not want to be vaccinated in both groups was that it was expensive.
Discussion: The knowledge levels of the participants about HPV and HPV vaccine were higher in the case group, and awareness of HPV infection and cervical cancer was insufficient in both groups. In order to prevent HPV-related infections and cancers, education should be given to increase the knowledge level among healthcare professionals.
Keywords: HPV, HPV Vaccine, Cervical Cancer, Women Healthcare Professionals
Human papillomaviruses (HPV) are small, non-enveloped, double-stranded circular DNA viruses, belonging to the Papillomaviridae family. They show tropism to the cutaneous and mucosal squamous epithelium . The main and best- known mode of transmission is sexual contact. Anogenital HPV infection is the most common sexually transmitted disease worldwide. Clinical manifestations caused by HPV range from benign skin lesions to cancers of the anogenital region and head and neck region. Cervical cancer, which is an important cause of morbidity and mortality all over the world, is almost always associated with HPV .
Cervical cancer is the third most common type of cancer in women worldwide and is the fourth most common fatal cancer among women . In our country, the Ministry of Health planned a 5-year screening program in 2014 to screen women between the ages of 30 and 65 for cervical cancer and until January 2018, HPV typing was carried out in 3.2 million women across the country. As a result of this study, the HPV positivity rate was found to be 4.1% .
In recent years, thanks to HPV vaccines and cancer screening programs, cervical cancer has gradually ceased to be a deadly disease. In our country, HPV vaccines are not included in the routine vaccination program and can be applied privately. However, many factors such as lack of information, financial concerns, and social stigmas prevent widespread use of the vaccine . Studies show that informing about HPV vaccines by health professionals and vaccination promotion studies play an important role in the vaccination of the society. In this study, it was aimed to determine the knowledge and attitudes of women healthcare professionals about HPV infections and the HPV vaccine, and to increase HPV awareness in society.
Material and Methods
This observational, analytical, case-control study was conducted between February and June 2020 with women healthcare professionals working at Health Sciences University Istanbul Training and Research Hospital. The total number of female health workers was 848, and they constituted the universe of the study. The sample size was calculated as a minimum of 234 people, with a 5% margin of error at a 95% confidence interval. In June 2020, 245 participants were reached and online data collection was terminated. Participation in the study was on a voluntary basis, and verbal consent was obtained from the participants. The participants were divided into case and control groups. Case group included female physicians, nurses and midwives who frequently encounter HPV infection in the clinic (gynecology and obstetrics, family medicine, infectious diseases and dermatology). Health workers working in branches other than these clinics were considered a control group.
The survey questions consisted of three parts and a total of 60 questions. In the first part, the participants were asked 21 questions about socio-demographic and gynecological characteristics. Participants who had heard of HPV before continued the second part and answered 19 questions measuring the level of knowledge about HPV. People who had heard of the HPV vaccine before were asked to complete the third part of the questionnaire and were asked 20 questions.
Statistical analysis was done with SPSS (Statistical Package for Social Sciences) 25.0 package program. In the analysis of continuous data, mean and standard deviation were used for the normal distribution, median and minimum-maximum values were used for non-normal distributions. Categorical data were presented with frequency and percentage. The Mann-Whitney U test was used for non-normal distribution in two-group comparisons of continuous data. Levene’s test was used to evaluate the homogeneity of variances, the Chi-square test and Fisher’s exact test were used to compare categorical data, and the Spearman correlation test was used for the relationship of continuous data. All tests were bilateral, and statistical significance was accepted as p<0.05.
A total of 245 female healthcare workers participated in the study, 90 of which were in the case group and 155 in the control group. The ages of the case and control groups were 28 (min.23- max.51) years and 28 (min.21-max.59) years, respectively, and there was no significant difference between the ages of the participants (p= 0.189). The duration of duty was 2.5 years (min.0-max.22) in the case group and 3 years (min.1-max.33) in the control group, and a significant difference was found between the participants (p=0.043). The first gestational age was 28 (min.19-max.37) in the case group and 27 (min.18- max.31) in the control group, and a significant difference was found between the two groups (p=0.043); 31.1% of patients in the case group and 25.2% of patients in the control group had at least one pap-smear test. There was no significant difference between the groups in terms of having Pap smear (p=0.167). While there was no history of sexually transmitted disease in the case group, it was present in 5.2% of the control group, and this difference was statistically significant (p=0.028). The number of healthcare workers who had HPV DNA test was 13. There was no significant difference between the groups in terms of age, marital status, smoking and using the birth control method (p>0.05).
Table 2 shows that the least correct answer to the questions about HPV was the transmission route. The rate of those who knew correctly that there was contamination from infected surfaces was 38.9% in the case group and 19.4% in the control group, and the difference between them was significant (p=0.001); 22% of the participants thought that HPV could be transmitted through blood and 7% through respiratory tract. The rate of those who knew all transmission routes was 18.9% in the case group and 10% in the control group; 91.1% of the case group and 73.8% of the control group answered ‘yes’ to the question about HPV DNA control in cervical cancer screenings, and the difference between the groups was significant (p=006). When the participants were asked whether they had heard of HPV, all of the case group did, while 21 people from the control group did not, and this difference was statistically significant (p=0.001).
When the participants were asked whether they had heard of the HPV vaccine before, 97.8% of the case group and 79.7% of the control group stated that they had heard of the HPV vaccine before, and this difference was found to be significant (p<0.001). Those who knew that there were two types of HPV vaccine in Turkey accounted for 69.3% in the case group and 66% in the control group, and there was no statistical difference between the two groups (p=0.454). When asked which groups of women could be administered the HPV vaccine, 78.4% of the case group and 70.6% of the control group answered ‘sexually active women’. When the same question was asked for men, 52.3% of the case group and 37.3% of the control group stated that sexually active men can get vaccinated. The least known issue about the HPV vaccine; The fact that the vaccine could be administered to men and the rate of correct answers to this question was significantly different between the two groups (p=0.038); 59.1% of the case group and 43.1% of the control group gave the correct answer to the HPV vaccine application to adolescent boys, and a significant difference was found between the groups (p=0.028).
Those previously vaccinated against HPV accounted for 17% in the case group and 17.5% in the control group; 11.1% of the case group and 25.3% of the control group gave the answer “I was not informed about the vaccine” as the reason for not vaccinating, and a significant difference was found between the groups (p=0.033). The most common reason for not vaccinating was that the vaccine was expensive, and a significant difference was found between the groups (p=0.259)
In our study, it was determined that the case group had more information about HPV and HPV vaccine compared to the control group. There was no significant difference between the groups in attitudes towards HPV vaccine and awareness of HPV; 9.8% of women healthcare professions participating in the study had not heard of HPV before. The rate of those who had heard of HPV but never heard of the HPV vaccine was 12.8%. In a study conducted by Sevinç et al. (2021) with 312 male university personnel, 86.2% of the participants had not heard of the HPV vaccine before . We think that the fact that our study was conducted with female healthcare professionals significantly increased the number of people who have heard of the HPV vaccine before.
The rate of participants’ awareness of cervical cancer screening methods was 95.9% for the pap-smear test and 81% for the HPV-DNA test; 72.6% of the participants had never been screened for cervical cancer; 15.8% of healthcare professionals had regular pap-smear tests, and no significant difference was found between the groups in this regard. In the study by Eke et al. (2016), 49.6% of female physicians had never had a pap- smear test, and 20.6% had a regular pap-smear test . In the study by Satılmışoğlu et al. (2018) regarding nurses, 32% of the participants stated that they had regular pap-smear tests . The low cervical cancer screening rate in our study may be due to the fact that the participants were young and not sexually active.
It was determined that 38.4% of the participants over 30 years of age and sexually active for at least three years had never had a pap-smear and/or HPV-DNA test. Sevinç et al. (2020) in their study with 507 female participants found that 48.5% of married women over the age of 40 had never had a pap- smear test before . The reason for this low rate in our study may be that the participants were healthcare workers. Social screenings aim to reach 60% of sexually active women and higher rates among health professionals. The current rates in our study were that health workers were not at the targeted level during the awareness and implementation phase.
The rate of participants who knew that HPV is the most common sexually transmitted disease was 73.5%, and 27.4% had sufficient information about transmission and prevention methods. Yuksel et al. found a significant difference between groups in the questions about infection in the study in which they measured the knowledge levels of healthcare professionals about HPV infection and vaccine. In their study, physicians were the group with the highest level of knowledge, with a rate of 76.6% .
The rate of knowledge among participants about the applicability of the vaccine to sexually active men accounted for 44.2% and 50.5% about its applicability to adolescent men.
Adiguzel et al. (2018) found that the rate of those who knew that HPV vaccine could be administered to men was 41% in their study with pediatric residents. Ozbakir Acar et al. (2019) found that 43% of healthcare professionals knew that HPV vaccine can be administered to both men and women in family health centers. Similar results were found in our study .
In our study, the rate of physicians who wanted to have HPV vaccine was 67.8%, and in the study of Naki et al. (2010), it was 84.3% . The reason for this low rate in our study can be explained by the fact that 22.1% of the physician participants had been previously vaccinated.
Studies have shown that healthcare professionals have a more positive attitude towards getting their children vaccinated against HPV. Vaccination of girls is more approved than that of boys in the general population [12-15]. In our study, 90.9% of the case group and 85.3% of the control group had positive thoughts about the vaccination of adolescent girls.
Yuksel et al. (2015) determined the rate of doctors who want to vaccinate their girls as 84.9%, the rate of nurses as 64%, the rate of doctors who want to vaccinate their boys as 58.4%, and the rate of nurses as 46% . In our study, while 89.7% of the doctors and 49% of the nurses and midwives wanted to vaccinate their girls, this rate was 74.2% for boys and 38% for nurses and midwives. In both studies, doctors were more likely to vaccinate their children than other healthcare professionals. In both studies, the HPV vaccine was more widely accepted for girls. The reason for this situation may be that HPV is the most important known cause of cervical cancer and it is not believed to cause cancer in men.
The biggest obstacle in vaccinating children in our study was the concern of side effects and unnecessary use of the vaccine. Studies have supported that sexually transmitted diseases are not increased in those who are vaccinated with HPV . Naki et al. (2010) stated that barriers preventing the participants from vaccinating their children were lack of knowledge and fear of side effects, while the cost of vaccination remained in the background . Adiguzel et al. (2018) stated in their study that the obstacles that pediatricians see in vaccination are that they find the vaccine unnecessary and that the vaccine is not included in the vaccination program of the Ministry . The participants’ concerns about vaccinating their children against HPV were similar to our study, but the biggest obstacle to vaccinating their children was the cost of the vaccine, with a rate of 36.2%.
Studies have shown that physicians recommend vaccines to their patients in proportion to their knowledge of HPV infection and vaccine, but the high cost of the vaccine is a factor that reduces their motivation [10,18,19]. In addition, families’ concerns about social stigma, risky sexual behaviors, and early sexuality prevent physicians from recommending vaccines [10,18-21]. Studies have shown that families do not do not vaccinate their children against HPV due to lack of knowledge rather than cost , and vaccination rates increase in families who receive education [22,23].
The level of knowledge and awareness of healthcare professionals about cervical cancer, screening methods, HPV and HPV vaccine is not sufficient. This situation prevents the vaccination incentives of health professionals and the acceptance of vaccinations by families. Training activities for healthcare personnel should be increased in order to increase awareness of cervical cancer and HPV and to spread HPV vaccines. In-service training should be increased especially for doctors, nurses and midwives working in primary care and the importance of preventive health services should be emphasized. In order to prevent the spread of this most sexually transmitted virus, it should be stated that HPV is not a virus that only affects women and polygamy should be prevented. In addition, parents should be informed about the period when the vaccine provides the most antibodies and protection in individuals, and their children should be vaccinated before their active sexual life begins.
Scientific Responsibility Statement
Animal and human rights statement
Conflict of interest
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6. Sevinc N, Korkut B, Nacar E, Öztürk E. The level of knowledge and awareness of male university professionalss about adult cancers and cancer screening. Konuralp Medical Journal. 2021;13(1):94-100.
7. Eke RM, Sezik HA, Özen M. Are female doctors aware of cervical cancer? Tepecik Edu Res Hosp Journal. 2016;26(1):53-7.
8. Satılmışoğlu ZZ, Aslan İÖ, Can N, Gülcivan G, Yıldız T, Şentürk M. Knowledge Level Assessment Survey of Nurses at Tekırdag Namik Kemal University Medical Research Center, About HPV Vaccination. Namık Kemal Medical Journal. 2018;6(3):104-8.
9. Sevinç N, Oral B, Korkut B. Assessment of Knowledge, Attitudes, and Behaviors of Turkish Women on Breast and Cervical Cancer in Karabük Province, Turkey. National Public Health Journal. 2020;15(4):211-18.
10. Adıgüzel A, Akgül S, Düzçeker Y, Derman O, Kanbur N. Knowledge and trends of pediatricians about human papilloma virus vaccines. Journal of Child Health and Diseases. 2018;61: 53-8.
11. Özbakır NA, Özşahin A, Edirne T. Knowledge levels and attitudes of primary health care workers about cervical cancer and HPV vaccine. Pamukkale Medical Journal. 2019;12(3):457-66.
12. Naki MM, Celik H, Api O, Toprak S, Ozerden E, Unal O. Awareness, knowledge and attitudes related to HPV infection and vaccine among non-obstetrician- gynecologist healthcare providers. J Turk Ger Gynecol Assoc. 2010;11(1):16-21.
13. Riedesel JM, Rosenthal SL, Zimet GD, Bernstein DI, Huang B, Lan D, et al. Attitudes about human papillomavirus vaccine among family physicians. J Pediatr Adolesc Gynecol. 2005;18(6):391-8.
14. Carvalho NS, Teixeira LM, Pradel EM, Gabardo J, Joly C, Urbanetz AA. Vaccinating against HPV: physicians and medical students point of view. Vaccine. 2009; 27(20): 2637-640.
15. Özdemir S, Akkaya R, Karaşahin KE. Analysis of community-based studies related with knowledge, awareness, attitude, and behaviors towards HPV and HPV vaccine published in Turkey: A systematic review. J Turk Ger Gynecol Assoc. 2020; 21(2): 111
16. Yüksel KB, Şencan H, Kucur SK, Gözükara İ, Seven A, Polat M, et al. The Knowledge and Tendency of Doctors, Nurses and Hospital Staff Working in Dumlupınar University – Evliya Celebi Research and Training Hospital About Human Papilloma Virus (HPV) infections and HPV Vaccination (In Turkish). J Gyn Obst & Neo. 2015; 12(2):64 -7.
17. Jena AB, Goldman DP, Seabury SA. Incidence of sexually transmitted infections after human papillomavirus vaccination among adolescent females. JAMA Intern Med. 2015;175(4):617-23.
18. Revanlı RA, Yüceer C, Şenol E, Erbay A, Çavuş SA. Awareness and Attitude of Family Physicians About Human Papilloma Virus and Herpes Zoster Vaccines. Klimik Journal. 2016;29(1):15-20.
19. Kartal M, Günvar T, Limnili G. What do primary care physicians know about cervical cancer and the HPV vaccine? Turkish Journal of Family Practice. 2011;15(1):1-6.
20. Yıldırım M, Düzovalı Ö, Kanık A, Kırık Ö. Knowledge and Attitudes of The Pediatricians in Turkey Regarding Human Papillomavirus (HPV) Vaccine. Journal of Pediatric Infection. 2009;3:62-8.
21. Tolunay O, Celik U, Karaman SS, Çelik T, Reşitoğlu S, Dönmezer C, et al. Awareness and attitude relating to the human papilloma virus and its vaccines among pediatrics, obstetrics and gynecology specialists in Turkey. Asian Pac J Cancer Prev. 2014;15(24):10723-28.
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Download attachments: 10.4328:ACAM.20901
Seren Ermiş Güven, Zuhal Aydan Sağlam, Ayşe İnci. A case-control study to evaluate awareness level of human papillomavirus among women healthcare professionals in tertiary health care facility. Ann Clin Anal Med 2021;12(12):1427- 1431
Use of serum osmolality as a risk marker in patients with coronary artery disease: A cross-sectional, case-control study
Elif Seda Topuzoğlu 1, Turgut Karabağ 2
1 Department of Family Medicine, Yazlık Family Health Center, Düzce, 2 Department of Family Medicine, Health Sciences University, Istanbul Training and Research Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.20903 Received: 2021-10-12 Accepted: 2021-10-27 Published Online: 2021-11-13 Printed: 2021-12-01 Ann Clin Anal Med 2021;12(12):1432-1436
Corresponding Author: Elif Seda Topuzoğlu, Yazlık Family Health Center, 50th ASM, Düzce, Turkey. E-mail: email@example.com P: +90 506 734 11 90 Corresponding Author ORCID ID: https://orcid.org/0000-0002-9149-7133
Aim: Cardiovascular diseases are the primary cause of mortality and morbidity from non- communicable diseases. The purpose of this study is to examine the role of serum osmolality level for coronary artery disease.
Material and Methods: A cross-sectional case-control study was conducted between July 2019 and January 2020. It included 113 patients aged 35 years older with coronary angiography indication. Eighteen questions were asked to evaluate the sociodemographic characteristics. The patients were divided into two groups: critical coronary artery disease patients (Group 1) and normal coronary artery patients (Group 2). the Syntax and Gensini scores were used to calculate the severity and prevalence of the disease. The venous blood of the participants determined the serum osmolality value.
Results: The median age of patients in Group 1 was 58 (min-max: 37-88) years and 53.5 (min-max: 37-82) years in Group 2. Male sex (p=0.003), age (p=0.02), smoking status (p=0.004), waist-hip ratio (p=0.001), and heart rate (p=0.024) variables in Group 1 were significantly higher than in Group 2. There was no statistical difference between groups in terms of mean osmolality values (p=0.19). Osmolality findings were compared; while Gensini score was statistically significant in Group 1 (p=0.04), the Syntax score was not (p= 0.24). In the correlation analysis of age and osmolality findings with Gensini and Syntax Scores in Group 1, the age variable did not expressively differ. Osmolality increased significantly with the Gensini Score (p= 0.04) and had a weak correlation (r = -0.24). There was no increase (p = 0.24) with the osmolality Syntax Score, and weak correlation (r = – 0.14) was observed.
Discussion: As a result of the study, no statistical difference was found between the two groups in terms of serum osmolality levels.
Keywords: Coronary Artery Disease, Serum Osmolality Level, Gensini Score, Syntax Score
Cardiovascular diseases (CVD) are the prominent cause of morbidity and mortality from non-communicable diseases in the world . Therefore, easy identification of CVD risks and health protection are critical for primary care health services, one of the most important tasks of which is preventive medicine. Atherosclerosis coronary artery disease (CVD) is the most common cardiovascular disease. The pathogenesis of atherosclerosis is a response to vascular damage. The vascular endothelium is affected by blood flow abnormalities, which are influenced by different risk factors. The viscoelastic structure of the blood flow is important in this process, which depends on the corpuscular and biochemical components of the blood [2,3]. Many CVD risk factors have been identified, but they are basically divided into two groups: modifiable and non- modifiable. Non-modifiable risk factors are as follows: family history, sex, and age. Modifiable risk factors include smoking, diabetes mellitus, hypertension, dyslipidemia, sedentary life, and obesity .
Some studies determined that hyperosmolality initiates inflammation and atherosclerosis, causing morbidity and mortality [5,6]. Other studies, proved that hematological parameters such as plasma viscosity, hematocrit, and hemoglobin level are associated with the incidence of CVD [7,8]. Measurement of serum osmolality is a simple and cost- effective method, and examining its usability is important, to determine the risk at the beginning of the atherosclerotic process and to prevent it early by taking preventive measures. The purpose of this study is to examine the correlation between serum osmolality and CVD and to assess its usability for risk models.
Material and Methods
This cross-sectional case-Control study was conducted with people aged 35 years and older, who applied to the Cardiology Polyclinic and Emergency of Health Sciences University Istanbul Training and Research Hospital between July 2019 and January 2020 with any complaint and were found to have an indication for coronary angiography. The population consisted of 113 participants. Participation in the study was voluntary, and the participants were first informed about the study and their verbal consent was obtained. Among the participants, 39 were female and 74 were male, with a median age of 55 years. Following patients were excluded from the study: patients with chronic renal failure, diabetes mellitus, connective tissue disease, malignancy, active infection, heart and/or liver failure, pregnant and lactating women, people who have undergone coronary artery bypass surgery, those who apply to the hospital with acute ST-Elevated Myocardial Infarction, use steroids, have a history of alcohol use in the last 24 hours, persons with fever, acute blood loss and signs of dehydration, patients using antihypertensives that affect electrolyte levels, patients with poor cooperation and orientation.
The study began after obtaining approval from the Ethics Committee of Health Sciences University Istanbul Training and Research Hospital dated 28/06/2019 and numbered 1892. The patients filled out a questionnaire asking age, sex, smoking status, hypertension, diabetes mellitus, renal failure, dyslipidemia, coronary artery disease, family history and medications. Systemic examination was performed before coronary angiography. Systolic and diastolic blood pressure, heart rate, body weight, height, hip, and waist circumference of the patients were measured with a tape measure (cm) and recorded. Weight measurements were made with the same scales. Morning venous blood samples were taken from all study patients after an overnight (at least 8 hours) fasting, and hemogram, pre-prandial blood glucose (PBG), urea, creatinine, AST, ALT, total cholesterol, HDL, LDL, TG, sodium, potassium, calcium levels of patients were measured afterwards. Plasma Osmolality was calculated using these values by the formula: (mOsm/kg) = (2xNa) + (Glucose/18) + (BUN/2.8).
Coronary angiography was performed, and for the assessment, >50% narrowing of the lumen in the main artery or its lateral branch was considered as critical stenosis. The coronary angiography images were examined by two cardiologists who were uninformed about the physical examination findings and complaints of the patients. Two cardiologists decided the level of narrowing in the coronary arteries. The patients were divided into two groups: critical coronary artery disease (stenosis greater than 50%-Group 1) and normal coronary artery disease (stenosis less than 10%-Group 2). Persons with 10%-50% stenosis detected by angiography were not included in the study.
It determined the prevalence of coronary artery disease and to assess the atherosclerotic plaque burden. Since all lesions evaluated in the scoring system, the patient’s total atherosclerotic plaque load can be calculated .
The score determining the prevalence and severity of coronary artery disease, assesses the number of lesions, their functional significance, location, and complexity . The Syntax score focuses on coronary vessel anatomy. This scoring system was prepared for the study named “Syntax”, which was planned to determine the most appropriate treatment strategy for patients with three-vessel and/or left main coronary artery lesions. Statistical Analysis
Statistical Package for the Social Sciences (SPSS 25.0 IBM Statistics for MAC, Version 25.0) version 25.0 statistical package program was used to obtain the data. Controls and analyzes of the data were performed with the same program. The Kolmogorov-Smirnov test was used to examine the compatibility of numerical type features with a normal distribution. Descriptive statistics for numerical variables were expressed as median, and descriptive statistics for categorical data were expressed as numbers and percentages. The independent T-test compared two independent groups when the numerical variables were normally distributed, and with the Mann-Whitney U test when they were not. For quantitative variables, for more than two independent groups, the one-way ANOVA test was used when the assumptions were met, and the Kruskal-Wallis test was used when they were not. The Pearson correlation test analyzed the pairwise correlations of the variables if the assumptions were met, and the Spearman Rho correlation test if they were not. The results were evaluated at a 95% confidence interval, and p<0.05 was accepted as significant.
The study included 113 volunteers; of these, 39 were female and 74 were male. In 71 patients, stenosis of more than 50% was detected in their coronary angiography. Coronary artery stenosis rate in 42 people was below 10%. The groups were divided into 2 groups as >50% stenosis (Group 1) and normal coronary artery (Group 2) to compare the data. Socio- demographic characteristics are presented in Table 1). The distribution of laboratory measurements is shown in Table 2. Correlation analysis was performed using Gensini and Syntax Scoring of serum osmolarity and age (Table 3).
Group 1 consisted of 16 female and 55 male participants, and 23 female and 19 male participants were included in Group 2. A statistically significant difference was found between the groups in terms of gender (p = 0.003). In the study, the mean age in Group 1 was 58.45 ± 10.89 years, and the mean age in Group 2 was 53.57 ± 10.11 years, and the age difference between the groups was statistically significant (p = 0.02). There were 41 smokers and 30 non- smokers in Group 1, and 13 smokers and 29 non-smokers in Group 2, and a statistically significant difference was found (p = 0.004). The mean Waist/ Hip Ratio was 0.94 ± 0.051 for Group 1, and 0.90 ± 0.076 for Group 2, being statistically significant (p = 0.001). The mean heart rate in Group 1 was 94.7 ± 13.6, in Group 2 it was 86.7 ± 23.5, and a statistically significant difference was found (p = 0.024).
The comparison of laboratory values of Group 1 and Group 2 was as follows: preprandial blood glucose (106.52 ± 22.61 mg/ dl vs. 97.23 ± 15.93 mg/dl; p = 0.02);
creatinine (0.78 ± 0.22 mg/dl vs. 0.68 ± 0.14 mg/dl; p = 0.01); total cholesterol (208.23 ± 65.07 mg/dl vs. 181.62 ± 42.77 mg/ dl; p = 0.02); triglyceride values were significantly higher in Group 1 compared to Group 2 (162.12 ± 87.14 mg/dl vs. 124.69 ± 71.47 mg/dl; p = 0.02), while Sodium values were statistically significantly higher in Group 2 than in Group 1 (138.87 ± 2.34 mg/dl vs.139.92 ± 1.73 mg/dl, p = 0.01).
Serum osmolality levels of Group 1 (with stenosis over 50%) and Group 2 (with stenosis below 10%) were 289.52 ± 5.21 mOsm/kg and 290.77 ± 4.31 mOsm/kg respectively. There was no statistically significant difference between Group 1 and Group 2 in terms of the calculated mean serum osmolality levels (p = 0.19)
While the age variable was not significantly different to the Gensini and Syntax scores, osmolality was observed to increase significantly with the Gensini score and form a weak correlation, while it did not create a significant increase with the Syntax score, but still had a weak correlation.
The calculated serum osmolality in the group with more than 50% stenosis in the coronary arteries and the group with less than 10% stenosis in the coronary arteries were with in the normal interval, and there was no statistically significant difference (p = 0.19). Despite this, the preprandial blood glucose (PBG) value of the group with severe coronary artery stenosis was statistically significantly higher than in the other group (p = 0.02). This was thought to be related to stress hyperglycemia. Blood urea nitrogen values were found to be normal, and no significant difference was found.
The sodium values were found to be within the normal interval for both groups and were found to be statistically significantly lower for the group with over 50% stenosis (p = 0.01). The gradual reverse regression of sodium value can also be attributed to stress hyperglycemia because each increase in glucose of 100 mg/dl causes a decrease in sodium value of approximately 1.6 mEq/dl . Hypothyroidism may also cause dilutional hyponatremia. Additionally, the significantly higher total cholesterol, LDL and TG values of patients with coronary artery stenosis >50% may have contributed to this situation by creating pseudohyponatremia.
In the study by Korkut and Sevinç (2021) examining the correlation between chronic diseases and death anxiety; the mean age was 43.62 ± 13.27 years, and the death anxiety score was the highest for 51 years old and over (50.13±12.04) . In our study, the mean age in Group 1, which experienced 50+% stenosis, was 58.4 ± 10.8 years, which is similar to the aforementioned mean age in which death anxiety is high. Wahab et al. (2002) studied 1664 patients who were admitted to the hospital with acute myocardial infarction (a study that did not exclude diabetic patients ) for one year. The study showed that hyperglycemia at the time of admission was associated with clinical outcomes with high mortality, especially for high- risk patient groups . Stress hyperglycemia, increased serum catecholamine and cortisol levels, decreased insulin sensitivity, and the associated increased presence of harmful free fatty acids can explain this .
While urea is absorbed by passive diffusion in the proximal tubule, its absorption from the distal tubule is mostly related to the absorption of water, occurring under the control of anti- diuretic hormone regulated by angiotensin II [15, 16]. Renal hypoperfusion occurring during acute coronary syndrome may cause an increase in BUN and is more valuable than creatinine and glomerular filtration rate (eGHR). A study by Kirtane et al. (2005) of 9420 people with normal and moderately reduced GFR who applied to the hospital with ACS, demonstrated that high BUN values, which contribute significantly to osmolality, can be used as a mortality factor independent of serum creatinine, creatinine clearance and eGFR .
A 10-year study conducted by Funk et al. (2010) including 151,486 people, showed that serum dysnatremia detected during hospitalization of patients admitted to the intensive care unit may be an indicator of poor prognosis regardless of the underlying diseases . Tatlisu et al. (2017) found that hyperosmolality can be an independent indicator in determining the duration of hospitalization and, in the long-term, mortality in a study including 3748 patients who applied to the hospital with ST-elevation myocardial infarction (STEMI) and underwent coronary angiography. Patients were divided into 4 quadrants (Q1, Q2, Q3, Q4) from lowest to highest according to their osmolality values at the time of admission to the hospital; it was observed that the quartile with the highest osmolality (Q4) experienced more cardiogenic shock, acute respiratory failure, ventricular arrhythmia, stent thrombosis, recurrent MI, revascularization, and mortality rate (95%) during the hospitalization. When the 3-year survival of these groups was examined, the complication and mortality rates of Q4 were higher . As a result, high serum osmolality value was determined to negatively affects the prognosis of coronary artery disease.
A six-year study by Kaya et al. (2017) including 509 people examined the success of plasma osmolality in determining mortality for heart failure patients with low ejection fraction (EF) and found that hypoosmolality was an indicator that could be used independently of EF, Brain Natriuretic Peptide (BNP) and functional capacity .
Excluding DM patients prevented us from making a comparison, but when we evaluated biochemical indicators, prediabetic patients were included in the study. A study of 315 people by Rasouli et al. (2008) found that there was a significant correlation between the severity of CAD and serum osmolality, especially between glucose and BUN values, but the correlation decreased for diabetic patients .
Zhao T et al. (2018) conducted a study to determine the predictive value of PBG in determining the severity of coronary artery disease. They revealed that PBG showed a positive correlation with the Gensini score for non-diabetic patients after applying coronary angiography to 64 people, but they did not find any correlation with the Syntax score . The results of the study are similar to ours. This may be because the significant positive correlation of the Syntax score starts with 50% coronary artery stenosis, while the Gensini score starts with 25% coronary artery stenosis. Considering this, Gensini scoring is a more sensitive scoring system for detecting early atherosclerosis.
This study was a single-center study. Diabetes mellitus and kidney failure diseases made the groups more sterile and caused a decrease in the number of cases. In addition, the use of calculated data instead of measured osmolality can be considered as a limitation. Not requesting TSH tests from patients who were to undergo angiography was also accepted as a limitation that prevents the implications of thyroid disorders on the findings.
This study sought an answer to the question of whether serum osmolality can be a risk factor that can be used to detect coronary artery diseases. We found that there was no significant difference between the serum osmolality of the two groups when we excluded diabetes mellitus and severe organ failure for the two groups who underwent coronary angiography and had >50% stenosis and <10% stenosis in the coronary arteries. Since we could not find another study with such broad exclusion criteria in the literature, we think that our study is specific in its field; besides, the importance of osmolality regarding the development of CAD can be discussed more clearly and reliably with multi-center studies with a higher number of cases. Values such as increased blood sugar, total cholesterol, triglyceride, waist-hip circumference ratio of the group with coronary artery stenosis above 50% suggested the possibility of prediabetes; the previous studies show that in cases where each parameter affecting osmolality is worsened, it poses a risk in terms of cardiovascular diseases, regardless of the underlying cause.
For the non-communicable disease group, it is critical for public health to determine the risk factors for coronary artery disease, and to take measures. It is possible to increase the life quality and expectancy by determining the risk score with an as inclusive approach as possible and taking protective measures for it.
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Elif Seda Topuzoğlu, Turgut Karabağ. Use of serum osmolality as a risk marker in patients with coronary artery disease : A cross-sectional, case-control study. Ann Clin Anal Med 2021;12(12):1432-1436
Pancreatic hydatid cyst located distally: A case report
Deniz Öçal 1, Tolga Kalaycı 2
1 Department of Gastroenterology Surgery, 2 Department of General Surgery, Erzurum Regional Education and Research Hospital, Erzurum, Turkey
DOI: 10.4328/ACAM.20631 Received: 2021-04-01 Accepted: 2021-06-22 Published Online: 2021-07-15 Printed: 2021-12-01 Ann Clin Anal Med 2021;12(12):1437-1439
Corresponding Author: Deniz Öçal, Department of Gastroenterology Surgery, Erzurum Regional Education and Research Hospital, Erzurum, Turkey. E-mail: firstname.lastname@example.org P: +90 505 297 33 30 Corresponding Author ORCID ID: https://orcid.org/0000-0002-8084-8866
A 52-year-old male patient admitted to the hospital with abdominal pain, postprandial bloating, and occasional nausea and vomiting for about 6 months. On abdominal physical examination, the patient had abdominal pain with deep palpation in the left upper quadrant. Echinococcus indirect hemagglutination antigen (IHA) test of the patient was positive in 1/640 titer. On CT scan, there was a cystic mass approximately 70 * 60 mm in size in the distal pancreas and bilateral renal cysts. Albendazole treatment was initiated with a dose adjustment according to the patient’s weight for 4 weeks. After a 14-day break from albendazole treatment, the patient was prepared for elective surgery. Total cyst resection was performed with partial distal pancreas resection without perforation. Control abdominal CT was performed to evaluate the abdominal cavity on postoperative day 5, and no pathology was observed. Therefore, both drains were taken out. The patient was discharged on the sixth postoperative day.
Keywords: Albendazole, Echinococcus Granulosus, Hydatid Cyst, Pancreas
Hydatid cyst (HC), caused by Echinococcus granulosus or Echinococcus multilocularis parasite, is mostly seen in the liver and lungs, it can rarely be seen in all organs and soft tissues. In the studies conducted, the incidence of isolated pancreatic hydatid cyst has been reported to be 1-2% . Due to the low prevalence of the disease, it is often confused with cystic lesions of the pancreas, often with pseudocysts. HC can be asymptomatic for a long time. Symptoms vary according to the size and location of the cyst. As the size of the cyst grows, symptoms occur due to compression on surrounding organs. Basic laboratory tests (hemogram, biochemical analysis, tumor markers), Echinococcus indirect hemagglutination antigen (IHA) test, and imaging tools can be helpful at diagnosis. In cases scheduled for operation, surgery should be planned after 1 month of albendazole treatment .
In this case report, we aimed to present a patient with HC localized distal to the pancreas.
A 52-year-old male patient admitted to Erzurum Regional Education and Research Hospital, Erzurum, Turkey in August 2019. He had abdominal pain, postprandial bloating, and occasional nausea and vomiting for about 6 months. The patient’s complaints had increased significantly in the last month. The patient had no additional disease, except for a history of tuberculosis 10 years ago. In addition, the patient underwent splenectomy due to trauma four years ago.
On evaluation, the vital findings of the patient were as follows: blood pressure: 134/72 mm Hg, pulse rate: 108 beats per minute, oxygen saturation on room air: 96%, and body temperature: 37.7o Celsius. The patient’s height was 172 millimeters and he weighed 82 kilograms. On physical examination of abdomen, the patient had abdominal pain with deep palpation in the left upper quadrant. A digital rectal examination was also normal. Other system examinations were normal. In laboratory findings, basic hemogram, biochemical parameters were unremarkable. Tumor markers (carcinoembryonic antigen, CA19-9, alpha- fetoprotein) of the patient were also normal. Echinococcus indirect hemagglutination antigen (IHA) test of the patient was positive in 1/640 titer.
Ultrasound revealed a mass with a diameter of 60 mm between the distal pancreas and left kidney (simple cyst or cyst hydatic). Both computed tomography (CT) and magnetic resonance imaging (MRI) were planned for the patient to evaluate the origin of the mass and the surrounding organ neighborhood. On CT scan, there was a cystic mass approximately 70 * 60 mm in size in the distal pancreas and bilateral renal cysts (Figure 1). According to the classification of echinococcal cysts by the World Health Organization (WHO), this mass was considered as CE 2 (active stage). On MRI, a cystic lesion 65x55x77 mm in size in the tail of the pancreas was seen (Figure 2).
After IHA test positivity, CT and MRI images were evaluated together, hydatid cyst was considered in the patient, and albendazole treatment was initiated by dose adjustment according to the patient’s weight (albendazole tablet 400 mg every 12 hours) for 4 weeks. After a 14-day break from albendazole treatment, the patient was prepared for elective surgery. Open surgery was performed with a midline incision. On intraoperative evaluation, a cystic mass was seen anterior of the left kidney. Sponges impregnated with the hypertonic solution were placed around the mass. The mass was resected completely without perforation. The cyst was opened on the operation table. There were multiple daughter cysts with germinative membrane. A drain was placed at the border of the distal pancreas (drain 1), while the other drain was placed at the left sub-diaphragmatic area (drain 2).
The patient was followed in the service during the postoperative period. Oral intake was opened 6 hours after surgery. On the postoperative day 1, about 200 cc serohaemorrhagic fluid came from drain 1, while there was no fluid coming out of drain 2. The amylase level of drain (1) fluid was measured as 1224 U/L, and the serum amylase level was 480 U/L at the same time (normal range= 30-118 U/L). On the postoperative day 2, about 100 cc of serous fluid came out of drain 1. The amylase level of drain (1) fluid was measured as 743 U/L, and the serum amylase level was 230 U/L at the same time. On the postoperative day 3, about 50 cc of serous fluid came out of drain 1. The amylase level of drain (1) fluid was measured as 243 U/L, and the serum amylase level was 78 U/L at the same time. On the postoperative day 4, no fluid came from drain 1, and the serum amylase level was 63 U/L. Control abdominal CT was performed to evaluate the abdominal cavity on the postoperative day 5, and no pathology was observed. Therefore, both drains were taken out. The patient was discharged on the sixth postoperative day with no complications. The postoperative pathology was suitable with hydatid cyst. Albendazole treatment, which was initiated preoperatively, continued for 2 more months.
Echinococcus granulosus or Echinococcus multilocularis cause hydatid cyst (HC) in humans. HC is an important public health problem, especially in undeveloped and developing countries in Africa and South Asia. It is also common in Turkey, especially in the Eastern Anatolia and Southeastern Anatolia regions . Approximately 2/3 of HC cases are located in the liver. The second most common site is the lungs. However, HC can develop in any organ or tissue. The clinical presentations of the echinococcus vary depending on the involvement of the organ and the size of the cysts. While small or calcified hydatid cysts may be asymptomatic, large hydatid cysts may exert pressure or may rupture. Cysts may grow 1-5 cm in size per year or may stay silent for years .
The incidence of isolated pancreatic HC is 1-2%, and 50% of these are located in the head of the pancreas [1, 3]. HC can be asymptomatic for a long time. Symptoms vary according to the size and location of the cyst. As the size of the cyst grows, symptoms occur due to compression on surrounding organs. Complaints such as abdominal pain, bloating and nausea may be seen. Rarely, obstructive jaundice and cholangitis may occur in cysts located in the head part due to compression on the bile ducts. Acute and chronic pancreatitis can also be seen in hydatid cysts that cause compression on the pancreatic canal and fistula .
Laboratory tests, Echinococcus indirect hemagglutination antigen (IHA) test and radiological imaging tools are used for diagnosing. There are no specific laboratory tests for making a diagnosis. Since it is a parasitic disease, eosinophilia was not observed in our patient. ELISA and IHA are commonly used during diagnosis. The sensitivity of IHA is 60-100%, but its specificity is reported to be low. Serological tests may be negative if the amount of antigen in the bloodstream is low . The septal structure and daughter vesicles can be seen on ultrasonography. Advanced imaging tools such as CT, MRI are used to evaluate the differential diagnosis and to evaluate the organ surrounding the cyst. It is difficult to distinguish HC located in an isolated pancreas from other cystic and solid lesions of the pancreas. It has been reported in the literature that the definitive diagnosis of pancreatic hydatid cysts can usually be made during surgery in many cases. Spontaneous perforation, abscess formation and compression findings such as vomiting, nausea are the main complications in untreated cases . In this patient, the diagnosis of hydatid cyst was diagnosed with a combination of IHA and CT/MRI.
Medical treatment is preferred both preoperatively and postoperatively. Depending on the weight of the patient, albendazole treatment is started 4 weeks before surgery. In patients weighing 60 kg and over, albendazole treatment is started with 400 mg twice a day. In patients weighing less than 60 kg, albendazole treatment is started at 15 mg/kg per day. Depending on the hepatotoxic effect of albendazole, treatment should be performed intermittently (1 month continuous treatment-15 days interval) .
Unlike liver hydatid cyst, percutaneous drainage has been reported in very few patients in pancreatic hydatid cyst . Partial cystectomy, cysto-enteric anastomosis, cystotomy drainage and omentoplasty can be applied in surgical treatment, depending on the location of the cyst and the relationship of the pancreatic duct. Distal pancreatectomy is preferred in cases with corpus and tail localization . In our case, the cyst could be completely removed by partial distal pancreatectomy.
In conclusion, pancreatic HC is a rare disease. The HC of the pancreas is mostly located in the head of the pancreas. Symptoms depend on the location of the cyst. Laboratory tests, Echinococcus indirect hemagglutination antigen (IHA) test and radiological imaging tools are used for diagnosis. The main purpose of treatment is complete excision of the cyst, if possible, and the continuation of albendazole treatment afterwards.
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Download attachments: 10.4328:ACAM.20631
Deniz Öçal, Tolga Kalaycı. Pancreatic hydatid cyst located distally: A case report. Ann Clin Anal Med 2021;12(12):1437-1439