September 2022
Evaluation of the radiocontrast nephropathy development due to the contrast-enhanced CT applications in emergency department
Gülçim Saraçoğlu 1, Sedat Yanturalı 2, Rıdvan Atilla 2, Başak Bayram 2, Pınar Yeşim Akyol 3
1 Department of Emergency, Muğla Sıtkı Koçman University, Research and Training Hospital, Muğla, 2 Emergency Department, Dokuz Eylül University, Izmir, 3 Emergency Department, Katip Çelebi University, Atatürk Research and Training Hospital, Izmir, Turkey
DOI: 10.4328/ACAM.20768 Received: 2021-07-26 Accepted: 2021-10-05 Published Online: 2022-08-24 Printed: 2022-09-01 Ann Clin Anal Med 2022;13(9):947-951
Corresponding Author: Pınar Yeşim Akyol, Department of Emergency Medicine, Izmir Katip Çelebi University, Atatürk Training and Research Hospital, İzmir, Turkey. E-mail: yesimakyol@gmail.com P: +90 505 357 29 41 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2477-1443
Aim: We aimed to determine the incidence of post-contrast acute kidney injury (PC-AKI), the demographic characteristics of patients, and the reasons that facilitate the development of PC-AKI in patients who were admitted to the emergency department and underwent computed tomography (CT) with intravascular contrast media.
Material and Methods: This study is a retrospective, cross-sectional and analytical study. Patients over the age of 18 who underwent CT with intravascular contrast media and were hospitalized for at least 48 hours were included in this study. The development of PC-AKI and the clinical and demographic characteristics of the patients were evaluated.
Results: A total of 816 patients were included in the study. Thirty-six (4.4%) patients developed PC-AKI. We found that the average length of hospital stay was 22.2 ± 41.7 days. Patients with a history of hypertension (HT) and diabetes mellitus (DM) and who had hypotension on admission to the emergency department were found to have a higher risk of developing PC-AKI (p<0.05 for all of them). The development of PC-AKI was significantly higher in patients receiving ACE inhibitors (p=0.004). When the clinical outcomes of the patients with PC-AKI were evaluated, it was observed that 47.2% (n=17) of them died. Mortality was statistically significantly higher in patients with PC-AKI than in the patients without PC-AKI (p<0.0001).
Discussion: PC-AKI led to an increase in the length of hospital stay of patients. The patients with PC-AKI had a higher mortality rate compared with the patients without PC-AKI.
Keywords: Contrast Material, Emergency Department, Nephropathy
Introduction
Post-contrast acute kidney injury (PC-AKI) is defined as an elevation of serum creatinine > 0.3 mg/dl (or > 26.5 µmol/l), or > 1.5 times baseline, within 48-72 hours of intravascular administration of a contrast agent. [1]
The development of PC-AKI depends on the physical and chemical properties of the agent used, together with the features of the patient. Because of the differences in the definition of acute renal failure (ARF) and the presence of comorbid conditions in patients, the incidence of PC-AKI in various studies ranged from 3.1% to 31%. [2] In patients with various risk factors, the incidence of PC-AKI can increase up to 50%.[3]
In this study, we aimed to determine the risk of developing PC-AKI in the emergency department (ED) and to demonstrate the risk factors for PC-AKI.
Material and Methods
Our ED is a center that receives an average of 85,000 patients annually. In our ED, a multidetector computed tomography (MDCT) (Siemens SOMATOM Sensation 16 Slice CT Scanner) is used for CT imaging. Iopromide (Iopromide, Ultravist©; 370-100 mLflk. Bayer Schering Pharma), which is a non-ionic second-generation contrast agent, is used as an intravenous contrast agent.
This is a retrospective, cross-sectional analytical study. Ethical approval was obtained from University Ethics Committee for Non-Interventional Studies (Decision No: 2011/41-09).
Research Method
Patients who were admitted to our ED and who underwent CT with intravascular contrast media were investigated using the Hospital Information Management System (HIMS). Among these patients, those over 18 years of age who received contrast material and who were transferred to any hospital ward or were hospitalized for more than 48 hours in the ED were included in our study. The demographic information, clinical and laboratory data, diagnoses, clinical outcomes and prophylactic treatment were evaluated by the researchers.
Exclusion criteria were as follows: age under 18 years, having chronic kidney disease or being under regular hemodialysis (HD) program, having inaccessible data files, patients who died within 48 hours after administration of contrast material, patients whose creatinine levels were not measured before or 48-72 hours after the administration of contrast material, patients who were discharged from the ED within the first 48 hours after administration of the contrast material or who were referred to another hospital or who were left from the ED at their own request.
Evaluation of PC-AKI
Patients with an elevation of serum creatinine of more than > 0.3 mg/dl (or > 26.5 µmol/l), or > 1.5 times baseline, within 72 hours of intravascular administration of a contrast agent were considered “Acute Renal Failure” (ARF). Patients who had any diagnosis [prerenal, renal, postrenal] that may increase serum creatinine levels and who were treated for secondary renal failure by physicians were classified as renal insufficiency due to other causes and were not evaluated as PC-AKI. Patients with ARF who did not have prerenal, renal, and postrenal causes were considered a PC-AKI. Patients who had an infusion of sodium chloride solutions (0.9% and/or 0.45%) at a rate ≥100 m L/hour for at least 4 hours before administration of contrast material were described as receiving prophylactic treatment for PC-AKI. [1]
Registration of data and statistical analysis
The obtained data were recorded in data forms in the Statistical Package for Social Sciences for Windows 15.0’’. The t-test was used to compare the difference between the two means. The Chi-square test was used to compare categorical variables. When the expected value was ≤5, it was evaluated using “the Fisher’s Exact test”. A p-value of <0.05 was considered statistically significant.
Results
Among the 816 patients included in our study, 46.8% (n=382) were female and 53.2% (n=434) were male. The mean age of the patients was 61.0 ± 17.7 years (range: 18-115 years). Nephropathy developed in 75 (9.2%) of the 816 patients after administration of contrast material. When patients with prerenal, renal, and postrenal conditions that may lead to ARF were excluded, 36 (4.4%) developed PC-AKI.
The mean age of the 36 patients with PC-AKI was 67.9±13.2 years (range: 40-86 years); of them, 52.8% (n=19) were females and 47.2% (n=17) were males. There was no statistically significant difference between men and women in terms of the development of PC-AKI (p=0.574)
Contrast media quantity
The quantity of contrast material in the 36 patients who developed PC-AKI is shown in Table1. There was no relationship between the amount of contrast material and the development of PC-AKI (p=0.403, Table-1).
Comorbid diseases
The relationship between comorbid diseases and the development of PC-AKI is shown in Table-2.
Drugs
Twenty-six (3.2%) of 816 patients received ACE inhibitors (ACEI) in the last week. It was found that 19.2% (n=5) of them developed PC-AKI. The development of PC-AKI was higher in those treated with ACEI compared to those treated without ACEI (p=0.004).
Prophylactic Treatment
When the patients who received only prophylactic IV fluid were compared with the patients who did not receive prophylactic IV fluid, there was no difference between them in terms of the development of PC-AKI (p>0.05).
Blood Pressure
Among the 36 patients who developed PC-AKI, 63.9% (n=23) were normotensive, 13.9% (n=5) were hypotensive, and 22.2% (n=8) were hypertensive. Hypotensive patients had a higher risk of developing PC-AKI compared with normotensive patients (p=0.035). There was no difference between hypertensive patients and normotensive patients in terms of the development of PC-AKI (p=0.103).
Surgical Intervention
Among the 816 patients, 80.8% (n=659) did not undergo surgical intervention within 48 hours after administration of contrast material, whereas 19.2% (n=157) underwent surgical intervention. When the patients were compared for surgical
intervention, there was no difference between them in the development of PC-AKI (p=0.2940).
HD Necessity
Among the 36 patients who developed PC-AKI, 94.4% (n=34) did not undergo HD, whereas 5.6% (n=2) underwent HD.
Prognosis after nephropathy
Among the 36 patients who developed PC-AKI, creatinine levels returned to baseline during follow-up in 50.0% (n=18). However, 47.2% (n=17) were clinically dead. We determined that one patient developed nephropathy with a lower creatinine clearance rate.
Duration of hospitalization
It was found that the average length of hospital stay was 13.9±17.6 days (range: 2-205 days). The average length of hospital stay was 22.2±41.7 days (range: 2-205 days) in the patients with PC-AKI and 13.5±15.5 days (range: 2-205 days) in the patients without PC-AKI, respectively. The average length of stay in the hospital was approximately two times higher in the patients with PC-AKI than in the patients without PC-AKI.(p<0,001)
Clinical Outcomes
The mortality rate was found to be higher in the patients with PC-AKI than in the patients without PC-AKI (p<0.001, Table-3).
Discussion
Nash et al. [4] determined that PC-AKI was the third most common cause of ARF in hospitalized patients. However, the number of studies on the incidence of PC-AKI in EDs is very limited in the current literature. The majority of the studies were performed in patients who underwent percutaneous coronary intervention (PCI). Studies reported the incidence of PC-AKI changing between 2,9% and 11% [5-7]. A large, single-center study reported that contrast agent did not increase acute renal failure in contrast to what is known [8]. In our study, the incidence of PC-AKI was found to be 4.4%. Our result is lower compared to other studies. In our study, because we could not evaluate patients discharged from the ED after administration of contrast material, it is not possible to mention precisely the incidence of PC-AKI in all patients in the ED. However, monitoring of patients in hospital wards is associated with the severity of the condition leading to emergency service applications. The fact that the incidence of PC-AKI was low in these patients despite the comorbid diseases suggests that contrast-enhanced diagnostic tests can be performed safely in these patients in the ED.
Previous studies have reported that the female gender is a risk factor for the development of PC-AKI. [3,9,10] In our study, there was no statistically significant difference between the genders in terms of the development of PC-AKI.
While Bartholomew et al. [11] considered a contrast agent dose ≥ 260 mL as a high-risk factor, Mehran et al. [3] determined a contrast agent dose ≥150 mL as an independent risk factor. Marenzi et al. [12] reported that a contrast agent dose ≥ 300 mL was an independent risk factor. However, it was reported that PC-AKI can be seen even at doses as low as 30 mL in very high-risk patients [13]. The PC-AKI Consensus Working Panel accepts that the use of contrast agent ≥100 ml increases the risk of developing PC-AKI [14]. In our study, there was no relationship between the amount of contrast material and the development of PC-AKI. In a study of 114 patients, they reported that the use of contrast agent ≤100 mL did not increase the risk of developing PC-AKI [15]. Unlike our study, only patients with serum creatinine levels <1.5mg/dl were included in this study. When the results of our study are evaluated, it can be said that there is no need to reduce the amount of contrast agent used in CT imaging in order to prevent PC-AKI in emergency services.
Several studies have shown that DM increased the risk of developing PC-AKI [3,11, 12,16]. In our study, we found that the development of PC-AKI was significantly higher in diabetic patients. This result is not surprising because diabetic patients tend to develop nephropathy, take medication excessively and are at greater risk of developing secondary diseases such as HT and CAD, which may be associated with kidney diseases. Studies reported that HT was a risk factor for the development of PC-AKI [3,9,16]. We found that there was a statistically significant increase in the risk of developing PC-AKI in the patients with HT. Further studies are needed to assess whether this is due to the primary effect of HT on the kidneys or to antihypertensive drugs used by these patients. Previous studies have reported that CHF increased the risk of developing PC-AKI [3,16,17]. In our study, there was no increase in the risk of developing PC-AKI in patients with CHF. We think that this is due to the fact that, unlike many other studies, our study was performed not only on patients who underwent PCI for cardiac problems, but also on patients who were admitted to the ED and received contrast material. ACEI have been defined as a risk factor for the development of PC-AKI due to their nephrotoxic effects [18]. Similarly, we found that the development of PC-AKI was higher in those treated with ACEI.
Many treatment methods have been tried for preventing the development of PC-AKI. Studies have shown that the development of PC-AKI significantly decreased if IV fluids were given at a rate of 100-150 mL/hour during 12 hours before and after PCI. [19] In our study, there was no significant difference between patients treated with and without IV fluids.
Hypotension has been defined as a risk factor for the development of PC-AKI [3,20]. Similarly, we found that hypotension was a risk factor for the development of PC-AKI. It is not surprising that the risk of PC-AKI development increased in these patients due to the effect of hypotension on the kidneys.
Many studies have been shown that ARF after surgical intervention was most commonly seen in patients who underwent cardiovascular surgery [21]. Major surgery has been defined as a risk factor for developing postoperative ARF. The most common cause of postoperative ARF is hemodynamic instability that occurs during the surgery (hypotension) [21]. In our study, there was no difference in the development of PC-AKI between patients treated with and without surgical intervention within 48 hours after administration of contrast material. We think that this is due to the fact that the majority of previous studies have been performed on patients undergoing PCI, and cardiac surgery has been frequently made after the procedure in these patients. However, in the literature, we could not find any study comparing the incidence of PC-AKI between other surgical procedures.
The need for dialysis after PC-AKI varies according to the risk factors of the patient at the time of contrast administration, but is usually less than 1% [14]. In a study by Nikolsky et al. [22], it accounted for 3.1%. We found that 5.6% of patients with PC-AKI underwent dialysis. Studies have reported that PC-AKI was associated with prolonged hospital stay [16,20,22]. Similar to other studies, we had the same result.
Many studies have been published on the relationship between PC-AKI and short- and long-term mortality. In previous studies, mortality rates in patients with PC-AKI ranged from 7.1 to 39, and between 1.1-1.4 in patients without PC-AKI [9,16,22,23]. We found that the mortality rate was 47.2% in patients with PC-AKI and 13.7% in patients without PC-AKI, respectively. Our patient population consisted mainly of elderly patients with comorbid diseases. Even a small reduction in renal function due to contrast material in the presence of comorbid conditions may lead to higher morbidity rates.
Limitations
Firstly, similar to other retrospective cross-sectional studies, information of all patients was not reached. Patients who were hospitalized for 48 hours or more after taking CT in the ED were included in the study.
Conclusion
Patients who had a history of HT and DM, who received ACEI within the last 1 week and who had hypotension on admission to the ED were at a higher risk of developing PC-AKI. It was determined that only 5.6% of the patients with PC-AKI required HD and that the patients with PC-AKI had a two-fold longer length of hospital stay.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Download attachments: 10.4328:ACAM.20768
Gülçim Saraçoğlu, Sedat Yanturalı, Rıdvan Atilla, Başak Bayram, Pınar Yeşim Akyol. Evaluation of the radiocontrast nephropathy development due to the contrast-enhanced CT applications in emergency department. Ann Clin Anal Med 2022;13(9):947-951
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Surgical removal of asymptomatic polyps detected on the day of egg collection increases fertility outcome
Ramazan Ozyurt
Department of Obstetrics and Gynecology, Istanbul IVF-Center, Istanbul, Turkey
DOI: 10.4328/ACAM.21014 Received: 2021-12-22 Accepted: 2022-08-11 Published Online: 2022-08-11 Printed: 2022-09-01 Ann Clin Anal Med 2022;13(9):952-954
Corresponding Author: Ramazan Ozyurt, Department of Obstetrics and Gynecology, Istanbul IVF-Center, Istanbul, Turkey. E-mail: atasagun02@hotmail.com P: +90 532 748 34 90 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6822-2222
Aim: In this study, we aimed to determine the impact of surgical removal of polyps that were detected incidentally on the day of egg collection on the fertility outcome.
Material and Methods: Forty-five patients who were suspected of having polyps in the ultrasonographic examination performed during egg collection were included in the study. The patients were informed about the endometrial polyp and hysteroscopy was recommended. While 30 of 45 patients accepted hysteroscopy, 15 patients did not. Patients who did not undergo hysteroscopy continued their routine treatment and embryo transfer was performed. Polyps of different localizations and sizes were detected in 28 of 30 patients who underwent hysteroscopy and were surgically removed. No polyps were found in two patients. Frozen embryo transfer was performed to the patients after polypectomy. A single embryo was given to the patients in both groups. The primary outcome measures of the study were detection of serum beta-hCG levels, clinical pregnancy rate (CPR), live birth rate (LBR), and miscarriage rate.
Results: The mean size of the polyps was 15 mm (range 2 mm to 25 mm). Beta hCG values measured after 12 days in the polypectomy group were positive in 14 of 28 patients (50%). Beta hCG positivity was detected in 6 of 15 patients in the control group (40%). Beta hCG positivity was significantly higher in the polypectomy group than in the control group (p<0.02). Clinical pregnancy was detected in 13 of 14 patients in the polypectomy group (46.4%). In the control group, clinical pregnancy was detected in 5 patients (33.3%). A significant increase was found in the polypectomy group in terms of CPR rates (p<0.01). While 11 patients in the polypectomy group had a live birth (39.2%), 5 patients in the control group had a live birth (33.3%). There was no difference between the groups in terms of live birth and miscarriage rates (p<0.76 and p<0.40 respectively).
Discussion: Surgical removal of asymptomatic polyps detected on the day of egg collection leads to a significant increase in clinical pregnancy rates.
Keywords: Polypectomy, Egg Retrieval Day, Clinical Pregnancy, Live Birth, Miscarriage
Introduction
Endometrial polyps are considered to be the most common acquired uterine cavity anomalies. They are single or multiple stalked or sessile endometrial neoplasms consisting of glands, stroma and blood vessel triad [1]. Although they are generally benign lesions, 0-10% malignant transformation may occur in the polyp or in the surrounding endometrial tissue [2]. Although it occurs mostly in the reproductive age, it can also be seen in the postmenopausal period. However, it is not clear whether the menopausal polyps are denova formation or polyps from the reproductive age. It may be asymptomatic or may lead to postcoital spotting, abnormal uterine bleeding, or infertility [3]. The incidence of polyps increases in the elderly, with the use of tamoxifen, in the presence of hypertension, PCOS, and obesity [4]. Although 2D or 3D transvaginal ultrasound, saline contrast sonohysterography and hysterosalpingography are the most used methods in the diagnosis of polyps, hysteroscopy is considered the most sensitive method because it offers both diagnosis and simultaneous treatment [5]. Although the incidence of polyps in asymptomatic infertile patients undergoing diagnostic hysteroscopy before IVF/ICSI varies between 6-32% [6], its incidence varies between 1-40% according to the patient group studied and the diagnostic tests performed [7].
Subfertility-producing effect of endometrial polyps may occur due to the mechanical or non-mechanical effect of the lesion, or may occur due to the combined effect of both. The fact that more than half of the patients who underwent hysteroscopic polypectomy became pregnant indicates the importance of surgical removal of polyps [8]. It has been reported that both hysteroscopic polypectomy before IUI [9] and surgical removal of polyps located at uterotubal junction before IVF/ICSI lead to a significant increase in pregnancy rates [10]. Opinions on the removal of asymptomatic polyps detected during egg collection are not clear [11]. This study was designed to determine the effects of surgical removal of polyps that were detected incidentally on the day of egg collection on the fertility outcome.
Material and Methods
Forty-five IVF/ICSI patients who were suspected of having polyps in the ultrasonographic examination performed during egg collection were included in the study. The patients were informed about the endometrial polyp and hysteroscopy was recommended. While 30 of 45 patients accepted hysteroscopy, 15 patients did not. Patients who did not undergo hysteroscopy continued their routine treatment and embryo transfer was performed. Polyps of different localizations and sizes were detected in 28 of 30 patients who underwent hysteroscopy and were surgically removed. No polyps were found in two patients. Frozen embryo transfer was performed to the patients after polypectomy. A single embryo was given to the patients in both groups. The primary outcome measures of the study were detection of serum beta-hCG levels, clinical pregnancy rate (CPR), live birth rate (LBR), and miscarriage rate. Clinical pregnancy rate is defined as evidence of a gestational sac, confirmed by ultrasound examination at the 4th week of the transfer. Live birth rate is defined as the delivery of a live fetus after 24 completed weeks of gestational age. Serum beta-hCG levels were measured in all patients on the 12th day of embryo transfer. The loss of the fetus before 20 weeks of gestation was defined as miscarriage. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and approval for the study was obtained from the Institutional Review Board.
Statistical analysis
SPSS 21.0 (IBM Corporation, Armonk, NY, USA) was used for the statistical analysis of the data. Quantitative data were expressed as mean ± standard deviation (SD). The normality distribution of data was analyzed with Shapiro–Wilk test and found to be normal. Continuous variables were analyzed using the Mann-Whitney U test. A p-value <.05 was considered significant.
Results
There was no difference between the group that underwent polypectomy and the group that did not, in terms of age, BMI, infertility periods, rFSH dose used, endometrial thickness, and basal hormone levels. MII oocyte and 2PN embryo counts were also similar. The mean size of the polyps was recorded as 15 mm (range 2 mm to 25 mm). Beta hCG positivity and clinical pregnancy rates were significantly higher in the polypectomy group than in the non-polypectomy group. Beta hCG values measured after 12 days in the polypectomy group were positive in 14 of 28 patients (50%). Beta hCG positivity was detected in 6 of 15 patients in the control group (40%). Beta hCG positivity was significantly higher in the polypectomy group than in the control group (p<0.02). Clinical pregnancy was detected in 13 of 14 patients in the polypectomy group (46.4%). In the control group, clinical pregnancy was detected in 5 patients (33.3%). A significant increase was found in the polypectomy group in terms of CPR rates (p<0.01). While 11 patients in the polypectomy group had a live birth (39.2%), 5 patients in the control group had a live birth (33.3%).
There was no difference between the groups in terms of live birth rates (p<.0.76). Abortion was detected in 3 patients (21.4%) in the polypectomy group and 1 patient in the control group (16.6%). There was no difference between the groups in terms of abortion rates (p<0.40).
Discussion
Endometrial polyps may interact mechanically with both sperm and embryo transport, leading to subfertility. The size, number, and location of the polyp determine the severity of the mechanical interaction between the embryo, sperm and the polyp [12]. It can be accepted that sessile polyps with a small implantation base are more innocent lesions than pedunculated and/or sessile polyps with a large implantation base in terms of the possibility of mechanical interaction [5,10,13]. In addition to their mechanical effects, polyps may also cause subfertility by disrupting endometrial receptivity. Potential mechanisms whereby endometrial polyps could adversely affect reproductive outcomes include the release of receptivity molecules and genes that adversely affect sperm transport or embryo attachment.
Based on clinicians’ practice or when the results of polypectomy studies are reviewed separately, the performance of polypectomy in subfertile patients who are asymptomatic for polyps comes to the fore. On the other hand, most of the available data do not have sufficient scientific basis to recommend routine polypectomy in subfertile patients with asymptomatic polyp [5]. Although the risk of subfertility due to a polyp that covers the tubal ostium or internal os seems to be more evident, polyps can cause subfertility regardless of their number, location and size and therefore need to be treated [8,10]. Despite the abundance of data supporting polypectomy, many of the studies showing that polypectomy improves fertility outcomes in infertile patients consist of low-quality and observational studies [14]. In our study, polyps were not classified according to their location. When the polyps in the entire location were evaluated together, we found clinical pregnancy in 46.4% of the patients who underwent polypectomy. In those who did not undergo polypectomy, the clinical pregnancy rate was 33.3%. Polypectomy resulted in approximately 13% of extra pregnancies. As a result, surgical removal of asymptomatic polyps detected on the day of egg retrieval, regardless of location, leads to a significant increase in clinical pregnancy rates. However, polypectomy did not lead to a significant increase in live birth rates. We found the abortion rates of both groups to be similar. It has been reported that polypectomy performed before intrauterine insemination increases clinical pregnancy rates [9]. Similarly, it has been suggested that polyps detected during routine examinations in IVF/ICSI patients should be considered for whether or not they should be operated according to their localization. It has been reported that removal of polyps located at the uterotubal junction significantly increases pregnancy rates compared to other locations. Yanaihara et al [10] reported 57% clinical pregnancy after IVF/ICSI procedures performed after removal of uterotubal polyps. While this rate was 28.5% in the posterior wall, it was reported as 14.8% in the anterior wall. Moon et al. reported that removing polyps detected on the day of egg retrieval while the patient is asleep is a patient-friendly option and increases pregnancy rates close to late polypectomy [11].
Conclusions
Despite the small number of participants, the results of our study showed that the removal of asymptomatic polyps detected on the day of egg collection led to a significant increase in clinical pregnancy rates. Interrupting treatment for a while to remove polyps detected on the day of egg collection may lead to a significant increase in the fertility outcome.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Munro MG. Uterine polyps, adenomyosis, leiomyomas, and endometrial receptivity. Fertil Steril. 2019;111(4):629-40.
2. Hase S, Mitsumori A, Inai R, Takemoto M, Matsubara S, Akamatsu N, et al. Endometrial polyps: MR imaging features. Acta Med Okayama. 2012;66 (6):475–85.
3. Al Chami A, Saridogan E. Endometrial polyps and subfertility. J Obstet Gynaecol India. 2017;67(1):9–14.
4. Nappi L, Indraccolo U, Di Spiezio Sardo A, Gentile G, Palombino K, Castaldi MA, et al. Are diabetes, hypertension, and obesity independent risk factors for endometrial polyps? J Minim Invasive Gynecol. 2009;16(2):157–62.
5.Vitale SG, Haimovich S, Laganà AS, Alonso L, Di Spiezio Sardo A, Carugno J. From the Global Community of Hysteroscopy Guidelines Committee. Endometrial polyps. An evidence-based diagnosis and management guide. Eur J Obstet Gynecol Reprod Biol. 2021;260:70-7.
6. Adomaitiene L, Nadisauskiene R, Nickkho-Amiry M, Cizauskas A, Palubinskiene J, Holland C, et al. Tumor Suppression in Asymptomatic Postmenopausal Endometrial Polyps. Anticancer Res. 2020;40(2):789-94.
7. Takeda T, Banno K, Kobayashi Y, Adachi M, Yanokura M, Tominaga E, et al. Mutations of RAS genes in endometrial polyps. Oncol Rep. 2019;42(6):2303-8.
8. Bosteels J, van Wessel S, Weyers S, Broekmans FJ, D’Hooghe TM, Bongers MY, et al. Hysteroscopy for treating subfertility associated with suspected major uterine cavity abnormalities. Cochrane Database Syst Rev. 2018;12:CD009461.
9. Perez-Medina T, Bajo-Arenas J, Salazar F, Redondo T, Sanfrutos L, Alvarez P, et al. Endometrial polyps and their implication in the pregnancy rates of patients undergoing intrauterine insemination: a prospective, randomized study. Hum Reprod. 2005;20(6):1632–5.
10. Yanaihara A, Yorimitsu T, Motoyama H, Iwasaki S, Kawamura T. Location of endometrial polyp and pregnancy rate in infertility patients. Fertil Steril. 2008;90(1):180–2.
11. Moon JW, Kim CH, Park SY, Kim SH, Chae HD, Kang BM. Comparison of ultrasound-guided endometrial polypectomy carried out on the oocyte retrieval day and the first day of ovarian stimulation in IVF-ICSI cycles. Reprod Biomed Online. 2016;33(3):376-80.
12. Rackow BW, Jorgensen E, Taylor HS. Endometrial polyps affect uterine receptivity. Fertil Steril. 2011;95(8):2690-2.
13. Di Spiezio Sardo A, Calagna G, Guida M, Perino A, Nappi C. Hysteroscopy and treatment of uterine polyps. Best Pract Res Clin Obstet Gynaecol. 2015;29 (7):908–19.
14. Tanos V, Berry KE, Seikkula J, Abi Raad E, Stavroulis A, Sleiman Z, Campo R, Gordts S. The management of polyps in female reproductive organs. Int J Surg. 2017;43:7-16.
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Experiencing pregnancy: Joy or pain?
Gulden Aynacı
Department of Obstetrics and Gynecology, Health Science Undergraduate School, Trakya University, Edirne, Turkey
DOI: 10.4328/ACAM.21022 Received: 2021-12-23 Accepted: 2022-06-09 Published Online: 2022-08-05 Printed: 2022-09-01 Ann Clin Anal Med 2022;13(9):955-958
Corresponding Author: Gulden Aynacı, Department of Obstetrics and Gynecology, Health Science Undergraduate School, Trakya University, Edirne, Turkey. E-mail: guldenaynaci@trakya.edu.tr P: +90 507 979 95 06 Corresponding Author ORCID ID: https://orcid.org/0000-0002-2112-8631
Aim: Pregnancy is a natural phenomenon and brings many psychological and social changes. Pregnancy is a unique life experience. The pregnancy period is expected to be a positive and satisfying time, bringing new life to the world; however, pregnant women may also experience some disorders. The aim of the study was to evaluate the quality of maternal well-being and the necessity of optimal care interventions in the follow-up of pregnant women.
Material and Methods: Our study was conducted from December 2020 to November 2021 with pregnant volunteers who presented to the Trakya University Hospital. The PES-Brief was administered.
Results: The study included 378 volunteers. There were positive correlations between uplifts frequency scores and motivation to breastfeed. Uplifts scores were lower among those who stated that pregnancy tired them. There was a statistically significant relationship between long-term breastfeeding plans and high hassles scores.
Discussion: Our study demonstrated that the PES-Brief can be used to identify women with less planned pregnancies who are at increased risk of possibly pregnancy negativity. Its application in routine pregnancy checks and maternity care will improve the identification of women.
Keywords: Pregnancy Experience, Uplifts, Hasless, Maternal Well-Being
Introduction
The pregnancy period, which is specific for each woman, is expected to be a positive and satisfying time, bringing new life to the world; however, pregnant women may also experience some physical and psychological disorders [1]. The quality of life of pregnants may be adversely affected by changes and discomfort experienced during pregnancy.
The pregnancy experience interacts with environmental factors such as family, culture, religion, social, and economic conditions. In this period, the role change of a pregnant women to motherhood, the presence of role models around the woman, whether the pregnancy was planned, having enough information about pregnancy and childbirth, and concept of self are some of the factors affecting pregnancy acceptance. Women who have more positive emotions during pregnancy have calmer pregnancies [2].
Studies on the potential effects of maternal psychological stress on the developing fetus, pregnancy, and infants are valuable [3,4]. It is particularly difficult to capture and accurately evaluate all experiences of pregnant women.
Our study examined the necessity of assessing the quality of maternal well-being and the requirement for increasing evidence-based patient care interventions. We tried to draw attention to the necessity of health workers to examine the stress levels and anxiety of pregnant women.
Material and Methods
Setting and Sample
Our study was conducted between December 2020 and November 2021 with pregnant volunteers who presented to the Perinatology Clinic of Trakya University. The women were questioned about their sociodemographic characteristics, and the Pregnancy Experience Scale-Brief version (PES-Brief) was administered.
Study Design and Measurements
With the practical use of PES-Brief in clinics, the necessity for providing positive support to pregnant women, especially in needy pregnancies, was evaluated.
The inability to solve problems during pregnancy limits the potential benefits of a good pregnancy. The scale measures daily exposure to ongoing challenges and pregnancy-specific changes, and contributes to measuring the impact on maternal health [5,6]. Pes-brief is used to evaluate pregnancy experience affecting maternal physiological arousal. Assessments of pregnancy-specific stress or examining such a measure within a range of psychosocial evaluations will help to improve the quality of maternal care.
Ethical Consideration
Approval for this study was obtained from Trakya University Ethics Committee on Scientific Research.
Data Analysis
All statistical analyses were performed using the Turcosa package program. The level of significance was determined as 0.05 in all statistical analyses.
Results
The study included 378 volunteers who presented to the Perinatology Clinic of Trakya University Hospital for pregnancy checks. Pregnant women were between the ages of 19 and 45. The mean gestational age of the pregnants in our study was 31.57±8.06 weeks; 119 (31.48%) women had their first pregnancy; 52 (13.75%) women had four and more pregnancies.
One hundred twenty-eight (33.86%) women had no living children; 148 (39.15%) participants had one living child.
Two hundred sixty-four pregnant women came for routine pregnancy checks; 28 pregnant women were treated for gestational hypertension and/or preeclampsia. The number of patients followed for gestational diabetes was 28 (7.40%).
Individual clinical features were examined; 309 (80.95%) had never had abortions in their previous pregnancies. The number of women who had abortions at least once was 69 (18.25%).
The participants were asked whether they were spiritually exhausted; 224 (59.25%) stated that pregnancy was a problem, 154 (40.74%) stated that pregnancy was not a burden for them. The pregnants were asked whether they were happy to be pregnant, and 348 (92.06%) participants reported that they were.
The participants were asked how long they thought that they would give breast milk when their babies were born; 202 (53.43%) pregnant women thought that they would give breast milk for two years, 161 (42.59%) thought that they would give breastmilk for 1-2 years, and 15 (3.96%) women thought that they would give breast milk for less than 1 year.
1. PES-Brief, first part: Uplifts
This was examined in two dimensions. There was a significant relationship between occupations, with the uplifts frequency score. The scores of housewives were higher than those of civil servants and academics (p=0.038). Positive correlations were found between uplifts frequency scores and fatigue and motivation to breastfeed. Uplifts frequency scores were lower among those who stated that pregnancy tired them. Pregnant women who received high scores on the PES-Brief thought that they could breastfeed their babies for a long time (p<0.001). Pregnant women whose PES-Brief uplifts density scores were high thought that they could breastfeed for a longer period (p<0.001).
2. PES-Brief, second part: Hassles
There was a statistically significant relationship between chronic disease entities, long-term breastfeeding plans, and high hassles scores (p<0.001).
Negative socio-cultural conditions affecting pregnancy were associated with high hassles scores. It was observed that pregnancy was seen as a process that communicates with the environment and maternal welfare had positive effects on pregnancy.
3. PES-Brief, third part: Frequency and density ratios
The frequency and intensity ratios and participant-dependent parameters were compared. As income level decreased, education level decreased, and negative scores from PES-Brief also increased (p<0.001) (Table 1).
Qualitative values of the pregnant women were examined individually. As the number of participants’ previous pregnancies decreased, the number of those who stated that their baby’s movements made them happy was higher. Those who were pregnant for the first time were most likely to feel happy, especially when they felt infant movements (p=0.018). However, there were more concerns about confinement in this group (p=0.008). Those with their first pregnancy had a tendency to respond to the change in their body more moderately and to worry less (p=0.046).
4. Sociodemographic parameters and PES-Brief Questions point-by-point
PES-Brief scores were evaluated according to the number of children of the pregnant women. A statistically significant relationship was found in question 4 in the uplifts section (p=0.035); the thought of nursery arrangements made pregnant women who had no children the most happy. In terms of hassles, there was a difference in question 6 (p=0.031). The thought of the appearance of babies made those who had no living children worried.
Among the women who were happy to be pregnant, it was observed that they perceived quality of life better and they felt happy (p=0.005) (Table 2).
Those who planned to give breast milk for a long time had high PES-Brief uplifts scores. During pregnancy, they felt happy, positive or uplifted ‘How much the baby is moving,’ ‘Discussions with the spouse about baby names,’ were highly motivational for giving breast milk (p<0.001) (Table 2).
Only routine pregnancy checks increased PES-Brief scores as the age of the participants increased (p=0.007). As the age of the participants increased, the changes in their bodies during pregnancy made them more unhappy (p=0.026).
Discussion
There are many studies using PES-Brief in various populations. The comorbidities of depressive and anxiety disorders add significantly more negative value to pregnancy [7].
It was reported that those who had higher PES-Brief uplifts scores had more positive attachment to their baby [1,5]. In addition, the relationship between higher PES-Brief scores is associated with higher fetal well-being.
Several studies have investigated prenatal depressive symptoms in working women or discussed the relationship between occupational factors and prenatal well-being [1,8]. Perceived factors related to working life among pregnant women were found to be significantly associated with antenatal depressive symptoms. Workplace conditions and benefits have been reported to be important factors to consider in the assessment of prenatal psychosocial well-being [9]. After improvements have been made to address factors known to be associated with poor mood, pregnant women should be provided with optimal conditions at work.
The results showed that PES scores of working women were not better than those of housewives. Our study has demonstrated the need to facilitate the implementation of a supportive workplace climate by employers and occupational health experts.
Maternal fatigue has been examined in different studies. The rate and severity of fatigue vary depending on the measurement tools, the time point of measurement in pregnancy, and the country of the study. It was found that 94.6% of pregnant women experienced fatigue symptoms. In another study, the fatigue rate of pregnant women was less than 50% [10]. The rate of pregnant women with fatigue was 59.25%. PES-Brief scores were lower in those who reported high fatigue levels.
Poor psychological well-being of mothers is a risk factor for late onset of breastfeeding and insufficient desire. Studies show that breastfeeding decreases in women with weak psychological conditions, and they start breastfeeding late. Socioeconomic difficulties reduce breastfeeding.
The motivation for breastfeeding was higher among women who shared their pregnancy experiences with their family. In addition to increasing maternal health, healthcare providers will provide additional care support to pregnant women who have been evaluated with PES-Brief and have low scores, which will increase the chances of babies to receive breast milk. Having a conscious and prosperous pregnancy will contribute to conscious puerperium and breastfeeding. Health professionals should ensure the healthy adaptation of the pregnant woman and her family to the pregnancy.
Conclusion
Our study demonstrated that the PES-Brief scale can be used to identify women with less planned pregnancies who are at increased risk of possible negative side effects of pregnancy.
After identifying pregnant women at risk, health workers can provide additional advice and support to ensure that they have access to adequate care and preventive practices. The prenatal PES-Brief score can be used to mark women at risk of postpartum psychological wear who need to be evaluated after childbirth.
Our findings are related to family planning, evaluation of maternal well-being during pregnancy and postpartum; It supports new ideas in societies with limited socioeconomic opportunities. Access to qualified birth processes by societies with low financial means should be increased. Our study can be used to improve reproductive, maternal, and child health policies.
Acknowledgment
We want to thank to Assoc. Prof. Dr. Selçuk Korkmaz for statical evaluation.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Pedersen P, Momsen A-MH, Andersen DR, Nielsen CV, Nohr EA, Maimburg RD. Associations between work environment, health status and sick leave among pregnant employees. Scand J Public Health. 2021;49(2):149-58.
2. Zijlmans MA, Beijers R, Riksen-Walraven MJ, de Weerth C. Maternal late pregnancy anxiety and stress is associated with children’s health: a longitudinal study. Stress. 2017;20(5):495-504.
3. Hendrix CL, Stowe ZN, Newport DJ, Brennan PA. Physiological attunement in mother–infant dyads at clinical high risk: The influence of maternal depression and positive parenting. Dev Psychopathol. 2018;30(2):623-34.
4. Nelson BW, Wright DB, Allen NB, Laurent HK. Maternal stress and social support prospectively predict infant inflammation. Brain Beha Immun. 2020;86:14-21.
5. DiPietro JA, Christensen AL, Costigan KA. The pregnancy experience scale–brief version. J Psychosom Obstet Gynecol. 2008;29(4):262-7.
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7. Peñalver Bernabé, B., Maki, P. M., Dowty, S. M., Salas, M., Cralle, L., Shah, Z., & Gilbert, J. A. Precision medicine in perinatal depression in light of the human microbiome. J Psychopharmacol. 2020; 237(4), 915-941.
8. Røhder K, Væver MS, Aarestrup AK, Jacobsen RK, Smith-Nielsen J, Schiøtz ML. Maternal-fetal bonding among pregnant women at psychosocial risk: the roles of adult attachment style, prenatal parental reflective functioning, and depressive symptoms. Plus One. 2020;15(9):2-19.
9. Tsai S-Y. Relationship of perceived job strain and workplace support to antenatal depressive symptoms among pregnant employees in Taiwan. Women Health. 2019;59(1):55-67.
10. Liu N, Wang J, Chen D-d, Sun W-j, Li P, Zhang W. Effects of exercise on pregnancy and postpartum fatigue: A systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2020; 253:285-95.
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Post-vaccination COVID-19 positivity and clinical situation analysis in healthcare professionals
Ilkay Bahceci 1, Feray Ferda Senol 2
1 Department of Medical Microbiology, Faculty of Medicine, Recep Tayyip Erdoğan University, Rize, 2 Department of Medical Microbiology, Elazıg Fethi Sekin State of Hospital, Elazıg, Turkey
DOI: 10.4328/ACAM.21139 Received: 2022-03-11 Accepted: 2022-04-13 Published Online: 2022-08-03 Printed: 2022-09-01 Ann Clin Anal Med 2022;13(9):959-962
Corresponding Author: Ilkay Bahceci, Department of Medical Microbiology, Faculty of Medicine, Recep Tayyip Erdoğan University, 53100, Merkez, Rize, Turkey. E-mail: mdilkaybahceci@gmail.com P: +90 464 223 61 26 Corresponding Author ORCID ID: https://orcid.org/0000-0003-3662-1629
Aim: Healthcare workers are an occupational group that is at the forefront of a pandemic process, where morbidity and mortality are intense. Deaths due to COVID-19 among workers in our country and in the world are reported mostly in healthcare workers. In this study, we aimed to analyze the rate of contracting COVID-19 among healthcare workers after vaccination and the clinical features of the disease.
Material and Methods: Between January 14, 2021 and June 29, 2021, the diagnosis of COVID-19 in healthcare workers who had clinical complaints after a single dose and two doses of vaccination was made as a result of the evaluation of the patients’ throat and nose swab samples by reverse transcriptase-polymerase chain reaction (RT-PCR). The disease table of the positive patients was grouped as home treatment and hospital treatment by accessing clinical and laboratory records from electronic medical records.
Results: At least one dose of vaccine was given to 11,540 (79.62%) of a total of 14,461 healthcare workers. COVID-19 positivity was detected in the PCR test performed on 51 single-dose vaccinated healthcare workers and 177 double-dose vaccinated healthcare workers with clinical complaints. While all patients vaccinated with a single dose were treated at home, 176 of the patients vaccinated with two doses were treated at home and 1 was treated in the hospital.
Discussion: It has been seen that if countermeasures against COVID-19 are not taken, it could be a great disaster for the whole world, that the most important defense against this pandemic is vaccination, and that those who have COVID-19 after vaccination have a mild illness even if they have the disease.
Keywords: COVID-19, Healthcare Workers, Vaccine
Introduction
Vaccines aim to prevent deaths and sequelae caused by infectious diseases. Throughout human history, it is known that deadly infectious diseases are the most frightening disasters that threaten social life. While wars and natural disasters were limited only to certain geographical regions, infectious diseases affected the whole of humanity and showed their effect to a great extent wherever people were [1,2]. The COVID-19 virus is a type of virus in the betacoronavirus (beta-coronavirus) family, which includes SARS-CoV and MERS-CoV, emerged in 2019 and quickly affected the whole world in a short time, and this became a global epidemic, that is, it has been accepted as a “pandemic” [3]. While the first measures taken against this epidemic all over the world were masks, distance, cleaning, vaccination studies against COVID-19 started due to the inadequacy of precautions and treatments to prevent the spread. As priority targets in the COVID-19 vaccination, health workers, adults over 60 years of age, with underlying diabetes or hypertension; and the vaccine produced should not cause undesirable effects on the immune system and should be suitable for stocking [4]. Due to the wide spectrum of COVID-19 infection, while the disease progresses with mild symptoms in many cases among healthcare workers, serious consequences, including deaths, have been reported [5]
Material and Methods
Elazıg and in the region, between January 14, 2021 and June 29, 2021, one or two doses of vaccine were administered to healthcare workers with clinical complaints (fever, headache, myalgia, malaise, sore throat, cough, shortness of breath, nausea, vomiting, diarrhea), and those who were diagnosed by taking a throat swab and studying on the RT-PCR BIORAD (Qiagen, Germany) device were included. Patients were separated from electronic medical records according to demographics (gender, age) and symptoms (home treatment and hospital treatment).
The number of samples in the data is shown as “n” and calculated as a percentage. In the statistical analysis of the data, IBM Inc; SPSS (Statistics for Windows Version 21.0, Armonk, NY, USA) package program was used.
The study was approved by the Ethics Committee of Fırat University Medical Faculty, Turkey (March 18, 2021) before the study period. The research was conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all participants, consistent with the Turkish National Research Ethics Committee resolution for research conducted during the COVID-19 pandemic.
Results
Of a total of 14,461 healthcare workers, 11,514 (79.62%) were vaccinated with at least one dose. PCR tests of 51 people who had clinical complaints 14 days after a dose of vaccine were positive. Twenty-one (41.18%) of 51 PCR-positive patients were female and 30 (58.82%) were male. Fifty-one (100%) of 51 positive patients were treated at home and regained their health. PCR tests were found to be positive in 177 of the 10,666 (73.76%) healthcare workers who completed two doses of vaccine and 14 days later had clinical complaints. One hundred (56.50%) of the 177 PCR-positive patients were female and 77 (43.50%) were male. While 176 (99.44%) of the 177 positive patients regained their health while being treated at home, 1 (0.56%) was treated in the hospital. It was determined that the patient who was treated at the hospital was treated in the COVID-19 wards and recovered without the need for intensive care. Between March 11, 2020 and June 29, 2021, a total of 3,435 (23.67%) healthcare workers were diagnosed with COVID-19. Between March 14, 2020 and January 28, 2021, 3,207 (93.36%) were found to be positive for COVID-19 before vaccination and 228 (6.63%) between January 28, 2021 and June 29, 2021 after vaccination. It is seen that positivity decreases with vaccination and there is no worsening in the clinical. In Tables 1 and 2, the vaccination status of male and female healthcare workers by age is given in detail.
Discussion
The most basic method of protection in viral epidemics is vaccination or prophylactic support of healthy individuals. Social distance and mask rules, general cleaning and hygiene rules, which are physical protection methods, should be strictly followed. However, although these practices seem to be the main practices in preventing the spread of the disease, they are the last link of the prevention control program [6]. The first ring is to determine the origin of the disease and to eliminate the factor.
Parameters such as the age of the vaccinated person, her/his previous immunity level, and the state of the immune system are factors that affect the response to the vaccine [7]. Although the effectiveness of the vaccine is seen at the rate of 70-90% in a healthy individual, this rate decreases to 30-40% in people over 65 years of age. However, despite this, the incidence of influenza-like disease in people over 65 years of age decreased by 33%, and the rate of serologically proven disease by 56% [8]. Although the rate of passing the disease with symptoms is 70-80% in infected individuals, the severity of these symptoms is much stronger in those with seronegative or low titer antibodies [9,10]. It is beneficial to immunize active, working members of the society, who are not from any risk group, with the flu vaccine. Upper respiratory tract infections were found to be 25% less common among vaccinated healthy individuals, and there was a 43% decrease in absenteeism and a 44% decrease in the rate of applying to workplace physicians [11]. To prevent influenza-like diseases in healthcare workers, early detection and treatment of infection with surveillance, reduction of contact, standard and droplet isolation precautions, and necessary cleaning and disinfection in the hospital should be provided. Vaccination of healthcare workers against flu-like diseases is another preventive measure [12]. As in the whole world, the number of vaccine opponents is increasing day by day in our country. Healthcare workers play a key role in increasing the vaccination of patients who refuse vaccination [13]. Unfortunately, opposition to vaccination is also very common among healthcare workers. Physicians who do not vaccinate themselves or their children do not recommend vaccines to their patients [14]. In a study conducted by Karadağ Öncel et al. [15] in 2015 with 179 healthcare workers, it was reported that 18.4% of them were vaccinated, and the most important reasons for not being vaccinated were not having the flu (53.4%) and fear of the side-effect profile of the vaccine (24.6%). In the study by Sarı T et al. [16], of those who answered the question of whether 115 healthcare workers had influenza vaccination or not, only 5 (4.3%) were vaccinated, 110 (95.7%) were not; It was learned that 59 (51.3%) of these 110 people had never been vaccinated against influenza in their lifetime. One of the most important reasons for not wanting to be vaccinated against influenza is not believing that the vaccine is necessary (64.5%); preferring other protection methods (40.9%), fear of the side effects of vaccines (39.1%), thinking that the vaccine has not been tested enough, that natural immunity is more effective, thinking that vaccines are produced for commercial interests, and thinking that the vaccine causes cancer. In a situation that has a significant impact on anti-vaccine thoughts, it is finding information about vaccines by chance. The best example of this is information obtained from the internet. In a study investigating the relationship between trust in health-related information sources, indiscriminate information, and concerns about the safety of vaccines, ethnicity was shown to be one of the reasons affecting vaccine-related concerns [17]. Healthcare workers need more training and support to manage rapidly changing vaccinations.
It has been announced that the number of 23.000 COVID-19 positive health workers, which have been notified to the WHO (World Health Organization) worldwide by the Geneva-based International Nursing Council regarding the COVID-19 pandemic, exceeded 90 thousand in a very short time. The Council reports that the actual number may be twice as high as declared [18]. In studies involving healthcare workers in China, it has been reported that the positivity of COVID-19 was between 3.46% and 28.9% [19,20]. In the United Kingdom, COVID-19 positivity in healthcare workers was 14.5% [21]; 12.9% in the US state of Massachusetts [22], 38% in Madrid, Spain [23], in studies conducted in different regions of Italy it was 12.9%. It has been reported that between 10.6%-20.0% health workers have COVID-19 positivity [6,23]. In Turkey, it has been reported that until September 2, 2020, 29,865 healthcare workers had COVID-19 positivity, constituting 10.9% of the total cases, and 52 of them died [24]. Vaccination has been found to significantly reduce morbidity and mortality in patients with flu-like symptoms. In our study, it was determined that 3,423 (23.67%) healthcare workers had COVID-19 between March 14, 2020 and June 29, 2021, and COVID-19 positivity decreased significantly after vaccination. The organization named COVAX, which was formed by the World Health Organization with the non-governmental organizations GAVI (Global Vaccine Alliance) and CEPI (Coalition for Innovations for Epidemic Preparedness) carries out studies for the fair and effective distribution of COVID-19 vaccines around the world. If these studies go well, it is estimated that 40% of the world population will be vaccinated by the end of 2021. In our study, 11,514 (79.62%) of a total of 14,456 healthcare professionals working were vaccinated, the PCR tests were positive in 51 people who had been vaccinated 14 days after the first dose of vaccine, and 177 people had clinical complaints after two doses of vaccine. PCR test positivity was detected together with the findings. It was determined that only one of the positive patients was hospitalized, and this patient recovered without worsening of the clinical picture, and all patients were healthy. Post-vaccination COVID-19 positivity has decreased considerably compared to pre-vaccination, which has clearly shown us the protection of the vaccine.
Conclusion:
There is a need for more scientific studies on the medical conditions that may occur with vaccination and non-vaccination, and the dissemination of social studies aimed at increasing confidence. Among the measures that can be taken against anti-vaccination, which is a risk for public health, that influential people of the country, and especially health workers, take a role in vaccination campaigns and enlighten the public in the light of scientific data by using social media, technology and communication tools.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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A potential therapeutic effect of miR-155 downregulation in an experimental model of demyelination
Ola Saed Elfetiany 1, Hala Abdelgawad 1, Nesrine M. El Azhary 1, Doaa Abdelmonsif 2, Samar El Achy 3, Maha A. Hegazy 1
1 Department of Medical Physiology, 2 Department of Medical Biochemistry, 3 Department of Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
DOI: 10.4328/ACAM.21203 Received: 2022-04-22 Accepted: 2022-06-19 Published Online: 2022-08-27 Printed: 2022-09-01 Ann Clin Anal Med 2022;13(9):963-967
Corresponding Author: Ola Saed Elfetiany, Department of Medical Physiology, Faculty of Medicine, Dr. Fahmy Abdel Meguid Street, Mowssat Building El Shatby, Alexandria, 2156, Egypt. E-mail: O_elfetiany13@alexmed.edu.eg P: +20 100 264 06 55 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6938-5760
Aim: The aim of this study was to investigate the possible effects of microRNA-155 inhibition in restoring remyelination after the establishment of lysolecithin- mediated demyelination in rats.
Material and Methods: Adult male albino rats were subjected to intrahippocampal injection of lysolecithin (LPC). LPC-treated rats received either antimicroRNA-155 NPs, blank NPs or phosphate buffer saline (PBS). One additional group was injected with PBS, acting as a negative control. After scarification of rats, histopathological examination of hippocampi, and quantitative PCR to detect mir-155 and myelin basic protein (MBP) were conducted.
Results: Our results showed that delayed treatment with antimicroRNA-155 nanoparticles was associated with histopathological improvement of demyelination score with no significant effect on biochemical markers.
Discussion: This study supports the promising therapeutic role of antimicroRNA-155-loaded nanoparticles in demyelinating disorders.
Keywords: Demyelination, miRNA 155, Multiple Sclerosis
Introduction
Many demyelinating diseases affect the central nervous system (CNS) with heterogeneous etiologies, varying from metabolic, infectious, or autoimmune processes to genetic disorders. With an estimated 3 million patients globally, multiple sclerosis (MS) is the most common of these illnesses. Focal regions or demyelination plaques in the CNS, which are surrounded by areas of inflammation and neurodegeneration, are the pathological hallmarks of all types of MS [1]. More than 50% of MS patients, chiefly those with progressive disease, will experience depression, decline in cognitive functions, and gait disability [2]. MicroRNAs (miRNAs) are small ~22 nucleotide RNA sequences that control genetic expression and can significantly impact the important cellular processes related to CNS repair after neuropathological conditions such as ischemic stroke and neurodegenerative diseases [3]. Numerous miRNAs have been strongly associated with different pathological conditions of CNS. Among them is microRNA-155, a multifunctional microRNA associated with the regulation of various physiological and pathological processes. miRNA-155 plays a remarkable role in the immune system and its augmented expression is consistent with bad prognosis in patients with epilepsy and amyotrophic lateral sclerosis [4,5]. In several animal models, miR-155 down regulation was accompanied by declined inflammation and improved regeneration processes. At the same time, miRNA-155 upregulation was noticed in experimental models of stroke, while downregulation of miRNA-155 reinforced post-stroke recovery [6,7].
One of the main difficulties of microRNA-based therapeutic strategies is to achieve accurate, healthy and fruitful regulation of miRNAs. Although oral administration of microRNA inhibitors (or mimics) is ineffective, intravenous and subcutaneous delivery of oligonucleotides is also difficult due to their toxicity and limited bioavailability. Nanoparticles, viral vectors, and biodegradable polymers are used for effective administration of miRNA [8]. At the present time, Poly lactic-co-glycolic acid (PLGA) is considered one of the most employed synthetic polymers. Thanks to its biocompatible, biodegradable and simple functionality, PLGA NPs were chosen as a carrier device in this study [9]. In the current work, the efficacy of delayed treatment with antimir-155 loaded nanoparticles in enhancing remyelination process in lysolecithin-mediated demyelination model was studied.
Material and Methods
1. Material
Poly (D, L-lactide-co-glycolide) lactide: glycolide (50:50), mol wt 30,000-60,000 and L-α-Lysophosphatidylcholine from egg yolk (LPC) ≥99%, Type I, powder, protease inhibitor cocktail and β-actin antibody were purchased from Sigma Aldrich (St. Louis, MO, USA). Anti-rno-miR-155-5p miScript miRNA Inhibitor and negative control and miRNeasy Mini Kit were purchased from Qiagen (Hilden, Germany). TaqMan miRNA Reverse Transcription Kit, TaqMan microRNA assay system, TaqMan® Universal PCR Master Mix II, SuperScript II Reverse Transcriptase, 1XSYBR® Green PCR Master Mix.
2. Preparation of antimir-155 loaded nanoparticles
PLGA nanoparticles were formed using emulsion technique followed by incubation of 100 μL of the nanoparticles solution with 700 μL of polyethylenimine aqueous solution for 15 minutes [10]. Then the nanoparticles suspension was mixed with the antimiRNA solution and incubated for 30 minutes at room temperature to form nanoparticle/antimiRNA complexes. The loading efficiency of the miR-155 inhibitor on the nanoparticles was analyzed using UV-Vis Spectrophotometer NanoDrop (Thermo Scientific, USA) [11].
3. Experimental protocol
3.1 Experimental animals
This study was carried out on adult male Wistar rats (12 weeks old) weighing 200–250 g in the animal house of the Medical Physiology department Faculty of Medicine, Alexandria University. The animals were kept under standard laboratory conditions, maintained under a 12-h light–dark cycle with free access to food and water. All animal experiments complied with the Guide for the Care and Use of Laboratory Animals, Faculty of Medicine, Alexandria University (IRB NO: 00007555-FWA NO: 00018699). Further, the Ethics Committee of Alexandria Faculty of Medicine approved this study.
3.2 Stereotaxic surgery
For induction of demyelination, fifteen rats were anesthetized with ketamine (100 mg/kg) and xylazine (10 mg/kg) mixture via intraperitoneal injection. The cranium was exposed and a dental lab drill was used to drill a hole to the dorsal hippocampus (AP = −3.8 mm; ML = −2 mm; DV = −3 mm) according to the stereotactic coordinates of Paxinos and Watson’s rat brain atlas [12]. Then, 1 μl of freshly prepared lysolecithin (LPC) in phosphate-buffered saline (PBS; ph 7.4) (1%) was injected bilaterally into the hippocampus of all rats [13]. One additional group was injected with an equivalent volume of PBS only into the same site as described above as a negative control. LPC injected groups were subdivided into 3 subgroups (five rats per group): the LPC group (untreated group), in which rats received bilateral intrahippocampal injection of 2 μl of phosphate buffer solution (PBS), blank NPs group, in which rats received 2 μl of blank nanoparticles and antimir-155 NPs group, in which rats received 2 μl of antimir-155 nanoparticles on day 7 after LPC injection. The syringe was left in situ for an additional 2 min before withdrawal to prevent solution leakage from backflow.
3.3 Tissue sampling and processing
Three days after the administration of the nanoparticles, the animals were sacrificed using ether anesthesia. After decapitation and craniotomy, the whole brain was removed and washed with ice-cold saline and the hippocampi were dissected. One hippocampus was fixed in formalin for histopathological examination, and the other one was stored at -80°C for molecular analysis.
3.4 Histopathological examination using hematoxylin & eosin (H&E)
Hippocampal samples were fixed overnight at 4 °C with 4% paraformaldehyde, and specimens were placed in a 10% neutral formalin solution, processed and embedded in paraffin for histological examination. Coronal sections (5 μm thick) were cut with microtome, and stained with hematoxylins & eosin (H&E) [14].
3.5 Assessment of demyelination score using Luxol fast blue (LFB) stain
Demyelination was assessed using LFB staining and scored as described: 0 = Normal, 1 = One small focal area of demyelination, 2 = 2-3 areas, 3 = 1-2 large areas of demyelination and 4 = Extensive demyelination involving >=20% of the white matter [13]. The extent of demyelination, as the ratio of lesion size per total area, was determined using and analyzed using a Leica Application Suite, Version 4.12.0 (Leica Microsystems CMS GmbH) image analysis system [14].
3.6 Quantitative reverse transcription PCR (qRT PCR) for expression of miR-155
TaqMan microRNA assay system was used for quantification of miRNA -155 using TaqMan® Universal PCR Master Mix II (Applied Biosystems, USA). Amplification was performed in a real-time PCR system StepOne (Applied Biosystems, USA). StepOne™ Software v2.3 was used for data analysis [15].
3.7 Quantitative reverse transcription PCR (qRT PCR) for expression of Myelin Basic Protein (MBP)
Reverse transcription was done using 100 ng of total RNA. The amplification of MBP cDNA was done in duplicate using a real-time PCR system StepOne using 1XSYBR® Green PCR Master Mix. Data analysis was performed using StepOne™ Software v2.3 using the comparative CT method for gene expression relative to the housekeeping gene GAPDH [15].
Statistical analysis
IBM SPSS software package version 20.0. (Armonk, NY: IBM Corp) was used for data analysis. Quantitative data were described using the mean and Standard Error of Mean (SEM), and the significance of the obtained results was judged at the 5% level. F-test (ANOVA) was used for normally distributed quantitative variables, to compare between more than two groups, and Post-Hoc test (Tukey) for pairwise comparisons.
Results
Anti-microRNA-155/ nanoparticles loading efficiency
To ensure the incorporation of anti-miRNA into the nanoparticles, the loading efficiency of anti-miRNA was measured as the percentage of adsorbed anti-miRNA to the total amount of anti-miRNA added and it was found to be around 70 %.
Effect of antimiR-155-NPs on hippocampal tissue using H&E stain.
Histological examination of the brain exhibited the normal architecture of the hippocampus in the control group. In contrast, the hippocampal tissue in LPC group revealed the presence of hippocampal and subcortical inflammatory plaques and infiltration by mononuclear inflammatory cells. On the other hand, antimir-155 treated group showed hippocampal and subcortical healed remyelinated lesions (Figure 1).
Effect of antimiR-155- NPs on the demyelination score.
Microscopic examination showed normal myelination of the hippocampi in control group. Hippocampal tissue in LPC group revealed the presence of hippocampal and subcortical demyelinated plaques (mean demyelination score 1.33, mean extent of demyelination area 9%) with a significantly higher demyelination score compared to the negative control group. However, antimiR-155 NPs treated group showed tiny hippocampal and subcortical remyelinated patches (mean demyelination score 0, mean extent of demyelination area 2%). The demyelination score was significantly lower compared to LPC groups and with no significant difference compared to the control groups (Figure 2).
Effect of antimiR-155-NPs on tissue expression of miRNA-155.
Although the expression of miRNA-155 in hippocampal tissue was 1.95 ± 0.18 fold change in LPC untreated group and decreased to 1.59 ± 0.24 fold change in antimir-155 NP group, which received the treatment with antimir-155 nanoparticles after the establishment of demyelination, there was no significant difference in the levels of miRNA-155 expression in the hippocampal tissue in the treated group when compared to LPC group (Figure 3A).
Effect of antimiR-155-NPs on tissue expression of myelin basic protein (MBP)
There was no statistically significant difference between MBP mRNA expression in all groups when compared to control group. Delayed treatment with antimir-155 NPs after establishment of demyelination did not lead to any significant change in MBP mRNA expression in the treated group when compared to the LPC group (Figure 3B).
Discussion
Despite major progress in different treatment modalities of MS, to date, immunotherapy cannot sufficiently prevent progression of clinical disability. In addition, currently available treatments for MS do not facilitate remyelination nor improve axonal repair in the central nervous system. There is strong evidence from disease models that upregulation of miRNA-155 leads to neuroinflammation and eventual neurodegeneration, while silencing of miRNA-155 has neuroprotective impact making the modulation of its expression an important target for the treatment of demyelinating disorders [4]. In this work, lysophosphatidylcholine (LPC) was chosen to induce toxic hippocampal demyelination due to its accurate temporal regulation, the definite anatomical location, and the consistency of LPC-induced demyelination [16]. In the current research, histopathological examination of the hippocampi revealed the presence of demyelinating lesions in the rats following stereotaxic injection of LPC. These histological findings are similar to the pathological features of LPC-induced demyelinated lesions, previously described [17].
Currently, one of the methods used to attenuate miRNA activity is administration of anti-miR antisense oligonucleotides into cells. These anti-miR molecules can be delivered to the cells using either viral or non-viral vectors. While viral vectors previously used to deliver genes in injured animal models of diseases showed evidence of toxicity and immunogenicity, non-viral vectors, mainly nanoparticles delivery systems, showed lower toxicity, lower immunoresponsiveness and easy handling properties [18]. In the present study, PLGA nanoparticles were chosen since they offer several advantages such as biodegradability, biocompatibility, low cytotoxicity, long-standing biomedical applications and targeted delivery [19]. A loading efficiency of about 70 % was achieved in this study, which is consistent with previous studies that support PLGA nanoparticles as encouraging non-viral vectors in miRNA-related diseases such as tumors and neurodegenerative diseases [20,21].
Previous studies on experimental demyelination models such as experimental encephalomyelitis revealed that microRNA- 155 knockout mice had a delayed onset, reduced disease severity and less CNS inflammation [22]. In addition, other researchers found that downregulation of microRNA 155 resulted in prolongation of survival in ALS-model mice [4]. In the present study, although delayed injection of anti-mir-155 nanoparticles after establishment of demyelination decreased the level of expression of microRNA-155, it did not significantly affect the level of microRNA-155 expression when compared to the control or untreated groups. These results can be due to the spontaneous remyelination process, which occurs in LPC demyelination model, in which extensive demyelination is followed by robust remyelination [16]. The results of this study support previous researche, which proved that normal levels of microRNA-155 expression are essential for efficient remyelination process. Also, this finding may highlight the importance of the time factor in the protocol of intervention during treatment of demyelination via inhibition of miRNA-155. Interestingly, the administration of antimir-155 nanoparticles was associated with significant histopathological improvement, which was evident by more compact hippocampal myelin structure and significantly decreased demyelination score when compared to the untreated group.
Myelin basic protein (MBP) is one of the most abundant myelin proteins in CNS myelin sheaths and is expressed in both immature and mature oligodendrocytes [23]. Oligodendrocytes are the myelinating cells of the CNS corresponding to the Schwann cells in the peripheral nervous system. Oligodendrocyte progenitor cells (OPCs) originally come during development from neural stem cells inside the ventricles in the brain and spinal cord. The results of this study showed increased levels of MBP up to normal levels in all groups compared to the control group. Also, delayed treatment with anitmir-155 nanoparticles did not significantly affect the level of myelin basic protein expression compared to the LPC group. Similar findings were observed in previous studies, which can be explained by the migration of oligodendrocyte precursor cells to the lesion site during remyelination phase and then their differentiation to mature oligodendrocytes. Also, the MBP expression is affected by the age of myelinating cells; hence, the presence of younger cells in the area of remyelination is associated with a higher level of MBP expression [24, 25].
In conclusion, although delayed treatment with antimir155 nanoparticles after induction of demyelination was not associated with a significant improvement in biochemical markers, there was evident histopathological improvement that deserves further studies to investigate the different treatment strategies via modulation of microRNA-155 expression.
Acknowledgment
We would like to thank the animal house of Medical Physiology department Faculty of Medicine, Alexandria University for housing the experimental animals, and the Center of Excellence for Research in Regenerative Medicine and its application (CERRMA), for providing all the needed equipment.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Evaluation of factors associated with time to diabetic ketoacidosis resolution in children
Mehmet Öztekin 1, Capan Konca 1,2, Mehmet Tekin 3, Semih Bolu 1
1 Department of Pediatrics, School of Medicine, Adiyaman University, Adiyaman, 2 Department of Pediatric Intensive Care Unit, School of Medicine, Adiyaman University, Adiyaman, 3 Department of Pediatrics, School of Medicine, Inonu University, Malatya, Turkey
DOI: 10.4328/ACAM.21164 Received: 2022-03-28 Accepted: 2022-06-02 Published Online: 2022-08-01 Printed: 2022-09-01 Ann Clin Anal Med 2022;13(9):968-972
Corresponding Author: Capan Konca, Department of Pediatrics, School of Medicine, Adiyaman University, Adiyaman, Turkey. E-mail: dr.capan@hotmail.com P: +90 505 489 69 04 F: +90 416 225 26 60 Corresponding Author ORCID ID: https://orcid.org/0000-0001-8625-9045
Aim: In this study, it was aimed to examine the relationship between clinical, demographic, and laboratory characteristics of patients at admission and time to diabetic ketoacidosis (DKA) resolution.
Material and Methods: The files of patients with the diagnosis of DKA between January 2013 and December 2018 were reviewed retrospectively.
Results: A total of 25 patients were included in the study. The mean age of the patients was 9.3 ± 3.41 years. In 19 patients (76%), diabetes mellitus (DM) was diagnosed simultaneously with DKA. The mean time to DKA resolution was found to be significantly longer among patients with a family history of DM, newly diagnosed DM, respiratory distress, odor of acetone on the breath, altered consciousness, and severe coma. There was a significant correlation between the time to DKA resolution and the Pediatric Risk of Mortality score and the length of stay. There was also a significant negative correlation between time to DKA resolution and both pH and HCO3 levels.
Discussion: DKA is an acute, severe, and life-threatening complication of type 1 DM in children. It is important to identify the factors affecting the prognosis and resolution time of comas in these patients in order to predict outcomes. Our findings show that the prognosis will be worse and the time to resolution will be longer among children with altered consciousness, newly diagnosed DM, respiratory distress, a high PRISM score, severe DKA coma, and severe acidosis at the time of admission.
Keywords: Children, Coma, Diabetic Ketoacidosis (DKA), Factors, Pediatric, Resolution Time
Introduction
Diabetic ketoacidosis (DKA) is an acute, severe, and life-threatening complication of type 1 diabetes mellitus (DM) in children. Although there have been improvements in the treatment and care of type 1 DM, DKA continues to be a major cause of hospitalization and the leading cause of death in children with type 1 DM [1,2]. Overall mortality in children with DKA varies from 0.15% to 0.35% in developed countries, and from 3.4% to 12.7% in developing countries [3-8].
The main lines of DKA treatment are as follows: supportive measures, clinical and biochemical monitoring, rehydration with isotonic saline, intravenous insulin therapy, and potassium supplementation [9,10]. With these forms of management, it is expected that patients will recover and DKA will resolve. However, both physicians and families want to estimate patient outcomes and time to DKA resolution with data at admission. There is a limited number of studies on this subject in the literature [6, 11], and sharing related experiences will increase awareness of the topic. For this purpose, in this study, it was aimed to examine the relationships between clinical, demographic, and laboratory characteristics of patients at admission and time to DKA resolution.
Material and Methods
Between January 2013 and December 2018, 30 DKA patients were admitted to the pediatric intensive care unit (PICU) of Adiyaman University Training and Research Hospital. Two patients died and were excluded from the study. Three patients were excluded because their records were missing data. Patient files were scanned in detail in terms of clinical, demographic, and laboratory features at the time of admission. The study was approved by the ethics committee of Adiyaman University (2018/2-29).
DKA diagnosis was defined according to the criteria established by the International Society for Pediatric and Adolescent Diabetes (ISPAD) Consensus of 2014, including blood glucose greater than 200 mg/dL, venous pH less than 7.3, or bicarbonate less than 15 mmol/L and ketonemia or ketonuria [12]. ISPAD 2014 guidelines were used to define DKA severity categories. Three groups were defined: (1) mild (venous pH < 7.3 or bicarbonate < 15 mmol/L), (2) moderate (pH < 7.2 or bicarbonate < 10 mmol/L), and (3) severe (pH < 7.1 or bicarbonate < 5 mmol/L).
Time to DKA resolution was defined as the interval in hours between the first vascular filling to treat the DKA and DKA resolution, defined as clinical improvement (normal vital signs, oral feeding tolerance without emesis, and full consciousness), pH greater than 7.3, bicarbonate greater than 15 mmol/L, and/or closure of the anion gap.
Statistical analyses were performed using SPSS for Windows version 23.0 (SPSS Inc, Chicago, IL, US). Descriptive statistics were calculated, and categorical variables were analyzed using the Chi-square test. The independent two-sample t-test was used to compare the quantitative variables and to analyze the differences between means. A one-way analysis of variance (ANOVA) test was used for evaluations involving more than two groups. The relationships between continuous data and time to DKA resolution were evaluated using the Pearson correlation test. Multivariate logistic regression (enter model) was performed to determine the independent factors affecting the time to DKA resolution. Then, the factors that were found to be significant in the multivariate logistic regression (enter model) were compared with the multivariate logistic regression (backward model). P-values less than 0.05 were considered statistically significant.
Results
Demographic features
A total of 25 patients were included in the study. The mean age of the patients was 9.3 ± 3.41 years (range 2–15 years). Eight (32%) of our patients were female and 17 (68%) were male. Fifteen patients (60%) were residing in the city center, seven patients (28%) lived in the district, and three patients (12%) lived in villages. Seven patients (28%) were admitted to the hospital in the spring, two patients (8%) were admitted in the summer, ten patients (40%) were admitted in the autumn, and six patients (24%) were admitted in the winter. Among 19 patients (76%), DM was diagnosed simultaneously with DKA. Four patients (11.1%) had a family history of DM.
The relationship between demographic characteristics and time to DKA resolution was examined (Table 1). The time to DKA resolution was longer among females living in the city center and presenting in the spring season, but these differences were not statistically significant. The mean time to DKA resolution was significantly longer among patients with a family history of DM (p = 0.037) and newly diagnosed with DM (p = 0.044). Although the time to DKA resolution was higher among younger patients, the correlation between the variables was not significant (r = 0.055, p = 0.794).
Clinical features
The most common complaints were polydipsia (80%) and polyuria (76%). While 23 patients (92%) presented with their first DKA attack, one patient presented with a second attack and one patient with a third attack. Ten patients (40%) were unconscious at admission. Eight patients (32%) presented with mild DKA, eight patients (32%) with moderate, and nine patients (36%) with severe DKA. Mean systolic blood pressure was 114.44 ± 15.34 mmHg (range 91–150 mmHg), and mean diastolic blood pressure was 69.70 ± 13.08 mmHg (range 41–90 mmHg). The mean Pediatric Index of Mortality (PIM) score was 1.00 ± 0.19 (range 0.8–1.4), and the mean Pediatric Risk of Mortality (PRISM) score was 7.22 ± 2.88 (range 1.5–18.7). The mean length of stay in the PICU was 36.37 ± 19.09 hours. The clinical characteristics of the patients are presented in Table 2.
The relationship between clinical features and time to DKA resolution was examined (Table 3). The time to DKA resolution was significantly longer among patients with respiratory distress (p = 0.047), odor of acetone on the breath (p = 0.039), altered consciousness (p= 0.006), and severe coma (p = 0.018). Although the time to DKA resolution was longer among patients who were experiencing their first admission for DKA, this difference was not statistically significant (p = 0.725). There was also a significant correlation between the time to DKA resolution and both the PRISM score (r = 0.584, p = 0.002) and the length of stay in the PICU (r = 0.689, p < 0.001).
Laboratory features
Mean laboratory values of the patients were determined as pH = 7.08 ± 0.17, pCO2 = 21.36 ± 8.19 mmHg, HCO3 = 8.72 ± 3.03 mmol/L, lactate = 1.75 ± 1.02 mmol/L, anion gap = 23.69 ± 5.17 mmol/L, WBC = 17.88 ± 9.53 /mm3 CRP = 0.89 ± 1.98 mg/L, glucose = 544.63 ± 161.24 mg/dL, sodium = 133.11 ± 4.68 mEq/L, corrected sodium = 139.78 ± 4.89 mEq/L, potassium = 4.46 ± 0.70 mEq/L, chloride = 106.37 ± 6.55 mEq/L, blood urea nitrogen = 29.51 ± 11.25 mg/dL, creatinine = 0.89 ± 0.29 mg/dL, calculated serum osmolarity = 319.79 ± 15.28 mOsm/L, HbA1c (%) = 12.31 ± 2.51, blood ketones = 5.62 ± 0.76 mmol/L.
Linear regression analysis performed for laboratory features revealed that pH (p = 0.001) and HCO3 levels (p = 0.005) were associated with the time to DKA resolution. In the backward model regression analysis, pH values had an independent significant effect on time to DKA resolution (p = 0.014). Finally, there was a significant negative correlation between time to DKA resolution and both pH (r = −0.616, p = 0.001) and HCO3 levels (r = −0.552, p = 0.005).
Discussion
DKA is an acute, severe, and life-threatening complication of type 1 DM in children. It is important to identify the factors affecting the prognosis and resolution time of comas in these patients in order to predict outcomes. Although many studies examine prognostic factors, very few explore those affecting the time to resolution. The present study, which comprehensively examines the factors affecting resolution time, will contribute to the literature.
It has been reported that DKA resolution time in children can vary between 16 and 75 hours [6,13,14]. In patients with prolonged time to resolution, the stay in the intensive care unit (ICU) is also prolonged. To shorten this time, associated factors must first be identified and followed by early intervention. In our study, mean DKA resolution time was calculated as 20.2 hours, and the mean ICU hospitalization time was 36.37 hours.
It is thought that insulin infusion algorithms may affect DKA resolution time. Younis et al. [15] reported that, compared with paper-based insulin infusion, computer-based insulin infusion resulted in a statistically significant decrease in various outcomes, including time to DKA resolution, time on insulin infusion, and ICU stay. Because we use a paper-based insulin infusion algorithm in our clinic, we did not have the opportunity to discuss this difference.
In a recent pediatric study, DKA was found to be significantly more severe among females, but there was no significant relationship between age or living location and DKA severity [14]. Meanwhile, Valero-Guzmán et al. [6] reported a significant negative correlation between age and DKA resolution time. In most studies, DKA resolution time was longer in newly diagnosed patients [6,16]. In our work, similar to Razavi et al. [14], there was no relationship between age or living location and DKA resolution time. Similar to previous studies, we found DKA resolution time to be significantly longer in patients with newly diagnosed DM. Although DKA resolution time was found to be longer among females in our study, the difference was not significant. Although it is not mentioned in other studies, we found DKA resolution time to be significantly longer in patients with a family history of DM.
It is predicted that some clinical characteristics of patients may change DKA episode severity and resolution time. Valero-Guzmán et al. [16] found that DKA resolution time increased significantly as the severity of the disease increased and the duration of symptoms at home lengthened. When they included in the multivariate analysis all variables that were significantly associated in the bivariate analysis, the authors found that, in the most severe DKA episodes, patients who received a larger volume of intravenous fluids with higher NaCl content, took longer to resolve. Baalaajı et al. [17] reported that time to resolution of DKA was significantly longer among patients with acute kidney injury (AKI) than among those without. Since none of our patients had AKI, the effect of this on the time to resolution could not be evaluated. Similar to previous studies, the time to resolution of severe episodes was found to be significantly longer in our study. Although not mentioned in previous research, we examined the relationship between complaints and physical examination findings and DKA resolution time. The time to resolution was found to be significantly longer in patients with respiratory distress, confusion, and a mouth smelling of acetone. In addition, the resolution time was longer in patients presenting with the first DKA attack (compared to the second or third), but the differences were not significant.
In a limited number of adult and pediatric studies, it has been shown that some laboratory values at the time of admission affect DKA episode severity and resolution time. Valero-Guzmán et al. [6] found that there was a significant negative correlation between pH, pCO2, and HCO3 levels at the time of admission and resolution time. In addition, they showed that the pH value at admission had an independent and significant effect on resolution time in their patients. Lee et al. [11] showed, in adult DKA patients, that a lower admission pH and a higher admission serum potassium level were both independent predictors of prolonged time to resolution of DKA. Similarly, in our study, a significant negative correlation was found between pH and HCO3 levels at the time of admission and resolution time. However, no significant correlation was observed between serum electrolytes and other biochemical tests and resolution time. In our study, pH value at admission had an independent effect on resolution time.
Study Limitations and Strength
Our study has several limitations. The main limitation of this study is that it is a retrospective single-center study. We had to exclude three medical records due to incomplete data, and the relatively small sample size limits the study’s statistical power.
Conclusion
The results of our study revealed that many factors are effective on resolution time. Although some risk factors prolonged the resolution time, this effect was not significant. Our findings show that the prognosis will be worse and time to resolution will be longer among children with altered consciousness, newly diagnosed DM, respiratory distress, high PRISM score, severe DKA coma, and severe acidosis at the time of admission. Also, pH value had an independent significant effect on time to DKA resolution.
Acknowledgment
The authors would like to thank the Head of the Department of Pediatrics, XXXX Medical Faculty for the assistance during this research.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Mehmet Öztekin, Capan Konca, Mehmet Tekin, Semih Bolu. Evaluation of factors associated with time to diabetic ketoacidosis resolution in children. Ann Clin Anal Med 2022;13(9):968-972
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Beta-lactam antibiotic-induced thrombocytopenia: MYH9 & TUBB1 genes
Didem Özkan 1, Yasemin Ardıçoğlu Akışın 2, Dilara Fatma Akın Balı 3, Nejat Akar 4
1 Vocational School of Health Services, Istanbul Okan University, Istanbul, 2 Department of Biochemistry, Faculty of Medicine, TOBB Economy and Technology University, Ankara, 3 Department of Medical Biology, Faculty of Medicine, Niğde Omer Halisdemir University, Niğde, 4 Department of Pediatrics, Medical School,TOBB Economy and Technology University, Ankara, Turkey
DOI: 10.4328/ACAM.21174 Received: 2022-04-05 Accepted: 2022-06-05 Published Online: 2022-06-09 Printed: 2022-09-01 Ann Clin Anal Med 2022;13(9):973-977
Corresponding Author: Didem Özkan, Vocational School of Health Service, Tuzla Campus, Istanbul Okan University, 34959, Akfırat, Tuzla, Istanbul, Turkey. E-mail: didemtorun@gmail.com P: +90 216 677 16 30 Corresponding Author ORCID ID: https://orcid.org/0000-0003-4210-5073
Aim: Macrothrombocytopenia is a congenital autosomal-dominant blood disorder characterized by increased platelet size and a decreased number of circulating platelets. In this study, it was aimed to show the MYH9 and TUBB1 gene changes, which are the genes associated with the disease, in a patient with thrombocytopenia receiving beta-lactam antibiotic therapy.
Material and Methods: In this study, coagulation parameters and platelet aggregation tests were performed after ingestion of a beta-lactam antibiotic in an 8-year-old boy with thrombocytopenia, the MYH9 and TUBB1 genes were scanned by PCR and DNA sequencing, and the results were subsequently analyzed using bioinformatics tools.
Results: We found previously described TUBB1 polymorphisms, p.R307H , p.Q43P, p.T178T and the novel mutation p.K64A in the MYH9 gene in a boy and his mother. Changes in genes important for thrombocytopenia in a boy after taking beta-lactam antibiotics prompted us to study the same genes in the mother, since her mother had macrothrombocytopenia, and we found a new mutation in her mother
Discussion: Determination of gene changes after beta-lactam antibiotic use in bleeding patients is important in terms of helping the clinic in the treatment.
Keywords: Platelets, Macrothrombocytopenia, MYH9
Introduction
Myosin heavy chain 9 (MYH9)-related platelet disorders belong to the group of inherited thrombocytopenias. The MYH9 gene, located in chromosomal region 22q12-13, encodes a hexameric protein called 453 kDa non-muscle myosin IIA (NMMIIA), which is involved in cell motility, megakaryocyte contraction, and maintenance of cytoplasmic structure. Studies have shown that mutations in the MYH9 gene cause premature release of platelets from the bone marrow, macrothrombocytopenia, and formation of cytoplasmic inclusion bodies in neutrophils. MYH9-related disorders can have many signs and symptoms, including bleeding problems, kidney disease, hearing loss, and cataracts [1-5]. Macrothrombocytopenia is a congenital autosomal dominant blood disorder characterized by increased platelet size and decreased circulating platelet count. Macrothrombocytopenia belongs to the genetically heterogeneous group of rare disorders associated with multiple genes, MYH9 (MIM155100), ACTN1 (MIM615193) GP1A (MIM606672), GP9 (MIM173515), FL1 (MIM193067), FLNA (MIM3000017), ITG2A/ITGB3 (MIM 607759/173470), GATA1 (MIM305371), NBEAL2(MIM614169) and VWF (MIM613160). The most common forms of these disorders, such as the May-Hegglin anomaly and Bernard-Soulier syndrome, are associated with mutations in MYH9, which forms a dominant-negative protein that inhibits the function of the wild-type heavy chain protein [6,7]
The gene associated with microtubules in platelets is TUBB1 (tubulin beta-1). Microtubules are known to be composed of alpha and beta heterodimers. Although αβ-tubulin heterodimers are an important component of the cell surface membrane skeleton, they are responsible for intracellular transport of vesicles, cell morphogenesis, and chromosome segregation during cell division in all eukaryotes [8]. Studies have shown that tubulin heterogeneity is important for tissue-dependent functional differences between microtubules of the different alpha/beta tubulin isoforms. The relationship between the membrane skeleton, cytoskeleton, and actin filaments, as well as the intertwining of microtubules, ensure the maintenance of normal platelet morphology [9-12]. Beta-tubulin 1 (class VI, TUBB1), which is specific for hematopoietic cells, is 90% present in the marginal band of platelets. For this reason, there are very few studies on the functions of tubulin proteins in platelet structure and determination of the protein effect of the changes found. The TUBB1 gene is located at position 20q13.32 on the chromosome and encodes 451 amino acids.
Normal platelet function, including secretion, adhesion, and aggregation, is triggered by the binding of agonists (adenosine diphosphate [ADP], epinephrine) to specific receptors on the platelet membrane. Beta-lactam antibiotics inhibit platelet functions in vitro, such as secretion, adhesion, and also aggregation. β-Lactam antibiotics cause platelet dysfunction with bleeding complications [12] Previous in vitro studies have documented reversible inhibition of agonist-receptor interaction. Platelet function does not normalize immediately after drug treatment, suggesting irreversible inhibition of platelet function. It is not worth mentioning that antibiotics, especially the beta-lactam antibiotics, are widely used nowadays [13,14].
In this study, we identified a novel missense mutation in MYH9 &TUBB1 genes and described a patient with significant inhibition of platelet function in adenosine diphosphate (ADP) under beta-lactam antibiotics.
Material and Methods
Patient history
We report an 8-year-old boy who was admitted to our department seven days after tonsillectomy for evaluation of the underlying defect with bleeding. His own history revealed two different bleeding episodes: one, as mentioned above, and the other, an epistaxis episode 2 years earlier. The common point for these two attacks was the administration of “beta-lactam antibiotics.” The values of all factors were within the normal range; platelet count: 234000/ [150000-450000]/μl, Mean platelet volume: (MPV) 11.1/ [7.20-11.1] fl, Procalcitonin (PCT): 0.26/ [0.10-0.41] %). While coagulation parameters were normal, platelet aggregation showed impaired aggregation in the boy ADP during “beta-lactam antibiotic” treatment. After discontinuation of therapy, the platelet aggregation test was repeated and proved to be normal. Family history indicated that her mother always had thrombocytopenia. Further examination of her mother revealed that she had macrothrombocytopenia. Her platelet count was 105000/ [150000-450000]/μl, mean platelet volume was (MPV) 13.9/ [7.20-11.1] fl, procalcitonin (PCT) was 0.15/ [0.10-0.41] %). Although the scenario and clinical evaluation of the child were quite straightforward and obviously unrelated to this possible finding in the mother.
Genotyping Analysis
Written, informed consent for genetic analysis was obtained from the patients. Approval was also obtained from the Ankara University Clinical Research Ethics Committee in order to comply with the ethical rules of the study. DNA was isolated by proteinase K and phenol/chloroform extraction. Following extraction, all exons of the MYH9 gene and TUBB1 gene were screened by polymerase chain reaction (PCR) with the primers. PCR reactions were performed using 25 ng DNA and GoTaq green master mix reagent in a 20 µL PCR volume (Promega, Wisconsin, USA). Primers were designed using an online tool from the Santa Cruz Genome Browser1. Sequences were analyzed with the Finch TV program.
In silico analysis for predicting pathogenicity of mutations
The potential effects of the missense mutations that were identified in the TUB1 and MYH9 genes were analyzed through two pathogenicity assessment tools. PolyPhen-2 (available at: http://genetics.bwh.harvard.edu/pph2/) is a versatile bioinformatics tool that estimates the potential structural and functional consequences of Mutation/Single Nucleotide polymorphisms on amino acid position. It provides the estimation results between the score interval of 0.0 (benign) and 1.0 (potentially damaging). SNAP 2 (available at: https://rostlab.org/services/snap2web/) is a bioinformatics program that analyzes the functional impact of mutations and SNPs on protein and predicts their effects on phenotypic properties through SNAP2 [17]. When the given values are between (−100-0) and (0–100), mutations are scored as neutral and affected, respectively, in the SNAP software. Furthermore, using the “Multiple sequence alignment” option of the detected missense mutations in the Poly-Phen2 program, a comparison of amino acid sequences affected by the detected mutations was made between different species.
Structural modeling of selected mutants was calculated by the SWISS-MODEL server. It is a standalone software that can generate mutated models of the proteins for the corresponding amino acid substitutions
Results
The TUBB1 gene functions in the building of the marginal band in platelets, a unique cytoskeleton structure that is composed of bundles of circumferential microtubules that support the maintenance of the shape and function of platelets. The 7401 base-pair gene is located on human chromosome 20q13.3 and consists of 4 exons, encoding 451 amino acids. When we investigated the boy and his mother, we showed the previously-described TUBB1 variant c.920 G>A (p.R307H) at exon 4 and described synonymous variant, c.803G>T (p.T178T ) in the boy; p.R307H and p.T177T mutations are important for the gene function, we detected p.Q43P polymorphism, which is frequently seen in the TUBB1 gene, in the mother. The human MYH9 gene contains 41 exons spanning about 33,320 bases and is located on chromosome 22q12-13 [2]. Over 80 different MYH9 mutations have been identified in the Human Gene Mutation Database. In the present study, we identified a novel missense mutation and added c.197G>C to the spectrum of MYH9 mutations. The mutation was predicted to be damaging by both SNAP and Poly-Phen2 software. Although the child’s scenario and clinical evaluation seem unrelated to this possible finding in the mother, it is important for the study that a novel mutation has been detected in the mother
MYH9 analysis
According to the analysis results of Poly-Phen2, SNAP and Mutation Taster Database Programs, it was determined that 1 missense nucleotide change detected in our study was not pathogenic because their pathogenic scores were close to 0 and “benign” according to the Poly-Phen 2 program. However, the novel p.K64A missense nucleotide change detected in MYH9 gene was determined to be disease-causing in the results of SNAP and Mutation Taster Programs. The mutations detected are shown in detail in Table-1.
In addition, the missense nucleotide change was detected. By using the “Multiple sequence alignment” option in the Poly-Phen2 program, the amino acid sequences affected by the detected nucleotide were compared between different species. As a result of this analysis, it was determined that 1 missense nucleotide change changed the amino acid at the critical point that were conserved among different species throughout the evolutionary process. Swiss model workspace was applied to model the molecular structures of the wildtype and mutant proteins. Figure 1 shows the location of codons affected by MYH9 and the molecular structures of wild-type and mutant proteins. The change of novel p.K64A missense mutation caused a significant conformational change.
TUBB1 analysis
When the results were analyzed using the Poly-Phen2, SNAP, and Mutation Taster Database programs, it was determined that the p.R307H alteration of the 2 missense nucleotide alterations detected in our study was not pathogenic because their pathogenic scores were close to 0 and “benign” according to the Poly-Phen 2 program. However, SNAP determined that the p.Q43P alteration was effective and disease-causing. Using the multiple sequence alignment option in the Poly-Phen2 program, the amino acid sequences affected by the detected mutations were compared between species. The Swiss Model Workspace was used to model the molecular structures of the wild-type and mutant proteins. Figure 2 shows the location of the codons affected by TUBB1 and the molecular structures of the wild-type and mutant proteins. Alteration of the p.Q43P and p.R307H missense nucleotides does not result in a significant conformational change.
Discussion
Antibiotic-associated thrombocytopenia results from platelet destruction or a reduction in the number of megakaryocytes by the immune mechanism. Studies have shown that beta-lactam antibiotics (penicillin, ampicillin, cefazolin, etc.) can stimulate platelet destruction [11,15]. Cazenave et al. found that beta-lactam antibiotics inhibit platelet functions such as secretion, adhesion and also aggregation in vitro. β-Lactam antibiotics cause platelet dysfunction with bleeding complications. Previous in vitro studies documented reversible inhibition of agonist-receptor interaction. Platelet function does not normalize immediately after drug treatment, suggesting irreversible inhibition of platelet function [16,17]. It is not worth mentioning that antibiotics, especially the beta-lactam antibiotics, are widely used nowadays. Here, we describe a boy and his mother with significant inhibition of platelet function in adenosine diphosphate (ADP) under beta-lactam antibiotics. In the case of beta-lactam-induced thrombocytopenia, when we examined MYH9 and TUBB1 genes, two important genes for platelet function, in the patient and his mother, we found important gene alterations for thrombocytopenia.
We found 3 types of previously described TUBB1 polymorphisms: p.R307H, p.Q43P, p.T178T, and the novel mutation p.K64A in the MYH9 gene. Recent studies have shown that these mutations cause worn cytoskeleton formation and affect platelet morphology. In humans, the R307H variant causes defects in microtubule growth and depolymerizes microtubules. Studies have shown that the p.R307H variant may be useful as a biomarker in immune thrombocytopenia because it may affect platelets, resulting in lower platelet turnover. The Q43P polymorphism is known to result in impaired tubulin organization. Heterozygous carriers of P.Q43P have been found to have spherocytic platelets and platelets enlarged in the cytoplasm. In this study, in which we demonstrated that beta-lactam antibiotics inhibit platelet function, including aggregation, we also detected the p.K64A mutation, identified for the first time in the literature, by maternal genetic and clinical analysis.
In conclusion, MYH9 and TUBB1 gene alterations have been defined in beta-lactam-induced thrombocytopenia, and clinical trials are aimed at investigating the underlying defects in patients with bleeding.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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3. Balduini CL, Pecci A, Savoia A. Recent advances in the understanding and management of MYH9-related inherited thrombocytopenias. Br J Haematol. 2011;154(2):161-74.
4. Kunishima S, Saito H. Advances in the understanding of MYH9 disorders. Curr Opin Hematol. 2010;17(5): 405-10
5. Golomb E, Ma X, et al. Identification and characterization of nonmuscle myosin II C, a new member of the myosin II family. J Biol Chem 2004,;279(4): 2800-8.
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7. Kunishima S, Kojima T, Matsushita T, Tanaka T, Tsurusawa M, Furukawa Y, et al. . Mutations in the NMMHC-A gene cause autosomal dominant macrothrombocytopenia with leukocyte inclusions (May-Hegglin anomaly/Sebastian syndrome). Blood. 2001;97(4):1147-9.
8. Freson K, De Vos R, Wittevrongel C, Thys C, Defoor J, Vanhees L, et al. The TUBB1 Q43P functional polymorphism reduces the risk of cardiovascular disease in men by modulating platelet function and structure. Blood. 2005; 106(7):2356-62
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10. Kunishima S, Kobayashi R, Itoh TJ, Hamaguchi M, Saito H. Mutation of the beta1-tubulin gene associated with congenital macrothrombocytopenia affecting microtubule assembly. Blood. 2009; 8;113(2):458-61
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Didem Özkan, Yasemin Ardıçoğlu Akışın, Dilara Fatma Akın Balı, Nejat Akar. Beta-lactam antibiotic-induced thrombocytopenia: MYH9 & TUBB1 genes. Ann Clin Anal Med 2022;13(9):973-977
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Assessment of thiol disulfide homeostasis in isolated head injury
Fatih Tanrıverdi 1, Ozcan Erel 2
1 Department of Emergency Medicine, 2 Department of Biochemistry, School of Medicine, Yıldırım Beyazıt University, Ankara, Turkey
DOI: 10.4328/ACAM.21177 Received: 2022-04-06 Accepted: 2022-05-31 Published Online: 2022-08-04 Printed: 2022-09-01 Ann Clin Anal Med 2022;13(9):978-982
Corresponding Author: Fatih Tanrıverdi, Department of Emergency Medicine, School of Medicine, Yıldırım Beyazıt University, Üniversiteler Mahallesi, 06800, Çankaya, Ankara, Turkey. E-mail: fatihtanriverdi12@gmail.com P: +90 312 552 60 00 Corresponding Author ORCID ID: https://orcid.org/0000-0001-9959-5769
Aim: This study aimed to differentiate traumatic brain injury (TBI) and non-traumatic brain injury (NTBI) among patients presenting to the emergency department with isolated head trauma. For this purpose, we investigated whether the combined use of the parameters of thiol/disulfide homeostasis, an oxidative stress marker, and IMA (Ischemia Modified Albumin) was useful in differentiating the two conditions.
Material and Methods: This study was prospectively conducted on 92 patients who presented to the emergency department between 01.06.2018 and 01.01.2019, and 40 healthy subjects as controls. Thiol/disulfide homeostasis parameters (Thiol, disulfide), are the oxidative stress markers measured by a novel method developed by Erel and Neşelioğlu, and IMA were studied in the patient and control groups.
Results: NT and TT values were significantly lower in the TBI group than in the NTBI group (p <0.001, <0.001, respectively). Disulphide, IMA, and index1 and index 2 values were significantly higher in the TBI group compared to the NTBI and the control groups (p =0.019, <0.001, < 0.001, and < 0.001, respectively).
Discussion: The results of the present study suggest that these easy-to-perform, cheap, and automated biomarkers may help make a differential diagnosis between the two conditions.
Keywords: Isolated Head Trauma, Traumatic Brain Injury, Thiol/Disulfide Homeostasis
Introduction
Traumatic brain injury (TBI) is a leading cause of mortality and morbidity. From the standpoint of public health, it has a significant share among deaths under the age of 45 years [1,2].
The incidence and mortality and morbidity due to head trauma have been increasing as a result of developing technology and social developments [3]. Primary brain injury occurs as a result of trauma and physical effect on the central nervous system (CNS). This results in scalp injury, skull fracture, shrinkage, brain laceration, diffuse axonal injury, and intracranial bleeding (epidural, subdural, intracerebral). Post-traumatic injury depends on trauma mechanism and trauma severity [4]. After a primary injury, neurophysiological and biochemical mediators initiate secondary cellular injury [5] Formation of reactive oxygen species and lipid peroxidation (LP) causes stimulatory glutamate and aspartate release, calcium influx to the cell, and formation of eicosanoids. This impairs cell membrane permeability and leads to secondary cellular injury. Many studies to date have shown that oxygen free radicals play an important role in the occurrence of secondary injury and cause neurotoxicity [6,7]
The imbalance between the cellular production of oxygen radicals and cellular defense mechanisms against them is called oxidative stress [8]. The latter begins right after TBI and initiates a cascade that results in neuronal dysfunction and death. It plays an important role in secondary injury and is responsible for morbidity and mortality after TBI. However, the underlying molecular mechanisms are complex and have not been completely understood [1] Oxidative stress, i.e an imbalance between oxidizing agents and antioxidants, contributes to the pathogenesis of TBI [9]
Until recently, only one aspect of the thiol-disulfide balance has been measured. However, both sides of the balance can be measured and thiol-disulfide status can be completely evaluated using novel test methods [10]
The main aim of the present study was to investigate whether thiol/disulfide homeostasis parameters, which are among the oxidative stress markers, are useful for the differential diagnosis of TBI and NTBI among patients presenting with isolated head trauma.
Material and Methods
This open-label, prospective, controlled study enrolled a total of 132 subjects, which consisted of 92 patients and 40 healthy volunteers. The patients were grouped into two as traumatic brain injury (TBI) (n=47) and non-traumatic brain injury (NTBI) (n=45) groups. The study was conducted at the Emergency Department Training and Research Hospital between 01.06.2018 and 01.01.2019 and was approved by the Local Ethics Committee. All patients read the informed consent form and gave written informed consent for study participation. Patients older than 18 years of age who presented to the emergency department with isolated head trauma were enrolled. Patients with isolated head trauma were categorized into two groups, namely the traumatic brain injury group, and the non-traumatic brain injury group. Patients who were pregnant, who refused to participate in the study, and who were immunocompromised were excluded.
Blood samples were taken within the first hour of emergency department admission, before starting any medication. The levels of the parameters used to evaluate THD were measured in an automatic analyzer by a novel spectrophotometric method [10]. This method quantifies native thiol (NT), total thiol (TT), and disulfide (D) levels. Then, the ratios of these three parameters to each other are calculated (index 1: D/NT, index 2: D/TT, index 3: NT/TT). Serum Ischemia Modified Albumin (IMA) levels were quantified by a previously described colorimetric experimental technique [11]. In short, it involved the admixture of the serum in question at an amount of 200 uL, and then 0.1% CoCl2 50 uL and incubated at 37° C in dark, followed by a 10-minute addition. It was followed by the addition of 50 uL dithiothreitol as a coloring agent. One milliliter of 0.9 % NaCl was added 2 minutes after incubation and the reduction agent and the blank control were prepared similarly. Absorbance spectrophotometry was used at 470 nm to obtain readings. IMA was recorded as the absorbance unit. Both samples were measured twice and their mean value was reported. Thiol/disulfide analysis results were compared in the patient volunteers.
Statistical analysis
Statistical analyses of the study data were performed with SPSS 16.0 for the Windows software package. The normality of the data was tested using the Kolmogorov-Smirnov test. Normally distributed variables were reported as mean±standard deviation, and non-normally distributed ones as median (min-max). Three independent groups were compared using the Kruskal-Wallis test for variables without normal distribution and One-way ANOVA with posthoc Bonferroni test for normally distributed variables. Receiver Operating Characteristics (ROC) curves with area under the curve, sensitivity, and specificity values were drawn to determine the predictive ability of oxidative stress parameters for disease prediction. Statistical significance was set at p<0.05.
Results
This study enrolled 47 patients with TBI, 45 patients with NTBI, and 40 healthy volunteers. There was no significant difference between the groups regarding sex distribution whereas they were significantly different concerning age (Table 1).
NT, TT, Disulfide, IMA, index 1, and index 2 were significantly different but there was no significant difference concerning index 3. The subgroup analyses showed that the difference originated from the TBI group. NTBI and control groups were not significantly different. NT and TT were significantly lower in the TBI group compared to the NTBI group. Disulfide, IMA, index 1 and index 2 values were significantly higher in the TBI group compared to NTBI and control groups (Table 2).
ROC analyses were performed and the area under the curve was calculated for NT, TT, Disulfide, IMA, index 1, and index 2 in the TBI and NTBI groups. The area under the curve was the largest for NT, with the latter’s sensitivity and specificity being presented below. To give an example, traumatic brain injury was present at a rate of 100% for an NT value below 461.70, while for values above that level one must assume that traumatic brain injury is not present at a rate of 24.40%. One must assume that traumatic brain injury is present at a rate of 78.70% for NT values below 403.65 and absent at a rate of 57.80% for NT values above 403.65 (Figures 1-2 and Table 3).
Discussion
Our study examined the change of oxidative stress parameters after isolated head trauma among patients presenting with TBI. Oxidative stress occurs after secondary injury and leads to permanent brain injury [12]. Therapeutic interventions during secondary brain injury are essential. Many hallmarks are exhibited during delayed secondary CNS damage, mainly including mitochondrial dysfunction, Wallerian degeneration of axons, excitotoxicity, oxidative stress, and eventually neuronal death and overactivation of glial cells [13]. Cerebral endogenous antioxidant defense mechanisms neutralize superoxide radicals and form enzymes such as catalase activity, superoxide dismutase (SOD), and glutathione peroxidase (GPx), all of which protect cells against OS-induced injury [14].
The plasma thiol pool is one of the antioxidant mechanisms. Thiols are oxidized by oxidants and form disulfide bridges. The latter may be reduced to thiol groups. This dynamic thiol/disulfide hemostasis has a vital role in antioxidant defense [10]. Erel and Neşelioğlu measured thiol/disulfide homeostasis with the automatic colorimetric method for the first time in the literature; they revealed that disulfide levels increased in smokers and patients with diabetes, obesity, and pneumonia and decreased in some cancer types [10]. We demonstrated that thiol/disulfide homeostasis parameters did not differ between healthy volunteers and the NTBI groups, but they were significantly reduced in the TBI group compared to the NTBI and control groups. Disulfide, IMA, index 1, and index 2 values increased to a greater degree in the TBI group compared to the NTBI and control groups. We believe that the significant reduction in NT and TT levels in the TBI group compared to the control group and healthy volunteers occurred as a result of an increased oxidative burden. A significant increase in disulfide level occurred, which we believe occurred by the reduction of thiols. Significant increases were detected in index1 and 2. We believe that the significant reductions in NT and TT levels occurred as a result of an increased oxidative burden; hence, an expected increase in Disulfide level occurred that we attributed to thiols’ reduction.
Kavaklı et al. enrolled adult patients presenting to the emergency department with isolated blunt traumatic brain injury and healthy adults as controls [15]. They studied serum oxidant status by analyzing the Total Oxidation Status (TOS) in patients with traumatic brain injury and healthy subjects. Serum antioxidant status was analyzed by measuring Total Antioxidant Status (TAS). They also calculated Oxidative Stress Index (OSI). TOS and OSI levels were increased in the patient group compared to the controls. Among patients that ultimately died, OSI, TOS, and TAS were higher. The authors suggested that oxidative stress parameters may be valuable prognostic markers and concluded that oxidative stress parameters may offer an opportunity for assessing the clinical severity of traumatic brain injury and predicting its outcome. We also demonstrated that NT and TT levels significantly decreased due to increased oxidative stress burden in the TBI group than in the NTBI and control groups. In addition, disulfide levels significantly increased as a result of thiols’ reduction.
De-Sheng et al. reported that Thioredoxin (TRX), a powerful antioxidant, was higher in patients with head trauma compared to controls [16]. They observed a drop in Glasgow Coma Score as the TRX level increased. They also found a correlation between TRX and mortality rate. They concluded that TRX may be used as a prognostic marker among patients with TBI. Our study detected a significant increase in IMA and disulfide levels in the TBI group. While an increase in IMA and Disulphide levels occurred in the TBI group, it was absent in the NTBI group. Therefore, we think that these parameters, in combination with the clinical presentation, can be used as a discriminator in making decisions for radiological tests.
Lilios et al. examined glutathione peroxidase, which is an antioxidant molecule, in pediatric patients presenting with multi-trauma. They reported a significant drop in antioxidant levels in the first three days followed by a rise starting on the 7th day [17]. Our study similarly showed reduced levels of antioxidant TT and NT in the TBI group. Our study only took into consideration the admission levels of these parameters. We believe that intermittent monitorization of NT and TT can be used to correlate them with clinical status.
Şahin A et al. studied IMA levels among patients who presented to the emergency department with a headache. They observed that migraine was the most common headache etiology (32.6%). A comparison of the study groups concerning serum IMA levels revealed no significant differences between the primary and secondary headache groups, between life-threatening and non-life-threatening headache groups, and between migraine, cluster, and stress-type headache subgroups within the primary headache group (p>0.05) [18]. In our study, it was significant in the TBI group compared to the NTBI and control groups. We believe that the mechanism underlying that finding is free radicals emerging in intracranial pathologies, especially secondary to ischemia, reperfusion, and hemorrhage passing to the systemic circulation through the blood-brain barrier, which leads to an increased IMA production. This suggests that this parameter can be used to indicate brain injury without needing any imaging study.
Gündüz et al. compared IMA levels of 43 patients with ischemic infarction, 11 patients with intraparenchymal hemorrhage, 52 patients with SAH, and 43 healthy controls [19]. Radwan et al. increased IMA levels in 49 patients with TBI who were admitted to the intensive care unit. Of the 49 patients with heightened IMA, 22 had a decrease in IMA, and 27 had an increase in 24 hours. IMA levels were higher in deceased patients than in survivors [20]. That study is in agreement with our study. IMA level increases in intracranial pathologies.
We did not come across any study that studied a combination of thiol/disulfide homeostasis and IMA in isolated head trauma. We believe that studying a combination of thiol/disulfide homeostasis parameters and IMA would be beneficial for making a differential diagnosis between TBI and NTBI. We believe that, in this way, unnecessary radiological evaluation can be avoided. We are of the opinion that this subject may also guide therapy and should be studied by larger studies.
Limitations
The main limitation of our study is the small sample size. In isolated head trauma, one must not depend solely on a single biochemical test to detect brain injury and make correlations with clinical signs and other radiological studies. Thiol/disulfide homeostasis parameters and IMA should be evaluated in combination with other clinical and radiological parameters.
Conclusion
Oxidative stress plays an important role in the pathogenesis of isolated head trauma. Pathogenesis was revealed by measuring thiol/disulfide homeostasis and IMA quantitatively with the technique developed by Erel and Neşelioğlu. The present study numerically demonstrated the difference between the groups with and without brain injury concerning oxidative stress levels using the above technique. Differences in the patient groups compared to the control group suggest that these biomarkers may aid in making a diagnosis of TBI and NTBI. In conclusion, we think that measured with an easy, cheap, and automated technique, these biomarkers would aid in making the differential diagnosis after being tested by larger studies. We also believe that studies using thiol/disulfide and IMA levels in homogenous patient groups would serve both to make a differential diagnosis and to avoid unnecessary radiological studies.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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3. Baldo V, Marcolongo A, Floreani A, Majori S, Cristofolettil M, Dal Zotto A, et al. Epidemiological aspect of traumatic brain injury in Northeast Italy. Eur J Epidemiol. 2003; 18(11): 1059-63.
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5. Lorente L. New Prognostic biomarkers in patients with traumatic brain injury. Arch Trauma Res. 2015; 4(4): e30165..
6. Bryan J, Galbraith SL. Pathology and natural history of head injury. In An introduction to neurosurgery. Head injuries. 1983; 42-3.
7. İnci S, Ozcan OE, Kilinc K. Time-level relationship for lipid peroxidation and the protective effect of alpha-tocopherol in experimental mild and severe brain injury. Neurosurgery. 1998; 43(2):333-6.
8. Gilgun-Sherki Y, Rosenbaum Z, Melamed E, Offen D. Antioxidant therapy in acute central nervous system injury: current state. Pharmacol. Rev. 2001; 54(2): 271-284.
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13. Ng SY, Lee A. Y. W. Traumatic brain injuries: pathophysiology and potential therapeutic targets. Frontiers in Cellular Neuroscience. 2019; (13): 528.
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Fatih Tanrıverdi, Ozcan Erel. Assessment of thiol disulfide homeostasis in isolated head injury. Ann Clin Anal Med 2022;13(9):978-982
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Sex estimation using palmprint measurements among a sample of adult Egyptians
Eman Adel Seif, Wafaa Mohamed Elsehly, Magda Hassan Mabrouk Soffar, Maii Farag Henaidy
Department of Medicine and Clinical Toxicology, Faculty of Medicine, Alexandria University, Egypt
DOI: 10.4328/ACAM.21178 Received: 2022-04-07 Accepted: 2022-06-05 Published Online: 2022-06-23 Printed: 2022-09-01 Ann Clin Anal Med 2022;13(9):983-988
Corresponding Author: Magda Hassan Mabrouk Soffar, Department of Medicine and Clinical Toxicology, Faculty of Medicine, Champollion Street, Alexandria, Egypt. E-mail: magda.mabrouk@alexmed.edu.eg P: +20 121 070 15 52 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6230-8591
Aim: Sex estimation is crucial in the forensic field. Palmprints are unique prints that are commonly recovered from crime scenes. A tri-radius ‘delta’ is a meeting point of three groups of ridges. Five tri-radii are identified on the palm, four at the base of Index (a), Middle (b), Ring (c) and little finger (d), and one axial tri-radius (t) near the wrist. This study assessed the validity of distance between palmar tri-radii (abcd-t) as a sex predictor in a sample of Egyptians.
Material and Methods: The study was conducted on 100 adult Egyptians (50 females and 50 males). Palmprints were obtained using fingerprint inked strips (6 x 10 inches). Palmprints were scanned and the distances between the axial tri-radius ‘t’ and other tri-radii (a, b, c, and d) were measured using Software. Also, combined abcd-t distance (sum of four distances) was calculated.
Results: Means of palmar tri-radii distances from (abcd) to axial t were significantly higher in males. ROC curve analysis was done for all palmar tri-radii distances. Male could be predicted on the right side when (d-t) distance >7.11cm or combined abcd-t distance > 32.17 cm with accuracy (88%). On the left side, male could be predicted when (b-t) distance> 8.65 cm or combined abcd-t distance>32.37 cm with accuracy (87%).
Discussion: Palmar tri-radii distances are significantly longer in Egyptian males. Subsequently, these measurements could predict sex with reasonable accuracies among adult Egyptians. Similar studies on other populations are recommended.
Keywords: Sex Estimation, Palmprint Measurements, Palmar Tri-Radii Distances, Egyptians
Introduction
Identification is important not only in legal medicine but also in criminal investigations and genetic research [1]. Dermatoglyphics is one of the reliable methods that can be used in medicolegal identification [2].
Dermatoglyphic traits refer to epidermal ridges and furrows on the fingers, palms, soles, and toes. The embryogenesis of the ridges is influenced by certain genes. Also, the intrauterine environment, such as the amniotic fluid content during the 10th to 16th week of intrauterine life, may affect ridge formation [3,4].
The palmprint is the print of the inner aspect of the hand from the base of fingers to the wrist joint. Three principal lines divide the palm into three parts: thenar (adjacent to the thumb), hypothenar (adjacent to the little finger), and inter-digital areas (adjacent to the base of fingers) [5,6].
Palmprints have many unique characteristics as fingerprints. However, palmprints have a significantly wider surface area in relation to fingerprints. Also, palmprints have additional distinguishing features such as principal lines and creases. Palmprints account for about 30% of the latent prints recovered from crime scenes. Subsequently, there is an escalating need for palmprints databases worldwide [7-9].
A tri-radius (also known as ‘delta’) is defined as a point at which three groups of ridges from three directions meet at angles of approximately 120° [10]. Generally, there are five tri-radii on the palm, four are located in the inter-digital areas at the base fingers {Index (a), Middle (b), Ring (c) and little finger (d)}, and one is located near the wrist, which is termed as axial tri-radius (t). In dermatoglyphic researches, the position of the tri-radii of the palms acts as a crucial landmark [11,12]
The application of distances between tri-radii (abcd-t) of the palm for sex determination is investigated only in the central Indian population [13]. It is important to consider that palmprint’s features are population specific. Thus, there is a necessity to evaluate the utility of distances between palmar tri-radii as a sex predictor in different populations. The current study aimed to assess the validity of the distance between palmar tri-radii (abcd-t) as a sex predictor in a sample of adult Egyptians.
Material and Methods
The current study was carried out in the Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Alexandria University, Egypt. This cross-sectional study was conducted on one hundred Egyptians (50 females and 50 males) aged between 18-and 30 years. The Ethics Committee of Alexandria, Faculty of Medicine approved the current study (FWA number: 00018699, IRB number: 00012098, approval serial number: 0201360), also informed consent was obtained from all participants.
Subjects with inflammation or injuries on the palm were excluded from the study. Any cases with physical abnormality due to fracture, amputation, burn, congenital deformity, or deformity due to surgical procedure were also excluded.
The following materials were utilized: 6 x 10 inches Fingerprint Inked Strips (New York-USA), which are composed of a fine layer of ink coated between two thin flexible plastic sheets, A4 white paper, soap, and dry towels.
The demographic data of each participant were recorded, including age, sex, and nationality. Then, the inked palmprint was obtained.
1. Obtaining inked palmprint: [13,14]
• Each participant was asked to wash both hands with soap and water.
• The fingerprint inked strips were pulled apart to reveal the inked layer.
• The palm was placed on these opened strips and the dorsum of the hand pressed forcibly to flatten the palm and open the creases.
• The inked hands were pressed firmly on white paper from the proximal to distal direction.
• The palms lifted away from the paper in opposite direction from the distal to the proximal end.
2. Examination and analysis of palmprints: [13,15]
The inked palmprints were scanned with resolution of 600 dots per inch (dpi) and analyzed using software (CorelDRAW 2020).
Figure 1 illustrates an inked palmprint with five Palmar tri-radii:
• Tri-radius at the base of the Index finger ‘a’
• Tri-radius at the base of the Middle finger ‘b’
• Tri-radius at the base of the Ring finger ‘c’
• Tri-radius at the base of the little finger ‘d’
• Axial tri-radius at the base of the fourth metacarpal near the proximal end of the palm and near the wrist ‘t’.
The distances of the tri-radii a, b, c, and d from the axial tri-radius ‘t’ were measured using a ruler tool. The combined abcd-t distance, which is the sum of the four distances (a-t + b-t + c-t + d-t) was calculated for each palm in all participants.
Statistical Analysis:
The IBM SPSS software package version 25.0 was used to analyze the data. The Kolmogorov-Smirnov test was employed to ensure the normality of the distribution. The student t-test was used for normally distributed quantitative variables, to compare two studied groups. The receiver operator characteristic (ROC) curve analysis was used to detect the cutoff values for sex prediction using distances between palmar tri-radii. The area under the ROC curve (AUC) was used to determine the accuracy.
Results
The study was conducted on 100 adult Egyptians (50 males and 50 females). The age of the participants ranged from 18 and 30 years. The mean age of males was 22.4±2.8 years, while that of females 22.5±3.1years. There was no statistically significant difference in age between males and females (p =0.595).
Inked palmprints were obtained and analyzed by two forensic experts. For the inter-observer reliability, the intra-class correlation coefficient (ICC) value was exceeding 0.9, which indicates excellent reliability. The repeatability of the measurements for the same observer (intra-observer agreement) also exceeded 0.9.
Table 1 reveals the measurement of distances from the interdigital tri-radii ‘a, b, c, d’ to axial tri-radius ‘t’ (a-t, b-t, c-t, d-t) in palmprints of both sexes. All measured palmprint tri-radii distances (a-t, b-t, c-t, d-t) were statistically higher in males with p<0.001.
Figure 2 (a, b) shows the comparison between males and females regarding the frequency of combined abcd-t distances on right and left palms.
• On the right palmprint, the highest frequency of combined abcd-t distance in males was in the range of 32.5-34.9 cm, representing 42% of the studied males. Meanwhile, in females’ right palm the highest frequency was in the range of 27.5-29.9 cm, representing 44% of the studied females.
• On the left palmprint, the most common frequency of combined abcd-t distance in males was in the range of 32.5-34.9 cm, representing 44% of the studied males. Meanwhile, in females’ left palm, the highest frequency was in the range of 30-32.4 cm, representing 46% of the studied females.
Table 2 and Figure 3 (a, b) demonstrate ROC curve analysis for palmar tri-radii distances and combined abcd-t distance on right and left palmprints.
• On the right palmprint, sex could be predicted with accuracies ranging from 80% to 88%. The best accuracy was at (d-t) distance and the combined abcd-t distance with 88% accuracy for each. Regarding (d-t) distance the cut-off point for male sex prediction was >7. 11cm (sensitivity 94%, specificity 82%, P<0.001, AUC=0.944) and for the combined abcd-t distance was >32.17cm (sensitivity 90%, specificity 84%, P<0.001, AUC=0.949).
• On the left palmprint, sex could be predicted with accuracies ranging from 83 % to 87%. The best accuracy was at the (b-t) distance and the combined abcd-t distance with 87% accuracy for each. Regarding (b-t) distance, male sex was predicted at a cut-off point > 8.65 cm (sensitivity 90%, specificity 84%, P<0.001, AUC=0.919) and for the combined abcd-t, distance was >32.37 cm (sensitivity 90%, specificity 82%, P<0.001, AUC=0.933)
Discussion
Sex estimation is one of the most challenging tasks in forensic practice. Dermatoglyphics is frequently used to provide evidence about sex [16]. Other than medicolegal purposes, literature linked palmar dermatoglyphics with certain medical conditions like idiopathic epilepsy [17], and coronary artery disease [18].
In forensic practice, palmprints have been utilized to distinguish different populations because of ethnic variance [19]. Also, different palmprint features were extensively investigated as sex predictors, such as ridge density [9] and palmprint measurements [20-21]. However, to date, there are limited data regarding the use of palmar tri-radii (abcd-t) distances as a sex predictor [13]. The present study investigated for the first time the use of these distances (abcd-t) for sex identification in the Egyptian population.
The current study was conducted on 100 Egyptians aged 18 to 30 years. Eighteen years was selected as a lower limit to ensure a well-established sexual dimorphism, above this age, the significant differences between both sexes regarding prints have been settled [22]. In this study, individuals above the age of thirty years were excluded to avoid the age-related changes on palmprints, especially the position of palmar tri-radii [15,23].
The current study used Fingerprint Inked Strips because they produce clear crisp permanent palmprints without over-inking due to the thin layer of ink coated on the strips. These inked strips are simply used with minimal hygiene or cross-infection risks. Also, they are non-toxic with no reported hypersensitivity [24]. Their reasonable price makes Inked Strips convenient, especially in developing countries including Egypt. The obtained palmprints in the current study were scanned and palmar tri-radii distances (abcd-t) were measured accurately using specialized software [15]. Badiye et al. in 2019 [13] studied inked palmprints directly under a hand-illuminated microscope, and the distances were measured using a scale. However, the method used in this study is less time-consuming and relatively more accurate than the method used by Badiye et al. in 2019.
Intra-observer and inter-observer agreements were excellent, indicating reliability and objectivity of the obtained palmar measurements. In the present research, the means of all palmprint tri-radii distances (a-t, b-t, c-t, d-t) were significantly higher in males than females, which agrees with Badiye et al. who conducted their study on the central India population in 2019 [13].
Regarding males, the highest frequency of combined abcd-t distance was 32.5-34.9 cm, representing 42% and 44% of the studied males on the right and left sides, respectively. This coincides with the results reported by Badiye et al. in 2019 [13] where the highest frequency of combined abcd-t distance was 32.5-34.9 cm, representing 41,5% and 32,3 % of the studied males on the right and left sides, respectively.
Regards females, on the right palm, the highest frequency was 27.5-29.9 cm, representing 44%, but on the left palm, the highest frequency was 30-32.4 cm, representing 46% of the studied females. Whereas Badiye et al who studied a population of central India stated that the commonest frequency of combined abcd-t distance on the right side was 30-32.4 cm, representing 33,3% and 27.5-29.9 cm on the left side, representing 36.5% of the studied females [13]. Population-related variation could explain the inconsistency between the current results and that of Badiye et al. (2019) regarding combined palmar tri-radii distances in females [15].
In the present work, ROC curve analysis was implemented to allow the practical applicability of the results. Sex could be predicted with an accuracy ranging from 80% to 88% on the right side with the best accuracies using d-t or combined abcd-t distance. Whereas on the left side, the accuracy ranged from and from 83 % to 87% with best accuracies using d-t or combined abcd-t distance.
Badiye et al. (2019) is the only previous study that investigated the utility of palmar tri-radii (abcd-t) distances. They analyzed their results in the Indian population using a probability test rather than a more applicable ROC curve analysis that challenges the comparability of their results with that of the present study. However, Badiye et al. (2019) pointed to the potential utility of palmar tri-radii distances in sex identification among Indians [13].
Different palmprint parameters had been previously used for sex prediction other than palmar tri-radii (abcd-t) distances, such as palmprint measurements, ridge density, and palmar digital intertriradial distances [9,15,20,21]. Ishak et al. 2012 [20] denoted that palmprints measurements could be used in sex prediction along with other hand dimensions in an Australian population. Also, Kolić et al. 2020 [21] proved that palmprint measurements could identify sex in the Croatian population. Considering palmprint ridge density, Krishan et al. 2014 [9] correctly identified the sex of the North Indians with 66.8% and 71.7% accuracies on right and left sides, respectively. Regarding the palmar digital intertriradial distances, Jerković et al. 2021 [15] claimed that the accuracy of using these measurements in both hands reached 87% in the Croatian population.
In crime scenes, the palmprint is not usually complete to the extent that allows obtaining whole palmprint dimensions. In such situations, the palmar tri-radii distances could be applied for sex identification with high accuracy. Also, measuring the distances between palmar tri-radii (abcd-t) is much easier than counting palmprint ridge density, where placing, orientating squares, and counting the ridges is difficult and time-consuming. However, it is important to consider that palmprint features, including palmar tri-radii, are affected by palmprint quality and persistence in the scene.
In mass casualties, the distances between palmar tri-radii could be used to identify the sex of the mutilated corpses as long as the palmprints are obtainable. On the other hand, in advanced decomposition and extensive mutilation, obtaining palmprints is impossible, which necessitates the use of other identification methods. In general, DNA analysis is the most precise method for identification. DNA could be extracted from any available tissue, even if the decay was advanced, however, complex analysis procedures along with high cost limit its utility [25].
Conclusion and Recommendations
The current study pointed to palmar tri-radii distances (abcd-t) as a valuable and convenient sex predictor with reasonable accuracies among adult Egyptians. This method could be used for sex prediction in mass disasters where the number of unidentified victims is large and also for sex identification of persons leaving their palmprints at the scene. Further studies on palmar tri-radii distances are recommended using larger samples in Egyptians. Similar studies are needed to verify the utility of palmar tri-radii distances in different populations. Also, other palmprints features such as handprint measurements and ridge density could be studied along with palmar tri-radii distances to further enhance the accuracy of sex identification.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Eman Adel Seif, Wafaa Mohamed Elsehly, Magda Hassan Mabrouk Soffar, Maii Farag Henaidy. Sex estimation using palmprint measurements among a sample of adult Egyptians. Ann Clin Anal Med 2022;13(9):983-988
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Is the heart of premature babies born as a result of IVF pregnancy different?
Fatma Hilal Yılmaz 1, Mehmet Burhan Oflaz 2, Hüseyin Altunhan 3, Nuriye Emiroğlu 3, Emin Ünal 2, Nazlı Dilay Gültekin 4
1 Department of Neonatology, Dr. Ali Kemal Belviranli Hospital for Obstetrics and Pediatrics, Konya, 2 Department of Pediatric cardiology, Necmettin Erbakan University Meram Medical Faculty, Konya, 3 Department of Neonatology, Necmettin Erbakan University Meram Medical Faculty, Konya, 4 Department of Neonatology, LÖSANTE Child and Adult Hospital, Ankara, Turkey
DOI: 10.4328/ACAM.21183 Received: 2022-04-12 Accepted: 2022-06-29 Published Online: 2022-06-30 Printed: 2022-09-01 Ann Clin Anal Med 2022;13(9):989-992
Corresponding Author: Fatma Hilal Yılmaz, Department of Neonatology, Dr. Ali Kemal Belviranli Hospital for Obstetrics and Pediatrics, Konya, Turkey. E-mail: f.h.yilmaz@hotmail.com P: +90 505 928 23 45 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1152-9773
Aim: This prospective study aims to reveal whether preterm births with ART-induced pregnancies are at greater risk of structural and functional cardiac pathologies compared to the control group of preterm births from spontaneous pregnancy.
Material and Methods: Between October 2017 and January 2020, 25 premature babies born by means of assisted reproductive techniques (AC) and 25 babies born from spontaneous pregnancy (SC) were included in the study. All babies recruited for the study were born at or below 34 weeks of gestational age. The groups were evaluated in terms of anatomical, m-mode and tissue Doppler systolic and diastolic functions using transthoracic echocardiography (ECHO).
Results: The groups were found to be similar in terms of anatomical, m-mode and tissue doppler systolic and diastolic functions by transthoracic ECHO (p=0.156).
Discussion: Early diagnosis of possible cardiac diseases is vital for pre- and post-natal management and ultimately for the survival of the infant. Studies should be focused on understanding and eliminating the pathophysiologies increasing the risk of CHD during ever-increasing ART practices.
Keywords: Assisted Reproductive Technology, Heart Defect, Prematurity
Introduction
Although the frequency and causes of infertility vary across societies, it is estimated to occur in approximately 15% of couples of reproductive age [1]. The highest prevalence of infertility worldwide is in Eastern Europe, North Africa/Middle East, Oceania, and Sub-Saharan Africa [2]. Over the last two decades, the increase in the population seeking help for infertility and the recent developments in Assisted Reproductive Technology (ART), which increases the probability of successful treatment, have led to developments in the field of infertility [3]. This technology includes in vitro fertilization (IVF), embryo culture, fresh and frozen embryo transfer, intracytoplasmic sperm injection (ICSI), preimplantation genetic diagnosis, and IVF with donor oocytes. Although most babies born with ART are healthy, they are thought to have more risk for various aspects of their health than natural pregnancy babies. This idea is based on an increased risk of multiple pregnancies in ART and the consequently increased rate of premature and low birth weight associated with an increased risk of perinatal morbidity and mortality [4]. Besides, the biological and genetic characteristics of the parents with low fertility may add additional health risks for the baby born, and interventions and drugs used for infertility treatment may also cause various complications in the fetus and newborn. Factors such as changing the follicle environment and oocyte structure by artificial stimulation of ovulation, encountering conditions that disrupt the natural functions of the sperm and embryo, freezing and manipulating the oocyte and embryo also may adversely affect this process [5]. Many studies from diverse ethnic populations have shown that embryos conceived after ART have poorer birth outcomes than spontaneously conceived embryos [6,7,8]. Studies have shown that birth defects are more common in these babies [9,10]. Congenital heart defects occur in approximately 0.76% of live births and it is 0.61% after excluding those with underlying genetic diseases [11]. CHDs account for 28% of all birth defects and they lead to a significant rate of morbidity and mortality. On this basis, early diagnosis permits optimal care during pregnancy, delivery, and in the newborn period (including surgical correction of the defect) as well as pregnancy termination for lethal and very severe heart defects. There is not any prospective study on the subject in our country yet. Thus, this study aims to reveal whether preterm birth with ART-induced pregnancies is at greater risk of structural and functional cardiac pathologies compared to the control group of preterm birth from spontaneous pregnancy.
Material and Methods
Study design
It was a prospective study performed at Necmettin Erbakan University in Turkey, between October, 2017 and January 2020.
Twenty-five premature babies born by means of assisted reproductive techniques (AC) and 25 babies born from spontaneous pregnancy (SC) were included. All babies recruited for the study were born at or below 34 weeks of gestational age.
Patients with congenital multiple anomalies (chromosomal anomalies, hydrops, spina bifida, patients with major surgical problems, etc.), perinatal asphyxia or metabolic disorders were excluded from the study. Demographic and clinical information of the infants and mothers were recorded. Gestational week of the baby, birth weight, gender, mode of delivery, multiple pregnancy status, 1st and 5th-minute Apgar scores, whether resuscitation was applied or not, surfactant was given or not, existence or non-existence of respiratory distress syndrome, patent ductus arteriosus, bronchopulmonary dysplasia, retinopathy of prematurity, pregnancy mom’s weight gain by week during pregnancy, invasive and non-invasive mechanical ventilator time, free oxygen intake time, discharge time and exitus status, age of the mother, comorbidities, if any, non-vitamin drugs used, prenatal steroid use were recorded. The groups were evaluated in terms of anatomical, m-mode and tissue Doppler systolic and diastolic functions using transthoracic echocardiography (ECHO).
Echocardiographic evaluation technique
Babies in both groups were evaluated underwent echocardiographic examination before they were discharged from the neonatal unit, while their clinical status was stable. Before echocardiography, all newborn infants underwent detailed cardiac examination. All echocardiographic assessments were performed by an experienced pediatric cardiologist with 15 years of experience using the GE, Vivid T8, China device. All data were recorded.
Ethics
Ethics Committee approval for this study was obtained from Necmettin Erbakan University with the Ethics Committee decision number of 2017/1026.
Statistical analysis
Data entry, statistical analysis and reporting procedures were performed electronically. Descriptive analysis was performed for the demographic and clinical characteristics of the patients. The distribution of data was assessed using a one-sample Shapiro-Wilk test. Data are demonstrated as mean ± standard deviation for normally distributed continuous variables and frequencies (percentile) for categorical variables. When the values between different groups are suitable for normal distribution, they were compared using the T-test, when not normally distributed, they were compared using the Mann-Whitney U test.
The χ2 test was used to assess differences between categorical variables. Test results with p<0.05 were considered statistically significant.
Results
Table 1 summarizes demographic characteristics of the patient. Infants in the AC and SC groups were similar in terms of demographic characteristics.
Table 1 summarizes the medical characteristics of the patients. More multiple pregnancies were found in the AC group (p=0.015). It was determined that the age of the mothers was significantly higher in the AC group (p=0.024).
Mothers’ drug use was higher in the SC group (p=0.001). Free oxygen duration was found to be longer in the SC group (p=0,017)
Tables 2 and 3 summarize the echocardiographic characteristics. The groups were found to be similar in terms of anatomical, m-mode and tissue doppler systolic and diastolic functions by transthoracic ECHO (p=0.156).
Discussion
It is estimated that more than 5 million children worldwide are born as a result of ART-induced pregnancy [12]. Although ART is generally considered safe, growing evidence suggests that ART is associated with worse perinatal outcomes and an increased risk for congenital malformations [13]. Rapid technological progress and the rapid increase in the popularity of ART techniques bring the importance of safety to the front [12]. In this context, there are many studies evaluating the health status of AC-infants as well as prenatal, perinatal and long-term risks. Nonetheless, as the rate of invasive intervention in the formation of conception increases, worse results may be encountered. Wen et al. have shown that IVF/ICSI may be more harmful than natural pregnancies, and ICSI may be more harmful than traditional IVF [14]. However, in the studies by Olson et al., there was no difference in the rates of defective births among all IVF offspring after ICSI or after transfer of cryopreserved embryos [15].
Infertility treatments increase the risk of cardiovascular disease due to the high level of hormones they are exposed to, damage to the endothelial tissue, and predisposition to coagulopathy [16]. As a consequence, it has been observed that sub-fertile individuals are more associated with metabolic diseases and cardiovascular disease later in their lives [17]. In our study, the groups were similar in terms of maternal disorders. However, maternal age was higher than expected in the AS group. We found that mothers tended to use more medication during SC pregnancies. We attributed this result to lower levels of anxiety about infant loss compared to the other group.
As a result of possible problems in the fetal development of AC-infants, cardiovascular remodeling has become one of the dreaded manifestations, and indeed some studies have reported the emergence of cardiovascular remodeling [18]. In this study, we did not find any difference between IVF and spontaneous pregnancy babies in terms of systolic and diastolic functions in CHD, m-mod and tissue dopplers. Previous studies have reported a slightly higher risk of CHD in ART-conceived infants compared to SC infants [19,20]. In a meta-analysis, Hooarsan et al. showed that ART-conceived infants were at a 43% higher risk of CHD (OR: 1.43, 95% CI: 1.30-1.60) compared to SC infants [21]. A cohort study reported the incidence of mild CHD in fetuses born with ART as 2.75% (10 out of 363 fetuses) [22]. Overall, previous meta-analyses have concluded that children born with IVF/ICSI pregnancy are at an increased risk for cardiovascular and other system defects [15].
ART techniques have also been associated with cardiovascular abnormalities. This has been attributed to multifactorial causes at the molecular level. Epigenetic changes, increased prematurity, and the ratio of low birth weight associated with ART are thought to cause poor cardiovascular and overall outcomes [22].
The limitations of this study include the small number of cases in the study and control groups. The ART group, which included only IVF infants, could not enclose infants from different ART procedures, and hence the results could not be compared among themselves.
Conclusion
In conclusion, although not confirmed by the results of our study, taking into account the literature, it is possible to say that IVF infants are at higher risk for CHD than SC infants. These infants require closer pediatric cardiology follow-up starting from fetal life to assess cardiac anatomy and function. Early diagnosis of possible cardiac diseases is vital for pre- and post-natal management and ultimately for the survival of the infant. Studies should be focused on understanding and eliminating the pathophysiologies increasing the risk of CHD during ever-increasing ART practices.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Anti-inflammatory therapy in patients with severe COVID-19 pneumonia: A single-center observational study
Gülnur Kul 1, Gürkan Değirmencioğlu 2
1 Department of Infectious Diseases and Clinical Microbiology, 2 Department of Infectious Diseases and Clinical Microbiology, Kırıkhan State Hospital, Hatay, Turkey
DOI: 10.4328/ACAM.21185 Received: 2022-04-13 Accepted: 2022-05-31 Published Online: 2022-06-24 Printed: 2022-09-01 Ann Clin Anal Med 2022;13(9):993-998
Corresponding Author: Gülnur Kul, Mimarsinan Mahallesi, İsmail Turan Bulvarı, No:40, Hatay, Kırıkhan, 31440, Turkey. E-mail: gkul2004@gmail.com P: +90 505 301 05 45 Corresponding Author ORCID ID: https://orcid.org/0000-0001-7317-3461
Aim: In our study, the effects of methylprednisolone and anakinra drugs in the treatment of hyperinflammation in severe COVID-19 patients were investigated.
Material and Methods: In this single-center retrospective study, severe COVID-19 patients followed up with signs of hyperinflammation were examined. The patients were examined in the Sequential Treatment Group receiving high-dose methylprednisolone followed by Anakinra, and the concomitant treatment group receiving both at the same time. Inflammatory parameters, imaging findings, and way of leaving the intensive care unit of the patients were compared.
Results: A total of 87 patients were included in the present study. In both treatment groups, an increase in lymphocyte levels and a decrease in CRP, lactate dehydrogenase (LDH) and ferritin levels were detected at the end of treatment values compared to the initial treatment values. (p<0.001 and p<0.001). Also, LDH values after the treatment were significantly lower in the concomitant treatment group than in the sequential treatment group (p=0.049). In the present study, 53 of the patients were discharged with good recovery and 34 died. The mortality rate was 31% in the concomitant treatment group and 43% in the sequential treatment group. In terms of mortality, numerical findings in favor of the concurrent treatment group were determined.
Discussion: In addition to the studies in the literature, it was found that the concomitant use of Methylprednisolone and Anakinra can be an effective treatment option that reduces mortality and improves inflammatory parameters.
Keywords: Anakinra, Methylprednisolone, Mortality
Introduction
COVID-19, caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), although mostly asymptomatic or mildly symptomatic disease, it may also require hospital treatment in 10-15% of cases with moderate to severe disease symptoms. Also, 3-5% of the cases are severe enough to require hospitalization in the Intensive Care Units [1,2].
The clinical manifestations of COVID-19 can be described in three phases [3]. High fever and pneumonia-like symptoms may occur following flu-like symptoms. While direct tissue damage by SARS-CoV-2 infection is seen in the lungs, an exaggerated host immune response triggered by this infection has also been demonstrated. Proinflammatory cytokines play an important role in the pathogenesis of COVID-19. A small proportion of COVID-19 patients proceed to stage three, where systemic hyperinflammation develops, in which there is an increase in cytokine storm markers such as C-reactive protein, ferritin, lactate dehydrogenase, and D-dimer and a significant decrease in lymphocytes. Acute Respiratory Distress Syndrome (ARDS) or cytokine storm, and cardiac and renal damage are the leading causes of mortality, especially for patients who have advanced age and comorbidities [1,4-6].
After the concept of cytokine storm was defined in COVID-19 patients, treatments to suppress proinflammatory cytokines such as interleukin 1 (IL-1) and interleukin 6 (IL-6) came to the fore [7]. The IL-1-receptor antagonist anakinra, which has a half-life of approximately 3-4 hours and is used in the treatment of rheumatological diseases, is one of the cytokine blocking agents used for the treatment of COVID-19 [8]. Along with ongoing randomized clinical trials, the results of studies conducted in more than one center are promising. Anakinra’s short half-life makes it suitable for use in critically ill patients, as its effect can be stopped quickly in case of possible secondary infections [9-11].
Corticosteroid therapy, on the other hand, is used in the treatment management of cytokine storm [8]. In prospective, randomized clinical trials in critically ill patients with COVID-19, corticosteroid use significantly reduced 28-day mortality compared to patients given placebo or standard care [12].
In the present study, the purpose was to investigate the effects of concurrent or successive use of Anakinra and methylprednisolone (anti-IL-1+MPD) on biochemical parameters, mortality, and oxygen need in severe COVID-19 patients.
Material and Methods
The present study is a single-center retrospective study that included the data of patients followed in the COVID-19 Intensive Care Unit of our hospital between October and December 2020.
Ethical approval for the study was obtained from the Non-Interventional Ethics Committee of Mustafa Kemal University with the date 06/05/2021 and the decision number 04.
Inclusion Criteria
The patients who were over 18 years of age and had SARS-CoV-2 infection proven by Polymerase Chain Reaction were included in the study. Those who responded to standard treatment, patients with negative SARS-CoV-2 PCR test, patients without Thorax Computed Tomography results, and patients with deficiencies in laboratory tests on the first and final day of the treatment were excluded from the study.
The definition and staging of ARDS were made in accordance with national COVID-19 guidelines.
Thorax Computed Tomography evaluation was made by the radiologists of the hospital. Classification was made in the reporting as “mild-moderate and severe involvement” according to the involvement rates of the lungs. Involvement of less than 25% of both lungs was considered mild, 25-50% of involvement was considered moderate, and involvement of more than 50% was considered severe pneumonia.
The criteria for patients who were thought to develop macrophage activation syndrome, despite treatment, were T.C. Ministry of Health General Directorate of Public Health COVID-19 anticytokine-anti-inflammatory treatments, which were determined in accordance with the coagulopathy management guidelines.
Treatment Protocol
Every patient who was hospitalized due to the diagnosis of COVID-19 was treated in line with the T.C. Ministry of Health General Directorate of Public Health Adult Patient Treatment Guideline; Favipiravir, low molecular weight heparin and proton pump inhibitor treatment were applied as standard protocol. High-dose corticosteroid and anti-cytokine treatments were applied for patients who were considered to develop macrophage activation syndrome despite treatment.
As pulse steroid treatment, in line with the COVID-19 Anticytokine-Anti-Inflammatory Treatment and Coagulopathy Management Guideline of the Ministry of Health, General Directorate of Public Health, 250 mg/day Methyl Prednisolone was administered for 3 days to patients with high oxygen demand due to respiratory distress and considered to have a non-infectious hyper-inflammatory clinical manifestation. In line with the same guideline, Anakinra treatment was subcutaneously administered in 4 equal doses with a maximum of 800 mg/day. According to the decrease in the daily oxygen need of the patient, 600 mg/day and 400 mg/day doses were given with 3-day follow-up periods. Anakinra treatment was administered for a maximum of 10 days.
If Anakinra was found in the hospital pharmacy, both concurrent treatments were initiated with MPD to start the treatment faster in the study, and if the drug was not available in the hospital pharmacy, Anakinra was administered first after the MPD. As a result of these compulsory treatments, the patients were divided into two groups as those who received successive treatment and those who received concurrent treatment.
Statistical Analysis
Continuous variables were presented as a mean ± standard deviation, median (min-max); and categorical data were expressed as numbers and percentages. Normality analyzes of the continuous variables were made with the Kolmogorov-Smirnov Goodness of Fit Test. T-Test was used for independent groups in the comparisons of the data with normal distribution, and the Mann-Whitney U-Test was used for those that did not. The comparisons of the categorical data were made with the Chi-Square Test. T-Test for Dependent Groups was used to compare the data with normal distribution in intra-group analyses, and Wilcoxon Ordered Signs Test was used for those that did not. The analyses were made with the IBM SPSS (Statistics Package Program for Social Sciences) version 22.0 (IBM Corporation, Armonk, NY, USA). Statistical significance level was taken as p<0.05.
Results
The study included 87 PCR-positive patients, 59 of whom were male, who were followed up in the COVID-19 Intensive Care Unit of our hospital between October and December 2020. The mean age of the patients was 63.24±11.85 years. In both treatment groups, patients had similar rates of comorbid diseases (diabetes mellitus, hypertension, coronary artery disease, etc.). Although it was not statistically significant, it was observed that the difference was numerically significant in favor of the group receiving simultaneous treatment.
The lymphocyte levels were found to be statistically and significantly higher in both groups after the treatment when compared to before (p<0.001 and p=0.008, respectively). The intra- and intergroup comparison of the whole blood parameters of the patients is given in Table 1. Also, in the results of biochemistry tests, there were no significant differences between the groups in terms of the urea, creatinine, AST, ALT, Procalcitonin (PCT), CRP, D-Dimer, and ferritin values on the first day of the treatment and at the end of the treatment (p>0.05), and the LDH values after the treatment were significantly lower in the concurrent treatment group than in the successive treatment group (p=0.049).
In the intragroup evaluations of both groups, the CRP, LDH, and ferritin values were statistically and significantly decreased after the treatment when compared to the pre-treatment period (p<0.001 and p<0.001, respectively). In the evaluation of the biochemical test results of the patients, a significant improvement compared to the initial values was more pronounced in the concomitant treatment group.
Also, when the patients were compared according to the way they left the Intensive Care Unit in the present study, 53 patients were discharged and 34 patients died. Statistically significant differences were detected in the discharged patient group in terms of ARDS and lung involvement in Thorax Tomography of these patients (Table 2).
In the comparisons made according to the discharge status of the patients from the hospital, it was found that SO2 and lymphocyte levels on the first day of the treatment and at the end of the treatment were significantly lower in the patients who died when compared to the patients who were discharged (p=0.019, p<0.001, p=0.002, and p=0.001, respectively). The LDH, CRP, and ferritin levels were significantly higher in those who died (p<0.001, p<0.001, p=0.021, p<0.001, p=0.014 and p<0.001, respectively).
It was observed in intragroup evaluations that SO2 and lymphocyte values increased at significant levels, and LDH, CRP, and ferritin values decreased at significant levels at the end of the treatment in patients who were discharged. However, no significant differences were detected in the patients who lost their lives after the treatment when compared to the initiation of treatment (p>0.05) (Table 3).
Discussion
The effects of concurrent or successive use of Anakinra and MPD treatment on clinical improvement and mortality were investigated in the study. Improvement was detected in oxygenation of the patients and improvement was detected in inflammatory parameters with the concurrent initiation of anti-inflammatory and anti-cytokine treatment. In our study, lymphocyte count increased with treatment, while LDH, CRP and ferritin values decreased.
There was no difference between the two groups in our study in terms of demographic characteristics and duration of treatment. Demographic data, age range, percentage of gender and similar rates of comorbid diseases were found compatible with the literature data [10,14-16]. Although no statistical differences were detected in terms of discharge rates in patients who received concurrent treatment, it is numerically promising that 22 (70%) out of 32 patients who received this treatment were discharged.
A total of 53 (60.9%) of the 87 patients who participated in the study were discharged, and 10 out of the 34 patients who lost their lives received concurrent treatment, while 24 received successive treatment. Studies in the literature mostly compared the patient group administered with anti-inflammatory/anti-cytokine treatment with patients who received standard treatment. A low 28-day mortality and invasive Mechanical Ventilation (MV) need rates were reported in the Randomized Evaluation of the COVID-19 Treatment (RECOVERY) Study, which had the largest number of patients among these studies [17]. Similarly, in other studies that were conducted with Methylprednisolone (MPD) in the USA and the Netherlands, Mechanical Ventilation and mortality rates were lower in the treatment groups [16,18-20]. In another study, in which 65 patients received Anakinra+MPD and 55 patients received standard treatment, mortality and MV rates were higher in patients who received standard treatment [14]. Patients were given MPD for three days first, followed by Tocilizumab and Anakinra treatment, which was administered to patients with worsening oxygenation in a study that was conducted in Spain. No deaths occurred in the group that received Anakinra as the last treatment in this study. The authors reported that Anakinra can be used instead of Tocilizumab in patients with severe COVID-19-related hyperinflammation if corticosteroid treatment fails with the current findings [21]. In the comparison of two different treatment groups in the present study, similar to the decreased mortality rates when compared to standard treatment in the studies in the literature, it was found that the concurrent treatment had positive effects on mortality. The low number of patients and the limited retrospective data are considered to have contributed to the lack of statistically significant rates in our study.
In the present study, there were 16 patients in the successive treatment group who received Noninvasive Mechanical Ventilation (NIMV) and MV support, and 6 patients in the concurrent treatment group; and 12 of the 16 patients who received support and 4 of 6 patients died. Mortality rates were found to be significantly higher in both treatment groups. However, Anakinra treatment that was administered to the patients who received NIMV support in Italy showed significant decreases in both 28-day and 90-day mortality rates [22]. In this study, the success of Anakinra treatment was shown even in patients who received NIMV support. However, we believe that the moderate-to-severe ARDS involvement in the patients who participated in the present study might have effects on our high mortality rates.
The number of lymphocytes was increased at statistically significant levels when compared to the first day of the treatment in both treatment groups. Also, ferritin, LDH and CRP values decreased with the treatment. A total of 65 patients were treated with Anakinra + Methylprednisolone in the study that was conducted by Bozzi et al. in Italy. It was found that the CRP values of the patients in the treatment group decreased rapidly throughout the treatment period [14]. In a prospective study that evaluated 21 patients followed up for 10 days before the treatment and 10 days after the start of treatment, a decrease was detected in CRP and ferritin values in patients who received Anakinra [16]. In a similar study conducted by Huet et al., a rapid decrease was detected in the CRP values of the patients in the treatment group on the 4th day of the treatment [10]. As a result of the decreased hypoxia levels with treatment, an improvement was detected in the end-of-treatment values of the parameters, which indicated tissue damage. In the results of our study, decreases were detected in the ferritin values that increased as an acute phase reactant, increased LDH levels after tissue hypoxia, and in the CRP values that increased with cytokine release after the anti-inflammatory and anti-cytokine treatment. Increased lymphocyte values were detected with these treatments applied to patients with lymphopenia in the course of COVID-19.
When the evaluation was made according to the discharge and mortality status of the patients, as expected, it was found that the number of patients with severe ARDS, severe involvement on tomography, and those who needed NIMV and MV support was higher among those who died. When compared to the first day of treatment, a decrease in LDH, CRP and ferritin, and an increase in lymphocyte and SO2 values were detected at the end of the treatment in the discharged patient group. According to the ROC analysis results, the sensitivity in predicting mortality over 875 µg/L for ferritin was found to be 63% and the specificity was 68%. An increase in ferritin value can be a good marker for predicting mortality and macrophage activation syndrome [9]. An increase in ferritin value without clinical worsening may help initiation of immunomodulatory treatment early to prevent cytokine storm syndrome.
There were some limitations in the present study. Firstly, the fact that it had a retrospective and single-center design affected the generalizability of the results. Secondly, the superiority of Anakinra and methylprednisolone alone over the standard treatment modality was not investigated because the patients were not compared with the group receiving standard treatment in the study. Its strengths were that mostly Anakinra and/or methylprednisolone treatment was compared with patients receiving standard treatment in the literature. The number of studies similar to the design of the present study is limited. We believe that we have contributed to the literature with positive results regarding the concurrent use of Anakinra and MPD.
Conclusion
In conclusion, concurrent treatment with Anakinra and MPD may become a safe and effective treatment option in decreasing the oxygen demand and control SARS-CoV-2-induced inflammation in COVID-19 patients with hyperinflammation and respiratory failure. In this respect, it is necessary to conduct studies with a larger number of cases and with longer follow-up durations. Prospective studies can be conducted to evaluate the effectiveness of targeted therapy by measuring interleukin levels.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
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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Gülnur Kul, Gürkan Değirmencioğlu. Anti-inflammatory therapy in patients with severe COVID-19 pneumonia: A single-center observational study. Ann Clin Anal Med 2022;13(9):993-998
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Anxiety levels of healthcare personnel in different stages of COVID-19 pandemic: A nationwide study from Turkey
Edip Bayrak 1, Ahmet Riza Sahin 1, Akkan Avci 2, Hilmi Erdem Sumbul 3, Erhan Kaya 4, Alperen Kilic 5, Mehmet Bugrahan Gurcan 6, Bekir Aktura 7, Celaleddin Turgut 8, Ramazan Azim Okyay 9
1 Department of Infectious Disease, Health Science University, Adana City Research and Training Hospital, Adana, 2 Department of Emergency Medicine, Health Science University, Adana City Research and Training Hospital, Adana, 3 Department of Internal Medicine, Health Science University, Adana City Research and Training Hospital, Adana, 4 Department of Public Health, Public Health Directorate of Osmaniye, Osmaniye, 5 Department of Psychiatry, Faculty of Medicine, Istanbul Medipol University, Istanbul, 6 Department of Psychiatry, Faculty of Medicine, Kocaeli University, Kocaeli, 7 Istanbul University, Institute of Health Sciences, Istanbul, 8 Department of Psychiatry, Faculty of Medicine, Kahramanmaraş Sütçü İmam University, Kahramanmaras, 9 Health Science University, Adana City Research and Training Hospital, Deputy Chief Physician, Adana, Turkey
DOI: 10.4328/ACAM.21186 Received: 2022-04-13 Accepted: 2022-06-18 Published Online: 2022-06-20 Printed: 2022-09-01 Ann Clin Anal Med 2022;13(9):999-1003
Corresponding Author: Edip Bayrak, Dr. Mithat Özsan Bulvarı, Kışla Mah., 4522 Sok. No: 1, Yüreğir, Adana, Turkey. E-mail: dredip82@hotmail.com P: +90 532 394 61 69 Corresponding Author ORCID ID: https://orcid.org/0000-0001-8641-122X
Aim: SARS CoV-2 transmission in healthcare personnel was first reported on January 20, 2020. The aim of this study was to evaluate the anxiety levels experienced by healthcare personnel in Turkey during the COVID-19 pandemic and the factors affecting these levels.
Material and Methods: A survey investigating sociodemographic features and examining anxiety levels was conducted among approximately 1000 healthcare personnel who were expected to take active roles in the pandemic across Turkey. The survey was conducted in three stages: before the pandemic spread to Turkey, at the beginning of the pandemic and when the pandemic became prominent. A logistic regression analysis was performed to determine the factors affecting anxiety and predictors of anxiety levels.
Results: In the first survey, always (odds ratio, 15.781; p<0.01) and often (odds ratio, 5.365; p<0.05) media use, in the second survey media use (p<0.05) and profession (odds ratio, 0.021; p<0.05) and in the third survey, marital status (odds ratio, 17.716; p<0.01) and gender (odds ratio, 4.431; p<0.05) were determined as the predictors of anxiety related to COVID-19.
Discussion: As a result of this study, healthcare personnel groups were defined (women, nurses, married people) who need special intervention and support to provide spiritual comfort when working on the front line in the fight against COVID-19. Further comprehensive studies are needed of the extent of psychological support required by healthcare personnel and to whom and how this support should be provided.
Keywords: COVID-19, SARS CoV, Anxiety, Healthcare Personnel
Introduction
The Chinese government declared to the world that a novel type of coronavirus (SARS CoV-2) had been isolated on January 7, 2020 [1,2]. As the rapidly spreading uncontrolled outbreak has affected the whole world, the World Health Organization (WHO) declared COVID-19 to be a pandemic [available at: http://www.who.int/docs/default-source/coronaviruse/transcripts/who-audio-emergencies-coronavirus-press-conference-full-and-final-11mar2020.pdf?sfvrsn=cb432bb3_2; 2020 (accessed 14 April 2020)]. The virus infected hundreds of millions of people, including healthcare workers, and killed more than 5 million people [available at: https://www.worldometers.info/coronavirus/; 2022 (accessed 10 October 2022)]. The first SARS CoV-2 transmission to healthcare personnel in Turkey was reported on January 20, 2020 [1]. Infections in healthcare personnel by Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS-CoV) have been well-defined [3,4]. Li Weilang, who shared his concerns about the disease before SARS CoV-2 was described in China, and the Turkish doctor, Cemil Tascioglu, are among the many healthcare personnel who have died because of COVID-19 [available at: https://www.nytimes.com/2020/02/06/world/asia/chinese-doctor-Li-Wenliang-coronavirus.html; 2020 (accessed 14 April 2020) and https://www.trtworld.com/turkey/the-first-turkish-doctor-to-succumb-to-the-coronavirus-35060; 2020 (accessed time: 14.04.2020)].
Healthcare personnel may often be exposed to infectious agents while providing healthcare services. A total of 26 viruses have been described and more than 50 pathogens have been shown to cause service-related infections in healthcare personnel [5]. Even if healthcare personnel are not infected through working in conditions of exposure to pathogens with high transmission rates, they can be psychologically affected [6]. There are studies showing that healthcare personnel who cared for COVID-19 patients in Wuhan and other regions of China are suffering psychological burden [7]. This affects not only China and healthcare personnel but also the psychology of all populations worldwide as people are kept at home in lockdown as “modern prisoners”, and the spreading of news about the end of the world and food shortages [available at: https://blogs.bmj.com/bmj/2020/01/24/coronavirus-the-psychological-effects-of quarantining-a-city/;2020 (accessed 14 April 2020)]. Previous studies have shown that healthcare personnel are anxious about transmitting the disease to their families, colleagues and social friends, feel discrimination and stigmatization, are reluctant to go to work and consider resigning during pandemics [8]. Therefore, it was considered necessary to examine the concerns, attitudes and psychological influence of healthcare personnel in the COVID-19 pandemic. The aim of the present study, was to evaluate possible anxiety levels experienced by the healthcare personnel in Turkey during the COVID-19 pandemic, and the factors affecting these levels.
Material and Methods
Type and Region of the Study
This study was approved by the Ethics Committee of Kahraman Maraş Sütçü İmam University Medical Faculty. The study was designed as a cross-sectional study and the measurements were taken before the first COVID-19 case was detected in Turkey, within three weeks after the first case, and finally within 1 week after the restriction of inter-province travel. The study was conducted in the hospitals that were planned for the care of COVID-19 cases. The first COVID-19 case was detected on March 11, 2020 in Turkey. Restriction of inter-province travel was started on April 4, 2020.
Participants
The survey was conveyed to 1000 healthcare personnel who were expected to take active charge in the pandemic across Turkey. In the pre-survey information text, a warning was issued about the non-participation of healthcare personnel who have been injured or lost their relatives within the last three years. Participation in the survey was completely voluntary. Survey participation consent was obtained from all participants with the information text. The participants were allowed to end the survey whenever they wanted. The researchers evaluating the survey were blinded to the participants and did not know who had completed which forms. Online links were created for the survey at three different times and these were conveyed to the healthcare personnel. There were no COVID-19 cases recorded in Turkey when the survey was sent for the first time. The second survey was sent within the first three weeks of the pandemic, and the third survey was sent when restrictions of inter-province travel were started. Data security was provided via SurveyMonkey enterprise.
Variables and Scales
Ten days after the survey was designed, it was sent to 10 volunteer healthcare personnel and any unclear parts were corrected. The survey consisted of 31 items: 11 questions investigating sociodemographic features of the participants, 7 questions examining their media use, and 3 questions investigating their measures of protection against COVID-19. The Modified Swine Flu Anxiety Scale (MSFAS) with 6 questions (Q12, 13, 14, 15, 16) adapted from the Swine Flu Anxiety Scale was used to investigate the anxiety level of the participants [9]. Two questions aimed to measure the anxiety level of the participants, one question to measure self-efficacy and knowledge level, and one question to measure anxiety-attitudes of the participants. The MSFAS anxiety score was calculated using a 5-point Likert scale and scores >18 represented increased anxiety. In order to evaluate news sources, the 21st question was used as a criterion, and the participants who answered as moderate influence were marked as having high media follow-up.
Statistical Analysis
Sociodemographic data of the participants were summarized as numbers and percentages. Pearson’s Chi-square test was used to measure the difference between paired variables. The MSFAS anxiety score was evaluated with the ANOVA test, and post-hoc Games-Howell test was applied to differences between the groups. Logistic regression analysis was performed to evaluate the factors affecting anxiety. Statistical analysis was performed using SPSS version 20.0 software (SPSS, Chicago, IL, USA).
Ethics Statement
Approval for the study was granted by the Ethics Committee of Kahraman Maraş Sütçü İmam University Medical Faculty (decision no 15, 2020).
Results
The measurements taken in this study were based on pre-pandemic data, within 3 weeks of the outbreak, and after restriction of inter-province travel. The surveys were conveyed to the same 1000 persons at each of the 3-time points. The number of respondents to the surveys showed variability, with 380 individuals responding to the1st survey, 133 to the 2nd survey and 143 to the 3rd survey.
When the data of all three surveys were compared, there were significant differences in terms of sociodemographic features. It was determined that 15.1% (n=99) of the study respondents were aged over 40 years, 51.7% (n=341) were males and 76.7% (n=505) were physicians. Of all the participants, 16.5% (n=108) had a chronic disease. A total of 41% (n=269) of the respondents were working in tertiary hospitals where all beds had been assigned for COVID-19 cases. The sociodemographic data of the participants are shown as numbers and percentages in Table 1.
When the cut-off value for the MSFAS anxiety score was taken as 18, a high level of anxiety was determined in 37.9% of the participants in Survey 1, 37.6% in Survey 2 and 79.7% in Survey 3. The difference between anxiety scores of the three surveys was statistically significant (F=58.075, p<0.001). In the Games Howel advanced analysis, the difference between the anxiety scores was found to result from Survey 3. The anxiety scores in Survey 3 were significantly higher than in the previous two surveys (Table 2).
Logistic regression analysis was applied to determine predictors of anxiety levels. In the first survey, media use was described as always (odds ratio, 15.781; p<0.01) and often (odds ratio, 5.365; p<0.05); in the second survey, media use (p<0.05) and profession (odds ratio, 0.021; p<0.05) and in the third survey marital status (odds ratio, 17.716; p<0.01) and gender (odds ratio, 4.431; p<0.05) were determined as the predictors of COVID-19 anxiety (Table 3).
Discussion
Pneumonia cases clustered in Hubei in December 2019, became the focus of interest not only in China, but also internationally [1]. Not long after the announcement of a novel type of coronavirus isolation, the virus was first detected in neighboring countries and later in 210 countries worldwide [available at: https://www.worldometers.info/coronavirus/; 2022 (accessed 10 October 2022)]. As of April 20, 2020 the number of cases in Turkey is greater than in China. Participation in the survey significantly decreased after the first case was detected in Turkey, which could be attributed to workload or unwillingness. The participation rate decreased for females and nurses. In this study, 15.1% (n:99) of the participants were aged over 40 years, 51.7% (n:341) were males and 76.7% (n:505) were physicians. Of all the participants, 16.5% (n:108) had a chronic disease. A total of 41% (n:269) were working in tertiary hospitals with beds completely reserved for COVID-19 cases.
The rapid and unexpected spread of SARS-CoV 2 to hospitals can be accepted as an acute part of a bio-disaster [10]. As in any disaster, the effects caused by SARS-CoV 2 may increase anxiety, concerns and unwillingness to work. During the previous SARS emergency, it was not known whether healthcare personnel were infected by exposure to the SARS virus. However, in the current pandemic, those working in healthcare services were known to be at the center of transmission from the second week [1]. Fighting a rapidly spreading fatal disease can create fear through the loss of the sense of safety [10]. In this study, anxiety level access limitation was seen to be 37.9% before the outbreak, 37.6% in the first period of the outbreak, and this rate increased significantly to 79.7% in the third period with the increased number of cases. The difference between the period before the outbreak and the third period of increasing cases was statistically significant in terms of the mean anxiety score, and the difference was determined to have originated from the third survey. The concern of healthcare personnel about their own health depends on how possible and severe a feared disease is perceived [11]. The Turkish media played two roles in this perception. Unscientific explanations were frequently included in the news before the outbreak, with comments such as this virus, which was not fully known before the pandemic, is difficult to transmit to the Turkish people racially, it can be prevented with some foods (e.g. sheep’s head and foot soup) and this is a fake outbreak. The respondents who stated that they did not follow the media were found to be more anxious in the surveys performed before and at the beginning of the outbreak. When the first cases were recorded in Turkey, the media then stated that this virus is easily transmitted, suggesting a high likelihood of exposure and becoming infected. An infection tally was kept across the country and was broadcast at 19:00 every evening. The attitudes of the media before the outbreak in Turkey might have caused an underestimation of the situation at the beginning of the pandemic.
The survey results in this study showed that the anxiety experienced by the healthcare personnel did not change with age. In a study by Lai et al., the reason for nurses’ anxiety was explained by younger age and lower experience [8]. In the current study, there was a high participation rate of young adults, and age did not affect anxiety. This may have been caused by the disease leading to higher morbidity and mortality in patients aged > 40 years. In a study from Turkey, forty-two percent of doctors indicated an increase in their anxiety about their education and career, with a negative impact on practical training being the most important predictor. Most (57.4%) considered extending their residency training to overcome the negative effects of the pandemic [12]. The increased anxiety level of nurses with the first cases seen in Turkey was remarkable. Nursing is performed more commonly by women in Turkey, and nursing duties that can be considered front-line such as follow-up of medical-physiological findings (temperature, pulse, arterial blood pressure) require close patient contact and this may have had an effect on these results. It was seen that women and married people had significantly higher anxiety during the quarantine implementation. The responsibility of married individuals for their family may be associated with the concern of transmission. In the study by Kılıç et al., they reported that the concern of transmission of COVID-19 to the baby during pregnancy/birth are predictors of clinical anxiety, including avoiding regular pregnancy check-ups of the COVID-19 pandemic [13]. Anxiety about infecting the close circle of healthcare workers with COVID-19 may manifest with reluctance to work [14]. The higher anxiety scores obtained by the female respondents may be due to stronger physical and psychological bonds with their children compared to males.
The sample determined in the study was not selected based on the regions where the healthcare personnel work, but was sent to the participants via web links. This may affect the ability to generalize the results of the study. In addition, although the same healthcare personnel were reached in all three periods, the changes in the participation rates could constitute another limitation of the study.
Conclusion
In this study performed on physicians and nurses working in hospitals delivering healthcare services to COVID-19 patients in Turkey, the results demonstrated that anxiety levels increased as the outbreak progressed and the factors were determined, which affected these levels. An important strong aspect of this study was that it was conducted in a period when the Turkish health system was exposed to the COVID-19 burden, and cross-sectional data were obtained about the anxiety status of healthcare personnel. The protection of healthcare personnel is an important component of the measures for fighting against COVID-19. From the results, healthcare personnel groups were identified (women, nurses, married people) who need special intervention and support to provide spiritual comfort while working on the front line in the fight against COVID-19. This research subject is of top priority for healthcare personnel because the time, dynamics and severity of the next pandemic are unpredictable. Further comprehensive studies are needed on the extent of the psychological support needed by healthcare personnel and to whom and how this support should be provided.
Acknowledgment
We thank Dr. Husnu Erkmen for helping us shape our hypothesis by sharing his field experiences.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Download attachments: 10.4328:ACAM.21186
Edip Bayrak, Ahmet Riza Sahin, Akkan Avci, Hilmi Erdem Sumbul, Erhan Kaya, Alperen Kilic, Mehmet Bugrahan Gurcan, Bekir Aktura, Celaleddin Turgut, Ramazan Azim Okyay. Anxiety levels of healthcare personnel in different stages of COVID-19 pandemic: A nationwide study from Turkey. Ann Clin Anal Med 2022;13(9):999-1003
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Impact of the lockdown in the pandemic period on admissions due to non-COVID-19 pneumonia: A retrospective, cohort study
Melahat Uzel Şener, Ayperi Öztürk, Zeynep Tilbe Saymaz, Aydın Yılmaz
Department of Chest Disease, University of Health Sciences, Ankara Atatürk Chest Diseases and Thoracic Surgery Training and Research Hospital, Ankara, Turkey
DOI: 10.4328/ACAM.21187 Received: 2022-04-14 Accepted: 2022-06-18 Published Online: 2022-06-21 Printed: 2022-09-01 Ann Clin Anal Med 2022;13(9):1004-1007
Corresponding Author: Melahat Uzel Şener, Department of Chest Disease, Ankara Atatürk Chest Diseases and Thoracic Surgery Training and Research Hospital, Keçiören, Ankara, Turkey. E-mail: melahatuzeldr@yahoo.com.tr P: +90 505 649 74 38 Corresponding Author ORCID ID: https://orcid.org/0000-0001-8309-9517
Aim: The pandemic period has led to social and individual behavioral changes all over the world. In this study, the differences in the admissions of non-coronavirus disease 2019 (non-COVID-19) community-acquired pneumonia cases during the pandemic lockdown period in Turkey were analyzed.
Material and Methods: Patients with suspected COVID-19 and under the age of 18 were excluded, and non-COVID-19, hospitalized community-acquired pneumonia cases were included in this retrospective, cohort study. The analyzes were carried out by creating two groups as before the pandemic (March-May 2019) and the lockdown period of the pandemic (March-May 2020). The number of admissions and mortality rates were taken into consideration as primary outcomes.
Results: There were 178 cases in the 2019 group and 63 cases in the 2020 group. Gender and age distribution were similar in these two groups. While the rate of intensive care hospitalization was high in the 2020 group, mortality was low (14.3% vs 19.1%); but these differences were not statistically significant. In addition, bilateral infiltration rates were significantly higher in the 2019 group (80.9% vs. 22.2%; p<0.001).
Discussion: The low number of admissions during the lockdown period shows that there is awareness of the pandemic in society. Again, it can be said that this closure process plays a role in reducing the transmission of infectious diseases such as pneumonia.
Keywords: Pandemic, Lockdown, Isolation, Admission, Pneumonia
Introduction
Community-acquired pneumonia (CAP) is the most important cause of hospitalization and mortality [1]. It is one of the most common infectious diseases worldwide [2]. Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-Cov2) infection that occurred in Wuhan, China in December 2019 spread rapidly and caused a pandemic, and the disease was named COVID-19 (Corona Virus Disease 2019) in February 2020 by the World Health Organization (WHO) (https://www.who.int/director-general/speeches/detail/who-director-general-s-remarks-at-the-media-briefing-on-2019-ncov-on-11-february-2020; access date: 12.02.2020). This period has greatly changed human behavior in society and has significantly reduced the crowding of people in public areas such as hospitals.
With the announcement of the pandemic, each country determined its own isolation and lockdown practices. COVID-19 cases in Turkey were first seen on March 11, 2020. After this date, the Ministry of Health imposed flexible working hours, intermittent curfew, and administrative leave for those with comorbid diseases, in addition to social distancing, self-isolation and frequent hand washing warnings. Entrance to crowded and closed areas, meetings, entrance to sports halls were prohibited. On March 21, a curfew was imposed on the population over the age of 65 and under the age of 20. These prohibitions were canceled along with the process of normalization on June 1, 2020. During this period, all communication ways were used by the Ministry of Health to announce the isolation and disinfection methods to the public. In order to maintain the operability of the health system, the public was informed and admissions to hospitals were reduced for non-urgent reasons.
In this study, the authors aimed to compare the lockdown period in 2020 and the period of the same months in 2019 (before the pandemic) in terms of the number of admissions, mortality and intensive care unit admission rates of the non-COVID-19 CAP patients and to investigate the effect of pandemic measures on the admissions of non-COVID CAP patients requiring hospitalization.
Material and Methods
This observational, retrospective, cohort study was carried out in a training and research hospital specialized in chest diseases. Approval for the study was obtained from the Atatürk Chest Diseases and Thoracic Surgery Training and Research Hospital Local Ethics Committee (28.05.2020/ 675). In accordance with the retrospective design, informed consent was not obtained from the patients.
Non-COVID-19 CAP patients admitted and hospitalized between 11 March-31 May 2019 and 11 March-31 May 2020 were included in the study. The diagnosis of CAP was made with the presence of cough, sputum, fever or shortness of breath, high levels of inflammatory biomarkers (increased C-reactive protein, leukocytosis, high procalcitonin) and infiltration on chest x-ray. Patients under 18 years of age, and pregnant patients were excluded from the study for all periods, and patients with suspected COVID-19 according to radiologic signs were excluded from the number of patients admitted during the pandemic period. In the institution where the study was conducted, COVID-19 differential diagnoses were evaluated according to radiological findings due to the difficulty in accessing the COVID-19 PCR test during the period of March-May 2020 (the period when the pandemic began in Turkey). Thus, no PCR testing was performed on the patients in this study. Thoracic computed tomography was performed in patients in whom the differential diagnosis of COVID-19 could not be made on the basis of clinical findings and chest X-ray. Patients with peripheral, bilateral (multilobar) ground glass opacities (GGOs), multifocal round GGOs on tomography were excluded as typical COVID-19 pneumonia. In addition, round or non-peripheral multifocal, diffuse, perihilar or unilateral GGOs and a small number of small round and non-peripheral GGOs were also excluded as an atypical involvement of COVID-19 (atypical cases). Patients discharged from the hospital within the last 15 days (hospital-acquired pneumonia) and who meet the definition of healthcare associated pneumonia were excluded. Exclusion and inclusion criteria were shown in Table 1. Age, gender, and additional comorbid disease data of the patients were recorded. Chest x-ray findings were divided into 3 groups as unilateral, bilateral and minimal infiltration. Additionally, intensive care admission, discharge and mortality rates were recorded. The hospitalized non-COVID-19 CAP patients were divided into two main groups according to the years of 2019 and 2020. Comparative analyzes were carried out among these two groups. Patient data were obtained retrospectively from the hospital information management system and patient follow-up files.
The data were analyzed with SPSS Statistics for Windows, version 16.0 (SPSS Inc., Chicago, Ill., USA). The normality analyzes of the data were performed with the Shapiro-Wilk test. Data were expressed as mean ± standard deviation and median and interquartile range in terms of distribution. Analyses of the categorical data were performed using the Chi-Square tests. The Mann Whitney-U test was used to compare the continuous data, which were not normally distributed. P<0.05 level was accepted statistically significant.
Results
This study included 178 patients hospitalized in March-May 2019 and 63 patients hospitalized in March-May 2020 with the diagnosis of community-acquired pneumonia. Analysis was performed between these two groups. The median age for the year of 2019 was 70 (min-max: 18-91), and 65 (min-max: 21-90) for 2020 (p=0.080). In 2019, 66.3% (n=118) of the patients were 65 years and older, and 50.8% (n=32) in 2020 (p=0.029). There was no statistically significant difference in terms of gender distribution between 2019 and 2020. The female rate was 32.6% in 2019 and 33.3% in 2020 (Table 2).
There was no statistical significance in terms of the total comorbidity rate. However, when analyzed by common diseases groups one by one, the rates of hypertension (HT), coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD) were statistically lower in 2020 (p<0.001, p=0.033, p<0.001, p<0.001, respectively) (Table 2).
When chest x-rays were evaluated, the rate of bilateral pneumonic infiltration was higher in the 2019 group (p <0.001). The atelectasis rate was statistically lower in 2020 (p=0,006). Sputum culture and/or tracheobronchial culture were sent in 41% of patients in 2019 and 46% of patients in 2020 (p=0.553). In the analysis of the patients who were sent culture, factors were isolated in 34.2% in 2019, and in 10.3% in 2020 (p=0.015) (Table 3).
There were no statistically significant differences between 2019 and 2020 groups according to the intensive care unit admission (10.1/12.0%, p=0.060) and mortality rates (19.1/14.3%; p=0.390). When the mortality rate was analyzed separately in age groups, there was no statistically significant difference (Table 3).
Discussion
COVID-19 pneumonia has shown its effects around the world and has led to significant behavioral changes both socially and individually in Turkey. Restrictions and lockdown practices applied during the pandemic period even affected hospital admissions. In this study, we found that the rate of non-COVID community-acquired pneumonia admission increased during the March-May 2020 lockdown period. Community-acquired pneumonia is one of the leading causes of mortality worldwide [1]. The frequency of CAP varies seasonally. In previous studies, it was found that due to the cold air CAP hospitalizations increased in winter, decreased in summer and varied in spring [3,4]. Our study was conducted in the spring months, and the air temperatures varied during this period. However, since the same period is valid for both years, seasonal variability is not decisive for this study.
In the EPIC study, it was observed that hospitalizations due to CAP were 4 times higher in the 50-64 age group, 9 times higher in the 65-79 age group and 25 times higher in the over 80 age group compared to the 18-49 age group [1]. In our study, although patient admission over 65 years of age was higher (n = 118) in 2019 similar with the literature, this number was found to be low in 2020 (n=32). Along with the quarantine, which was applied at different levels all over the world during the pandemic period, intermittent lockdown, ban on entrance to crowded environments, the closure of schools and universities, and the lockdown for those aged 65 years and above who are the high-risk age group, were applied. In our study, we think that this approach has an effect on the decrease of the number of hospitalizations over 65 years of age. In addition, with the curfew imposed under the age of 20, it was planned to reduce both household transmission to the older people and to reduce crowding in daily life. A significant decrease was found in the total number of patients admitted to our hospital due to CAP during the pandemic period compared to the same period in 2019. We thought that these measures reduced social contact so that normal seasonal pneumonia transmission might have decreased. In addition, as in the rest of the world, due to the COVID-19 quarantine, the factories stopped working, resulting in a reduction in vehicle use and carbon emissions and improved air quality [5]. Increased air quality may also have been effective in reducing the frequency of infections, however there is no data on this subject in this study.
Studies have shown that vaccination against pneumonia at a young age and in children has a protective effect on the elderly [6-8]. Similarly, it suggests that the closure of schools during the pandemic period and the lockdown of the group under the age of 20 reduced the carrier and domestic transmission of pneumonia factors other than SARS CoV-2.
In our study, comorbidity prevalence in the CAP group other than COVID-19 was 89.3% in 2019 and 82.5% in 2020. In the previous study conducted in Nepal, this rate was found to be 63.4%, and it was found that the most common comorbidity was COPD [9]. In this study, we found that there was no statistically significant difference in terms of total comorbidity in patients hospitalized for CAP between two years. However, when evaluated individually, we found that CAD, COPD, CKD and HT were significantly less in 2020 cases. Based on these results, it can be said that especially those with comorbid disease paid more attention to follow the measures. Similarly, more complicated findings on chest X-ray such as bronchiectasis, pleural fluid and atelectasis were found more in 2019. Underlying lung disease and modifying factors (comorbidities) that cause complicated course of pneumonia are effective. When these two variables are considered together, it can be said that patients with comorbid diseases pay more attention to isolation. As concomitant comorbidity decreased, the complicated findings detected on the chest X-ray decreased. In addition, bilateral pneumonia was mostly detected in chest radiographs in 2019, while minimal infiltration and unilateral pneumonia were detected more in 2020. The reason for this may be due to the fact that the modifying factors are less in 2020, and because of the pandemic period, patients with bilateral infiltration were followed up in COVID-19 suspected patient areas. More studies with larger numbers of cases are needed to evaluate this issue more clearly.
There was no significant difference between the two years in terms of mortality and need for intensive care. As expected, mortality was higher in the 65-year-old group, but when the age groups were analyzed separately, no significant difference was found between the 2019 and 2020 groups. While Jain et al. expressed an in-hospital mortality rate of 2% [1], it is stated in the literature that this rate can reach 28.8% in severe patients [10]. In the study by Şener et al., it is seen that mortality is high (13.7%), however, the median age is 77 [11]. The high mortality rate found in our study can be attributed to the inclusion of only hospitalized patients. In addition, higher rates have been identified in advanced age, as expected.
The limitations of the study are that it is single centered and retrospective. In multi-center and prospectively designed studies, the effects of quarantine practices can be analyzed better. The main limitation should be considered that the radiologic findings, used in the differentiation of PCR-negative cases in the study, are not the gold standard for diagnosis of COVID-19 pneumonia.
Conclusion
In conclusion, in this study, a significant decrease in the number of patients admitted to our hospital with a diagnosis of non-COVID CAP during the pandemic period was detected, however, it is noteworthy that there was no difference in mortality between two years. The COVID-19 pandemic is a very popular topic and we anticipate that there will be many studies on the differences and similarities between COVID-19 pneumonia and non-COVID pneumonia in the near future. It is obvious that lockdown practices have many psychosocial, environmental, and economic consequences, but as shown in this study, they may have reduced the incidence of non-COVID CAP. We can say that awareness of the pandemic takes place in society. Although there is no clear data about any parameter that can be shown as the reason for this decrease, such as the use of masks and the social distance rule. There is a need for multicenter and multinational studies on CAP, which investigate the results of lockdown practices in these outbreaks.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
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Calcium Channel Blockers Increase Sunitinib Effectiveness in Metastatic Renal Cell Carcinoma Treatment
Celal Alandağ 1, Elif Yüce 2, Feyyaz Özdemir 2
1 Department of Medical Oncology, Sivas Numune Hospital, Sivas, 2 Department of Medical Oncology, Karadeniz Technical University, Trabzon, Turkey
DOI: 10.4328/ACAM.21190 Received: 2022-04-15 Accepted: 2022-06-16 Published Online: 2022-06-20 Printed: 2022-09-01 Ann Clin Anal Med 2022;13(9):1008-1012
Corresponding Author: Celal Alandağ, Department of Medical Oncology, Sivas Numune Hospital, Sivas, Turkey. E-mail: dralandag@hotmail.com P: +90 506 912 83 19 Corresponding Author ORCID ID: https://orcid.org/0000-0002-2589-8174
Aim: Repurposing non-cancer drugs may be a new hope for cancer treatment. It has many advantages. Sunitinib is a tyrosine kinase inhibitor that inhibits vascular epithelial growth factor receptors. It is used for metastatic renal cell carcinoma (mRCC) treatment. We planned to investigate the effects of noncancer drugs like calcium channel blockers (CCBs) and others on sunitinib in mRCC patients.
Material and Methods: We retrospectively scanned the files of mRCC patients applied to our center between January 2013 and April 2019 and used sunitinib. We analyzed some parameters of these patients and their effects on overall survival (OS) and progression-free survival (PFS). A χ2 or Fisher’s exact test, Kaplan-Meier and Cox regressions were used in the statistical analysis.
Results: Thirty-five patients were examined, 15 of them were taking CCB for arterial hypertension and sunitinib for RCC, simultaneously. The 36-Months OS rates of CCB users and non-users were 61.1 and 38.9%, respectively (OR:5.1, 95% CI: 1.17-22.1, P=.041). The 24-Months PFS rates of CCB users and non-user were 68.8 and 31.3%, respectively (OR:8.25, 95% CI: 1.79-38.01, P=.007).
Discussion: It is a new idea to combine the targeted cancer drugs and non-cancer drugs for better anticancer outcomes. There were 36-months OS and 24-months PFS advantages with simultaneously taking CCBs and sunitinib. Sunitinib and CCBs combination should be studied in preclinical studies and their additive effect mechanisms should be clarified.
Keywords: Calcium Channel Blocker, Renal Cell Carcinoma, Repurposing, Sunitinib
Introduction
Sunitinib is a multitarget tyrosine kinase inhibitor (TKI); it is mainly an antiangiogenic drug. Also, it has direct antitumoral and immune activator effects [1]. Sunitinib has been used in the treatment of metastatic renal cell carcinoma (mRCC) treatment since 2006. Sunitinib provided an advantage of approximately 5 months of overall survival (OS) and 6 months of progression-free survival (PFS) over interferon-alfa in mRCC [2]. While we can observe a very good survival advantage in some patients, we cannot see this advantage in others, and we don’t know why. So far, there are no biomarkers predicting the efficacy of sunitinib. Can we do anything to increase the effectiveness of sunitinib? Repurposing a drug means using a drug out of its indication. Especially during the COVID-19 pandemic, drug repurposing studies have been carried out frequently. Repurposing non-cancer drugs for cancer is a popular issue nowadays, also. Repurposing has many advantages. We can save time and money while getting a reliable drug quickly. We recently showed that calcium channel blockers (CCBs) and erlotinib have additive effects in metastatic non-small cell lung cancer [3]. We also showed in another study that CCBs and regorafenib have additive effects in metastatic colorectal cancer [4]. We aimed to investigate whether CCBs and sunitinib have additive effects in mRCC.
Material and Methods
It was a retrospective study conducted on 35 metastatic RCC patients who received sunitinib, diagnosed between 2013 and 2019, admitted to our center. All patients enrolled in the study had pathologically confirmed clear cell histology and stage IV RCC. Patients not taking sunitinib were excluded. We noted the patient’s clinical characteristics from their files. Data about the medications of the patients were recorded from their medical charts. We used descriptive statistics to show clinical characteristics (Table 1). Parameters that may affect the outcome of mRCC such as age, sex, comorbidities (hypertension [HT], and diabetes mellitus [DM]), and other medications including CCB, renin-angiotensin system inhibitor, proton pump inhibitor, inhaled steroid, insulin were noted. We analyzed the OS, which was defined as the time elapsed from the sunitinib starting date to the date of death from any cause or study termination date. Progression-free survival is defined as the time elapsed from starting sunitinib date to progression or study termination date. The follow-up time was defined as the time from the date of diagnosis to the date of death or the last follow-up date. The statistical analyses were conducted using Statistical Package for Social Sciences (SPSS) version 22 (SPSS Inc, Chicago, IL). A univariate analysis was performed using the Kaplan–Meier method to estimate the OS of different patient groups, and the groups were compared with the log-rank test. Cox-regression analysis was used to determine the association of factors with the OS in the multivariate analysis. In the multivariate analysis, confounders were included if they were significant at a 0.05 level in the univariate analysis (log-rank test) or thought to be important for OS or the effect of the factors. The results were expressed as median OS, median PFS, and hazard ratios (HRs) with 95% confidence intervals (CIs). A p-value of <0.05 was considered statistically significant. Also, χ2 or Fisher’s exact test was used for statistical analysis. Ethical approval was obtained by the Ethics Committee of our center on 12.04.2019 with protocol number 2019/76.
Results
This study included 35 patients with metastatic RCC and who received sunitinib. There were 15 CCBs users (11 amlodipine, 3 nifedipine, 1 benidipine). The median age was 60 (40-85) years. The median follow-up time was 36.9 months for the entire group. Median OS was 20.8 (95% CI, 9.8 – 31.8) months, median PFS was 14.4 (95% CI, 8.5 – 20.3) months. The objective response rate was 29%. The patient characteristics and their effects on OS and PFS are summarized in Table 2 and Table 3, respectively.
Calcium channel blocker taking (93.8 vs 24.1 months, p = 0.03), renal impairment (59.7 vs 12.7 months, p =0.03) significantly improved OS in the univariate analysis, ACE inhibitor and beta-blocker using numerically improved OS but not statistically meaningful. After adjusting multivariate analysis CCB taking significantly improved OS (HR: 78.63, 95% CI: 4.61-1332.1, p=.03). In multivariate analysis, renal impairment did not improve OS (HR: 0.81, 95% CI: 0.16-4.02). Taking any type of anti-hypertensive drug improved OS in univariate analysis but it reduced OS in multivariate analysis (HR: 0.2, 95 CI: 0.004-0.82, p =0.03). Effects of CCB using on OS showed the Kaplan-Meier and Cox-regression curves in Figure 1.
Patients who were younger than 65 years old (18.5 mo. vs 9.1 mo., p=.024) received sunitinib as first-line treatment (27.7 mo. vs 11.8 mo., p= .025) had a better median PFS in univariate analysis. Calcium channel blocker users had numerically improved median PFS in the univariate analysis, but it was not statistically meaningful (18.5 vs 8.8 months, p = .065). After adjusting multivariate analysis, CCB users had significantly improved median PFS (HR: 3.01, 95% CI: 1.32-6.85, p=.008). Effects on median PFS of CCB taken concomitantly with sunitinib showed the Kaplan-Meier curves in Figure 2. In multivariate analysis, patients who were younger than 65 years old (HR: 2.88, 95% CI: 1.25-6.64, p=.013) and who received sunitinib at first-line (HR: 3.5, 95% CI: 1.32-9.26, p=.012) had better PFS.
Also, CCB users and non-users were compared in terms of 36-months OS and 24-months PFS rates. The 36-Months OS rates of CCB users and non-users were 61.1 and 38.9%, respectively (OR:5.1, 95% CI: 1.17-22.1, p=.041). The 24-Months PFS rates of CCB users and non-user were 68.8 and 31.3%, respectively (OR:8.25, 95% CI: 1.79-38.01, P=.007).
Discussion
This retrospective study showed that CCBs and sunitinib have powerful additive effects in mRCC. In multivariate analysis, CCB users have statistically meaningful better OS and PFS compared to non-users. There are nearly 2-fold better 36-months OS (61 vs 38%), 24-months PFS rates (68 vs 31%) of CCB users.
Drug repurposing in cancer has many advantages. For example, CCBs already have sufficient safety, toxicity, and pharmacological data. Drug repurposing reduces the risk of clinical trial failure [5]. Developing a new anticancer drug needs a lot of money and time [6]. Are these additive effects of sunitinib and CCBs come from pharmacokinetic or pharmacodynamic features? No drug interactions have been previously reported with sunitinib and amlodipine. A study reported that amlodipine did not change the plasma concentration of sunitinib [7]. So, what is the mechanism of the additive anticancer effect of these drugs?
Calcium plays role in protein phosphorylation, enzyme regulation, gene transcription, and translation. Calcium channels in the cell membrane and endoplasmic reticulum maintain the calcium balance between the inside and outside of the cell. There are two major calcium channel categories: voltage-gated channels and non-voltage-gated channels. L, P/Q, N, R, and T types are the subtypes of voltage-gated calcium channels. Recently, an increasing number of articles have been published about tumorigenesis and tumor progression role of calcium channels [8]. Dihydropyridines (amlodipine, nicardipine, etc.), verapamil, and diltiazem are all L-type CCBs. Some preclinical and clinical studies reported antitumoral effects of L-type CCBs. In a study, CCBs had shown antitumoral activity on some of 578 human cancer cell lines [9]. Tingle et al. showed that metastatic pancreatic cancer patients who had previously been prescribed L-type CCBs for hypertension had numerically better OS (15.3 vs. 10.1 months, p=.131) [10]. Altered calcium channels play roles in colon tumorigenesis and breast cancer pathogenesis [11, 12]. N-type calcium channel facilitates the progression of NSCLC, blocking this channel inhibits the progression [13]. Marwa H et al. reported that T-type CCBs strengthen the anticancer effects of cisplatin-etoposide combination in in-vitro tests [14]. Also, CCBs can alter the tumor microenvironment and this may be another possible mechanism of anticancer action [8]. Phosphatidylinositol triphosphate kinase-Akt pathway plays a role in some cancer types and CCBs can inhibit this pathway, which may be another anti-cancer mechanism [13].
It is a new idea to combine the targeted cancer drugs and non-cancer drugs for better anti-cancer outcomes. Numerous articles have shown the relationship between calcium channels and cancer. In our study, we showed that taking CCB improves the median OS and PFS with sunitinib, in mRCC. The limitations are that the number of patients included in the study was small and it was a retrospective study. Larger and prospective studies need to show that CCB and sunitinib combinations can be used in mRCC treatment.
Acknowledgment
We would like to thank our clinic team who were not involved in this article’s idea, application, or writing process.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Has anything changed in the last decade in the long-term outcome of patients with antenatal hydronephrosis?
İsa Yılmaz 1, Harun Peru 1, Metin Gündüz 2
1 Department of Pediatric Nephrology, 2 Department of Pediatric Surgery, Faculty of Medicine, Selcuk University, Konya, Turkey
DOI: 10.4328/ACAM.21193 Received: 2022-04-15 Accepted: 2022-06-16 Published Online: 2022-06-20 Printed: 2022-09-01 Ann Clin Anal Med 2022;13(9):1013-1016
Corresponding Author: İsa Yılmaz, Department of Pediatric Nephrology, Faculty of Medicine, Selcuk University, Konya, Turkey. E-mail: drisayilmaz@hotmail.com P: +90 332 235 42 05 F: +90 332 237 60 25 Corresponding Author ORCID ID: https://orcid.org/0000-0001-8654-9173
Aim: We tried to determine the etiological causes of antenatal hydronephrosis (AH) patients in their postnatal follow-ups in order to stress the importance of vesicoureteral reflux (VUR), to reveal the frequency of urinary tract infection (UTI) and scarred kidney in patients with hydroureteronephrosis or obstructive hydronephrosis with (VUR), and its effect on prognosis according to the degree of hydronephrosis.
Material and Methods: In this retrospective study, 251 patients diagnosed with AH were evaluated between January 2011 and January 2021. According to the renal pelvis antero-posterior (AP) diameter measurement, patients were classified into 3 groups as mild (group-1 with 121 cases, 48.2%), moderate (group-2 with 84 cases, 33.5%) and heavy (group-3 with 46 cases, 18.3%) grades. The groups were compared in terms of demographic data, laboratory results, imaging findings and prognosis.
Results: There was a significant difference in the frequency of UTI, bilateral hydronephrosis and hydroureteronephrosis between the groups (p<0.001, p=0.003, p=0.006, respectively). The incidence of pathological causes of hydronephrosis was higher in patients with bilateral hydronephrosis (p=0.040). Urinary tract infection was found to be higher in patients with hydroureteronephrosis, obstructive hydronephrosis and VUR (p=0.012, p=0.001, p=0.006, respectively). The incidence of renal scar was found to be higher in patients with hydroureteronephrosis, VUR and UTI (p=0.001, p<0.001, p<0.001). A significant difference was detected in the incidence of VUR, obstructive hydronephrosis and renal scar between the groups (p=0.002, p<0.001, p=0.006). Expectedly, the rate of surgical operation was higher in group-3 than in group-1 and 2 (p<0,001).
Discussion: In addition to the degree of antenatal hydronephrosis, the presence and bilaterality of hydroureteronephrosis are determining factors for the diagnostic imaging method and prognosis. Mild AH tends to improve spontaneously more compared to the other two groups. Patients with moderate to severe AH should be followed up for a long time with a more established approach.
Keywords: Antenatal Hydronephrosis, Long-Term Outcomes, Childhood
Introduction
Antenatal hydronephrosis, which is defined as enlargement of the renal pelvis with or without the calyces, has begun to be diagnosed more frequently and early with the widespread use of perinatological follow-ups in recent years [1]. Antenatal hydronephrosis, the most common congenital anomaly, is detected in 1-4% of all pregnancies [2]. It is bilateral at a rate of 20-40%, with twice the incidence in boys compared to girls [3]. Although it is often thought to be caused by a congenital abnormality of the kidney and urinary tract (CAKUT), a specific underlying disorder could not be detected in many patients. However, it is known that the prognosis is closely related to the underlying cause, if any. On the other hand, 36-80% of AH cases resolve spontaneously at the end of pregnancy or in the first year of life [4]. Dilatation of the calyces of the renal pelvis, the presence of parenchymal atrophy are the parameters used by the Society of Fetal Urology (SFU) to grade hydronephrosis. According to this classification, the kidney is graded as grade 0-4 hydronephrosis. Another method used to evaluate antenatal hydronephrosis is renal pelvic diameter measurement [5]. Measurement of the maximum AP distance of the renal pelvis in the transverse plane is the most commonly used method to define AH [5, 6]. Among the CAKUT diagnoses that cause antenatal hydronephrosis, there are ureteropelvic junction stenosis (UPJS), ureterovesical junction stenosis (UVJS), vesicoureteral reflux (VUR), posterior urethral valve (PUV), megaureter, multicystic dysplastic kidney (MCDB), ureterocele and renal cysts [5]. However, despite ongoing advances in understanding the genetic basis and consequences of CAKUT, there is still no consensus on the clinical significance, postnatal evaluation and management of infants with AH [7,8]. In the absence of regular follow-ups in the postnatal period, there is a risk of recurrent UTI, damage to the kidney parenchyma, impaired kidney function and kidney failure sequentially [9]. Our aim in this study is to determine the etiological causes of AH patients in their postnatal follow-ups, to stress on the importance of VUR, to reveal the frequency of UTI and renal damage, and its effect on prognosis in relation with the hydronephrosis in patients with hydroureteronephrosis, obstructive hydronephrosis and VUR.
Material and Methods
Ethical approval was obtained for this study from the local ethics committee of Selcuk University Faculty of Medicine with the decision number of 2021/40. The files of the patients who applied to Selcuk University Faculty of Medicine Pediatric Nephrology Clinic were analyzed retrospectively. The demographic data of the patients were age, gender; laboratory findings of urea, creatinine, fully automatic urinalysis, urine culture; urinary system ultrasonography (US), voiding cystourethrography (VCUG) from radiological imaging; technetium-99m-labeled (Tc-99m) dimercaptosuccinic acid (DMSA), Tc-99m mercaptoacetyltriglycine (MAG-3) from nuclear imaging and urinary system surgery reports data were collected. All patients followed up with the diagnosis of AH at this time were included in the study. Patients with a follow-up period of less than 3 months or insufficient data were excluded from the study.
In the perinatological period, patients with suspected PUV, oligohydramnios or a history of severe bilateral hydronephrosis were evaluated with ultrasonography within 24-48 hours, while other AH cases were between 3 and 7 days or 4 and 6 weeks. Patients with renal pelvis AP diameter of <9 mm in postnatal ultrasonography were considered mild, patients with 9-15 mm were considered moderate, and patients with >15 mm were considered severe AH. Patients with normal initial ultrasonography scans were followed-up with 2 more ultrasonographic imagings at 6-month intervals, and patients with an AP diameter of <7 mm in the renal pelvis were graduated from the follow-up. During the follow-up period, the patients’ fully automatic urinalysis, urine culture, urea and creatinine values were asked. Urine culture was taken from mid-stream urine in patients with toilet training, and by inserting a urinary catheter in patients who were not toilet trained. The results of the patients who underwent voiding cystourethrography were recorded as the presence or absence of VUR. Voiding cystourethrography was performed when the urine cultures were clean. MAG-3 results from nuclear imaging were classified as non-obstructive or obstructive dilatation, while DMSA scintigraphy results were classified as normal or scarred kidney.
Statistical Analysis
Data entry, statistical analysis and reporting procedures were conducted electronically. Descriptive analysis was performed for demographic and clinical characteristics of the patients. The distribution of data was evaluated using the one-sample Kolmogorov-Smirnov test. Data were presented as mean ± standard deviation for normally distributed continuous variables, and frequencies (percentile) for categorical variables. Values between two different groups were compared using independent samples t-test. If the data were not normally distributed, the Mann-Whitney U test was used. The χ2 test was used to evaluate the differences between categorical variables. The Kruskal-Wallis test was used to compare the data of more than two groups that did not fit the normal distribution. Test results with P <0.05 were considered statistically significant.
Results
Two hundred fifty-one patients were included in the study, and 310 kidneys were evaluated; 78.5% (n=197) of the patients were male and 21.5% (n=54) were female. The male/female ratio was 197/54. The demographic characteristics of the patients included in the study are shown in Table 1. The mean urea value measured at the first admission of the patients was 16 (min=4, max=128), and the creatinine value was 0.34 (min=0.12, max=2.56). UTI was detected in 80 (31.9%) patients at any time during follow-up. Four patients had an acute renal failure at the time of initial diagnosis.
According to the classification made according to renal pelvis AP diameter measurement, 121 (48.2%) patients were mild (group-1), 84 (33.5%) patients were moderate (group-2), 46 (18.3%) patients were severe grade (group-3) hydronephrosis. The details are shown in Table 2.
While pathological causes were detected in 30 (50.8%) of 59 patients with bilateral hydronephrosis, pathological causes were detected in 69 (35.9%) of 192 patients with unilateral hydronephrosis. The incidence of pathological causes of hydronephrosis was higher in patients with bilateral hydronephrosis (p=0.040).
There was a significant difference in the frequency of UTI, bilateral hydronephrosis and hydroureteronephrosis between the groups (p<0.001, p=0.003, p=0.006, respectively).
The rate of urinary tract infection was higher in patients with hydroureteronephrosis (48.7%), patients with obstructive hydronephrosis (70.3%) and patients with VUR (66.6%) compared to those without (p=0.012, p=0.001, p=0.006, respectively).
Vesicoureteral reflux was detected in 20 (48.8%) of 41 patients with hydroureteronephrosis, and VUR was detected in 22 (10.5%) of 210 patients without hydroureteronephrosis. Vesicoureteral reflux was seen at a higher rate in patients with hydroureteronephrosis (p<0.001). The incidence of renal scar was found to be higher in patients with hydroureteronephrosis, VUR and UTI (p=0.001, (p<0.001, p<0.001, respectively).
There was a significant difference in the incidence of VUR between the groups (p=0.002). Vesicoureteral reflux rate was found to be higher in group-2 and 3 compared to group-1. A significant difference was found between the groups in the rate of obstructive hydronephrosis in the extracted MAG-3 (p<0.001). The rate of obstructive hydronephrosis was found to be higher in Group-3. In the DMSA results, a significant difference was found between the groups in the frequency of renal scarring (p=0.006). Renal scar rate was found to be higher in Group-3. Surgical operation rate was found to be higher in group-3 compared to group-1 and 2 (p<0.001). The distribution of clinical and imaging findings of the kidneys with hydronephrosis included in the study according to the groups is shown in Table 3. Two patients developed chronic kidney disease in the follow-up.
Discussion
Most of the existing literature on the prognosis of infants with AH consists of retrospective studies. In this study, we touched upon important aspects in terms of the pathological causes of AH, the management and prognosis of patients, of our ethnic structure, of changing technical equipment conditions and of up-to-date medical approaches over the last ten years. In line with the literature, the proportion of male patients was higher, which remains similar in the last few decades and in different societies [10]. In our study based on patient records admitted to the pediatric nephrology clinic in the postnatal period, we found that two-thirds of the patients were prenatally diagnosed. Most prospective and retrospective literature related to the subject consists of prenatally diagnosed cases. Therefore, we cannot compare our study. We interpret this prenatal diagnosis rate as a result of recent perinatal developments in our country and the increase in pregnancy follow-up rates.
The rate of self-recovery in the mild AH group was higher than in the other two groups. However, although the increased likelihood of underlying pathological causes increased among the groups, the rate was significantly higher among the kidneys in the mild AH group at 21.5%. Gökaslan et al. [11] also grouped patients as mild to moderate-heavy, and emphasized the importance of follow-up in this group in accordance with our study because urological abnormalities in the mild AH group showed a highly heterogeneous distribution. A meta-analysis involving 1,678 babies diagnosed with fetal hydronephrosis showed that CAKUT was the underlying cause of fetal hydronephrosis in a third of patients in postpartum evaluation [6]. In our study, we found CAKUT as 36.1% among all kidneys, similar to the literature. Unlike the literature, the most common anomaly detected in our study was VUR and second frequency was UPJS. Although the frequency of UPJS increases with the severity of hydronephrosis, we found that VUR, which is our most common diagnosis, is also seen at a higher rate in moderate and severe hydronephrosis groups [6]. Similar to our results in the literature, Dias et al. showed that moderate to severe-grade VUR was associated with higher grade renal-pelvic dilatation in both intrauterine and postpartum periods [12]. Passerotti et al. and Ansari et al. similarly reported increased reflux dilatation with a degree of cervical dilactation in postpartum US [13,14].
In addition, it is known that postnatal normal ultrasound imaging does not exclude VUR. Valavi et al. detected a large number (89%) of patients with mild AH had moderate to severe VUR. In that cohort, renal sonography was not a reliable method for the prediction of VUR and its severity in patients with mild postnatal AH. However, it was reliable for high grades of VUR. These authors suggested that VCUG is mandatory for all patients diagnosed with AH. In contrast, other studies suggested that VCUG is not mandatory in children with moderate or mild AH [16-18].
In addition to all this controversial literature, the frequency of UTI and the rate of VUR were higher in patients with hydroureteronephrosis on urinary ultrasonography in our study. Unlike us, Visuri et al. in their 10-year cohort determined that the incidence of UTI was higher in patients with grade 4-5 VUR in the follow-up of a total of 192 patients with hydronephrosis, hydroureteronephrosis and VUR [19]. In their studies, hydroureteronephrosis was not prominent in terms of UTI. In addition, in our study, the rate of underlying pathological diagnosis was higher in patients with bilateral hydronephrosis. Since we have determined a higher rate of renal scarring in patients with hydroureteronephrosis, urinary tract infection and VUR, we think that VCUG should be routinely performed in patients with hydroureteronephrosis and a history of UTI, regardless of the grade of AH. In other patients, this decision should be made on an individual basis. However, in our study, the necessity of imaging methods comes to the fore in this group, since we found that the obstructive pattern and surgical requirement were higher in MAG-3 in the group with severe AH. In our study, the rate of spontaneous regression decreased as the degree of AH increased, which was consistent with the literature [6,11].
Although it covered a period of 10 years, a low number of patients in our study was the limitation of our study as our center was a tertiary care clinic dealing with complicated cases in general. Due to the retrospective nature of the study, ultrasonographic imaging was performed by different radiologists, which might have led to individual measurement errors due to experience. Another limitation is that we did not retrieve all antenatal period recordings of our patients due to their retrospective nature. Therefore, we could not obtain a conclusion about the prognosis of patients with intrauterine resolution and intrauterine recovery.
Conclusion
In conclusion, the presence of hydroureteronephrosis and bilaterality, as well as the grade of AH, are determinants of the diagnostic imaging modality and prognosis. VUR should be excluded in patients with hydroureteronephrosis and UTI. Cases with mild AH tend to resolve more spontaneously than moderate and severe cases. Patients with moderate and severe AH should be followed for a long time with a more comprehensive imaging method.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
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2. Woodward M, Frank D. Postnatal management of antenatal hydronephrosis. Bju Int. 2015; 89(2):149–56.
3. Gaeta G, Pozzoni M, Serafini A, Lesma A, Paesano PL, Candiani M, et al. Prenatal dagnosis of severe fetal hydronephrosis due to pyeloureteral junction syndrome with false neonatal resolution. Reprod Med. 2021; 2:163-70
4. Oliveira EA, Oliveira MCL, Mak RH. Evaluation and management of hydronephrosis in the neonate. Curr Opin Pediatr. 2016; 28(2):195–201
5. Nguyen HT, Benson CB, Bromley B, Campbell JB, Chow J, Coleman B, et al. Multidisciplinary consensus on the classification of prenatal and postnatal urinary tract dilation (UTD classification system). J Pediatr Urol. 2014; 10(6):982–99
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7. Policiano C, Djokovic D, Carvalho R, Monteiro C, Melo MA, Graça LM. Ultrasound antenatal detection of urinary tract anomalies in the last decade: outcome and prognosis. J Matern Fetal Neonatal Med. 2015; 28(8):959–63.
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10. Nguyen HT, Benson CB, Bromley B. Multi disciplinary consensus on the classification of prenatal and postnatal urinary tract dilation (UTD classification system). J Pediat Urol 2014;10(6):982-99.
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19. Visuri S, Jahnukainen T, Taskinen S. Incidence of urinary tract infections in infants with antenatally diagnosed hydronephrosis- A retrospective single center study. J Pediatr Surg. 2017; 52(9):1503–6.
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Applicability of the ROX index in decision-making for hospitalization in COVID-19 patients
Umut Sabri Kasapoglu 1, Engin Burak Selcuk 2, Murat Yalcınsoy 3, Kadir Uckac 2, Abdullah Fahri Sahın 4, Recep Bentlı 5
1 Department of Pulmonary and Critical Care Medicine, Malatya Training and Research Hospital, 2 Department of Family Medicine, Inonu University School of Medicine, 3 Department of Chest Diseases, Inonu University School of Medicine, 4 Department of Pathology, Turgut Ozal University School of Medicine, 5 Department of Internal Medicine, Inonu University School of Medicine, Malatya, Turkey
DOI: 10.4328/ACAM.21196 Received: 2022-04-17 Accepted: 2022-06-18 Published Online: 2022-06-20 Printed: 2022-09-01 Ann Clin Anal Med 2022;13(9):1017-1021
Corresponding Author: Engin Burak Selcuk, Department of Family Medicine, Inonu University School of Medicine, Turgut Ozal Medical Center, 44280, Battalgazi, Malatya, Turkey. E-mail: drenginselcuk@hotmail.com P: +90 532 488 20 43 Corresponding Author ORCID ID: https://orcid.org/0000-0001-8484-0223
Aim: Data on the outpatient follow-up of COVID-19 cases is still scarce. Also, the significance of the ROX index in decision-making for hospitalization in the ambulatory COVID-19 cases remains unknown. The aim of this study is to determine the general characteristics of COVID -19 patients treated as outpatients and to investigate whether the ROX index is applicable in hospitalization decisions.
Material and Methods: This retrospective cohort study was conducted in confirmed adult COVID-19 cases between 15 October 2020 and 01 March 2021. A total of 5240 confirmed COVID-19 patients were included in the present study. Factors affecting hospitalization were investigated.
Results: The study population was divided into two groups as those who require hospitalization (n=672) and those who did not (n=4568). The number of male patients and the mean age of the patients were significantly higher in hospitalized patients group (p=0.046, p<0.001). ROX index that was calculated at the home visit on the third day of disease was found significantly lower in the group of hospitalized patients (p<0.001). There was a significant correlation between ROX index and inflammatory biomarkers in the present study (p<0.001). The ROX index was found the most accurate parameter for decision-making for hospitalization in ambulatory COVID-19 patients (AUC=0.794 CI=0.773-0.814, p<0.001).
Discussion: The ROX index can be a useful and objective clinical tool for decision making for hospitalization in the ambulatory COVID-19 cases.
Keywords: COVID-19, Ambulatory, Hospitalization, Predictors, ROX Index
Introduction
In the novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), approximately 80% of the cases have mild disease that do not require hospitalization, and these cases can be followed up in ambulatory settings [1, 2]. However, data on the outpatient follow-up of COVID-19 cases is still scarce, and clinical experience from the onset of the pandemic to the present forms the bulk of current strategies. Patient management in COVID-19 outpatients includes early initiation of antiviral treatment, supportive care, measures to reduce the risk of SARS-CoV-2 transmission, and recommendations on when patients should present to the hospital [3].
Although the risk of hospitalization and mortality is higher in the elderly and comorbid COVID-19 cases, COVID-19 severe illness and death can occur in any age group. As a result, early diagnosis of potentially sudden clinical deterioration in outpatients is a critical step in patient management. To this end, clinicians need quick and easy diagnostic tools to support their clinical decisions [1, 4].
The ROX Index (Respiratory rate-OXygenation) was developed by Roca et al. in 2016 to evaluate the success of high flow nasal cannula (HFNC) oxygen therapy. The ROX index is calculated by dividing the peripheral oxygen saturation (SpO2) by the fraction of inspired oxygen (FiO2) and the respiratory rate (RR). It has been shown that a ROX index of <4.88, calculated 12 hours after initiation of HFNC therapy, is associated with a high risk of intubation [5, 6].
The significance of the ROX index in decision-making for hospitalization in the ambulatory COVID-19 cases remains unknown. This study aimed to determine the general characteristics of COVID-19 patients treated as outpatients and to investigate whether the ROX index is applicable in hospitalization decisions.
Material and Methods
Study design
This study protocol was approved by the Turkish Ministry of Health and Clinical Ethics Committee of Inonu University (protocol code:2021/2142). The retrospective cohort study comprised patients over 18 years of age who were diagnosed with COVID-19 between 15 October 2020 and 01 March 2021 in Malatya followed up and treated at home.
Exclusion and inclusion criteria
Inclusion criteria for the study included confirmed COVID-19 cases, cases aged 18 years and older. Exclusion criteria for the study included suspected COVID-19 cases, non-COVID-19 patients, patients with missing data, and patients aged <18 years.
Data collection and definitions
A confirmed case of SARS-CoV-2 infection was defined as follows: a symptomatic case with positive SARS-CoV-2 real-time reverse transcription-polymerase chain reaction (RT-PCR) from the nasopharyngeal and/or oropharyngeal swab, and/or an asymptomatic person with a positive SARS-CoV-2 RT-PCR who is a contact of a probable or confirmed case.
COVID-19 cases treated at home were examined on the 3rd day after a positive PCR test result for COVID -19 by a team consisting of a doctor and a nurse from the Malatya Provincial Health Directorate. Vital signs of COVID-19 cases on the day of their home assessment include diastolic blood pressure (mmHg), systolic blood pressure (mmHg), respiratory rate (breaths per minute), oxygen saturation in the room air (%), heart rate (beats per minute), body temperature ( C), and Glasgow Coma Scale), initial symptoms, demographics, comorbidities, laboratory data (including complete blood count, glucose, urea, creatinine, albumin, aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), creatine kinase (CK), total bilirubin, sodium (Na), chloride (Cl), potassium (K), C-reactive protein (CRP), D-Dimer, cardiac troponin I (cTnI), ferritin ), ROX indices, and hospitalizations were recorded. Patients’ oxygen saturation in the room air and heart rate were measured for 1 minute with the same pulse oximetry device (Covidien Nellcor™ Bedside SpO₂ Patient Monitoring System), while the patient resting in a sitting position for 15 minutes.
Statistical analysis
We used the SPSS (Statistical Package for Social Sciences) program for macOS 25.0 for the statistical analysis. Normally and homogeneously distributed variables are reported as mean± and standard deviation, data that do not have a normal and homogeneous distribution are reported as median (min-max), categorical variables are reported as numbers and percentages. When comparing two independent groups, the independent variable t-test was used when analyzing parametric data. The Mann-Whitney U test was used when analyzing nonparametric data. The Chi-Squared test was used when analyzing categorical data. The prediction performance of the parameters for the hospitalization was evaluated by calculating the area under the curve (AUC), the receiver operating characteristic (ROC) curve. The study used the ROC curve to determine the appropriate cut-off value of the parameters. Independent variables associated with hospitalization in the univariate analysis were evaluated with multivariate logistic regression models. Odd ratio and 95% confidence interval (CI) were calculated with the “Enter” method. Pearson’s correlation analysis was used for the examination of the correlation between the ROX index and inflammatory parameters. The results were analyzed with a 95% confidence interval and a significance level of p<0.05
Results
Baseline general characteristics of the study population
A total of 5240 confirmed COVID-19 patients were included in the present study. The study population was divided into two groups as those who require hospitalization (n=672) and those who did not (n=4568). In the group of hospitalized patients, the number of male patients and the mean age of the patients were significantly higher (p=0.046, p<0.001). Coronary artery disease (CAD) (5.8% vs 3.1%) and chronic obstructive pulmonary disease (COPD) (11.3% vs 5.8%) were found significantly higher in the group of hospitalized patients respectively (p<0.001, p<0.001) (Table 1).
The proportions of the patients with dyspnea, fatigue, cough and fever were significantly higher in the group of hospitalized patients compared with the non-hospitalized patients (p=0.001, p=0.022, p<0.001, p=0.005). At the home visit on the third day of the course of the disease, the respiratory rate and heart rate were significantly higher in the group of hospitalized patients (p<0.001, p<0.001). Also, oxygen saturation measured in room air was significantly lower in the group of hospitalized patients compared with the non-hospitalized patients (p<0.001). Moreover, the ROX index calculated at the home visit on the third day of disease was found to be significantly lower in the group of hospitalized patients compared with non-hospitalized patients (p<0.001) (Table 1).
Lymphocytes and platelets level were significantly lower in the group of hospitalized patients (p<0.001, p<0.001). Also, the level of serum albumin was significantly lower in the group of hospitalized patients compared with non-hospitalized patients (p<0.001). Moreover, level of inflammatory markers including serum CRP and ferritin were found significantly higher in the group of hospitalized patients compared with non-hospitalized patients (p<0.001, p<0.001) (Table 2). Also, there was significantly negative correlation between ROX index and inflammatory biomarkers including serum CRP, LDH and ferritin level in the present study (p<0.001).
Predictors of hospitalization
We performed ROC analysis to predict hospitalization n performance of the parameters including respiratory rate, ROX index, CURB-65 score, and the oxygen saturation measured in the room air. Analysis of the ROC showed that the ROX index (AUC=0.794, p<0.001) was superior to the CURB-65 (AUC=0.682, p<0.001), respiratory rate (AUC=0.624, p<0.001), and oxygen saturation measured in the room air (AUC=0.691, p<0.001) for the prediction of hospitalization. Also, the cut-off value of ROX index was found 20.00 for the prediction of the hospitalization. For the prediction of hospitalization, among the compared parameters, the ROX index was found to be the most accurate parameter for decision-making regarding hospitalization in the ambulatory COVID-19 patients (Figure 1). Multivariate logistic regression analysis was performed for the prediction of the hospitalization. ROX index and age were independent predictors in decision making for hospitalization, respectively (OR=1.412 95% CI=1.239-1.978 p<0.001, OR=1.108 95% CI=0.988 -1.086, p<0.001).
Discussion
The current study revealed that the ROX index was the most accurate parameter for the prediction of hospitalization. We believe that patients with a lower ROX index (<20.0) should be followed carefully and closely in the outpatient settings.
In clinical studies examining risk factors for hospitalization and mortality in COVID-19 cases, it was found that the rate of hospitalization due to COVID-19 was higher in men than in women, and correspondingly, the mortality rate was higher in men. However, other studies have found that mortality rates do not differ by patient gender [7-9]. In clinical studies conducted since the onset of the pandemic, age and comorbidity have been shown to be essential determinants of hospitalization, illness severity, and mortality in COVID-19 cases. Hospitalized patients have been shown to be older than outpatients with COVID-19. In addition, the course of COVID-19 disease has been shown to be more severe in elderly patients, and the mortality rate is higher in elderly patients. In addition, the prevalence of comorbidities has been shown to be higher in hospitalized COVID-19 cases and, more importantly, the disease was more severe, and the mortality rate was higher in COVID-19 cases with comorbidities [2, 8-11]. No statistical difference in gender was identified in hospitalized COVID-19 cases in our study, in which mortality rates were not evaluated. However, in the present study, in accordance with the literature, hospitalized COVID-19 cases were older than those who were not hospitalized, and 70% of hospitalized cases had at least one comorbid condition. However, although patient age was a significant risk factor for hospitalization in our study, comorbidity was not an independent risk factor.
The rapid increase in the number of cases has led to a significant increase in demand for hospital beds and a shortage of medical equipment, resulting in the collapse or shortages of healthcare systems worldwide [13]. To reduce the burden on healthcare systems while providing the best possible care to patients, it is necessary to quickly and accurately identify low-risk patients who can be followed at home or high-risk patients who need to be hospitalized. Furthermore, early detection of possible disease progression and early salvage treatment initiation in outpatient COVID-19 cases are essential steps in treating patients [1, 4, 13, 14]. Many new risk assessment models for COVID-19 have been developed, or scoring systems previously designed for sepsis or pneumonia have been used for this purpose. However, all these models carry a high risk of bias. Therefore, clinicians need objective, rapid, and simple risk assessment tools to support their clinical decisions [13-15].
The CURB-65 score, developed by Lim WS et al., is a scoring system designed to identify patients at high risk of mortality from community-acquired pneumonia [16]. Thanks to this scoring system, it is also easy to determine, which case requires inpatient treatment. While pneumonia cases with CURB-65 scores of 0 and 1 can be followed up on as outpatients, pneumonia cases with a CURB-65 score of ≥2 should be hospitalized and treated. In addition, studies have shown that mortality is higher in patients with the CURB-65 score ≥2 community-acquired pneumonia [15-17]. During the pandemic, most clinical studies examining the applicability of the CURB-65 score in COVID -19 cases were conducted in hospitalized COVID-19 cases. The success of CURB-65 in predicting hospital mortality and transfer to ICU has produced contradictory results [15, 18, 19]. In addition, the applicability of CURB-65 in deciding hospitalization in outpatient COVID-19 cases is not clearly known [17]. In our study evaluating the general characteristics of outpatient COVID-19 cases, the success of CURB-65 in predicting hospitalization lagged behind the ROX index, although hospitalized COVID-19 cases had a higher CURB-65 score.
The ROX index, developed by Roca et al. to assess the success of HFNC in critically ill patients is a simple and quick tool to calculate and reproduce [4, 5]. Low ROX index values (ROX index < 4.88), calculated particularly after initiation of HFNC therapy, have been shown to be associated with a high risk of intubation [5, 6]. It was found that the ROX index can be an applicable and useful predictor for intubation decisions and evaluation of HFNC success in clinical studies evaluating the applicability of the ROX index in cases of COVID-19 pneumonia treated with HFNC therapy during the pandemic [20].
Although the ROX index is a parameter that is easy to calculate and repeat in clinical practice and does not require laboratory results, there are few clinical studies examining its applicability in deciding hospitalization in COVID-19 cases. In the study by Gianstefani A et al., the ROX index was shown to have higher accuracy in estimating hospitalization than respiratory rate alone in COVID-19 cases presented to the emergency department. Furthermore, the study demonstrated that the ROX index (ROX index < 25.7) is an effective tool to distinguish patients who presented to the emergency department because of COVID-19 and require hospitalization from those who can be safely discharged. In addition, lower ROX index values have been shown to be associated with increased mortality in COVID-19 cases presented to the emergency department [4].
We found that the ROX index was statistically significantly lower in hospitalized patients than in outpatients. In addition, the ROX index was found to have a significant correlation with inflammatory parameters, which have been associated with disease severity and mortality in many previous clinical trials in COVID-19 cases, and to have higher accuracy in estimating hospitalization than respiratory rate and CURB-65 alone. More importantly, the risk of hospitalization increased 1.56-fold in patients with a lower ROX index (ROX index <20.0).
Conclusion
We found that the ROX index is the most accurate predictor of requirement for admission to the hospital rather than ambulatory care. Another identifiable risk factor for hospitalization includes the patient’s age. The ROX index can be a useful and objective clinical tool for making hospitalization decision in the ambulatory COVID-19 cases, regardless of the radiological and laboratory findings. In addition, the ROX index may be a parameter that can be readily used in triage practice and patient management of COVID-19 cases presented to the emergency department and outpatient clinic. However, further clinical studies are required to confirm these findings.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Download attachments: 10.4328:ACAM.21196
Umut Sabri Kasapoglu, Engin Burak Selcuk, Murat Yalcınsoy, Kadir Uckac, Abdullah Fahri Sahın, Recep Bentlı. Applicability of the ROX index in decision-making for hospitalization in COVID-19 patients. Ann Clin Anal Med 2022;13(9):1017-1021
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Evaluation of scoring methods in trauma patients with rib fractures
Muharrem Cakmak
Department of Thoracic Surgery, Faculty of Medicine, Fırat University, Elazig, Turkey
DOI: 10.4328/ACAM.21197 Received: 2022-04-18 Accepted: 2022-06-17 Published Online: 2022-06-18 Printed: 2022-09-01 Ann Clin Anal Med 2022;13(9):1022-1025
Corresponding Author: Muharrem Cakmak, Department of Thoracic Surgery, Faculty of Medicine, Fırat University, Elazig, Turkey. E-mail: drcakmak@gmail.com P: +90 533 301 68 97 F: +90 424 233 35 55 Corresponding Author ORCID ID: https://orcid.org/0000-0002-9504-2689
Aim: In thoracic traumas, it is very important to provide accurate treatment after determining the severity of the trauma. Therefore, scoring systems are used to determine morbidity and mortality rates. These scoring methods include the Rib Fracture Score (RFS), Chest Wall Injury Score (CWIS), Chest Trauma Score (CTS), Thoracic Trauma Severity Score (TTSS), and Injury Severity Score (ISS). In our study, we aimed to evaluate the scoring systems in patients with post-traumatic rib fractures and accompanying pathologies, and to determine the trauma severity, mortality and morbidity rates with these scorings.
Material and Methods: The records of 482 patients followed up and treated for post-traumatic rib fractures. The patients were divided into two groups as survivors (n: 418) and those who died (n: 64). The mean number of fractures, RFS, CWIS, CTS, TTSS, ISS values, and mortality and morbidity rates were recorded.
Results: The mean number of fractures was 3.02±2.92, RFS; 4.84±4.71, CWIS; 1.68±0.79, CTS; 5.01±1.46, TTSS; 6.58±2.20, ISS; 7.90±8.64. When surviving and deceased patients were compared in terms of the mean number of fractures, RFS, CWIS, CIS, TTS, and ISS, the number of deceased patients was statistically significant compared to the surviving patients (p<0.05).
Discussion: It was observed that mortality rates increased in trauma patients as the number of rib fractures increased with concomitant pathologies such as pneumomediastinum, hemothorax, pneumothorax, contusion, and flail chest as well as concomitant organ injuries such as spleen, kidney and liver. These pathologies and the presence of concomitant injuries were significant in mortality and morbidity.
Keywords: Fractures, Ribs, Scoring, Trauma
Introduction
The rate of rib fractures in thoracic traumas is 35-40% [1]. Due to fractures, pneumothorax and hemothorax may develop in the early period, while atelectasis and pneumonia may occur in the late period. The number of fractures, respiratory distress, and concomitant organ injuries cause serious problems [2].
In thoracic traumas, it is very important to provide accurate treatment after determining the severity of the trauma, to predict complications and the need for intensive care, and to explain the prognosis. In these patients, if the assessment of trauma severity is done correctly, the implementation and follow-up of treatment protocols will become more accurate. Therefore, scoring systems are used to determine morbidity and mortality rates [3]. These scoring methods include the Rib Fracture Score (RFS), Chest Wall Injury Score (CWIS), Chest Trauma Score (CTS), Thoracic Trauma Severity Score (TTSS), and Injury Severity Score (ISS) [4].
In our study, we aimed to evaluate the scoring systems in patients with post-traumatic rib fractures and accompanying pathologies, and to determine the trauma severity, mortality and morbidity rates with these scorings.
Material and Methods
Patients
The records of 482 patients who were followed up and treated for post-traumatic rib fractures between 2015 and 2021 were evaluated.
Procedures
The patients were divided into two groups as surviving (n: 418, 87%) and deceased patients (n: 64, 13%), regardless of the number of fractures. Age, gender, symptoms, localization of fractures, radiological findings, diagnosis and treatment methods, complications, concomitant injuries, mean number of fractures, RFS, CWIS, CTS, TTSS, ISS values, and mortality and morbidity rates were recorded.
Statistics
IBM SPSS Statistics version 22.0 was used for data analysis. Continuous variables were expressed as mean±standard deviation, while categorical variables as number-ratio. Results were evaluated with the Kruskal-Wallis test, analysis of variance and the Mann-Whitney-U tests. p<0.05 was considered significant.
Results
The total number of patients was 482, and the mean age was 55.2±18.17 years. Etiological causes were traffic accidents in 286 (59%), falling from a height in 153 (32%), and assault in 42 (9%). There were 445 males and 37 females among the patients. In 221 of the patients, the fractures were on the right, 226 had fractures on the left, and 35 had bilateral fractures (Table 1).
Concomitant pathologies were contusion in 45, pneumothorax in 34, hemothorax in 29, flail chest in 13, and pneumomediastinum in 7. Concomitant injuries were sternum in 34, clavicle in 20, scapula in 13, vertebra in 12, vertebra+scapula in 9, liver in 5, liver+kidney in 2, kidney in 1, spleen+kidney in 1, and liver+kidney+spleen in 1 (Table 2). The mean number of fractures was 3.02±2.92, RFS; 4.84±4.71, CWIS; 1.68±0.79, CTS; 5.01±1.46, TTSS; 6.58±2.20, ISS; 7.90±8.64.
The mean age of the surviving patients was 56.01±17.98; 384 were male while 34 were female; 199 had right-sided localization, 200 had left-sided localization, and 19 had bilateral localization. Contusion was found in 31, pneumothorax in 26, hemothorax in 16, flail chest in 5 and pneumomediastinum in 3 patients. As concomitant injuries, 27 had sternum fracture, 11 had scapula, 17 had clavicle, 10 had vertebrae, 7 had vertebra+scapula, 1 had kidney injury, 4 had liver injury, and 1 had liver+kidney injury. The mean number of fractures was 2.78±2.58, RFS; 4.27±3.58, CWIS; 1.60±0.70, CTS; 4.87±1.39, TTSS; 6.32±1.99, ISS; 6.98±8.04 (Tables 1,2,3).
The mean age of the deceased patients was 60.10±19.16 years; 61 were male, while 3 were female. Fractures were on the right side in 22, on the left side in 26, and bilateral in 16. Contusion was detected in 14, pneumothorax in 8, hemothorax in 13, flail chest in 8 and pneumomediastinum in 4 patients. As concomitant injuries, 7 had sternum fracture, 2 scapula, 3 clavicle, 2 vertebra, 2 vertebra+scapula, 1 spleen+kidney, 1 liver, 1 liver+kidney, 1 liver+kidney+spleen injury. The mean number of fractures: 4.62±4.24, RFS; 8.54±8.30, CWIS; 2.20±1.12, CTS; 5.93±1.59, TTSS; 8.34±2.68, ISS; 13.89±10.03 (Tables 1, 2, 3).
When comparing survivors and deceased patients in terms of mean number of fractures, RFS, CWIS, CIS, TTS, and ISS, the number of deceased patients was statistically significant compared to the surviving patients (p<0.05). It was observed that mortality rates increased in trauma patients as the number of rib fractures increased with concomitant pathologies such as pneumomediastinum, hemothorax, pneumothorax, contusion, and flail chest as well as concomitant organ injuries such as spleen, kidney and liver. These pathologies and the presence of concomitant injuries were significant in mortality and morbidity.
In the treatment, 60 (12%) patients underwent tube thoracostomy, 10 (2%) underwent thoracotomy (7 bleeding control+hematoma evacuation, 3 primary diaphragmatic repair), 2 (0.41%) underwent chest wall reconstruction. Additionally, 10 (2%) of the flail chest patients were followed in the intensive care unit, and 3 (1%) had fixation+intensive care follow-up. Finally, fiberoptic bronchoscopy+esophageal passage graphy and endoscopy were performed in all patients with pneumomediastinum.
The most common morbidities in patients were wound infection (n: 103, 21%), pneumonia (n: 42, 9%), and atelectasis (n: 52, 11%). The mean length of stay was 7±5 days.
Discussion
The incidence of rib fractures due to trauma has been reported to be 7-9%, and the mortality rate to be 10-12% [5, 6]. Karadayi et al. reported that the mean age was 51.50 (17-96) in 214 patients with rib fractures, 75.7% were over 65 years old, while 24.3% were under 65 years old; 52 of the patients had isolated fractures, 53 had 2, and 111 had more than 2 rib fractures, and there was a correlation between the increased number of broken ribs and mortality and morbidity [7]. In our study, the mean age of patients was 55.2±18.17 years, and the mortality rate was 13%.
Early complications in rib fractures are contusion, pneumothorax, and hemothorax, while late complications are atelectasis and pneumonia. Broken rib ends may lacerate the intercostal muscles and rupture the internal mammary and intercostal arteries, resulting in massive hemothorax. Fracture ends can puncture the lung, diaphragm, and abdominal organs [8, 9]. In our study, 45 patients had contusion, 34 pneumothorax, 29 hemothorax, 13 flail chest, and 7 pneumomediastinum. As concomitant injuries, 34 had sternum, 20 clavicle, 13 scapula, 12 vertebra, 9 vertebra+scapula, 5 liver, 2 liver+kidney, 1 kidney, 1 spleen+kidney, and 1 liver+kidney+spleen injuries.
The Rib Fractures Score is used to determine the risk ratio of complications that may develop due to rib fractures, especially in adult patients [10, 11]. In this scoring system, the number of broken ribs, the location of injury and the age are the parameters used. In addition, in the same study, they formed 4 groups with pain scores of 3-6, 7-10, 11-15 and above 15, and found positive results by applying different pain relief methods to each group. As a result, they reported that patients with RFS above 7 pounds should be referred to pain relief units (algology or anesthesia) [12]. In our study, RFS values were higher and statistically significant in the deceased group compared to the surviving patient group, and they correlated with the number of broken ribs, bilateral injury, and patient age.
The Chest Wall Injury Scale is a method that is between 1 and 5 according to the number of fractures, the location of the fracture, the presence or absence of sternum fracture, laceration or avulsion in the soft tissue and skin. This helps to determine the treatment method according to the condition of the injury to the chest wall. In their study with 88 patients, Taylor et al. reported that this scale system is a guide for the decision of surgical intervention, and that an increase in scoring indicates an increase in mortality and morbidity [11]. In our study, CWIS values were higher and statistically significant in the deceased group compared to the surviving patient group.
The Chest Trauma Score is a scoring method based on the patient’s age, number of broken ribs, location of the fracture, and lung contusion. Chen et al. reported that the probability of poor outcomes such as complications and mortality can be predicted in patients with thoracic trauma with a CTS above 5 [13]. In our study, CTS values were higher and statistically significant in the deceased group compared to the surviving patient group, and correlated with increased number of broken ribs, bilateral injury, patient age, presence of contusion, presence of hemothorax and pneumothorax.
The Thoracic Trauma Severity Score includes patient age, PaO2/FIO2 ratio, pulmonary contusion, pleural pathology and rib fracture, ranges between 0-25, and is closely related to mortality and morbidity [14]. Elbaih et al. reported that TTSS is a very significant mortality and morbidity scoring system [15]. Although very high values were not observed in our study, they were especially higher and statistically more significant in the group of patients who died compared to the surviving patient group.
The Injury Severity Score is a scoring system that provides a numerical calculation and definition of the total severity of injury in patients with multiple body injuries. It is associated with mortality, morbidity, and length of hospital stay. Using ISS, injuries that are not life-threatening alone have been shown to significantly affect mortality when combined with other organ injuries. If the ISS is greater than 16, major trauma is present. The mortality rate does not increase directly with higher ISS scores, and different injury combinations may yield the same ISS values even though they have different mortality rates. All injuries must be identified when performing the calculation, which is possible only when the patient is discharged. ISS is a calculation method made after the patient is discharged [16]. In our study, ISS values were higher and statistically significant in the group of deceased patients compared to the surviving patient group.
The main approach in the treatment of rib fractures is pain control and breathing exercise. It is essential for elderly patients to be observed in the hospital and a good pain treatment to be provided. Although the treatment of rib fractures is conservative, complications caused by broken ends may require surgical intervention. In these cases, platinum application is an important method that facilitates stabilization [17]. In our study, 60 patients underwent tube thoracostomy, 10 patients underwent thoracotomy (7 bleeding control+hematoma evacuation, 3 diaphragmatic rupture repair), and 2 patients underwent chest wall reconstruction. Additionally, 10 patients with flail chest were followed up in the intensive care and 3 had fixation+intensive care follow-up.
Conclusion
In trauma patients with isolated thoracic or multiple organ injuries, except ISS, trauma scoring provides preliminary information about mortality and morbidity that may occur. When the number of broken ribs increases, when the rib fracture is accompanied by concomitant intrathoracic pathologies and other organ injuries, rapid and accurate trauma scoring is life-saving. In treatment, patients should be monitored and oxygen saturation, arterial blood pressure, cardiac rhythm and arterial blood gas should be followed. Additionally, pain control and respiratory physiotherapy should be provided. While the primary treatment method in patients with intrathoracic complications is simple tube thoracostomy, larger surgical interventions can be performed in necessary cases despite high mortality. Especially in patients with a high CWIS value, surgery can be performed depending on the condition of the accompanying organ injuries.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Evaluation of dental anxiety: Nyala Region, Sudan
Elif Esra Ozmen 1, Metin Ocak 2
1 Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Ahmet Keleşoglu University, Karaman, 2 Department of Emergency, Gazi State Hospital, Samsun, Turkey
DOI: 10.4328/ACAM.21198 Received: 2022-04-20 Accepted: 2022-06-19 Published Online: 2022-06-21 Printed: 2022-09-01 Ann Clin Anal Med 2022;13(9):1026-1030
Corresponding Author: Elif Esra Ozmen, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Ahmet Keleşoglu University, Karaman, Turkey. E-mail: elifesraozmen89@gmail.com P: +90 507 152 42 13 Corresponding Author ORCID ID: https://orcid.org/0000-0003-1920-4655
Aim: Dentists may commonly meet fear and anxiety during dental procedures. Patients may be frightened due to the expectation of pain, and this may cause them to delay their dental treatment. Physicians should be able to plan treatment by noticing anxiety and fear situations. Numerous scales were developed for this purpose. The Dental Anxiety Scale (DAS) and Modified Dental Anxiety Scale (MDAS) are the most commonly used scales. The aim of the present study was to evaluate the dental anxiety of a group of adult individuals in the Nyala region of Sudan.
Material and Methods: The study was conducted on adults who have been referred to the Nyala Training and Research Hospital. The present study included 104 individuals, including 43 (41.35%) males and 61 (58.65%) females with ages ranging between 20 and 57 years. The participants were asked to fill in the prepared questionnaire. Dental anxiety level was determined through the Dental Anxiety Scale (DAS) and Modified Dental Anxiety Scale (MDAS).
Results: In this study, which examined levels of dental anxiety, it was concluded that there was no difference in anxiety level between the genders (p>0.05). It was observed that the use of aerators in dentistry practices increases anxiety (p<0.05). It was concluded that the heads of the dental scaler used during scaling also increased the level of anxiety (p<0.05). However, it was detected that they do not have a fear of local anesthesia (p>0.05).
Discussion: Considering the results of the study reveals that it has not been determined under what conditions the emerging anxiety can develop. However, it was observed that anxiety level differs among nations.
Keywords: Dental Anxiety, Dental Procedures, Dental Anesthesia
Introduction
Anxiety is the struggle of an individual under stress. It is not only a psychological but also a physiological process. The individual psychologically has delusions and fear, as well as a panic that he will experience bad things. This deteriorates the sleep pattern of the individual and initiates a process that progresses to distraction. Beyond psychological problems, headache, dizziness, arrhythmia, difficulty in breathing, paresthesia and even dry mouth may be experienced physiologically. Sweating, cold and moist skin appearance, chills, tachycardia, arrhythmia, facial flushing or pallor may be observed during clinical practice [1,2].
Dental anxiety is the strong negative emotions that an individual feels about dental practices. Sanikop et al. defined dental anxiety as an individual’s concern that something bad will happen related to their dental treatment. This anxiety may be affected by the individual’s personality traits, fear of pain or even the traumatic dental experience he may have had in childhood [3-5]. Even experiences that do not belong to him may affect an individual [6]. The most important reason noticed so far in the development of dental anxiety is considered the pain that the individual fears during the procedure. However, many other factors cause this condition. The most important difficulty in this situation for dentists is that patients will complicate their treatment because of this feeling [1,3,7].
Most of the physicians often encounter reactions due to fear and anxiety in their patients during dental applications. Apart from the negative dental experiences of the patients in the past, the approach of the physician to them affects these reactions. Since pediatric patients usually adopt the behaviors of the individuals around, comments of their families and friends about their experiences have a great effect. Furthermore, the instruments preferred in dental applications, the length of time spent in the waiting room can increase anxiety. When the patient sees the injector to be used, the injection and use of rotary tool (aerator) may increase this anxiety more. This increased anxiety may cause them to delay their treatment appointments, make irregular appointments, or even miss their appointments. When they realize this, their anxiety may have increased even more. Oral and dental diseases may increase and cause serious problems if they delay their dental treatments [1, 3, 8]. Oral health affects an individual’s quality of life and even self-esteem. The individual’s self-esteem may compromise due to dental problems because of the anxiety [9].
According to Saatchi et al., the most important reason for the development of dental anxiety is negative dental experiences in the past [10]. High dental anxiety affects physicians when creating a treatment plan. Dentists should allocate more time for these patients. Listening to the patient’s complaint before the treatment and giving detailed information about the treatment are also effective to diminish these negative effects because such concerns make the treatment difficult for both the patient and the physician [1].
However, studies show that dentists do not adequately perform screening for this anxiety. It was detected in a previous study conducted on dentists that only 20% of them regularly screen the anxiety level of their patients [10]. Numerous scales were developed for this purpose. The most frequently preferred anxiety scales, especially in adults may be listed as Dental Fear Questionnaire, Dental Anxiety Scale (DAS), Modified Dental Anxiety Scale (MDAS), Corah Dental Anxiety Scale and State-Trait Anxiety Inventory [6,9,12]. A study on 1392 individuals in England concluded that MDAS had a higher reliability in patients [13]. In previous studies conducted on the Turkish population, MDAS was found to be reliable if a value of ≥19 is accepted as the intersection point, as in our study [14, 15]. In this study, we aimed to measure the level of dental anxiety in adults in the Sudan Nyala region, DAS and MDAS were used in the light of these studies to determine the anxiety levels of the patients.
Material and Methods
Following approval from the ethics committee of Sudan Nyala Training and Research Hospital, 104 patients were informed about the study and their written consents were obtained from the Dental Clinic of Nyala Training and Research Hospital between June 2019 and January 2020. Adult volunteer patients without any psychological disorders were enrolled in the study. Patients with anxiety disorder, minors and patients over 65 years of age were excluded. Assistance was obtained from a translator who was fluent in the language of the region while preparing the questionnaire, and care was taken to ensure that the questions were in their own language. In the first part of the questionnaire, demographic data were included and questions related to gender, age, and reason for applying, which were thought to affect the level of dental anxiety were included. In the other part, DAS and MDAS which are commonly used in the evaluation of dental anxiety in adults today were used [12,16,17]. Dental procedures planned were performed on the patients after filling in the questionnaires.
The DAS was developed by Corah in 1969. This scale consisted of four questions with five options related to the patient reactions in different situations. The patients mark the answers that seem closest to them. Options are scored between 1 and 5, and the total score is calculated. A score between 5 and 20 is obtained. It is accepted that as the score increases, the level of dental anxiety increases. Scores at and over 15 indicated the highest level of anxiety. The application is easy and reliable; therefore, its use is widespread. A validity and reliability study of the scale was performed [18].
MDAS was created by adding a question to the DAS about the injection. The scoring method is the same as for DAS. Two studies conducted in Turkey demonstrated that the scale is valid and reliable [14,15].
After filling out the questionnaire forms, statistical analyzes were carried out with the help of the SPSS version 17.0 program. Consistency with normal distribution was evaluated with histogram graphics and the Kolmogorov-Smirnov test. Mean, standard deviation, and median values were used in descriptive analyses. Pearson’s Chi-Square test was used when evaluating categorical variables. While the non-normally distributed (nonparametric) variables were evaluated between the two groups, they were evaluated with the Mann-Whitney U test. Evaluation between multiple groups more than two was made with the Kruskal-Wallis test. Any p-value below 0.05 was accepted as statistically significant.
Results
The present study included 104 individuals, including 43 (41.35%) males and 61 (58.65%) females with ages ranging between 20 and 57 years. The number of people who find it fun to have a dentist appointment on the DAS scale and wait impatiently was 54; however, the number of people who stated that they would be afraid of this situation was only 1 person. On the other hand, there were 36 people who stated that waiting in the waiting room would not disturb them; only 9 people stated that they would be very worried. While there were 36 people who stated that the dentist would not be disturbed by the use of a rotatory head tool during dental procedures, there were 33 people who stated that they would be very worried. Forty-three people said that they would not be disturbed by the head used in dental cleaning; however, there were 10 people who said that it would make them feel very bad (Table 1).
Considering the effect of age variable on anxiety, the average age of those who are not worried because they have a dentist appointment is higher than those who are less worried. It was observed that the age variable did not cause a significant difference in the answers given to the other questions (Table 2).
When the effect of the gender variable on anxiety was examined, it was detected that the dentist appointment caused less anxiety in men when compared to women, and women had higher anxiety about a painful experience. On the other hand, the use of a rotating head device (aerator) by the dentist makes men more uncomfortable than women. Similarly, women feel less anxiety about the tool used during tooth cleaning compared to men. No significant results could be obtained when comparing the genders regarding the other questions (Table 3).
Discussion
It was concluded in many studies that the anxiety experienced during dental practices affects the oral health and quality of life of the person [19].
In our study, we aimed to evaluate the level of anxiety observed among residents of the region.
A higher dental anxiety value was reached in 7% of the individuals who participated in our study. It was reported that the dental anxiety value evaluated with MDAS in Turkey was 8.8% [14]. Dental anxiety was evaluated with MDAS in UK and was found to be 19 % [16]. A previous study conducted in Hong Kong reported the dental anxiety rate as 12.5% [20]. This situation shows us that dental anxiety situation varies according to geographical regions.
Many patients experience varying degrees of anxiety prior to dental practice. Oral surgery practices are particularly associated with a high level of anxiety (Olson S. A Examination of Dental Distress and Anxiety-Related Vulnerability Factors. University of Mississippi. 2018.). Sanikop et al. listed the factors most associated with increasing levels of dental anxiety as follows: the use of rotating head instruments and local anesthesia procedure. In our study, the use of a rotary tool is similar to this study in terms of leading to anxiety in individuals. However, individuals in our study stated that local anesthesia applications did not worry them [3].
Ozcelik et al. and Sanikop et al. stated that the long time spent in the waiting room before treatment may increase this anxiety, it was observed in our study that the time spent in the waiting room did not have an increasing effect on dental anxiety [1, 3].
In the present study, men were more courageous for going to their appointments than women. There are many studies addressing those women who have higher dental anxiety; however, in our study, women were more anxious about going to an appointment, they seemed to be more fearless about the procedures to be performed [21]. When male and female individuals were examined, it was seen that results such as tooth polishing, which is performed with rotary tools and more aesthetically, are less of a concern for women. We can attribute this to the courage of women in aesthetic practices. However, it was concluded in consideration of the general population that the patients were not worried about procedures such as filling or calculus removal and they were eager for these treatments (p>0.05). Considering the difficulty of accessing dental treatments in this region, we can say that their anxiety does not prevent them from having dental procedures.
Conclusion
As a result of the research, it was observed that approximately 7% of the patients who have been referred to the dental clinic had a higher level of dental anxiety. Gender, age, and the instruments chosen during dental treatment may cause a change in this anxiety. In the light of these results, dental anxiety continues to exist in the whole society to an undeniable extent; however, it was observed that it does not affect the desire for dental treatment in geographies where it is difficult to reach treatment. These studies should be conducted on large patient series in wider geographies. The responsibility of dentists is to determine the dental anxiety of individuals and make appropriate treatment plans.
Limitations
The main limitations of this study include a lack of questioning past dental experiences, conducting the study on a limited number of people, and getting help from an interpreter for communication.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Glucose-to-potassium ratio: A novel index associated with the clinical status in acute coronary syndrome patients
Ferit Boyuk 1, Serhat Caliskan 2, Rumeysa Yigen 3
1 Department of Cardiology, Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, 2 Department of Cardiology, Bahçelievler State Hospital, 3 Depertmant of Emergency Medicine, Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.21200 Received: 2022-04-21 Accepted: 2022-06-18 Published Online: 2022-07-02 Printed: 2022-09-01 Ann Clin Anal Med 2022;13(9):1031-1035
Corresponding Author: Ferit Boyuk, Belgrad Kapı Yolu Caddesi, Kazlisesme Mahallesi, No: 1, Zeytinburnu, Istanbul, Turkey. E-mail: doctorferit.fbyk@gmail.com P: +90 212 409 02 00 F: +90 212 409 22 10 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2313-1495
Aim: Acute coronary syndrome is the foremost cause of death in the world. Hyperglycemia and hypokalemia have been found to be associated with poor prognosis in ACS. In this study, we aimed to assess the diagnostic value of GPR in ACS.
Material and Methods: The study was designed as a retrospective cross-sectional clinical cohort study of patients with ACS. A total of 169 participants were enrolled in the research and divided into two groups: ACS (n:88) and Control (n:81). GPR was calculated by dividing serum glucose by potassium levels and its results were compared with Troponin, WBC, and NEU.
Results: Troponin was measured as 2261.76±3629.42 in the ACS group and found to be higher than in the Control group (4.8±3.11) (p=0.001). WBC (100±83,5 to 30,9±42,7mg/L; p=0,0001) and Neutrophil (49,5±11,9 to 34,8±7,3 mm Hg; p=0,0001) were found to be increased in the ACS group. GPR strongly increased in the ACS group compared to controls (25.61 to 24.15; p=0.001). GPR showed stronger diagnostic value (AUC: 0.97; p=0.001; Sensitivity: %92; Specificity: %86; Cut-off: 24.09).
Discussion: GPR as a novel and cheap marker, which can be useful for the diagnostic differentiation of ACS, but weaker than troponin and better than WBC and Neutrophil count.
Keywords: Acute Coronary Syndrome, Glucose-to-Potassium Ratio, WBC, Neutrophils
Introduction
Acute coronary syndrome (ACS) is the main cause of death in the world. ACS can be defined as a spectrum between unstable angina and acute myocardial infarction. In acute coronary syndrome, coronary plaque ruptures and a platelet-rich thrombus forms. Coronary blood flow in the myocardium decreases and myocardial ischemia develops. The severity and duration of the imbalance between oxygen supply and demand results in reversible myocardial ischemia (unstable angina) or irreversible myocardial damage (AMI) [1, 2].
Many studies have shown that hyperglycemia is a major problem in critically ill patients, even if they are not diabetic. Epidemiological studies have shown that 25-50% of hospitalized acute coronary syndrome patients have hyperglycemia. Studies have shown that the prognosis is different between diabetic and non-diabetic patients with hyperglycemia during acute coronary syndrome. It has been observed that the frequency of adverse events is higher in diabetics with hyperglycemia in those diagnosed with ACS than in those without diabetes mellitus [3-5].
In the case of acute coronary syndrome, increased sympathetic activity activates the sodium potassium pump, and this causes extracellular potassium to be taken into the cell, causing hypopotassemia [6]. Even mild hypopotassemia is associated with poor prognosis in those with cardiovascular disease. Hypopotassemia has been associated with poor prognosis in patients with heart failure. In patients hospitalized with acute myocardial infarction, ventricular arrhythmia and cardiac arrest rates were found to be higher in patients with hypopotassemia at admission [7, 8].
Hyperglycemia and hypopotassemia appear to be an important problem during acute coronary syndrome. Although many indices have been suggested recently to determine the severity of acute coronary syndrome, research continues on tests that will be useful in rapid, practical and prognostic determination. Recently, studies have been published showing that the glucose/potassium ratio, which is a new index, will be useful in many acute clinical situations [9]. In our study, we aimed to investigate whether the glucose/potassium ratio, which we think would be cheap, easy and prognostic, could be useful in determining the severity of acute coronary syndrome.
Material and Methods
Before starting, the study protocol was approved by the local ethics committee of our hospital (Date: 17/05/2021, No: 2021-10-21)
Study design
The study was designed as a retrospective cross-sectional clinical cohort study, which compared patients with ACS according to the ESC guidelines in the emergency department (n=88) with the control group (n=81).
The data of the participants that included demographic information (age and gender), medication use and previous illness were collected from the electronic medical health records.
Patients whose condition was caused by changes in glucose and potassium levels due to medication or comorbidities such as ischemic heart disease (11), diabetes diagnosis and related pharmaceuticals (19), acute kidney failure (5) and corrupted potassium levels as a result of previous medication (7) were excluded from this study.
Laboratory Data
All patients with chest pain underwent atraumatic venipuncture, and venous blood samples were tested, including glucose, potassium, cardiac troponins, and other blood components, EDTA tube was used in the process. The complete blood count measurement, including differential biochemical parameters was worked on autoanalyzers (Mindray BC 6800, China), Cobos 6000 (Roche Diagnostics, USA), respectively. Glucose Potassium Ratio was determined using MS Excell by dividing the glucose level by the potassium level.
Statistical Analyses
SPSS (Statistical Package for the Social Sciences) 24.0 program was used for statistical analysis. While evaluating the study data, the Mann-Whitney U test was used in the two-group comparisons of the descriptive statistical methods (Mean, Standard Deviation, Median, Frequency, Ratio, Minimum, Maximum), as well as an independent sample t, and also the Mann- Whitney U test was used for non-normally distributed parameters in the comparison of two groups. One Way Anova test was used in comparisons of three or more normally distributed groups, and the Kruskal-Wallis test was used in comparisons of three or more groups that did not show a normal distribution. The Bonferroni correction test was used in cases where there was a difference between the groups. ROC CURVE test was used to calculate the sensitivity and specificity values according to the groups (cut-off). Significance was evaluated at p<0.01 and p<0.05 levels.
Results
In the demographic evaluation of the patients, there was no difference in main factors such as age and gender, as shown in Table-1. Thus, it was accepted that demographics did not have a biased effect on the study (Table-1).
Total cholesterol values and LDL values did not show statistically significant differences between the groups (p>0.05).
The glucose/potassium ratio shows statistically significant differences between the groups (p=0.001; p<0.01). According to the pairwise comparisons, it was found that the glucose/potassium values of the control group were lower than those in the Non-ST myocardial infarction (NSTEMI) (p=0.001) group and those in the ST elevation myocardial infarction (STEMI) (p=0.001) group.
HDL values showed statistically significant differences between the groups (p=0.001; p<0.01). According to the pairwise comparisons, it was found that HDL values were lower in the control group, NSTEMI (p=0.008) group and STEMI (p=0.007) group (Table-2).
Troponin values showed statistically significant differences between the groups (p=0.001; p<0.01). According to the paired comparisons, it was found that those in the control group had lower troponin values than those in the non-st (p=0.001) group and those in the st (p=0.001) group. It was found that those in the non-st group had lower troponin values than those in the st group (p=0.001) (Table-3).
Total cholesterol values did not show statistically significant difference between the groups (p>0.05).
Glucose/potassium values show statistically significant differences between the groups (p=0.001; p<0.01). Glucose/potassium values of those with acute coronary syndrome (ACS) were found to be higher than in the control group (Figure-1).
HDL values show statistically significant differences between the groups (p=0.001; p<0.01). HDL values of those in the ACS groups were found to be lower than in the control group.
LDL values differed statistically significantly between the groups (p=0.047; p<0.05). LDL values of those in the ACS groups were found to be higher than in the control group.
Troponin values showed statistically significant differences according to the groups (p=0.001; p<0.01). Troponin values of those in the ACS groups were found to be higher than in the control group.
Cut-off according to Glucose/Potassium ratio
Sensitivity and specificity values are calculated for the positivity limit (cut-off). The value with the highest specificity rate is determined as the cut off value (Figure-2). The cut-off value in determining the diagnosis according to the glucose/potassium ratio was 24.09 with a sensitivity of 92% and specificity of 86%.
Discussion
In our study, we determined that the glucose/potassium ratio would be useful in determining the severity of acute coronary syndrome. Our study is regarded as the first study conducted when looking at the available literature. Stress-induced hyperglycemia (SIH) is observed in many critical clinical situations. Hyperglycemia is a common clinical picture in the stress environment of acute coronary syndrome [10]. As a result of many observational studies, it has been observed that hyperglycemia is frequently observed in patients hospitalized with acute coronary syndrome, even without a diagnosis of diabetes [11, 12].
Although SIH is frequently associated with adverse outcomes in patients admitted to the hospital with ACS, there is still no clear definition for SIH. In the literature, blood glucose measured in the first 24 hours in patients hospitalized with ACS is the recommended method for sanitation, but there is still no common consensus on this issue. The cut-point used for hyperglycemia in patients presenting with ACS varies from study to study. The American Heart Association recommends that a cut-point blood glucose value above 140 mg/dl can be taken under certain conditions. This recommendation of the American Heart Association is based on retrospective observational studies [13].. In an observational study by Kosiborod et al, 30-day and 1-year mortality increased significantly in non-diabetic patients with acute coronary syndrome at glucose levels of 110-140 mg/dl, whereas mortality increased at blood glucose levels >240 mg/dl in diabetics [14]. According to the results of the CARDINAL study, 30-day mortality increased significantly in patients with blood glucose >140 mg/dl at admission [15]. In the study by Capes et al., in their meta-analysis, which included 15 studies, in-hospital death rate was found to be 3.9 times higher in non-diabetics with blood glucose values >110 at admission. On the other hand, in-hospital mortality increased when the blood glucose level was >180 in diabetics [10]. When we look at the observational studies, hyperglycemia has been found to be associated with adverse events in patients presenting with acute coronary syndrome, but the cut-point could not be clearly defined, and the cut-point was seen to differ significantly between diabetic and non-diabetic patients [16].
Serum potassium level is regulated by the ATP-Na/K pump on the cell surface. An increase in the level of stress hormones in acute clinical events activates this pump, and potassium entry from extracellular to intracellular increases [17]. During an acute coronary syndrome, increased stress hormones and consequent hyperglycemia, increased intracellular K uptake, and insulin secretion will have clinical consequences. GPR, a new index recently described, has been associated with many clinical conditions [18]. Matano et al. found a strong relationship between GPR and vasospasm in patients with cerebral infarction [19]. In a study of patients with subarachnoid hemorrhage, GPR with both rather than glucose or potassium alone showed better bleeding status [20].
In our study, we aimed to investigate whether the GPR differs between the patients with acute coronary syndrome and the control group, considering the troponin, ck and ckmb levels. The similarity of the two groups decreased the bias rate. As expected in our study, trop, ck and ckmb levels were significantly higher in the axis group. GPR level was found to be high in the acute coronary syndrome group in correlation with trop, ck and ckmb levels. Our study showed that GPR is an inexpensive and easy indicator of acute coronary syndrome, which will both shed light on future prospective studies and guide the treatment approach.
Our study had some limitations. First of all, the study was designed retrospectively. HBA1c, insulin, glucagon hormone levels and cortisol levels of the patients included in the study were not checked, which can be counted as a limitation. The number of patients included in the study was limited and the study was conducted in a single center. Despite all these limitations, it is important because it is the first study to investigate the relationship between GPR and ACS. Our study will shed light on future multicenter and prospective studies.
Conclusion
In our study, GPR was found considerably higher in the group of patients with ACS, alike Troponin, WBC, NEU. GPR was more meaningful than WBC, NEU and weaker than Troponin as a diagnostic value. We can conclude that GPR may be a new diagnostic parameter in the cases of ACS after further investigation.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Download attachments: 10.4328:ACAM.21200
Ferit Boyuk, Serhat Caliskan, Rumeysa Yigen. Glucose-to-potassium ratio: A novel index associated with the clinical status in acute coronary syndrome patients. Ann Clin Anal Med 2022;13(9):1031-1035
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Relationship between plasma omentin-1 levels and newly diagnosed Stage I hypertension
Mehmet Ozyasar 1, Alim Erdem 2
1 Department of Cardiology, Konya City Hospital, Konya, 2 Department of Cardiology, Faculty of Medicine, Abant Izzet Baysal University, Bolu, Turkey
DOI: 10.4328/ACAM.21201 Received: 2022-04-21 Accepted: 2022-06-17 Published Online: 2022-06-18 Printed: 2022-09-01 Ann Clin Anal Med 2022;13(9):1036-1039
Corresponding Author: Mehmet Ozyasar, Department of Cardiology, Konya City Hospital, Konya, Turkey. E-mail: ozyasar33@gmail.com P: +90 332 310 50 00 / +90 505 732 85 62 F: +90 332 310 50 50 Corresponding Author ORCID ID: https://orcid.org/0000-0001-5227-1716
Aim: Omentin-1 is an adipose tissue-derived cytokine with unknown biological function. The impact of omentin-1 on hypertension has been questioned due to its relation to obesity. This study is aimed to investigate omentin-1 levels in hypertensive patients.
Material and Methods: A prospective, case-control study evaluated patients admitted to outpatient cardiology clinics between January 2012 and December 2013. We designed two groups: the patient group comprised hypertensive patients with newly diagnosed stage-1 hypertension, and the control group comprised normotensive patients. The demographic and anthropometric characteristics and laboratory parameters of the patients in both groups were recorded. Plasma levels of omentin-1 were the primary outcome in this study.
Results: Patient group consisted of 52 hypertensive patients, whereas the control group consisted of 36 patients without hypertension. There was no significant difference between the groups in terms of demographic and clinical characteristics (p>0.05). The median omentin-1 level of the patient group was higher than that of the control group (756.2 ng/mL vs. 664.4 ng/mL); however, the difference was insignificant (p=0.161).
Discussion: The findings of this study did not suggest a significant relationship between the plasma omentin-1 levels and the newly diagnosed Stage I hypertension.
Keywords: Hypertension, Adipokines, Omentin
Introduction
Omentin-1 is the major circulating isoform of an adipose tissue-derived cytokine (adipokine) expressed in the visceral adipose tissue [1]. The biological function of omentin-1 is mainly unknown; however, it has been reported to play a role in promoting insulin-mediated glucose transport in human adipocytes, and vasodilatation of blood vessels occurs [2, 3]. The fact that overweight and obese people have low levels of omentin-1 led to the hypothesis that omentin-1 may be directly related to several metabolic, endocrine, and cardiovascular diseases associated with diabetes [2].
Hypertension, smoking, diabetes, and hyperlipidemia are the risk factors for the development of coronary artery disease [4]. Given its close association with diabetes and its anti-atherogenic properties, it has been speculated that omentin-1 may function as a biomarker in the context of the development of coronary artery disease, acute myocardial infarction, atrial fibrillation, and hypertension [4-8].
The findings regarding the omentin-1 levels in atherosclerotic and hypertensive patients in the literature are contradictory. There are studies that reported low levels of omentin-1 as well as studies that reported high levels of omentin-1 [9-11]. A negative correlation of omentin-1 concentrations with waist circumference, insulin resistance, and body mass index (BMI) has been shown [6]. To date, there is no study that comprehensively investigated any possible relation between omentin-1 and hypertension. In this context, the objective of this study is to investigate and compare the plasma levels of omentin-1 in hypertensive patients and healthy normotensive subjects in view of the hypothesis that low levels of omentin-1 are associated with hypertension.
Material and Methods
Study Design
This study was designed as a prospective, case-control analysis of the plasma omentin-1 levels in hypertensive patients and control subjects. The local ethics committee approved the study (Abant Izzet Baysal University, Ethics Committee for Clinical Studies, 20.12.2012/465). Written informed consent was obtained from the patients and the control subjects. The study was carried out in accordance with the Declaration of Helsinki.
Population and Sample
The study population comprised all patients admitted to the outpatient clinics of Abant Izzet Baysal University, Faculty of Medicine, Turkey, Department of Cardiology. The patient group comprised all consecutive patients above 18 years of age with a newly diagnosed stage I hypertension. The diagnostic criteria for stage I hypertension based on the 2017 American College of Cardiology (ACC) and American Heart Association (AHA) guidelines were as follows: systolic blood pressure of 130 to 139 mmHg or diastolic blood pressure of 80 to 89 mmHg [12]. Patients with significant cardiac pathologies such as coronary artery disease, valvular heart disease, atrial fibrillation, secondary hypertension, and congestive heart failure (ejection fraction <45%), as well as patients with chronic inflammatory and rheumatoid diseases, diabetes mellitus, cerebrovascular diseases, chronic renal failure, a body mass index (BMI) ≥ 30 kg/m2, who were actively smoking, and had anti-hypertensive treatment were not included in the study. The control group consisted of normotensive individuals randomly selected from the outpatient clinic admissions without any clinical cardiological diagnosis in the same period.
Measurements and Variables
Blood pressure measurements of the patient and control groups were performed twice in the outpatient room between 08.00 and 10.00 AM after they had rest for at least 10 minutes. The mean blood pressure value was regarded as the cut-off value for inclusion in the control group [6]. Peripheral blood samples to measure omentin-1 levels were taken after the patients fasted overnight. The samples were centrifuged for ten minutes at 4000 ppm and then stored in a deep freezer at – 22C˚. The plasma concentration of omentin-1 (ng/ml) was measured using a commercially available ELISA (enzyme-linked immunosorbent assay) kit (BioVendor serum/plasma omentin-1, Brno, Czech Republic).
Demographic and anthropometric characteristics of the patients (age, gender, BMI, and waist circumference) were recorded. Patients’ waist circumferences were measured at the mid-level between the lower rib margin and the iliac crest [13]. The laboratory tests included the measurement of the complete blood count, biochemical analysis (fasting blood glucose, urea, creatinine, sodium, potassium, aspartate aminotransferase, alanine aminotransferase levels), lipid profile (cholesterol, high-density lipoprotein, low-density lipoprotein, triglyceride levels), and the measurement of the serum thyroid-stimulating hormone (TSH) levels. Hypertensive patients were evaluated using conventional and M-mode echocardiography (GE Healthcare, Vivid S6 Echocardiography).
Statistical Analysis
The plasma levels of omentin-1 were the primary outcome in this study. In this context, omentin-1 levels of hypertensive patients and normotensive control subjects were compared.
Descriptive statistics were expressed as mean ± standard deviation and median with minimum-maximum values in the case of continuous variables and depending on whether they conform to normal distribution. Categorical variables were expressed as numbers and percentages. Shapiro-Wilk, Kolmogorov-Smirnov, and Anderson-Darling tests were used to determine whether the numerical variables conform to normal distribution or not.
The Independent Samples t-test was used to compare two independent groups in the case of numerical variables that conform to normal distribution; otherwise, the Mann-Whitney U test was used.
Pearson’s Chi-Squared test was used to compare differences between categorical variables in 2×2 tables.
For statistical analysis, “Jamovi project (2020), Jamovi (Version 2.0.0.0) [Computer Software] (Retrieved from https://www.jamovi.org) and JASP (Version 0.15) (Retrieved from https://jasp-stats.org) were used. In all statistical analyses, the significance level (p-value) was set at 0.05.
Results
The patient group consisted of 52 hypertensive patients, whereas the control group consisted of 36 patients without hypertension. The demographic and clinical characteristics of the patients are given in Table 1. The mean age of the patient group was higher than that of the control group; however, the difference was not statistically significant (p=0.241). There was also no statistical difference between the groups in terms of gender, BMI, and waist circumference (p>0.05).
The echocardiographic measurements of the hypertensive patients are summarized in Table 2. The mean ejection fraction was determined as 62.2 ± 3.5%.
The results of the laboratory tests are summarized in Table 3. There was no significant difference between the groups in laboratory parameters. The median omentin-1 levels were determined as 664.4 ng/mL and 756.2 ng/ml in the control and patient groups, respectively. The difference between the omentin-1 levels of the groups was insignificant (p=0.161).
Discussion
The findings of this study revealed no significant relationship between plasma omentin-1 levels and the newly diagnosed stage 1 hypertension. There was also no indication of a physiological impact of omentin-1 on the complex interactions that lead to the development of hypertension.
Previous studies have focused on the relationship of omentin-1 levels with several endocrine diseases, including diabetes, metabolic syndrome, obesity [4, 9, 14]. Lower omentin-1 levels were associated with diabetes and its complications. The impact of omentin-1 on the development and progression of cardiac diseases such as myocardial infarction, coronary artery disease, carotid atherosclerosis has also been studied [1, 7, 15, 16]. The omentin-1 levels were found to be significantly lower in patients with the said diseases [1, 4, 7, 9, 15]. Baig et al. [7] demonstrated that omentin-1 is an independent risk factor for the development of myocardial infarction. A negative correlation has been reported between the omentin-1 levels and the severity of coronary artery disease [17]. It is the belief of the authors of this study that clinically significant endocrine and coronary diseases, i.e., diabetes with diabetic complications, metabolic syndrome with atherosclerosis, and angiographically diagnosed coronary artery disease, are significantly associated with lower levels of omentin-1. Nevertheless, the nature and extent of this association are not clear. Thus, prospective studies are needed to clarify whether omentin-1 is involved in the pathogeneses of these studies or whether it is an end-product generated secondary to such diseases.
The results of the relevant animal studies revealed that omentin-1 has a vasodilating effect on the isolated blood vessels mediated via the endothelium-derived nitric oxide [2]. Lower levels of omentin-1 would be expected in hypertensive patients considering the action mechanism of omentin-1. Celik et al. [6] reported decreased omentin-1 levels in hypertensive patients. Nevertheless, contrary to this study, they included both the patients with stage 1 and stage II hypertension in their study and found the lowest levels of omentin-1 in Stage II patients. They attributed this finding to the endothelial dysfunction, which was determined to be positively correlated with the hypertension stage [18]. Sanlialp et al. [14] speculated that omentin-1 level might be a reliable predictive factor for the development of metabolic syndrome in hypertensive patients. They evaluated all hypertensive patients in respect of the coexistence of metabolic syndrome.
Contrary to the results of the above-mentioned studies, [6, 14] Cinemre et al. [11] found higher omentin-1levels in the patients with stage I to stage 3 hypertension than in the healthy control subjects. In comparison, there was no difference between the omentin-1 levels of hypertensive patients and the control subjects in this study. It is possible that the severity and duration of hypertension in patients included in this study were insufficient to obtain the desired outcomes. Thus, large-scale prospective studies are needed to clarify the impact of omentin-1 on the development of hypertension.
Several authors have suggested that gender is effective on omentin-1 levels. In parallel, Liu et al. [1] demonstrated higher omentin-1 levels in women with metabolic syndrome. The differences between the serum levels of patients of different genders reported in the literature are contradictory [19]. In one of these studies, a population-based study conducted with 864 unselected middle-aged, elderly adults, Onat et al. [13] found that the lower omentin-1 levels were associated with lower systolic blood pressure, HbA1c, and glucose levels. Additionally, they found that omentin-1 was an independent predictive factor for hypertension and diabetes, yet only in male patients. Systolic blood pressure values were 128.6 ± 17, 134±21, and 134±21 mmHg in adults with tertiles of omentin-1 from 1 to 3. There was no significant difference in diastolic blood pressure measurements. Therefore, these findings should be considered as a piece of pathophysiological evidence without hypertension’s clinical significance. Contrary to the findings reported in other studies, no correlation was found between gender and omentin-1 levels in the patient and control groups in this study [14]. It is possible that the differences between the characteristics of the study samples have led to such conflicting outcomes.
Study Limitation
The study’s small sample size and single-center study design were its primary limitations. Secondly, only the repeated office blood pressure measurements were used to diagnose hypertension. The 24-h ambulatory blood pressure monitoring could be of more help in terms of getting better results.
Conclusion
In conclusion, the findings of this study did not suggest a significant relationship between the plasma omentin-1 levels and the newly diagnosed Stage I hypertension. Further studies with extensive and diverse samples are needed to verify the findings of this study.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Liu R, Wang X, Bu P. Omentin-1 is associated with carotid atherosclerosis in patients with metabolic syndrome. Diabetes Res Clin Pract. 2011;93(1):21-5.
2. Yamawaki H, Tsubaki N, Mukohda M, Okada M, Hara Y. Omentin, a novel adipokine, induces vasodilation in rat isolated blood vessels. Biochem Biophys Res Commun. 2010;393(4):668-72.
3. Tan BK, Adya R, Randeva HS. Omentin: A Novel Link Between Inflammation, Diabesity, and Cardiovascular Disease. Trends Cardiovasc Med. 2010;20(5):143-8.
4. Eimal Latif AH, Anwar S, Gautham KS, Kadurei F, Ojo RO, Hafizyar F, et al. Association of Plasma Omentin-1 Levels With Diabetes and Its Complications. Cureus. 2021;13(9):e18203.
5. Lin S, Li X, Zhang J, Zhang Y. Omentin-1: Protective impact on ischemic stroke via ameliorating atherosclerosis. Clin Chim Acta. 2021;517:31-40.
6. Çelik M, Nar R, Nar G, Sökmen E, Günver G. Serum omentin-1 levels in hypertensive patients. J Hum Hypertens. 2021;35(3):290-5.
7. Baig M, Alghalayini KW, Gazzaz ZJ, Atta H. Association of Serum Omentin-1, Chemerin, and Leptin with Acute Myocardial Infarction and its Risk Factors. Pak J Med Sci. 2020;36(6):1183-8.
8. Chen Y, Liu F, Han F, Lv L, Tang CE, Xie Z, et al. Omentin-1 is associated with atrial fibrillation in patients with cardiac valve disease. BMC Cardiovasc Disord. 2020;20(1):214.
9. Biscetti F, Nardella E, Rando MM, Cecchini AL, Angelini F, Cina A, et al. Association between omentin-1 and major cardiovascular events after lower extremity endovascular revascularization in diabetic patients: A prospective cohort study. Cardiovasc Diabetol. 2020;19(1):170.
10. Askin L, Duman H, Ozyıldız A, Tanriverdi O, Turkmen S. Association between Omentin-1 and Coronary Artery Disease: Pathogenesis and Clinical Research. Curr Cardiol Rev. 2020;16(3):198-201.
11. Serinkan Cinemre FB, Cinemre H, Bahtiyar N, Kahyaoğlu B, Ağaç MT, Shundo H, et al. Apelin, Omentin-1, and Vaspin in patients with essential hypertension: association of adipokines with trace elements, inflammatory cytokines, and oxidative damage markers. Ir J Med Sci. 2021;190(1):97-106.
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13. Onat A, Ademoglu E, Karadeniz Y, Can G, Uzun AO, Simsek B, et al. Population-based serum omentin-1 levels: Paradoxical association with cardiometabolic disorders primarily in men. Biomark Med. 2018;12(2):141-9.
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Retrospective evaluation of hemicolectomies in obstructive colon tumors: A single center experience
Metin Yalcin 1, Serdar Oter 2
1 Department of General Surgery, Antalya Training and Research Hospital, Antalya, 2 Department of Gastroenterological Surgery, Manisa City Hospital, Manisa, Turkey
DOI: 10.4328/ACAM.21205 Received: 2022-04-23 Accepted: 2022-06-21 Published Online: 2022-06-22 Printed: 2022-09-01 Ann Clin Anal Med 2022;13(9):1040-1042
Corresponding Author: Metin Yalcin, Department of General Surgery, Antalya Training and Research Hospital, Antalya, Turkey. E-mail: drmetinyalcin@hotmail.com P: +90 535 585 61 63 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2843-3556
Aim: The most common complications of colon cancer requiring emergency surgery are perforation and obstruction; 15-40% of patients with colon cancer initially show these conditions. The aim of this study is to evaluate clinical findings and perioperative outcomes of colon cancer patients who were emergently operated for obstruction in our center.
Material and Methods: After obtaining local ethical committee’s approval, a retrospective study was designed. Patients who underwent emergent surgery for obstructive colon cancer in our clinic were evaluated between February 2009 and February 2020.
Results: A total of 79 patients were included in the study. Forty (50.63%) of these patients, were male, 39 (49.37%) were female, and the mean age was 54.55 ±17.95 years (min-max: 17-87 years). In the postoperative period, according to the Clavien-Dindo classification, 12 (15.18%) complications were grade 1-2 and 9 (11.39%) were grade 3 and above. Postoperative wound infection was observed in 10 patients. Anastomotic leak was detected in only 2 patients. Totally 5 patients (6.32%) died during the first 30 days. The cause of mortality was sepsis in the early postoperative period in two patients, massive pulmonary embolism in two patients and myocardial infarction in one patient.
Discussion: Obstructive colon cancers requiring emergency surgery constitute a more challenging group than the elective surgery patient group. Our study showed that good results can be achieved in this group in terms of postoperative complications and early mortality.
Single-stage resection and anastomosis surgery can be safely preferred instead of the Hartman procedure in the selected patient group with left colon tumors.
Keywords: Hemicolectomy, Obstructive Colon Tumors, Early Mortality, Results
Introduction
The most common complications of colon cancer requiring emergency surgery are perforation and obstruction; 15-40% of patients with colon cancer initially show these conditions [1].
The rate of obstructive colon tumors requiring surgery has been reported to be 15-30% [2]. The mortality rate in patients of this group is 10%. In the elderly population, this rate was 22 % [3].
In the literature, it is seen that it is associated with higher complication rates and poor survival rates in patients who underwent emergency surgery compared to elective surgery. It is not clear whether the short survival is due to inadequate surgery or the advanced stage of the tumor [4,5]
The aim of this study is to evaluate clinical findings and perioperative outcomes of colon cancer patients who were emergently operated for obstruction in our center.
Material and Methods
After obtaining ethical approval, a retrospective study was designed. Patients who underwent emergent surgery for obstructive colon cancer in our clinic were evaluated between February 2009 and February 2020. Informed consent was taken from all patients. The study was approved by the Ethics Committee of the Medical Faculty of … University (Date: 06/09/2021; Decision No: HHRU/21.15.38).
Inclusion criteria: Patients over 18 years of age underwent emergency surgery for an obstructed colon tumor.
Exclusion criteria: Emergency cases, colon surgery performed for benign reasons, colon surgery due to other cancer involvements, rectal cancer patients, patients with missing data and metastatic colon cancer patients.
Demographic, clinical findings and perioperative outcomes of the patients were evaluated.
The time of drain removal, peroperative amount of blood loss, postoperative hospital stay, tumor localization, stage of tumor, lymph node status, complication in postoperative period, state of the early mortality, and cause of early mortality were retrospectively collected and evaluated.
Statistical Analysis
Data were analyzed with SPSS 21.0 for Windows (SPSS, IBM). Quantitative data were presented as mean±standard deviation (SD) and qualitative data were presented as number and percentage.
Results
A total of 79 patients were included in the study. Forty (50.63%) of the patients who underwent emergent hemicolectomy for obstructed colon tumor were male, 39 (49.37%) were female, and the mean age was 54.55 ±17.95 years (min-max: 17-87 years). Demographic and clinical findings of the patients are summarized in Table 1. The most common comorbid disease was hypertension (50.63%) and the second was diabetes mellitus with 34.4%. The mean operative time was 140 ± 90 (min-max: 50-240) minutes. At least one drain was placed in the abdomen in all patients.
The drains were removed in an average of 6.4 (5-8) days postoperatively. The blood loss during the operation was 250 ± 150 ml. The mean postoperative hospital stay was 8.17 ± 6.71 days.
Caecum and ascending colon were the most common tumor localizations in 35 (44.30%), patients, the second localization was sigmoid colon in 20 (25.31%) patients (Table 2). The tumor type was reported as adenocarcinoma in all cases. T3 or T4 stage cancers were seen in 74 (93.67%) patients, 12 or more lymph nodes were extracted in the specimen in 63 (79.74%) patients, and pN2 was present in 22 (27.84%) patients. Protective ileostomy or colostomy was performed in 34 (43.03%) patients. In the postoperative period, according to the Clavien-Dindo classification 12 (15.18%) complications were grade 1-2 and 9 (11.39%) were grade 3 and above. Postoperative wound infection was observed in 10 patients. All wound infections healed with drainage, dressing of the wound and antibiotics. Anastomotic leak was detected in only 2 patients. The patients were re-operated and a permanent colostomy was performed for these patients on the fifth postoperative fifth day. Totally 5 patients (6.32%) died during the first 30 days. The cause of mortality was sepsis in the early postoperative period in two patients, massive pulmonary embolism in two patients and myocardial infarction in one patient.
Discussion
Complicated colon cancer surgery has poor outcomes than elective colon tumor surgery. The two main factors for this entity are occlusion and perforation of the colon. In the literature, bowel obstruction in the tumor area is associated with poor survival [6-8]. In our study, both morbidity and early mortality rates were found to be high in patients who underwent emergency surgery for obstructed colon cancer. The advanced stage of the tumor in patients with obstruction of the colon has a great effect on this poor prognosis.
Previous literature has revealed that obstructed colon cancer is associated with an increased incidence of distant metastases disease; on the contrary, metastatic disease was detected in only 1 patient in our study [9,10]. Patient characteristics, subsequent patient and physician delays, tumor biology, and patient immune factors may influence our results to differ from other studies.
The type of surgery to be performed as an emergency surgery for colon cancer may differ depending on patient-related factors, tumor location, tumor-related findings in the operation, and surgical experience [11]. In this study, the reason why almost all of the cases were operated using the open method was the poor medical condition, especially the high ASA values, the surgical equipment facilities of the hospital, and the co-morbidities in the elderly group.
In tumors located on the right side of the colon, causing obstruction, primary anastomosis or end ileostomy (41.4% (n=78)) surgery was preferred after right hemicolectomy. The incidence of leaks detected in cases with anastomosis after resection is 2.53% (n=2), which is consistent with the literature [12]. Obstruction is the most common complication in colon tumors originating from the left colon. In our study, unlike the literature, obstructive tumors were also observed numerically more in the right colon [13].
Hartmann end colostomy procedure, which is used in emergency surgery instead of anastomosis, completely eliminates the risk of anastomotic leakage. It is applied in left-sided colon tumors, especially in tumors that are obstructive and caused advanced dilatation in the proximal colon segments. However, current literature suggested that one-stage resection and anastomosis, which will be performed in accordance with oncological principles, can be safely applied even in complicated cases [14].
In our study, one-stage resection and anastomosis were preferred instead of the Hartman procedure in the selected patient group with left colon tumor, and anastomotic leakage was not observed in any patient.
Limitations of our study; Since it is a retrospective study and a single-center experience, the number of cases is low.
Conclusion
Obstructive colon cancers requiring emergency surgery constitute a more challenging group than the elective surgery patient group. Our study showed that good results can be achieved in this group in terms of postoperative complications and early mortality.
Single-stage resection and anastomosis surgery can be safely preferred instead of the Hartman procedure in the selected patient group for left colon tumors.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Biondo S, Martí-Ragué J, Kreisler E, Parés D, Martín A, Navarro M, et al. A prospective study of outcomes of emergency and elective surgeries for complicated colonic cancer. Am J Surg. 2005;189(4):377-83.
2. Demiral G, Sagiroğlu S, Bayraktar O, Demiral G, Sağıroğlu J, Bayraktar O. Colorectal stenting for palliation and as a bridge to surgery: A 5-year follow-up study. World J Gastroenterol. 2015;21(31):9373-9.
3. Costa G, Frezza B, Fransvea P, Massa G, Ferri M, Mercantini P, et al. Clinico-pathological features of colon cancer patients undergoing emergency surgery: a comparison between elderly and non-elderly patients. Open Med (Wars). 2019;14: 726-34.
4. Skala K, Gervaz P, Buchs N, I Inan, M Secic, B Mugnier-Konrad, et al. Risk factors for mortality-morbidity after emergency colorectal surgery. Int J Colorectal Dis. 2009; 24(3): 311–16.
5. Bayar B, Yılmaz KB, Akıncı M, Şahin A, Kulaçoğlu H. An evaluation of treatment results of emergency versus elective surgery in colorectal cancer patients. Ulus Cerrahi Derg. 2015;32(1):11-17.
6. Chen TM, Huang YT, Wang GC. Outcome of colon cancer initially presenting as colon perforation and obstruction. World J Surg Oncol. 2017;15(1):164.
7. Banaszkiewicz Z, Woda L, Tojek K, Jarmocik P, Jawien A. Colorectal cancer with intestinal perforation—a retrospective analysis of treatment outcomes. Contemp Oncol (Pozn). 2014;18(6):414-18.
8. Boeding JRE, Ramphal W, Crolla RMPH, Boonman-de Winter LJM, Gobardhan PD, Schreinemakers JMJ. Ileus caused by obstructing colorectal cancer-impact on long-term survival. Int J Colorectal Dis. 2018;33(10):1393-400.
9. Sibio S, Di Giorgio A, D’Ugo S, G Palmieri, L Cinelli, V Formica, et al. Histotype influences emergency presentation and prognosis in colon cancer surgery. Langenbecks Arch Surg. 2019;404(7):841-51.
10. Cortet M, Grimault A, Cheynel N, Lepage C, Bouvier AM, Faivre J. Patterns of recurrence of obstructing colon cancers after surgery for cure: a population-based study Colorectal Dis. 2013;15(9):1100-6.
11. Balducci L, Aapro M. Complicated and complex: helping the older patient with cancer to exit the labyrinth. J Geriatr Oncol. 2014;5(1):116-18.
12. Hsu TC. Comparison of one-stage resection and anastomosis of acute complete obstruction of left and right colon. Am J Surg. 2005;189(4):384-7.
13. Tan KK, Sim R. Surgery for obstructed colorectal malignancy in an Asian population: predictors of morbidity and comparison between left- and right-sided cancers. J Gastrointest Surg. 2010;14(2):295-302.
14. Webster PJ, Aldoori J, Burke DA. Optimal management of malignant left-sided large bowel obstruction: do international guidelines agree? World J Emerg Surg. 2019;14:23.
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Metin Yalcin, Serdar Oter. Retrospective evaluation of hemicolectomies in obstructive colon tumors: A single center experience. Ann Clin Anal Med 2022;13(9):1040-1042
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How should we enter peritoneum in vaginal hysterectomy?
Emine Türen Demir, Hasan Energin
Department of Obstetrics and Gynecology, Faculty of Medicine, Necmettin Erbakan University, Konya, Türkiye
DOI: 10.4328/ACAM.21206 Received: 2022-04-25 Accepted: 2022-06-20 Published Online: 2022-06-21 Printed: 2022-09-01 Ann Clin Anal Med 2022;13(9):1043-1046
Corresponding Author: Emine Türen Demir, Abdulhamid Han Caddesi, Hocacihan Mahallesi, No: 3, 42080, Konya, Türkiye. E-mail: eturen1@hotmail.com P: +90 332 323 64 15 Corresponding Author ORCID ID: https://orcid.org/0000-0001-5510-4411
Aim: Anterior and posterior entrances to the peritoneal cavity are essential steps in vaginal hysterectomy. The objective of this study was to compare surgical techniques and results in women who had primarily anterior colpotomy or primarily posterior colpotomy to enter the peritoneum in vaginal hysterectomy.
Material and Methods: We analyzed the data of 90 women who underwent vaginal hysterectomy by the same surgical team in a university hospital between 2017 and 2021. The patients have divided into two groups: primarily anterior colpotomy or primarily posterior colpotomy. Operation time, amount of bleeding, and complication rates were compared between the two groups.
Results: First anterior colpotomy was performed in 44 patients, and the first colpotomy posterior was performed in 46 patients. Patient characteristics were similar in both groups. The mean age of the patients was 63.6±8.6 years, and the mean number of pregnancies was 3.07±1.05. The mean preoperative and postoperative hemoglobin difference was 1.5±0.6 g/dl. The mean uterine length was 9.33±2.07 cm, and the mean uterine weight was calculated as 118.1±42.2 g. The operation time was significantly shorter in the first colpotomy posterior group (67.5±7.7 min vs. 78.1±12.6 min p<0.05). While no significant complications were observed in the first posterior colpotomy group, one bladder injury was observed in the first anterior colpotomy group.
Discussion: In a vaginal hysterectomy, when posterior colpotomy is performed first, Entrance into the peritoneal cavity is safer and quicker. Thus, surgeons feel more comfortable and secure while performing a vaginal hysterectomy and return to abdominal procedures minimally.
Keywords: Vaginal Hysterectomy, Anterior Colpotomy, Posterior Colpotomy, Peritoneal Reflection
Introduction
Hysterectomy is one of the most frequently performed operations in women [1]. It can be abdominal (AH), laparoscopic (LH), or vaginal (VH). Vaginal hysterectomy has better results and fewer complication rates than other methods and is the first method preferred in suitable patients [2,3]. However, nowadays, vaginal hysterectomies are gradually decreasing due to the increasing use of laparoscopy, the decrease in vaginal hysterectomy experience, and technical difficulties. In vaginal hysterectomy, unlike AH and LH, colpotomy is performed first, and the round ligament is ligated last. Classically, a circular incision is made around the cervix. The peritoneum is opened after the bladder dissection with anterior and posterior colpotomy. The uterosacral and cardinal ligament complex is clamped, and hysterectomy is started. Opening the peritoneum is a critical step in vaginal hysterectomy, and failure at this stage may result in conversion to laparotomy or laparoscopy. Our study aimed to compare surgical techniques and results of women who had primarily anterior colpotomy or posterior colpotomy at this critical stage and thus increase the frequency of vaginal hysterectomy.
Material and Methods
Ninety patients who underwent vaginal hysterectomy by the same surgical team for benign gynecological reasons in the university hospital between 2017 and 2021 were included in this study. Vaginal hysterectomy was performed on patients who met the following criteria: Pubic arch greater than 90 degrees, uterine descent is present, and uterine size is less than 12 weeks of size. Perineoplasty was also performed routinely in all patients who underwent vaginal hysterectomy. Vaginal hysterectomy was not preferred in patients with suspected malignancy, endometriosis, and no uterine descent. Patient files were scanned retrospectively, and the demographic characteristics of the patients, indications for surgery, uterine dimensions, operation times, and preoperative and postoperative hemoglobin differences were noted. Uterine weight was estimated sonographically using the formula of Harb and Adam: weight (g) = 50+(4/3 x π(Pi) x L/2 x W/2 x AP/2), where (L) is the length of the uterus from the dome of the fundus to the level of the external os, (W) is the maximum width of the uterus at the level of the cornea, and (AP) is the anteroposterior diameter of the uterus [4]. The patients were divided into two groups: those who underwent anterior colpotomy first and those who underwent posterior colpotomy first, and it was compared whether there was a difference between the two groups in terms of the operation time, amount of bleeding, and complications.
The ethics committee of university approved the protocol of this study.
Surgical Technique
The patients were placed in the dorsal lithotomy position under spinal anesthesia. A Foley catheter was placed in the bladder to prevent bladder injury. The cervix was held with a tenaculum, and a circular incision was made around the cervix at the level of the cervicovaginal junction.
In patients who primarily underwent anterior colpotomy, the uterus was pulled down, the anterior surface of the vaginal mucosa was held and stretched, and sharp and blunt dissection was performed to separate the vaginal mucosa from the cervical stroma until anterior peritoneal reflection was observed. The peritoneum was found, the peritoneal cavity was entered sharply, and a Deaver retractor was placed in the peritoneal cavity to protect the bladder. Afterward, the peritoneum was found by holding and stretching the vaginal epithelium with an Allis clamp from the posterior part of the incision made around the cervix. The peritoneal cavity was entered sharply. Then hysterectomy was started.
In patients who underwent posterior colpotomy first, the uterus was pulled upwards after a circular incision was made around the cervix. The peritoneum was found by holding and stretching the posterior vaginal epithelium with an Allis clamp. Once the posterior cul-de-sac was clear, the peritoneal cavity was entered sharply. The vesicouterine space was reached after the incision was widened by sliding the index and middle fingers over the uterus. When the fingertips were felt on the anterior peritoneum, the bladder was pushed bluntly to make the peritoneum visible on the fingertips.
A small incision was made between two fingers with scissors, and a Deaver retractor was inserted into the peritoneal cavity. Then hysterectomy was started.
Statistics
SPSS 23 software (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. All tests were two-sided, and p-values < 0.05 were considered statistically significant. Continuous variables were given as mean, standard deviation (SD), and categorical variables were given as the number of patients and percentages. The Kolmogorov-Smirnov test was used to evaluate the normal distribution of variables. The χ2 test was used to analyze categorical variables, the t-test was used for normally distributed variables, and the Mann-Whitney U test was used for abnormally distributed variables.
Results
Ninety patients were included in the study. The patients were divided into two groups according to the order of colpotomy; first anterior colpotomy and first posterior colpotomy. While colpotomy anterior was performed first in 44 patients to enter the peritoneum, colpotomy posterior was first performed in 46 patients.
The mean age of the patients was 63.6±8.6 years, the mean number of pregnancies was 3.07±1.05. The mean operation time was 72.7±11.6 minutes, and the mean preoperative and postoperative hemoglobin difference was 1.5±0.6 g/dl. The average uterine length was 9.33±2.07 cm, and the mean uterine weight was calculated as 118.1±42.2 g; 21.1% of the patients had DM and asthma. VH was performed in 76 (84.4%) patients for pelvic organ prolapse, while 14 (15.6%) patients underwent VH due to abnormal uterine bleeding; 25.6% of the patients had a history of previous pelvic surgery, of which 18.9% a cesarean section.
According to the International Continence Society POP-Q classification [5], the degree of uterine prolapse was staged. In this system, pelvic organ prolapse is divided into five stages. No prolapse could be demonstrated in stage 0. In stage 1, the most distal point of the prolapse is 1 cm above the hymen level. In stage 2, the most distal point of the prolapsus is 1 cm distal or proximal to the hymen level. In stage 3, the most distal point of the prolapse is more than 1 cm distal to the hymen level. In stage 4, there is a total eversion of the lower genital tract. According to this staging system, 33 patients (36.7%) had stage 4, 18 patients (20%) had stage 3, 30 patients (33.3%) had stage 2, and 9 patients (10%) had stage 1 uterine prolapse (the demographic characteristics of the two groups are compared in Table 1.). The operation time was significantly shorter in the first colpotomy posterior group (67.5±7.7 min vs. 78.1±12.6 min p<0.05). The operative time, hemoglobin difference and ultrasound variables between the two groups are shown in Table 2. Duration of the operation was not only affected by the priority of colpotomy but also inversely proportional to the degree of prolapse (p<0.05). While no major complications were observed in the first posterior colpotomy group, one bladder injury was observed in the first anterior colpotomy group.
Discussion
While the vaginal approach is the most recommended hysterectomy option with low complication rates and proven advantages, it is being applied with decreasing frequency [6-8]. Although laparoscopic-assisted vaginal hysterectomy, total laparoscopic hysterectomy, and robotic-assisted hysterectomy show similar recovery times, complications, and patient comfort, the cost of the vaginal approach is more affordable [7,9-11]. According to a secondary analysis of the United States National Surgical Quality Improvement Program Database, which included 161,626 women undergoing vaginal or laparoscopic hysterectomy between 2008 and 2018, vaginal hysterectomy rates decreased from 51 to 13 percent, while total laparoscopic hysterectomy rates increased from 12 to 68 percent [12].Increasing use of laparoscopy, insufficient training, and surgical experience have been blamed for decreasing vaginal hysterectomy rates [13-15]. In the survey study conducted in the United States to determine the attitudes of gynecologists towards hysterectomy and barriers to minimally invasive hysterectomy applications, the main barriers to performing VH were technical difficulty, the potential for complications, and caseload of VH [16]. One of the critical points in vaginal hysterectomy is the opening of the peritoneum. Peritoneal reflection may be higher than expected, especially in patients with cervical elongation.
In addition, the scar between the bladder and uterus in patients with a previous cesarean section may make anterior peritoneal access more complicated. This may cause bladder injury during dissection and bleeding from the bladder column due to the dissection shifting too much laterally. In our study, methods of entry into the peritoneum, which is one of the most critical steps of VH, were compared to increase VH frequency. It was found that the operation time was significantly shorter in the group in which the first colpotomy was performed posteriorly, and this is due to the surgeon not losing much time for bladder dissection. After entering the peritoneum with a posterior colpotomy, the vesicouterine junction is made visible, and the anterior peritoneum is entered more securely, which makes the surgeon feel confident during a vaginal hysterectomy. Thus, even complex cases will be completed vaginally without the need to return to laparotomy. Bladder injuries are most common during vaginal hysterectomy with a prevalence of 2% [17-19]. The risk of bladder injury is increased in women with previous pelvic and bladder surgery, including cesarean section. Bowel injuries were reported in 0.4% of women who underwent VH [20]. In our study, bladder and bowel injuries were not observed in 46 patients who underwent the first posterior colpotomy.
Conclusion
In a vaginal hysterectomy, when posterior colpotomy is performed first, it is entered into the peritoneal cavity more safely and quickly. Thus, surgeons feel more comfortable and safer while performing a vaginal hysterectomy and return to abdominal procedures minimally.
The study’s limitations are its retrospective nature and small number of cases. Randomized controlled studies with a large number of cohorts are needed in this regard.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Wright JD, Herzog TJ, Tsui J, Ananth CV, Lewin SN, Lu YS, et al. Nationwide trends in the performance of inpatient hysterectomy in the United States. Obstet Gynecol. 2013;122(2):233-41.
2. No authors listed. Committee Opinion No 701: Choosing the Route of Hysterectomy for Benign Disease. Obstet Gynecol. 2017;129(6):155-9.
3. Aarts JW, Nieboer TE, Johnson N, Tavender E, Garry R, Mol BW, et al. Surgical approach to hysterectomy for benign gynaecological disease. Cochrane Database Syst Rev. 2015; 8:CD003677. DOI: 10.1002/14651858.CD003677.pub5.
4. Harb TS, Adam RA. Predicting uterine weight before hysterectomy: ultrasound measurements versus clinical assessment. Am J Obstet Gynecol. 2005;193(6):2122-5.
5. Persu C, Chapple CR, Cauni V, Gutue S, Geavlete P. Pelvic Organ Prolapse Quantification System (POP-Q) – a new era in pelvic prolapse staging. J Med Life. 2011;4(1):75-81.
6. Moen MD, Richter HE. Vaginal hysterectomy: past, present, and future. Int Urogynecol J. 2014;25(9):1161-5.
7. Dayaratna S, Goldberg J, Harrington C, Leiby BE, McNeil JM. Hospital costs of total vaginal hysterectomy compared with other minimally invasive hysterectomy. Am J Obstet Gynecol. 2014;210(2):120.e1-6.
8. Gressel GM, Potts JR 3rd, Cha S, Valea FA, Banks E. Hysterectomy Route and Numbers Reported by Graduating Residents in Obstetrics and Gynecology Training Programs. Obstet Gynecol. 2020;135(2):268-273.
9. Sandberg EM, Twijnstra ARH, Driessen SRC, Jansen FW. Total Laparoscopic Hysterectomy Versus Vaginal Hysterectomy: A Systematic Review and Meta-Analysis. J Minim Invasive Gynecol. 2017;24(2):206-17.e22.
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Infantile Esotropia: Clinical features and surgical outcomes
Sule Bahadir Coskun, Nazife Sefi Yurdakul, Ahmet Maden
Department of Ophthalmology, Izmir Ataturk Training and Research Hospital, Izmir, Turkey
DOI: 10.4328/ACAM.21207 Received: 2022-04-25 Accepted: 2022-06-20 Published Online: 2022-06-21 Printed: 2022-09-01 Ann Clin Anal Med 2022;13(9):1047-1051
Corresponding Author: Sule Bahadir Coskun, Basın Sitesi, Atatürk Eğitim ve Araştırma Hastanesi, 35360 Karabağlar, İzmir, Türkiye. E-mail: sulebcoskun@yahoo.com.tr P: +90 232 243 43 43 Corresponding Author ORCID ID: https://orcid.org/0000-0003-1713-899X
Aim: The objective of this study was to investigate clinical features and surgical outcomes of Infantile esotropia (IET) patients and to evaluate the effect of surgery age on binocular function.
Material and Methods: A total of 28 patients who underwent surgery were enrolled. Medical history of the patients was received, and the age of IET onset, prenatal history, family history and ocular therapies performed (closure therapy, using eyeglasses) were recorded. After cover-uncover test, patients’ deviation angles were determined utilizing prism cover test using an accommodative target for far/near. Visual acuity was evaluated according to the optotypes, objects or fixation on the Snellen chart depending on the cooperation of the patients. Bilateral medial rectus recession was applied in all patients.
Results: The mean age of IET onset was determined as 2.11±2.18 months. Patients’ age of surgery differed between 10 months and 25 years with a mean age of 5.3±6.1 years. In all patients, the preoperative amount of the far deviation was 48.39±1.06 PD (25-80 PD) and preoperative amount of near deviation was 48.57±12.97 PD (25-80 PD). Twenty-six patients first underwent bilateral medial rectus recession (maximum: 6.5 mm). When pre- and postoperative deviation angles were compared, postoperative deviation angles were significantly improved (p<0.05).
Discussion: The most appropriate time for surgery in IET cases should be taken as the earliest time when the amount of deviation can be accurately determined, refractive errors should be determined before and after surgery in all cases, treatment of amblyopia and early completion of surgical correction should be aimed at gaining binocular functions.
Keywords: Infantile Esotropia, Visual Acuity, Strabismus, Binocularity, Amblyopia
Introduction
Strabismus is a misalignment of the eyes in which the visual axes deviate from bifoveal fixation. It can be divided into esotropia and exotropia. Infantile Esotropia (IET) is defined as the onset of constant strabismus in children less than 6 months of age. The incidence of IET is 1%, making it an important issue for pediatric ophthalmologists [1]. It can be congenital or acquired, intermittent or constant and may change patterns from intermittent to constant over time. In a meta-analysis, Hashemi et al. estimated the prevalence of IET as 0.77% [2].
A detailed history and physical exam are essential for all patients with esotropia presenting to the outpatient clinic. Medical history should include patients’ age, onset of deviation, constant/intermittent and unilateral/alternating IETs. In addition, abnormal head posture, headaches, complaint of closing one eye in bright sunlight, and complaint of double vision should also be considered when receiving history [3]. In IET, children typically have a large angle of deviation, usually greater than 30 degrees. In children with IET, visual acuity or retinoscopy values are in general within normal range because of cross fixation, and no significant underlying refractive errors are expected [4]. However, there is still no consensus on the pathogenesis of IET and numerous studies have been performed about the treatment of this disorder. The widely adopted option is to treat IET as early as possible in order to obtain good motor and sensory results [5].
IET produces a convergent squint in a neurologically normal child. If a child with IET is not corrected timely, this wide-angle esotropia can affect life-long vision [6]. The ideal timing for surgery in patients with IET is not clear. In patients with IET, the ideal time for surgery is between 6 months and 2 years of age. The decision for surgery is based on the measurement of squint. The preference of surgery is also made by physician’s discretion. Since the presence of amblyopia affects the surgery success negatively, it must be detected and treated postoperatively. Complications of IET surgery include residual esotropia, infection, suturing induced granuloma, anterior segment ischemia or lost muscle [7]. In addition, complications related to general anesthesia should also be taken into account in these patients.
The objective of this study was to investigate clinical features and surgical outcomes of IET patients and to evaluate the effect of surgery age on binocular function.
Material and Methods
This retrospective study included patients diagnosed with IET in the Strabismus Unit of the 1st Eye Clinic of the Ministry of Health, Izmir Ataturk Training and Research Hospital. A total of 28 patients who underwent surgery were enrolled.
Patients’ informed consent forms were waived since the study was retrospectively designed. However, the necessary permission was obtained from the hospital management for using archive files. The study was performed in accordance with the relevant ethical principles of the Declaration of Helsinki.
The age and gender of the patients were recorded at the time of physical exams. Medical history of the patients was received, and the age of IET onset, prenatal history, family history and ocular therapies performed (closure therapy, using eyeglasses) were recorded. The cases were included in the study where strabismus was known to have started before 6 months of age, based on the history taken from the families and the patients and information obtained from the old photographs. Since obtaining a medical history from the patients who presented late was difficult, cases in which strabismus started under 6 months of age were also included if they carried other features of IET.
All patients underwent anterior segment examination. Cyclopentolate of 1% was dropped 3 times with 10-minute intervals, and after waiting for 45 minutes to achieve cycloplegia and pupil dilation, fundus examination and skiascopy were performed. Cycloplegia was provided with cyclopentolate 0.5% in infants. After cover-uncover test, patients’ deviation angles were determined utilizing prism cover test using accommodative target for far/near. In whom we could not perform these tests, the amount of deviation was determined with the Krimsky test. Titmus and Worth 4-point tests were applied to the patients who could cooperate. Patients who could see the butterfly in the titmus test (3000 sec/arch) were considered to have stereopsis. Visual acuity was evaluated according to the optotypes, objects or fixation on the Snellen chart depending on the cooperation of the patients. The presence of amblyopia was accepted in patients with 2 or more lines of visual loss on the Snellen chart. Following glasses and closure treatment administered according to the result of cycloplegic refraction, alternation was provided and surgery was scheduled. Deviation angle was measured at least three times preoperatively. The amount of the surgery performed was calculated taking into account the amount of deviation and clinical features of the patients.
The patients were operated under local or general anesthesia according to age and coordination. Bilateral medial rectus recession was applied in all patients. In cases where the procedure was insufficient, resection of the lateral rectus was performed as the second surgery. Standard medial rectus recession and lateral rectus resection when necessary were performed through limbal incision. Inferior oblique myectomy was performed in the patients who developed inferior oblique hyperfunction (IOHF) and superior rectus recession in those who developed dissociated vertical deviation (DVD). 6/0 polyglactin (Vicryl) was used as the suturing material. All measurements were made at the insertion point of the muscles.
Antibiotic and steroid drops were applied 4 times a day for 5 days postoperatively to all patients. After the 1st, 10th days and 1st month, the patients were followed for a minimum of 6 months and a maximum of 48 months. The amount of deviation was re-evaluated postoperatively. In the follow-up, esotropia or exotropia cases with a deviation of 10 PD or less were considered successful, while cases with a deviation of more than 10 PD were considered unsuccessful.
Statistical Analysis
The data obtained in this study were statistically analyzed using SPSS version 13.0 (SPSS, Statistical Package for Social Sciences, IBM Inc., Armonk, NY, USA). Study data were expressed with descriptive statistical methods (mean ± standard deviation), and quantitative data were compared using Student’s t-test. Qualitative variables were compared with the Chi-square test. P<0.05 values were considered statistically significant.
Results
A total of 28 patients operated due to IET were included in the study. The mean age at the time of admission was 5.07±6.24 years (4 months – 25 years). Of the 28 patients, 15 (53.60%) were boys and 13 (46.40%) were girls. No statistically significant difference was found in terms of gender. The mean postoperative follow-up duration was 1.73±0.95 years (6 months – 4years).
The mean age of IET onset was determined as 2.11±2.18 months. Family history was questioned in IET patients. Of all patients, 14.29% had a family history of IET, while 85.71% had not. Three (10.71%) patients had a history of preterm, while medical history was unremarkable in the remaining 25 (89.29%) patients.
Patients’ age of surgery differed between 10 months and 25 years with a mean age of 5.3±6.1 years (Figure 1).
In all patients, the preoperative amount of the far deviation was 48.39±1.06 PD (25-80 PD) and the preoperative amount of near deviation was 48.57±12.97 PD (25-80 PD) (Figure 2). Twenty-six patients first underwent bilateral medial rectus recession (maximum: 6.5 mm). One patient underwent unilateral recession and resection and one patient had medial rectus recession and bilateral inferior oblique myectomy as the first operation. Four (14.29%) patients were operated for the second time on average 21.00±17.34 months after the first operation. These interventions were performed for residual esotropia and IOHF and carried out as resection to the lateral rectus and/or inferior oblique myectomy.
Two patients underwent two and two patients three operations. Horizontal deviation angle of 10 PD and below was accepted as the success criterion in the post-surgical examination performed from a distance of 6 meters. After the surgical correction, deviation angle was found as ≤10 PD in 22 patients, 10-20 PD in 3 patients and >20 PD in 3 patients (Figure 3).
When pre- and postoperative deviation angles were compared, postoperative deviation angles were significantly improved (p<0.05).
As a result of the surgeries, 22 patients (78.57%) were orthophoric, 4 patients were esotropic (12.28%), and 2 patients (7.15%) were exotropic (Table 1).
Preoperative refraction values were ≤ +2.00 D in 14 (50%) patients, between +2.5 and 5.00 D in 8 (28.57%) patients, emmetropia in 4 (14.29%) patients, >5 D in one (3.57%) patient and myopia in one (3.57%) patient.
Postoperative refraction values were ≤ +2.00 D in 15 (53.57%) patients, emmetropia in 4 (14.29%) patients, between +2.5 and 5.00 D in 6 (21.43%) patients, >5 D in two (7.14%) patients and myopia in one (3.57%) patient.
IET was accompanied by amblyopia in 15 (53.57%) patients, DVD in 4 (14.29%) patients, and IOHF in 8 (28.56%) patients with being bilateral in 3 (10.71%) patients and unilateral in 5 (17.85%) patients.
Binocular functions could be evaluated in 23 (82.14%) of 28 cases. In the evaluation performed with titmus tests, there was no binocularity postoperatively in 14 (60.86%) of these 23 patients. These patients were evaluated as the patients operated before 2 years of age, 2-4 years of age and after 4 years of age. Binocularity could not be evaluated in 3 of 6 patients who were operated before the age of 2 years. In the other 2, stereo acuity was detected at 3000 sec/arc level. Ten of 12 patients between the ages of 2 and 4 who were operated on could be evaluated. Stereo acuity of 3000 sec/arc was detected in 4 of 10 patients. Stereo acuity of 3000 sec/arch was detected in 3 of 10 patients who were operated after the age of four. No statistically significant difference was found between these patient groups in terms of the development of binocularity. There was a statistically significant difference between the 1st group and the 3rd group in terms of binocular vision (p=0.045).
Medial rectus recession was adjusted according to the deviation angles of the patients. According to the success criteria of 10 PD and below, a successful outcome was achieved with the first surgery in 20 patients (Table 2).
Discussion
IET is a fixed wide-angle nonaccommodative esotropia with an unexplained etiology, which is not accompanied by neurological findings, and occurs in the first 6 months of life [8]. It is inevitable that the binocular functions will be affected in IET because the deviation develops in the early period when the binocular functions are susceptible to be affected, and because it has a wider angle than other deviation types. Cross-fixation, IOHF, DVD, and latent nystagmus are often associated with IET [9].
The amount of deviation angle is higher in IET compared to the esodeviations occurring in advanced ages [10]. In our study, it was found as 48 PD. This angle was reported as 43 by Rajavi et al [11], 37.3 by Kim et al. [12], and 49 by von Noorden [13].
In the cycloplegic refraction distribution, in our study, hyperopia was found to be +2.0 D or less in 64.29% of cases, between +2.5 and +5.0 D in 28.57% of cases, over +5.0 D in 3.57% of cases, and myopia in 3.57% of cases. The prevalence of hyperopia ≥+4 diopters was 3.2% in the worse eye, with both eyes involved in 64.4% of cases in a study [14].
Vertical deviations and especially IOHF are common findings in IET. IOHF has been reported in the literature between 36-78%. [15, 16]. DVD has been reported to be between 21-90% in the literature [15, 16]. In our study, we found IOHF in 28.56% and DVD in 14.29%. von Noorden et al. found IOHF as 68 % and DVD as 51% in their 408 cases [13].
There is consensus on early surgery for the development of binocular functions in IET [13]. Deepa et al. found reduced stereopsis in 42.6 of 246 cases [17]. In a study published by Xu, normal contrast sensitivity binocular summation ratio in IET after surgical treatment suggest that the ability of the visual cortex in processing binocular information is intact at the contrast threshold level [18], subnormal binocular vision was obtained in 20 (80%) of 24 patients who were operated under the age of 1 year, and similar results were observed in only 40% of those who underwent surgery after 1 year of age. In the study by Yang et al. [19], the mean age of surgery was found to be 78.1 days months in the group with binocular vision. In a study published by the ELISS (Early vs. Late Infantile Strabismus Surgery Study) group, 532 patients were evaluated and stereopsis was observed to be better in patients who underwent surgery at an early age [20]. In a study by Yang et al. there was a significant difference between the age groups in terms of binocular vision [19]. In our study, there was no significant difference in stereopsis between those who underwent surgery before the age of 2 and between the ages of 2 and 4, and those who underwent surgery after the age of 4, but a significant result was obtained when the group who underwent surgery before the age of 2 years and the group who underwent surgery after the age of 4 years were compared in terms of stereopsis. This indicates that surgery should be performed as soon as possible, immediately after correcting the refractive error and amblyopia.
The aim of surgical correction in IET is to bring the eyes to the orthophoric position with a minimum number of surgeries. von Noorden [13] reported that an average of 2.1 surgeries per case were required to re-parallel the eyes with unilateral surgery. Önal et al. [21], in their study comparing the results of symmetric and unilateral surgery, compared the deviation angle differences before and after surgery for two surgery types and found unilateral surgery to be more effective in the treatment of IET.
Bilateral medial rectus recession is a popular surgical method in IET and we prefer to perform bilateral medial rectus recession in our study. We found a success rate of 78% as a result of bilateral medial rectus recession in our study. We did not observe any limitation of adduction or weakness of convergence in any of our cases with bilateral medial rectus recession.
Study Limitations
The major limitations of our study are its retrospective design and being conducted in a single center. In addition, more parameters related to IET could be studied. However, we believe that our results will serve as a guide for future studies on this topic.
Conclusion
In conclusion, the most appropriate time for surgery in IET cases should be taken as the earliest time when the amount of deviation can be accurately determined, refractive errors should be determined before and after surgery in all cases, treatment of amblyopia and early completion of surgical correction should be aimed at gaining binocular functions, albeit limited. For long-term stabilization after surgery, patients should be followed carefully for the development of amblyopia, DVD, primary IOHF and accommodative esotropia.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Sule Bahadir Coskun, Nazife Sefi Yurdakul, Ahmet Maden. Infantile Esotropia: Clinical features and surgical outcomes. Ann Clin Anal Med 2022;13(9):1047-1051
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Predictive power of blood urea nitrogen and albumin ratio for mortality in acute ischemic stroke
Mazlum Kılıç 1, Davut Tekyol 2
1 Department of Emergency Medicine, Fatih Sultan Mehmet Education and Research Hospital, 2 Department of Emergency Medicine, Haydarpaşa Numune Education and Research Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.21328 Received: 2022-07-23 Accepted: 2022-08-25 Published Online: 2022-08-26 Printed: 2022-09-01 Ann Clin Anal Med 2022;13(9):1052-1055
Corresponding Author: Davut Tekyol, Selimiye, Tıbbiye Cd, No:23, 34668, Üsküdar, İstanbul, Türkiye. E-mail: dtekyol56@gmail.com P: +90 530 233 08 82 Corresponding Author ORCID ID: https://orcid.org/0000-0001-9353-6063
Aim: Globally, acute ischemic stroke (AIS) is one of the leading causes of death and permanent disability. The ratio of blood urea nitrogen to serum albumin (BAR) is a prognostic biomarker that combines two important determinants and has excellent predictive potential for mortality in critically sick patients. This study investigated the relationship between BAR and in-hospital mortality in AIS patients diagnosed in the emergency department (ED).
Material and Methods: A retrospective analysis of data of AIS patients aged 18 and older who presented to our emergency department during the study period was performed. Data were acquired from the hospital’s computerized information system. Each discriminant mortality cut-off value was evaluated using the receiver operating characteristic (ROC) curve and area under the curve (AUC).
Results: The study included a total of 300 patients with a mean age of 67.1±14.4 years; 156 (52%) of them were male. The mean length of stay in the hospital was found to be 7 days, and 67 patients were transferred to the intensive care units. Fifteen patients (5%) died during their follow-up in the hospital. As a result of the ROC analysis of BAR to predict the presence of in-hospital mortality, the AUC value was determined as 0.756 (95% confidence interval: 0.704-0.804), the Youden index as 0.47, and the p-value as 0.001. At a cut-off value of >4.21, BAR had a sensitivity of 93.3%, specificity of 54.4%, positive predictive value of 9.7, and negative predictive value of 99.4 in determining the presence of in-hospital mortality.
Discussion: BAR is a simple and useful in-hospital mortality predictor in patients with AIS.
Keywords: Stroke, Albumin, Blood Urea Nitrogen, Mortality
Introduction
Globally, stroke is among the most crucial cause of mortality and long-term disability (available at: https://www.cdc.gov/stroke/facts.htm). In the USA, 795,000 adults die or become disabled due to stroke every year [1], and approximately 77% of stroke cases occur for the first time and 23% are recurrent [2]. Stroke ranks as the fifth leading cause of death in United States, causing approximately 140,000 deaths annually, with an estimated annual effect on health resources (lost work days, healthcare, and treatment) of $46 billion. [1].
The early prediction of poor outcomes following cerebral ischemia might improve decision-making steps, such as early admission to dedicated stroke units, and hence aid in patient management. However, the outcomes of stroke remain difficult to predict. Therefore, various studies have been undertaken to investigate the effects of various scoring systems and blood parameters on the prognosis of stroke [3-5].
The ratio of blood urea nitrogen (BUN) to serum albumin (BAR) is a recently found prognostic biomarker that combines two essential markers (BUN and albumin) and accurately predicts the mortality of critically ill patients [6,7]. BUN is a measure of dehydration in patients, and increased BUN levels have been connected with in-hospital mortality among acute ischemic stroke patients (AIS) [8]. As a negative acute phase reactant, albumin is an important inflammatory marker that plays a role in maintaining osmotic pressure and transporting important molecules in the body [9]. Studies have shown that a low serum albumin level is linked to a negative outcome for people with AIS [10].
This study examined the relationship between BAR and in-hospital mortality in individuals diagnosed with AIS who presented to the emergency department.
Material and Methods
Study design
A tertiary-level hospital’s emergency department was the setting for this retrospective, observational study. The study was conducted between January 1, 2020 and June 1, 2021. Due to the retrospective nature of the investigation, the institutional review board approved the analysis and waived the need for written informed consent (Ethics Committee ruling number: HNEAH-KAEK 2022/72, date: 04.04.2022).
Selection of patients
Patients diagnosed with AIS were identified among individuals over 18 years old who presented to the emergency department during the study period, using the International Classification of Diseases 10th Revision (ICD-10) codes. Patients with a diagnosis other than AIS, those with deficiencies in BUN and/or albumin, those referred from another hospital, and those that died at or were discharged from the emergency were excluded from the research.
Data collection and outcome measurement
The following data were collected by screening each patient’s electronic medical records: age, gender, vital parameters (systolic-diastolic blood pressures, body temperature, and pulse), laboratory parameters, including BUN and albumin, in-hospital mortality, length of hospital stay and admission to the intensive care unit. If an eligible patient presented to the emergency department more than once during the study period, only the data belonging to the first visit were included in the analysis. BAR was determined by dividing the BUN level by the albumin level. The data were entered into an Excel database (Microsoft Corporation, Richmond, WA) and examined by the first researcher. Following analysis of the data, the other researcher made recommendations for enhancing quality. The primary outcome of the study was in-hospital mortality due to all-causes.
Statistical Analysis
Statistical analyses were carried out using IBM SPSS Statistics version 26.0 (SPSS Inc., Chicago, IL, USA) and MedCalc Statistical Software version 19.0.6 (MedCalc Software bvba, Ostend, Belgium). The Chi-square and Mann-Whitney U tests were used for the analysis of categorical and continuous data, respectively. Continuous data were reported as median and interquartile range values. Categorical data were given as frequency and percentages. A p-value that was less than 0.05 was used to indicate statistical significance. The receiver operating characteristic (ROC) analysis was performed using the DeLong method to assess the prognostic performance of BAR. The area under the curve (AUC) was calculated to evaluate the prognostic performance of BAR. Lastly, a Youden’s J index (YJI) calculation was conducted for sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the cut-off value at which AUC was the highest [11].
Results
The study included 300 patients with a mean age of 67.1 ± 14.4 years. There were 156 men and 144 women among the patients. Sixty-seven patients were taken to the hospital’s intensive care units. The mean duration of hospital stay was found to be 7 days. Fifteen patients (5%) died during their follow-up in the hospital.
Table 1 shows the characteristics of the patients included in the study and some laboratory parameters.
The patients were separated as survivors and non-survivors, and their various characteristics were compared (Table 2). When various laboratory values were compared, it was determined that the mean values of BUN, creatinine, C-reactive protein and BAR were statistically higher in the group of non-survivors than the group of survivors (Table 2).
As a result of the ROC analysis of BAR in the prediction of in-hospital mortality, the AUC value was determined as 0.756 (95% confidence interval: 0.704-0.804), YJI as 0.47, and the p- value as 0.001. According to the statistical analysis, BAR had a statistically significant power in predicting the presence of in-hospital mortality (p=0.001). At a cut-off value of >4.21, BAR had 93.3% sensitivity, 54.4% specificity, 9.7 PPV, and 99.4 NPV in the prediction of mortality of AIS patients in the hospital.
Discussion
In this study, we determined that BAR was a good predictor of in-hospital mortality in patients with AIS who presented to the emergency department. There are many studies in the literature investigating BAR as a prognostic predictor. BAR has been linked with negative outcomes in a variety of diseases and conditions, including pneumonia, bacteremia, and gastrointestinal bleeding [12-14]. Previous studies have shown that BAR can be defined as a prognostic marker for patients with AIS [15]. Although the relationship between high BUN levels and in-hospital mortality in patients with AIS has not yet been fully explained, there are some hypotheses concerning the underlying mechanism. First, a high BUN level at the time of hospital admission may be associated with hemodynamic deterioration, which is known to be associated with adverse outcomes in AIS patients [16]. Second, sympathetic nerve activity associated with urea reabsorption may lead to increased BUN after AIS, resulting in increased mortality [17]. Finally, BUN is a marker of hydration status. In case of dehydration, the blood flow to the organs decreases. Reduced blood flow to the brain may also lead to increased mortality in patients with AIS [18].
Albumin is a nutritional and hydration marker [19]. There are various mechanisms that explain the relationship between albumin and prognosis of AIS. It is known that albumin carries various drugs, free fatty acids, hormones, and amino acids in the blood. Thus, it can be suggested that albumin contributes to the improvement of brain perfusion by regulating the colloid osmotic pressure in the blood [20]. Lastly, there are also studies showing that hypoalbuminemia is associated with a high vascular thrombotic risk, emphasizing that albumin may play a role in inhibition of platelet aggregation [21].
Studies examining the correlation between elevated BUN and low albumin levels in predicting the prognosis of AIS can be found in the scientific literature. In a multi-center study, You et al. analyzed the data of 3,355 patients with AIS and concluded that elevated BUN levels at the time of admission to the hospital were independently associated with all-cause in-hospital mortality, but not with poor outcomes at discharge [8]. In a retrospective cohort study by Bae et al., the AUC value of BAR was found to be 0.687 in the prediction of in-hospital mortality in 1,164 patients with AIS [16]. In the same study, the cut-off value of BAR was calculated as 5.25, at which it had a sensitivity of 64.9% and specificity of 67.8% in determining the presence of in-hospital mortality. In our study, the AUC value of BAR was found to be 0.756 in the prediction of in-hospital-mortality in patients with AIS. At a cut-off value of >4.21, BAR had 93.3% sensitivity and 54.4% specificity in this prediction, which is consistent with the data reported in the literature.
This study had certain limitations. First, the results of a single-center study cannot be applied to the general population. Second, due to the retrospective design of the study, the patient data were obtained from the electronic medical records, which may have led to the use of incomplete or erroneous data.
Conclusion
AIS continues to be a leading cause of death and disability worldwide. The admission of patients with AIS to the hospital begins at the emergency departments, and the early recognition of critically ill patients in this department contributes to their prognosis. In this study, we concluded that the BAR value of patients with AIS at the time of presentation to the emergency department had a good performance in predicting in-hospital mortality.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Comparison of intra-abdominal pressure in open surgery and endovascular aortic repair procedures
Sefer Usta 1, Gönül Erkan 2
1 Department of Cardiovasculary Surgery, 2 Department of Anesthesiology and Reanimation, Health Sciences University, Ahi Evren Training and Research Hospital, Trabzon, Turkey
DOI: 10.4328/ACAM.21331 Received: 2022-07-27 Accepted: 2022-08-27 Published Online: 2022-08-29 Printed: 2022-09-01 Ann Clin Anal Med 2022;13(9):1056-1060
Corresponding Author: Sefer Usta, Department of Cardiovasculary Surgery, Health Sciences University, Ahi Evren Training and Research Hospital, Trabzon, Turkey. E-mail: seferusta2000@yahoo.com P: +90 532 252 64 75 F: +90 462 231 04 83 Corresponding Author ORCID ID: https://orcid.org/0000-0003-4988-3978
Aim: Surgery and endovascular aortic repair (EVAR) procedures performed in abdominal aortic aneurysm (AAA) disease can lead to increased intra-abdominal pressure (IAP). In this study, we aimed to determine IAP values in intact infrarenal AAA patients who underwent surgery and the EVAR procedure, and to contribute to the literature with our results.
Material and Methods: Thirty-six patients who underwent open surgery and EVAR treatment for infrarenal AAA between June 2018 and September 2021 were retrospectively analyzed.
The patients were divided into three groups. Group 1: Patients treated with open surgery and no drains; Group 2: Patients treated with open surgery in whom a drain was placed; Group 3: Patients treated with EVAR.
Results: Demographic data and comorbidities of the groups were similar. IAP values were lower in the EVAR procedure group (Group 3) compared to the other groups at each measurement period. This difference was statistically significant, especially at the postoperative 12th, 18th, and 24th hours (p<0.05). Among the groups that underwent open surgery, the postoperative IAP values in Group 2 were lower compared to Group 1.
Discussion: We found that placing a drain in patients undergoing open surgery is more beneficial to prevent IAP increase. However, endovascular surgery was much more effective than open surgical repair in preventing IAP increase.
Keywords: Abdominal Aortic Aneurysm, Intraabdominal Pressure, Endovascular Aortic Repair, Surgery
Introduction
Intraabdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are pathological conditions that occur because of increased intra-abdominal pressure (IAP) and can result in mortality and morbidity. Kron et al. defined ACS as a term in four patients who underwent ruptured abdominal aortic aneurysm repair [1]. In 2004, the World Society of the Abdominal Compartment Syndrome put forward consensus definitions of ACS and IAP. The normal value of IAP was specified as 5-7 mmHg in critical adult patients. Intra-abdominal hypertension (IAH) was defined as IAP≥12 mmHg twice in consecutive measurements. ACS was defined as an acute increase in IAP above 20 mm, end-organ damage, abdominal pain, and improvement in the patient’s condition after decompression [2,3] .
Risk factors for IAH and ACS were categorized into four categories, including decreased compliance of the abdominal wall, increased intraluminal content, increased intraabdominal content, capillary leak, and fluid resuscitation. It is important to know the risk factors that cause IAH and ACS to prevent end-organ damage [4]. One of these causes may be an abdominal aortic aneurysm or rupture. In the literature, there are studies on IAP increase in patients with abdominal aortic pathologies who underwent open surgical repair and endovascular treatment procedure [5-7].
Our study aimed to determine and compare the IAP values of patients who did and did not have drains placed in the open surgical approach and those who underwent EVAR procedure for the treatment of infrarenal AAA, and to contribute to the literature with our results.
Material and Methods
This study was conducted retrospectively in patients who underwent open surgery and EVAR treatment for abdominal aortic aneurysm. Patient data were obtained from the hospital data processing system and patient files. The patients were divided into three groups as follows:
Group 1: Patients treated with open surgery for intact infrarenal AAA in whom no intraabdominal drains were placed during the closure.
Group 2: Patients treated with open surgery for intact infrarenal AAA in whom an intraabdominal drain was placed during the closure.
Group 3: Patients treated with EVAR for intact infrarenal AAA
The groups were compared in terms of demographic data, comorbidities, radiological examination results, and intraabdominal pressure values. Intact infrarenal AAA patients over 18 years of age who underwent open surgery or EVAR were included in the study. Those younger than 18 years of age, patients who had infrarenal AAA rupture and dissection, and those whose data could not be reached were excluded.
Routine Monitoring and Related Parameters
Before starting open surgery or EVAR, the patients were monitored with electrocardiography, and pulse oximetry. The radial artery was catheterized from the nondominant arm for systemic arterial pressure measurement. Central venous pressure values were monitored in patients who had a central catheter inserted into the internal jugular vein using the Seldinger technique. After systemic heparinization, activated coagulation time was measured for anticoagulation follow-up. A Foley urinary catheter was placed in the bladder and urinary output was monitored in all patients. IAP values were measured using an unometer abdo-pressure sterile and noninvasive pressure monitoring system attached behind the bladder catheter (Figure 1). The first IAP was measured before the operation started. Postoperatively, it was performed and recorded sequentially as recommended by the World Society of the Abdominal Compartment Syndrome [2,3]. The sequential measurement time was determined as every six hours [8,9] , at the 6th, 12th, 18th, and 24th hours.
Routine Anesthesia Procedure
In patients undergoing general anesthesia, anesthesia was induced with 1-2 μ/kg fentanyl (Talinat, Vem Pharmaceuticals, Turkey), 2mg/kg propofol (Propofol Fresenius Vial, Germany), and 0.6 mg/kg rocuronium (Myokron, Vem Pharmaceuticals, Turkey) intravenously. After the patients were intubated endotracheally, ventilation was provided with an anesthesia device (Drager Primus, Germany). All patients underwent decompression by inserting a 14 Fr nasogastric tube before surgery. At the end of the surgery, patients with stable hemodynamics and adequate respiratory effort were extubated in the operating room. Patients who could not be extubated were transferred to the intensive care unit intubated.
After providing aseptic conditions in the sitting position for spinal anesthesia, 10-15 mg of heavy bupivacaine (0.5%) was administered with a 25-gauge spinal needle in the lumbar 3-4 or 4-5 interspaces. Patients were sedated by intravenous administration of 0.05-0.1 mg/kg midazolam (Zolamid, Vem Pharmaceuticals, Turkey) to achieve a Ramsey sedation scale of 3-4.
Routine Surgical Procedure
In patients who underwent open surgery, the abdomen was opened with a median incision under general anesthesia and an aortobifemoral or aortoiliac 16×8 Dacron Y graft was placed in all patients after aneurysmectomy. The retroperitoneum was closed with 3/0 vicryl in all patients who underwent open surgery. In some patients who underwent open surgery, before the abdomen was closed, a chest drain was placed above the retroperitoneum when deemed necessary. In patients to be treated with the EVAR procedure, spinal anesthesia and sedation were performed. In the EVAR procedure, after preparation of both femoral arteries, the grafts were inserted into the aneurysm sac, in the infrarenal aorta in the main trunk, and in the contralateral iliac leg. All patients were transferred to the intensive care unit after the procedures were complete.
Statistical Method
SPSS 21.0 (Statistic Inc. version Chicago, IL, USA) software program was used for the statistical analysis of the data. Descriptive statistics were presented as mean ± standard deviation for continuous variables, and the number of patients (%) for nominal variables. Results were considered statistically significant when they were at 95% confidence intervals and when p<0.05.
Results
A total of 36 patients underwent surgery and EVAR procedure for intact infrarenal abdominal aortic aneurysm between June 2018 and September 2021. Eleven patients underwent open surgery without drains (Group 1), eleven underwent open surgery and a drain (Group 2), and 14 patients underwent EVAR (Group 3). Among all, 77.78% (n=28) were males and 22.22% (n=8) were females (p<0.05). The genders did not significantly differ in intergroup comparisons (p>0.05) (Table 1). The mean age of the patients in Groups 1, 2, and 3 were 65.27 ± 3.98 years, 64.54 ± 4.18 years, and 64.79 ± 4.64 years, respectively (p>0.05) (Table 1). The demographic data and comorbidities of the groups are summarized in Table 1.
Preoperative and postoperative IAP measurements of the groups are indicated in Table 2. IAP measurement was lower in the group that underwent the EVAR procedure (Group 3) compared to the other groups at each measurement time. This difference was significant, especially at 12, 18, and 24 hours (p<0.05) (Table 2).
The IAP values in Group 2 were insignificantly lower in the postoperative period than in Group 1 (p>0.05). The IAP value of 20 mmHg, the limit for ACS, was not exceeded at any time in any of the groups (Table 2).
The groups were also compared in terms of postoperative complications and mortality. Respectively, neurological complications were seen in 1 (9.09%) patient in Group 1 and in 1 (9.09%) patient in Group 2, it was not detected in Group 3. Infection was detected in 1 (9.09%) patients in group 1, 2 patients (18.18%) in group 2, and 2 (14.29%) patients in group 3. Bleeding was detected in 1 (9.09%) patient in Group 1, in 3 (27.27%) patients in Group 2, and 2 (14.29%) patients in Group 3. Mortality was detected in 1 (9.09%) patient in Group 1.
Discussion
An abdominal aortic aneurysm is a life-threatening disease characterized by the enlargement of the abdominal aorta. Although it is usually asymptomatic, it has a high mortality rate in case of rupture. Hypertension, smoking, advanced age, and male gender are stated among the risk factors for atherosclerosis [10,11]. Our study patients were also older and had a higher male sex ratio with comorbidities such as hypertension, smoking, and coronary artery disease, which developed because of atherosclerosis.
Endovascular procedure and open surgical repair are treatment methods for abdominal aortic aneurysms [12]. Increased IAP and abdominal compartment syndrome are serious complications that can develop after both an endovascular procedure and open surgical repair. It can be successfully treated with early diagnosis, early conservative treatment to reduce intra-abdominal pressure, and decompression laparotomy if compartment syndrome develops [5].
The guideline published by the World Society of the Abdominal Compartment Syndrome suggests that IAP should be measured through the bladder [2,3]. IAP increase was also defined and classified by the World Society of the Abdominal Compartment Syndrome, with a grade 1 increase indicating an IAP of 12-15 mmHg, a grade 2 increase, an IAP of 16-20 mmHg, a grade 3 increase, an IAP of 21-25 mmHg, and a grade 4 indicating an IAP of >25 mmHg [3,4].
In our clinic, IAP is also measured through the bladder, per the guideline. In our study, the level of IAP increase was grade 1 at 12t, 18t, and 24 hours postoperatively in Group 1, and at 12 and 18 hours postoperatively in Group 2. In Group 3, an IAP increase was not observed at all postoperatively (Table 2). Therefore, the increase in IAP did not exceed grade 1 in any of our groups. In Group 3 patients, who underwent endovascular repair, IAP remained at a normal level at all postoperative measurement times.
In ACS, organ dysfunction develops after significant IAH. The intrathoracic pressure that develops when the diaphragm is pushed cephalad compresses the heart and reduces ventricular compliance and contractility. In addition, reduced venous return decreases cardiac output, which all create cardiac dysfunction [4,13] . Increased intrathoracic pressure also negatively affects the pulmonary system. Alveolar volutrauma occurs when intrathoracic pressure increases, ventilation-perfusion mismatch occurs with increased peak airway pressure, and pulmonary compliance decreases. Total lung capacity and functional residual capacity are limited. Therefore, ventilation decreases due to decreased tidal volume and ventilation failure occurs [4,13]. Decreased renal blood flow and compression of the renal artery, vein, and parenchyma are among the crucial factors contributing to renal dysfunction, which causes a decrease in urine output [4,13]. Developing vascular pathologies lead to the compression of the inferior vena cava and increased systemic vascular pressure, resulting in an increased risk of venous thrombosis, peripheral edema, and venous stasis [4,13]. In cases where the IAP value exceeds 25 mmHg, a laparotomy is recommended for decompression [14].
Rubenstein et al. investigated the relationship between open surgical repair and endovascular repair and ACS in patients diagnosed with a ruptured abdominal aortic aneurysm and found that ACS developed in 6 (21%) of 29 patients who underwent EVAR and 15 (34%) of 44 patients who underwent open repair [5]. In a study on 6612 patients conducted by Ersyrd et al., open surgery and endovascular procedure were performed for abdominal aortic aneurysms and their relationship with ACS was investigated [6]. The study population consisted of 1341 patients (20.3%) with ruptured abdominal aortic aneurysms and 5271 patients (79.7%) with intact abdominal aortic aneurysms. They reported that ACS developed more frequently in patients diagnosed with ruptured abdominal aortic aneurysms. Patients in both groups were also compared in terms of ACS development according to the procedure. The rate of ACS development in patients who underwent open surgery due to ruptured aortic aneurysms was 6.8%, while it was 6.9% in patients who underwent EVAR, and in patients with intact aortic aneurysms, the rate of ACS development was 1.6% in those who underwent open surgery and 0.5% in those who underwent EVAR [6]. In the literature, information has taken its place that significantly less ACS develops in EVAR in intact abdominal aortic aneurysms. In our study, ACS did not develop in any of our patients. However, while the cases in our study were treated due to intact abdominal aortic aneurysm, the cases in the study by Rubenstein et al. had ruptured abdominal aortic syndrome. We think that this is the reason for the development of ACS in the cases of Rubenstein et al. In our study, although ACS did not develop in any of our patients, intra-abdominal pressure values were lower in our patients who underwent the EVAR procedure than in patients who underwent open surgery .
The limitations of our study include the small number of patients compared to the study by Rubenstein et al. and its retrospective nature.
Conclusion
Abdominal aortic surgery and endovascular procedures are two of the main subjects of cardiovascular surgery clinics. We observed that abdominal closure by placing a drain in patients who underwent open surgery for the abdominal aorta is more reliable in terms of IAP values, although not statistically significant. Patients undergoing endovascular treatment for aneurysms are statistically less at risk for increased IAP. We believe that the IAP values, which can be easily obtained non-invasively via the catheter inserted into the bladder, will help surgeons to monitor pressure changes promptly before abdominal compartment syndrome and related organ dysfunctions develop.
Considering the findings that EVAR procedures are safer in terms of IAP increase, we think this treatment method should be preferred, especially in risky patients.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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