October 2022
Hinged prosthesis in the knee revision surgery: Is there a great need?
Mahmut Özdemir 1, Yüksel Uğur Yaradılmış 2, Ahmet Ateş 2, Ali Teoman Evren 2, Mustafa Caner Okkaoğlu 2, Murat Altay 2
1 From Department of Orthopaedics and Traumatology, VM Medikal Park Hospıtal, 2 Department of Orthopaedics and Traumatology, University of Health Sciences, Keçiören Health Practice and Research Center, Ankara, Turkey
DOI: 10.4328/ACAM.20990 Received: 2021-12-10 Accepted: 2022-04-19 Published Online: 2022-09-23 Printed: 2022-10-01 Ann Clin Anal Med 2022;13(10):1061-1065
Corresponding Author: Yüksel Uğur Yaradılmış, Department of Orthopedics and Traumatology, Keçiören Health Practice and Research Center, 06280, Keçiören, Ankara, Turkey. E-mail: ugur_yaradilmis@outlook.com P: +90 532 769 78 02 F: +90 312 356 90 02 Corresponding Author ORCID ID: https://orcid.org/0000-0002-7606-5690
Aims: Two main different prosthesis designs are frequently used in revision surgery: the Constrained condylar knee (CCK) prosthesis and the Rotating hinge knee prostheses (RHK). The aim of this study is to present the successful results of the CCK prosthesis to the literature and compare these results with the RHK design.
Material and Methods: One hundred and ninety patients who underwent total knee revision surgery between February 2014 and October 2018 were retrospectively evaluated. They were classified in terms of age, gender and etiology, and bone defects were evaluated according to the AOIR classification. A total of 148 patients, 129 with CCK and 19 with RHK, were included. Functional results were evaluated with the WOMAC Osteoarthritis Index, and a Likert analysis was applied to measure patient satisfaction.
Results: According to the AORI classification, 34.5% of the patients were type I, 45% were type II, and 20.5% were type III. The mean preoperative WOMAC was 74 ± 9.6 in the CCK group, and 73.6 ± 10.6 in the RHK group postoperatively. In assessing patient satisfaction, t 5-Likert score was 4.2±0.6 in the CCK group, and 4.27±0.4 in the RHK group. There were no statistical differences in WOMAC and Likert analysis between CCK and RHK groups (respectively: p=0.876, p=0.962).
Discussion: CCK design implants provide sufficient successful functional outcomes in all types of bone defects in knee revision surgery. RHK-type prostheses are rarely required and more preferable for AORI type III bone loss.
Keywords: Knee Arthroplasty, Revision, Hinged Prosthesis, Constrained Prosthesis, Survivorship
Introduction
The number of patients who underwent total knee arthroplasty is increasing worldwide and the need for revision also increases at the same rate. Recent projections expect the number of knee replacements performed in the United States to grow by about 673% in 2005 to 2030 [1]. The increase in primary and revision surgeries not only decreases patient satisfaction but also creates a significant increase in health expenditures [2,3]. Re-revision rates are higher than the need for revision after primary knee arthroplasty due to many reasons such as impaired ligament balance, decreased bone stock, joint line imbalance, more extensor mechanism problems and high infection rates due to long operation time [4,5].
While the most common cause of failure after revision knee prosthesis is infection, the second reason is prosthesis-related causes such as mechanical loosening and implant failure [6]. Apart from infection, the most important issue to be considered during revision surgery is to achieve good ligament balance with implants of appropriate size and appropriate mechanical properties in order to prevent aseptic loosening, wear and instability [7,8]. Therefore, the choice of implant is critical in revision surgery. Two different prosthesis designs are frequently used in revision surgery: Constrained condylar knee (CCK) prosthesis and Rotating hinge knee prostheses (RHK). Hinged prosthesis design is often used in ligament insufficiency or absence and provides high stability. However, mechanical complications such as wear and loosening are its main disadvantages [9,10]. CCK design implants have been manufactured more recently, are less constrained than hinged designs, and have been suggested for use in moderate ligament insufficiency and bone loss [11,12].
Two different prosthesis designs have been evaluated and compared in many studies in terms of many parameters such as survival rates, functional results and complications [13-15]. Despite many studies, there is no consensus on which design has better functional results and longer survival and which type of design should be preferred. Although it has been claimed that CCK design revision prostheses cause instability in severe insufficiency or absence of ligaments, we observed that the wide and deep post provided sufficient stability in our clinical practice. Therefore, our hypothesis is CCK design sufficient in revision knee surgery and RHK is rarely needed.
The aim of this study is to present the successful results of CCK prothesis to the literature and compare this results with the RHK design.
Material and Methods
Patients and study design
We retrospectively reviewed 190 patients who underwent total knee revision surgery between February 2014 and October 2018, after ethics committee approval. Exclusion criteria were revision with primary components (n = 2), arthrodesis (n = 1), amputation (n = 1), ex (n = 2), fracture fixation due to periprosthetic fracture (n = 4), missing data (n:12) and refusing to participate in the study (n = 20). A total of 148 patients, 129 with CCK and 19 with RHK, were included. Written informed consent was obtained from the legal guardian of each patient. The study was conducted in accordance with the principles of the Declaration of Helsinki.
The patients were classified in terms of age, gender, etiology and bone defects were evaluated according to the AOIR classification. Details of any complications developing after surgery were also recorded from hospital charts and clinic records. Bone defects during revision were documented intraoperatively by a research fellow present for each revision surgery and corroborated by operative recorders. Patients were followed up every 3 months in the first postoperative year and then annually. During these follow-ups, it was recorded whether additional interventions or surgical procedures were applied to the patients and whether complications developed in the patients. Functional results were evaluated with the WOMAC Osteoarthritis Index, and a Likert analysis was applied to measure patient satisfaction at the last visit.
Clinical treatment
Before surgery, routine blood tests, ECG, PA chest radiography, ESR, CRP and, if necessary, joint fluid analysis were applied to the patients. In case of clinical suspicion, radiological examinations such as CT, MRI or scintigraphy were performed and the etiology was clarified. Two-stage revision surgery was performed in all patients with septic etiology. Antibiotic treatment was given according to the results of the cultures or according to the recommendations of the infectious diseases specialist in patients with negative cultures. The treatment was terminated after the recommended period was completed, and the ESR and CRP values returned to normal. After the end of antibiotic treatment, normal infection parameters, measured twice at one-week intervals were accepted as the termination of the infection and revision process has been applied. All revision surgeries were performed by a fellowship trained adult reconstruction surgeon at our institution. Culture-specific antibiotics were administered at recommended doses in septic patients, and 2 g cefazolin sodium in aseptic revisions as a prophylaxis 30 minutes before surgery.
Surgical procedure and decision of implant design
The procedure was applied after tourniquet application in the supine position under spinal or general anesthesia. An anterior longitudinal incision was made, and after reaching the joint capsule, arthrotomy was performed through a medial parapatellar incision. In cases where an adequate approach could not be achieved, quadriceps snip was applied. Pin fixation was applied to strengthen the attachment of the patellar tendon, and none of the patients needed a tuberositas tibia osteotomy. Implants were removed with the help of narrow saws, osteotomy blades, gig saws, various hand tools, cement extractors and special prosthesis extractors, and then bone defects were evaluated. Femoral and tibial bone cuts were made with the help of an intramedullary guide, and a fluoroscopy was used when the joint level could not be determined exactly. The decision to use CCK or RHK was made intraoperatively. The wedges to be added were measured. First of all, stability and motion control were done with CCK implant design. If there is instability despite the insertion with a wedge and CCK design, the RHK implant design has been used. Afterwards, two different brands of original implants, Zimmer (Synthes GmbH, Oberdorf, Switzerland) or Biomet (Biomet, Warsaw, Indiana, USA) were randomly applied with antibiotic cement and their stability was checked,
Follow-up
On the first postoperative day, patients were mobilized and physical therapy was initiated after x-ray control. Prophylactic antibiotic treatment was continued intravenously for 3 days. CPM (continuous passive motion) device was applied to all patients during their hospitalization and 90 degrees of knee flexion without any complication was accepted as a discharge criterion. All patients received enoxaparin sodium 40 mg/day (Clexane; Aventis, Strasbourg, France) for pulmonary embolism and deep vein thrombosis prophylaxis for a month. Followed-up periods were every 3 months in the first postoperative year and then annually.
Statistical analysis
The data obtained in the study were analyzed statistically using SPSS v.22 software with a confidence interval of 95%. Qualitative data were stated as frequency distribution and quantitative data were stated as mean, minimum and maximum values. Inter-observer and intra-observer reliability was assessed using the interclass coefficient. Demographic data were evaluated with the Mann-Whitney U-test. The normal distribution was examined using the Kolmogorov-Smirnov test. The relationship between WOMAC values and Likert analysis results was examined using the Spearman correlation test. The categorical variables of CCK and RHK groups were evaluated with the Chi-square test, and numeric values not showing a normal distribution were evaluated with the Mann-Whitney U test. Categorical variables of AORI subgroups were evaluated with the Chi-square test, and numeric values not showing a normal distribution were evaluated with the Mann-Whitney U test. A p-value <0.05 was considered statistically significant.
Results
The mean age of the patients was 68.4 ± 7.27 (50-89) years, 17 patients were male and 147 were female (M/F: 1/9). The mean follow-up period was 2.8 ± 1.3 years (range;1- 6). According to the AORI classification, 34.5% of the patients were type I, 45% were type II, and 20.5% were type III (Figure 1). The reasons for revision were infection in 72 patients, wear and osteolysis in 78 patients, instability in 7 patients and others in 5 patients (Figure2). The distribution of the data of the patients is given in terms of frequency and percentage in Table 1.
CCK was applied to 87% (n = 129) of the patients, and RHK type prosthesis was applied to 13% (n = 19). There was no statistically significant difference between the age and follow-up time of the patients who underwent CCK and RHK (respectively; p=0489, p=0.844). When the prosthesis preference in revisions due to etiological factors was examined, the revision rate due to both septic and aseptic reasons was 40% in both the RHK and CCK groups, and there was no statistical difference between septic/aseptic etiology (p = 0.256). RHK implants were not required to AORI type 1, which were used in 4 patients (12%) of AORI type 2 and 15 patients (78%) of AORI type 3. While the mean preoperative WOMAC score was 38 ± 5.8 in the CCK group, it was 74 ± 9.6 postoperatively. However, the mean preoperative WOMAC score in the RHK group was 34.5 ± 3.7. while, postoperatively it was 73.6 ± 10.6. In assessing patient satisfaction, 5-Likert score was 4.2±0.6 in the CCK group, and 4.27±0.4 in the RHK group. There were no statistical differences in WOMAC and Likert analysis between CCK and RHK groups (respectively: p=0.876, p=0.962). The complications rate was %8 (n=12), periprosthetic fracture (n=8), wound infection treated with oral antibiotics (n=1), re-infection (n=1), arterial thrombosis (n=1) and drop foot (n=1). There was no statistically significant difference between the complications in patients who underwent CCK and RHK (p>0.05, Table 2).
According to the AORI classification, all AORI type 1 patients were treated with CCK design, and CCK design had enough stability in 93% of the AORI type 2 and %50 of AORI type 3. There were no significant differences between subtypes functional scores (Table 3). A correlation was observed between WOMAC and 5-Likert results (p<0.001, Figure 3).
Discussion
One of the most important principles of revision surgery is the selection of the most appropriate revision implant [16]. There are two different types of prostheses commonly used in revision knee surgery, CCK (constrained condylar knee) design and RHK (rotating hinged knee) design. It is still controversial which type of prosthesis is appropriate for revision surgery. Studies have shown that basically, RHK is a more constrained prosthesis and is considered to result in higher complication rates and lower survivorship compared to CCK. Therefore, CCK-type implants have gained popularity in revision surgery because they may require less bone resection and allow for future salvage-type procedures such as RHK if necessary [17,18]. In contrast, the RHK prosthesis is reported superior for patients with a severe deformity or instability [19]. There are few studies comparing these two different designs, which observed a significant difference between CCK or RHK usage rates. In this study, we demonstrated that CCK-type prosthesis design has as successful results, and RHK- type implants were rarely needed.
Several factors are effective in the selection of implants used in revision surgeries, ligament balance, bone loss, patient performance status and patient expectations [20]. However, there is no consensus on which design revision prosthesis should be used in different situations. Some authors claim that a hinged type revision prosthesis should be used in ligament insufficiency [21]. In contrast, some authors emphasize that, for cases with ligamentous insufficiency and moderate bone loss, a constrained condylar knee design is appropriate [21]. In a study evaluating implants used in revision surgery in stiff knee, it was claimed that using a rotating hinged device can provide excellent results in selected cases [13]. The literature comparing these RHK and CCK designs in the revision surgery include Vasso et. al. CCK (n:35) and RHK (n=18), Farfaelli et. al. CCK (n=50) and RHK (n=36) Bali et. al. CCK (n=19) and RHK (n=19) [20,22,23]. In our study, ligament balance was evaluated in the intraoperative period after the bone defect was replaced with a wedge. This preference reduced the need for an implant such as RHK design by up to 10%.
In a study by Shen et al., 496 patients who underwent revision knee prosthesis were examined, and adequate prosthesis design according to AORI classification was investigated [24]. They stated that, unlinked constrained prostheses displayed greater improvement in KSS when used in cases of aseptic AORI type III defects. However, patients undergoing revision for infection, may benefit from the use of linked constrained prostheses. Similarly, in our study, we found that RHK-type prostheses were used in patients with significantly reduced bone stock. In addition, we observed that CCK-type prostheses had similar results in all types of bone defects. As a result, we recommended the use of hinged prostheses in cases of excessive bone defect, but it should be kept in mind that CCK prostheses also give successful results.
Limitation
This study has several limitations. First, different techniques were applied to the patients such as graft, cement, structural allograft, metaphyseal cones or sleeves or augments for the bone defects, and no standard method was specified. Second, the number of patients is insufficient to compare complication rates and short follow-up.
In conclusion, CCK design implants provide sufficient successful functional outcomes in all types of bone defects in knee revision surgery. RHK-type prostheses are rarely required and more preferable for AORI type III bone loss.
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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Mahmut Özdemir, Yüksel Uğur Yaradılmış, Ahmet Ateş, Ali Teoman Evren, Mustafa Caner Okkaoğlu, Murat Altay. Hinged prosthesis in the knee revision surgery: Is there a great need? Ann Clin Anal Med 2022;13(10):1061-1065
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The duration of progesterone administration determines pregnancy outcome in frozen-thawed embryo transfer
Ramazan Ozyurt 1, Arzu Yurci 2, Nurettin Turktekin 3, Aret Kamar 1, Bertan Demir 4
1 Istanbul In Vitro Fertilization (IVF) Center, Istanbul, 2 IVF Unit Center, Memorial Kayseri Hospital, Kayseri, 3 Department of Operating Room Services, Nisantasi University, Vocational School, Istanbul, 4 Department of Obstetrics and Gynecology, Kayseri City Training and Research Hospital, Kayseri, Turkey
DOI: 10.4328/ACAM.21099 Received: 2022-02-06 Accepted: 2022-09-12 Published Online: 2022-09-21 Printed: 2022-10-01 Ann Clin Anal Med 2022;13(10):1066-1069
Corresponding Author: Ramazan Ozyurt, Istanbul In Vitro Fertilization (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 compare the effects of different progesterone treatment durations on pregnancy outcomes in patients undergoing frozen-thawed embryo transfer (FET).
Material and Methods: A total of 1468 patients who were scheduled for frozen-thawed embryo transfer were included in the study. The patients were divided into four groups according to the duration of progesterone administration. The patients in the first group received progesterone treatment for 3 days, the patients in the second group for 4 days, the patients in the third group for 5 days and the patients in the fourth group for 6 days, followed by FET. The primary outcome measure of our study was to evaluate clinical pregnancy rate, ongoing pregnancy rate, live birth rate and miscarriage rate per pregnancy.
Results: The frequencies of gestational sac, fetal heartbeat, ongoing pregnancy, live birth and miscarriage rates were significantly higher in the patients who were given progesterone for 6 days than in other groups (p <0.001, for each). In a multivariate analysis, we found that 5-day embryos have 1.6-fold higher live birth rates than day 3 embryos (OR: 1.677, 95%CI: 1.328-2.117, p<0.001). In addition, we found that lower numbers of transfer (p=0.008), lower 3rd day P4 values (p=0.001), higher CZP day P4 values (p<0.001) and higher cycle days during transfer (p<0.001) are associated with higher live birth rates
Discussion: In FET cycles, giving progesterone for six days before transfer significantly increases the fertility outcome compared to 3,4 or 5 days of progesterone treatment.
Keywords: Frozen-Thawed, IVF, Pregnancy Rate, Live Birth, Progesterone
Introduction
While planning in vitro fertilization (IVF), the embryo may need to be frozen due to various causes. Collected oocytes can be frozen and stored under appropriate conditions until embryo transfer is performed with thawed embryos in later cycles given that required characteristics or conditions are met [1,2]. Finding the best time for implantation in frozen embryo transfer is crucial for successful clinical outcomes. There are various approaches that enable synchronization of the frozen embryo day and endometrium development. The transfer process can be performed by ensuring that the most suitable time of the endometrium for implantation is synchronized with the frozen embryo day by closely monitoring the endometrium, or by utilizing interventions that prepare the endometrium from the first day of menstruation [3]. However, to date, there has been no consensus on the optimal duration of progesterone use for endometrium preparation in frozen embryo transfer [4,5]. This study was planned to compare the effects of different progesterone treatment durations on pregnancy outcomes in patients undergoing frozen-thawed embryo transfer (FET).
Material and Methods
This retrospective cohort study was performed among patients admitted to the Memorial Kayseri and Istanbul IVF centers between 01.01.2017 and 31.12.2018. The data of 35,670 patients who received IVF treatment were scanned. A total of 1468 women with frozen embryos aged between 18-42 years were included in the study. Women older than 42 years of age and those who had undergone fresh cycle transfers were excluded. Ethical approval was obtained from the Ethical Committee of Erciyes University. The patients were divided into four groups according to the duration of progesterone administration. The patients in the first group received progesterone treatment for 3 days, the patients in the second group for 4 days, the patients in the third group for 5 days and the patients in the fourth group for 6 days, followed by FET.
The primary outcome measure of our study was to evaluate clinical pregnancy rate, ongoing pregnancy rate, live birth rate and miscarriage rate per pregnancy. Clinical pregnancy rate was defined as evidence of a gestational sac, confirmed by ultrasound examination. The ongoing pregnancy rate was defined as evidence of a gestational sac with fetal heart motion at 12 weeks, confirmed with ultrasound examination. The live birth rate was defined as 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. In the presence of a positive pregnancy test, luteal support was continued and USG was performed at the 4th week of the transfer and the presence of gestational sac and thus clinical pregnancy was confirmed.
Statistical Analysis
All analyses were performed on SPSS v21 (SPSS Inc., Chicago, IL, USA). Q-Q and histogram plots were used to determine whether variables are normally distributed. Data are given as mean±standard deviation or median (1st quartile – 3rd quartile) for continuous variables according to normality of distribution and as frequency (percentage) for categorical variables. Normally distributed variables were analyzed with one-way analysis of variances (ANOVA). Non-normally distributed variables were analyzed with the Kruskal-Wallis test. Multiple logistic regression analysis (forward conditional method) was performed to determine significant factors of the live birth. P-value of less than 0.05 was considered statistically significant.
Results
A summary of embryo transfer and duration of progesterone use are shown in Table-1. The age of the patients who received progesterone for 4 days was higher than in other groups (p<0.001). The prevalence of gestational sac, fetal heartbeat, ongoing/missed pregnancy and live birth were significantly higher in the patients who were given progesterone for 6 days than in other groups (p<0.001). Additionally, the gestational sac, fetal heartbeat, ongoing pregnancy, live birth rates of the patients who received progesterone for 5 days were statistically significantly higher than the patients who received progesterone for 4 days (p<0.001) (Figure-1). Male factor (p=0.016), progesterone levels (p<0.001), endometrial thickness (p=0.035), embryo day (p<0.001) and cycle day during transfer (p <0.001) were found to be significantly associated with live birth. We performed multiple logistic regression analysis to determine significant factors of the live birth. We found that 5th embryo day (p<0.001), lower numbers of transfer (p=0.008), lower 3rd day P4 values (p=0.001), higher CZP day P4 values (p<0.001) and higher cycle days during transfer (p<0.001) are associated with higher live birth rates. Number of days P4 used (p=0.273), age (p=0.550), presence of male factor (p=0.605), endometrial thickness on the CZP day (p=0.151), endometrial thickness on the ET day (p=0.273) and embryo count (p=0.134) were found to be non-significant (Table 2).
Discussion
In this study the effect of the day of progesterone treatment on fertility outcome was examined and we found that the duration of progesterone administration improves live birth rates. When the studies conducted with the inclusion of various progesterone durations and embryo days were examined, the results seemed confusing. For instance, in a study that examined 4-day embryo transfer with progesterone administration for 3 days and embryo transfer 5-day embryo transfer with progesterone administration for 4 days, Sharma and Majumdar reported that the frequency of pregnancy was 41% in the group who received progesterone for 3 days, and 18.5% in the group who received progesterone for 4 days. They reported that both pregnancy and implantation rates were significantly better in the 3-day progesterone group [6]. However, it is possible that their findings were confounded by the day of transfer and the embryo quality. In a similarly designed study, Prapas et al. showed the exact opposite, indicating that 4 day- progesterone administration was more effective in terms of successful clinical results [7].
In a study examining the results of frozen-thawed embryo transfer after 6 or 7 days of progesterone administration, Ding et al [8] reported that there was no significant difference between the groups, however, implantation rate was higher in women under the age of 39 as a result of 6-day embryo transfers, although the difference was not statistically significant. They concluded that a less developed endometrium may have increased the chance of successful implantation by ensuring embryo presence within the critical window of implantation [8]. In two different studies, it has been shown that there is no significant difference in terms of clinical results between 2 or 3 embryo day transfers after different durations of progesterone administration [7,9]. Therefore, even though there are a considerable number of combinations to consider on this subject it is apparent that different progesterone administration times either do not have superiority to each other or the results are contradictory to other studies. Although our univariate analyzes showed that the day of progesterone administration affects live birth rates, multivariate analyzes revealed that the progesterone day administration did not affect live birth rates. Lu and colleagues examined the results of a total of 4 different progesterone administration groups [10]. They reported that there were no significant differences in terms of any important parameters when comparisons were performed with regard to progesterone administration. We also determined two other studies, both conducted by Vijver et al., that seemed to be somewhat comparable to our study. In the first of these studies, they examined the results of 5 and 7 days of progesterone administration, and reported that frequency of pregnancy was 28% after 7 days of progesterone administration and 33% after 5 days of progesterone administration; however, there was no statistically significant difference between the groups [11]. In the second study comparing the results of 5 and 3 days of progesterone administration, the authors reported a pregnancy rate of 27% with 5 days of progesterone administration and 19% with 3 days of progesterone administration. Again, there was no significant difference between these two groups. In addition, they suggested that early pregnancy losses were statistically significantly higher in the 3-day progesterone administration group, concluding that 5 days of progesterone administration could be preferred [12]. Similar to our study, none of the other studies comparing the results of similar groups found significant differences between the groups in terms of live birth rate.
It was determined that, the number of embryos transferred, embryo day, 3rd day and progesterone day progesterone levels, and cycle day during transfer independently influenced the live birth rate. It was seen that our results were in agreement with the majority of the literature. Various studies have shown that transfers with day 5 & 6 embryos had better results compared to earlier embryo transfers [13,14]. Furthermore, day 5 transfers are also reported to be superior to day 6 transfers [15], even though some studies have found similar success with 5 and 6 days of development [16].
Conclusion
It is evident that the cycle day at transfer is affected by embryo day; however, multivariate analysis revealed that higher cycle day during transfer positively affected live birth rate, whereas embryo day was not significant. Another factor that is frequently associated with IVF success, namely the number of transfers, was also found to be effective on live birth rate; however, the relationship in this study was in direct contrast to the majority of studies, which report that the probability of live birth increases in parallel with the number of transfers [17]. The effect of serum progesterone level on live birth rate, similar to prior publications, was also determined to be significant on live birth rate in our study [18]. In conclusion, our results show that gestational sac, fetal heartbeat, ongoing pregnancy, and live birth rates increased with the prolonged day of progesterone treatment, and there was no significant effect on live birth rate in multivariate analysis.
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. Glujovsky D, Pesce R, Fiszbajn G, Sueldo C, Hart RJ, Ciapponi A. Endometrial preparation for women undergoing embryo transfer with frozen embryos or embryos derived from donor oocytes. Cochrane Database Syst Rev. 2010; 20(1): CD006359. DOI: 10.1002/14651858.CD006359.pub2.
2. Sunkara SK, Siozos A, Bolton VN, Khalaf Y, Braude PR, El-Toukhy T. The influence of delayed blastocyst formation on the outcome of frozen-thawed blastocyst transfer: a systematic review and meta-analysis. Hum Reprod. 2010; 25 (8):1906-15.
3. Mackens S, Santos-Ribeiro S, van de Vijver A, Racca A, Van Landuyt L, Tournaye H, et al. Frozen embryo transfer: a review on the optimal endometrial preparation and timing. Hum Reprod. 2017; 32 (11): 2234-42.
4. Franasiak JM, Ruiz-Alonso M, Scott RT, Simón C. Both slowly developing embryos and a variable pace of luteal endometrial progression may conspire to prevent normal birth in spite of a capable embryo. Fertil Steril. 2016; 105 (4):861-6.
5. Gomaa H, Casper RF, Esfandiari N, Bentov Y. Non-synchronized endometrium and its correction in non-ovulatory cryopreserved embryo transfer cycles. Reprod Biomed Online. 2015; 30 (4): 378-84.
6. Sharma S, Majumdar A. Determining the optimal duration of progesterone supplementation prior to transfer of cryopreserved embryos and its impact on implantation and pregnancy rates: a pilot study. Int J Reprod Med. 2016; 2016: 7128485. DOI: 10.1155/2016/7128485
7. Prapas Y, Prapas N, Jones EE, Duleba AJ, Olive DL, Chatziparasidou A, et al. The window for embryo transfer in oocyte donation cycles depends on the duration of progesterone therapy. Hum Reprod. 1998;13(3): 720-3.
8. Ding J, Rana N, Dmowski W. Length of progesterone treatment before transfer and implantation rates of frozen-thawed blastocysts. Fertil Steril. 2007; 88: S3301.
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12. Van de Vijver A, Polyzos NP, Van Landuyt L, Mackens S, Stoop D, Camus M, et al. What is the optimal duration of progesterone administration before transferring a vitrified-warmed cleavage stage embryo? A randomized controlled trial. Hum Reprod. 2016; 31(5):1097-104.
13. Lattes K, Checa MA, Vassena R, Brassesco M, Vernaeve V. There is no evidence that the time from egg retrieval to embryo transfer affects live birth rates in a freeze-all strategy. Hum Reprod. 2017; 32(2): 368-74.
14. Krasnopolskaya KV, Beketova AN, Sesina NI, Chinchenko NK, Badalyan GV, Sudarikova NM, et al. The effect of short-term disturbance of day 3 embryo culture on the development and implantation. Gynecol Endocrinol. 2019; 35: 1-4.
15. Ferreux L, Bourdon M, Sallem A, Santulli P, Barraud-Lange V, Le Foll N, et al. Live birth rate following frozen-thawed blastocyst transfer is higher with blastocysts expanded on Day 5 than on Day 6. Hum Reprod. 2018; 33(3): 390-8.
16. Kaye L, Will EA, Bartolucci A, Nulsen J, Benadiva C, Engmann L. Pregnancy rates for single embryo transfer (SET) of day 5 and day 6 blastocysts after cryopreservation by vitrification and slow freeze. J Assist Reprod Genet. 2017; 34(7): 913-19.
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Ramazan Ozyurt, Arzu Yurci, Nurettin Turktekin, Aret Kamar, Bertan Demir. The duration of progesterone administration determines pregnancy outcome in frozen-thawed embryo transfer. Ann Clin Anal Med 2022;13(10):1066-1069
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Prevalence of overweight/obesity and associated factors in children underfive years – of age in Marrakesh, Morocco
Soufiane El Moussaoui 1, 2, Kamal Kaoutar 1, Ahmed Chetoui 1, Keltoum Boutahar 1, Abdeslam El Kardoudi 1, Fatiha Chigr 1, Mounir Borrous 2, Mohamed Najimi 1
1 Department of Biology, Biological Engineering Laboratory, Faculty of Sciences and Techniques, Sultan Moulay Slimane University, Beni Mellal, 2 Department of Pediatrics, Mohamed VI University Hospital, Marrakesh, Morocco
DOI: 10.4328/ACAM.21150 Received: 2022-03-19 Accepted: 2022-06-17 Published Online: 2022-07-15 Printed: 2022-10-01 Ann Clin Anal Med 2022;13(10):1070-1074
Corresponding Author: Soufiane El Moussaoui, Department of Paediatric Physician, Biological Engineering Laboratory, Faculty of Sciences and Techniques, Sultan Moulay Slimane University, 23000, Beni Mellal, Morocco. E-mail: soufiane.lueur@gmail.com P: +21 266 211 97 23 Corresponding Author ORCID ID: https://orcid.org/0000-0001-8454-1733
Aim: Childhood overweight and/or obesity is becoming a significant public health problem in the 21st century. This study aimed to determine the prevalence of overweight/obesity and its determinants among under-five children in Marrakesh, Morocco.
Material and Methods: A community-based cross-sectional study design was used to determine the prevalence of overweight/obesity and its associated factors among children under five years of age. A structured questionnaire was used to collect data from 450 children paired with their mothers. Anthropometric measurements and determinant factors were collected. SPSS version 19.0 statistical software was used for the analysis. Multivariate logistic regression analysis was conducted to identify factors associated to overweight/obesity in children. Statistical association was declared significant if p- value was less than 0.05.
Results: In this study, the prevalences of overweight and obesity were 112 (24.9%) and 84 (18.7%), respectively. Mother’s age, parental educational level and birth order were significantly associated with the problem.
Discussion: The current study showed a relatively high prevalence of overweight/obesity among children under five years of age. Mother’s age, parental educational level and birth order were the predictors of overweight/obesity. Therefore, nutritional educational intervention programs in Marrakesh province should focus on these factors.
Keywords: Overweight/Obesity, Under age of five, Children; predictors, Marrakesh, Morocco
Introduction
According to the World Health Organization (WHO), overweight and obesity are defined as abnormal or excessive fat accumulation that can impair health. Childhood obesity has been progressively increasing over the last few decades, being considered a worldwide epidemy by the WHO. Thus, it is estimated that 43 million children under 5 years are overweight worldwide, including 35 million in developing countries and 8 million in developed countries. Furthermore, 92 million children are at risk of being overweight [1].
The worldwide increase is related to the nutrition transition, including urbanization, economic growth, and globalization, leading to lifestyle changes, including reduced physical activity and poor dietary habits with increased intake of highly processed, high-energy foods [2]. Although childhood overweight and obesity have been considered the problems of high-income countries, they are now on the rise in low- and middle-income countries like Morocco. While these countries continue to deal with the problems of infectious diseases and undernutrition, childhood overweight and obesity are the “double burdens” and the most serious public health challenges of the twenty-first century. Since 2000, the number of overweight children under the age of 5 has increased by nearly 24% in Africa according to WHO.
Overweight/obesity during the childhood period affects physical and psychological health with the likelihood to stay obese during the adulthood period. According to WHO, childhood overweight and obesity are linked to more deaths than underweight and are associated with a higher chance of breathing difficulties, increased risk of fractures, hypertension, early markers of cardiovascular disease, insulin resistance, psychological effects, and adulthood obesity, premature death, and disability and resulting in an increased risk of non-communicable diseases and reproductive disorders later in their life .
Several studies have been dedicated to identifying risk factors for excess weight in children, such as birth weight [3], breastfeeding [4], family income [5], environmental factors [6] and socioeconomic status [7].
Indeed, studies on breastfeeding have shown a protective effect on the development of child obesity. However, this relation is yet quite controversial in the literature, because of its delineations, samples and different diagnostic methods, making the comparison between them rather difficult [4].
WHO (1988) indicates the importance of early life overweight and/ or obesity management used for mitigating the risk of obesity later in life. Globalization and nutrition transition improved the living standards of individuals. However, they had some negative consequences that directly or indirectly led to poor dietary consumption and physical activity patterns. Because of this, the occurrence of overweight and/or obesity among children under five years of age, besides diet-related chronic non-communicable diseases later in life increased persistently.
In Morocco, literature on overweight/obesity in children under five years of age is scarce, except for data from Pan Arab Project for Child Development (PAPCHILD 1997), which has shown that undernutrition persists among children under five years of age (24% stunting and 9% under-weight), while overweight is rising (13.7% in 1997 compared with 5.6% in 1987 for children under five years of age).
Indeded, determining the magnitude and identifying risk factors for child undernutrition in the study area is important to guide public health planners, policy makers and implementers to plan and design appropriate intervention strategies in order to enhance the nutritional status of children. Therefore this study was designed to estimate the prevalence of overweight/obesity and its associated factors among children under five years of age in Marrakesh province, Morocco.
Material and Methods
Research design
A community-based cross-sectional study was conducted from January to December 2020 in Marrakesh.
Data collection tool and procedures
A pretested, structured questionnaire was used to collect data. Five data collectors (clinical nurses) and two supervisors (pediatrician) were recruited for the task. To maintain consistency, the questionnaire was first translated from French to Arabic, the native language of the study area. It contains socio-demographic, environmental characteristics and healthcare conditions. Women were recruited from health centers that were selected on the basis of the following criteria: accessibility to our field team and a large attendance of women enough to cover the required number for the study age range.
Anthropometric data were collected using the procedure stipulated by the WHO (2006) for taking anthropometric measurements. Before taking anthropometric data for children, their age should first be determined to ensure the study population. The child’s age was asked of the mother and confirmed with a birth certificate or vaccination cards.
Weight was measured by an electronic digital weight scale with minimum/lightly/clothing and no shoes. Calibration was done before weighing every child by setting it to zero [8].
In line with a study carried out by Brasilian Institute of Geography and Statistics, the length of children aged up to 24 months was estimated.
Overweight and obesity were determined according to the WHO definition. Overweight was defined as a BMI that was 2 standard deviations above the WHO growth standard median, and obesity was defined as a BMI that was 3 standard deviations above the WHO growth standard median [9].
Data processing and analysis
Data were entered into Epi-info version 7 and exported to the Statistical Package for Social Sciences (SPSS) version 19 for analysis. Descriptive statistics, including frequencies and proportions were computed and presented using texts, and tables. The multivariate logistic regression model was carried out. The technique was a backward stepwise regression method. Finally, a p-value of less than 0.05 in the multivariable logistic regression analysis was used to identify variables significantly associated with overweight/obesity.
Ethical considerations
Participation was voluntary and anonymous. Participants were informed about the study objective. All data were confidential and protected at all stages of the study. This study was performed in accordance with the ethical standards of the committee and with the Helsinki Declaration. The study was approved by the institution of Maternal and Child Hospital. It was approved, and numbered with a Ref. (SAA N°252/2020).
Results
Socio-demographic and economic characteristics
A total of 450 mothers were included in the study. Nearly half (46.4%) of mothers were in the age range of 19–29 years. Two hundred nine (48.2 %) of the mothers and 132 (30.7%) of the fathers were illiterate. The majority (92.9%) of the mothers were housewives. One-quarter, (22.4%) of the households had lower income (Table 1).
Health service and environment related characteristics
About 250 (55.6%) of the children were males. The two-third, 307 (68.2%), of the households had a second newborn and above for birth order. A large proportion, 296 (65.8%), were primiparous. The majority (97.3%) of births were in a health institution. When the delivery way was considered, 77.3% of women delivered vaginally (Table 2).
Prevalence of overweight/obesity and feeding practices in children
In this study, the prevalences of overweight and obesity were 112 (24.9%) and 84 (18.7%) respectively. One-quarter of children (102 (21.8%)) children did not get the first milk (the colostrum). One-half (235 (52.2%)) of the children were on exclusive breastfeeding. About 128 (28.4%) of mothers had supplementation during pregnancy (Table 2).
Factors associated with overweight/obesity among children under five years of age
In the bivariate analysis, mother’s age, mother’s education level, husband’s education level, household size, birth order and parity were factors associated with overweight at a p-value of less than 0.05. Consequently, these variables were subjected to multivariate logistic regression analysis, and it was noted that mother’s age, mother’s education level, husband’s education level and birth order were significantly associated with overweight/obesity at a p-value of 0.05.
According to the multivariable logistic regression analysis, the chances of having overweight/obese children among mothers younger 24 years of age were 8 times higher compared with mothers over 30 years of age (aOR = 8.806; 95% CI: (1.05-5.52)). The odds of overweight/obesity were more observed among children of parents with high educational level. Similarly, the odds of overweight children among the first baby in birth order were 8 times more likely compared to second and subsequent babies (aOR = 8.86 ; 95% CI: (1.09-6.47)) (Table 3).
Discussion
In this study, the overall prevalences of overweight and obesity was 24.9% and 18.7%, respectively. In comparison with some African countries, our finding was higher than in studies conducted in Ethiopia [10], Cameron (8%) [11], sub-Saharan Africa (6.8%), Malawi 8.7% and Mozambique 7.7% [12].
The prevalences of overweight and obesity are high in developing countries. In accordance with analysis of economic viability, it was found that overweight prevalence showed a gradual reduction from upper-middle-income to low-income countries, with intermediate prevalence in lower-middle-income countries. According to some estimates, the prevalence of childhood obesity in Africa and Asia is still far below (<10%). The levels seen in the Americas and Europe were 20% [13].
Indeed, in a study in the United States, the prevalences of overweight and obesity in children were 31.7% and 16.9%, respectively [14]. Another study found that 25.6% of the children in the United States were obese [15]. These differences may stem from disparities in social and economic status.
The present study showed that maternal age was significantly associated with overweight/obesity in children under-five years of age. Indeed, the chances of having overweight/obese children among mothers younger 24 years of age were 8 times higher compared with mothers above 30 years of age. This result can be explained by the lack of experience among young mothers.
Furthermore, the likelihood of overweight/obesity was more often observed among children of parents with high educational level, which was supported by a study in India [16]. In Nepal, mothers are the primary caregivers of the children. Educated mothers have a higher chance of employment resulting in lesser time to monitor their children’s physical activities or sedentary behaviors like watching TV, which in turn, significantly increases their BMI. Previous studies in Ethiopia [10], South Asia [17], sub-Saharan Africa [18], and Guangzhou, China [19] reported that children born from rich households were at high risk of overweight and/or obesity. Thus, financial well-being in the household is associated with obesogenic behaviors (high intakes of calories rich food and physical inactivity) [24].
The present study also showed that birth order was significantly associated with overweight /obesity of children under five years of age. Indeed, the first child in birth order was 8 times more likely to be overweight than the second child and subsequent babies (aOR = 8.86 ; 95% CI: (1.09-6.47)). In line with a study carried out in kindergartens in São Paulo with a sample of 556 children aged 4 to 84 months, having 2 or more siblings was a protective factor against overweight (aOR= 0.28) compared to children who had no siblings. In this later study, it was demonstrated that in children who were the only one in the family, the prevalence of overweight was 26% higher than in those who had one or more siblings [21]. The possible explanation might be the lack of experience in nutrition for the first baby.
Conclusions
Based on the findings of the current study, it can be concluded that in this community, the prevalence of overweight/obesity was higher. In addition, the study found that overweight/obesity was linked to various factors. Mother’s age, parental education level and birth order were significantly associated with the problem. These findings indicate the need for broader and longer-term interventions focusing on maternal and child nutrition promotion to reduce overweight/obesity among children under five years of age.
Acknowledgment
We would like to thank all mothers and children who participated in this study.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: PPR Type B (M.Najimi) Project from Ministry of Higher Education and Scientific Research in Morocco.
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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6. Robinson TN. Reducing children’s television viewing to prevent obesity: a randomized controlled trial. JAMA. 1999; 282(16): 1561-7.
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9. de Onis M, Onyango AW, Borghi E, Siyam A, Nishida C, Siekmann J. Development of a WHO growth reference for school-aged chil-dren and adolescents. Bull World Health Organ. 2007; 85(9):660–7.
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Download attachments: 10.4328.ACAM.21150
Soufiane El Moussaoui, Kamal Kaoutar, Ahmed Chetoui, Keltoum Boutahar, Abdeslam El Kardoudi, Fatiha Chigr, Mounir Borrous, Mohamed Najimi. Prevalence of overweight/obesity and associated factors in children underfive years – of age in Marrakesh, Morocco. Ann Clin Anal Med 2022;13(10):1070-1074
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The effect of lifestyle on the course of COVID-19 infection
Yildiz Yigit 1, Nuriye Esen Bulut 2, Cem Nazikoglu 3
1 Department of Anesthesiology and Reanimation, 2 Department of General Surgery, 3 Department of Family Medicine, University of Health Sciences, Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.21214 Received: 2022-04-27 Accepted: 2022-06-20 Published Online: 2022-06-22 Printed: 2022-10-01 Ann Clin Anal Med 2022;13(10):1075-1079
Corresponding Author: Yildiz Yigit, E5 Karayolu Üzeri, İçerenköy, Ataşehir, 34752, İstanbul, Türkiye. E-mail: yildizyigityigit@gmail.com P: +90 533 244 64 06 F: +90 216 575 04 06 Corresponding Author ORCID ID: https://orcid.org/0000-0002-8665-6646
Aim: Our study’s goal was to see how pre-illness lifestyle affected the course of COVID-19 infection in patients hospitalized with COVID-19.
Material and Methods: From January to May 2021, 66 patients aged 50 years and older whose PCR tests were positive for COVID-19 were studied in the pandemic service. The Pittsburgh Sleep Quality Index (PSQI), Mini Nutritional Assessment (MNA) scale, and International Short Physical Activity Questionnaire (IPAQ) were utilized to examine the impact of COVID- 19 infected individuals lifestyles such as sleep, nutrition and physical activities on the illness before the infection.
Results: According to the PSQI scale; the increases in discharged lymphocyte measurements were significant compared to the first hospitalization in the good and bad sleep group cases. A higher increase in NLR for the first hospitalization was seen in the bad sleep group compared to good sleep group. According to the MNA scale, all three groups had increased lymphocyte counts in discharge disposition in comparison to the first hospitalization. Patients at risk of malnutrition had higher increases in lymphocytes at discharge than malnourished individuals (p=0.049). Normal nutritional status had greater platelet measures than patients at risk of malnutrition (p=0.028). According to the IPAQ survey, very active cases had higher platelet measurements than minimally active cases.
Discussion: In our study on the effect of lifestyle on the course of COVID-19 infection, patients with proper nutrition, good sleep quality, and sufficient physical activity did not require treatment in the ICU. This finding revealed the importance of adopting and maintaining a healthy lifestyle.
Keywords: Pre-Hospital Lifestyle, COVID-19, Prognosis
Introduction
The COVID-19 disease is a severe infection with varying clinical presentations that has spread globally since 2019 [1]. The COVID-19 disease is a result of the interaction between the Sars-Cov-2 virus of the coronavirus family and the host immune system. The immune response of the host depends on the age, gender, genetics, nutrition, sleep, and physical activity of the individual [2].
A healthy lifestyle is consistently associated with reduced all-cause mortality and a longer lifespan [3]. Risk of cardiovascular diseases, cancer, and all-cause mortality decrease in non-smokers, in those who are more physically active and have a balanced diet [4].
Sleep is another important period for immune function with recovering and regulating properties [5]. Sleep deprivation, disrupted sleep patterns, or poor sleep quality results in the vulnerability of the host against many infectious agents [6]. Likewise, diet and the immune system are related where an unbalanced diet disrupts the host immune response against pathogens causing susceptibility to infections [7]. Physical activity acts as an immune system modulator by contributing to the host defenses and strengthening the immune response, especially against viral diseases [1]. Proinflammatory and anti-inflammatory cytokines are released during and after physical exercise with an increase in the circulation of lymphocytes and cellular uptake of immune cells [1].
COVID-19 patients present with symptoms and findings similar to SARS and MERS with fever, nonproductive cough, dyspnea, musculoskeletal pain, malaise, low leucocyte counts, and radiological signs of pneumonia [2]. In this study, we aimed to investigate the effect of lifestyle (sleep, nutrition and physical activity) on the course of COVID-19 infection in patients admitted to the hospital with COVID-19 disease.
Material and Methods
The study was conducted on patients aged >50 years who were admitted to the pandemic wards of Fatih Sultan Mehmet Research and Training Hospital with PCR-confirmed COVID-19 infection between 31 January and 31 May 2021. Patients aged <50 years, with negative COVID-19 PCR tests, lymphatic system, or hematological diseases were excluded. The study was approved by the ethics board (E-17073117-050.06).
Age, gender, education status, duration of COVID-19 disease outside the hospital, duration of hospital stay, alcohol or tobacco habits, body mass index, comorbidities, medications, presence of lesions on thoracic CT, discharge to home, intensive care unit (ICU), or a different ward, lymphocyte count, neutrophil-lymphocyte ratio (NLR) and platelet counts at admission and at discharge were recorded.
To assess the lifestyle before the COVID-19 infection, sleep habits were evaluated with the Pittsburg Sleep Quality Index (PSQI) [8], nutritional status with Mini Nutritional Assessment (MNA) [9], and physical activity with the short International Physical Activity Questionnaire (IPAQ) [10].
Statistical Analysis
NCSS (Number Cruncher Statistical System) 2007 (Kaysville, Utah, USA) was used for statistical analysis. Descriptive statistics were given using mean, standard deviation, median, interquartile range, frequency, percentage, minimum, and maximum values. The normal distribution of continuous variables was tested using Shapiro-Wilk’s test and graphical evaluation. Groups with normal distributions were compared using the independent samples t-test and groups without normal distribution were compared using the Mann-Whitney U test, Kruskal-Wallis test, and Dunn-Bonferroni test when appropriate. Wilcoxon’s signed-ranks test was applied to compare paired samples without normal distribution. The correlation of continuous variables was tested with Spearman’s correlation. P<0.05 was considered statistically significant.
Results
A total of 66 patients were included in our study; 24 (36.4%) were female and 42 (63.6%) were male. The mean age of the patients was 53.53 ± 11.13 years, and the mean body mass index (BMI) was 29.29 ± 5.94. University graduates accounted for 21.5% of the patients; 19.7% were active smokers and 4.5% consumed alcohol.
The most frequent comorbidity was hypertension, seen in 50% of the patients. Of patients with comorbidities, 71.2% were on medications.The most frequent COVID-19 related symptom was malaise, followed by musculoskeletal pain in 68.2% of the patients and cough in 66.7% of the patients.
The mean duration from symptom onset to hospital admission was 7.42 ± 3.81 days, and the mean duration of hospital stay was 11.56 ± 6.22 days.
Bilateral pulmonary infiltrates were found in 84.8% of the patients on chest CT; 81.8% of the patients were discharged to home, while 4.5% required ICU care, and 13.6% were transferred to a different ward, following their COVID-19 treatment (Table 1). The PSQI, MNA, and IPAQ results are shown in Table 2.
The patients were grouped according to sleep quality and compared in terms of days of admission, along with lymphocyte count, NLR and platelet count at the time of discharge. Both groups had a significant increase in lymphocyte counts at discharge compared to the counts at admission, but the groups were not different for the change in lymphocyte counts.
The decrease in NLR from admission to discharge was significant in the poor sleep quality group, and the NLR at admission was higher in the poor sleep quality group, while the groups did not differ for the difference in NLR from admission to discharge. The platelet count at admission was not different between the groups, while they were higher in the good sleep quality group compared to the poor sleep quality group (p=0.040). At the time of discharge, the platelet count did not differ between the groups (p=0.201), but the increase in platelet counts was significant in both groups. Days of hospital stay were not different between the groups.
Patients were grouped according to the MNA scale as normal, at risk, or malnourished. Mean lymphocyte counts increased significantly in all three groups at discharge compared with their levels at admission. The groups were different in the increase in lymphocyte count (p<0.005), with the risk group being higher than the malnourished group (p=0.049). In addition, the normal and risk groups had significantly lower NLR at discharge compared to NLR values at admission. Platelet counts at admission and at discharge were different between the groups. The mean platelet count in the normal group was higher than in at risk group at admission (p=0.028) and at discharge (p=0.008). In the normal and risk groups, there was a significant increase in platelet counts at the time of discharge (p=0.001 and p=0.012), while a significant change was not observed in the malnourished group. The change in platelet counts between admission and discharge was different between the groups (p=0.024). The change in the risk group was lower than in the normal group (p=0.022). The three groups were not different for days of hospital stay.
According to the IPAQ scores, the patients were categorized as inactive, minimally active, and active groups. All three groups had significantly higher mean lymphocyte counts at discharge than at admission. The groups were different for mean platelets counts at admission (p=0.043) The active group had a significantly higher mean platelet count at admission than the minimally active group (p=0.048). The active group had a significantly higher mean platelet count at discharge than the inactive group (p=0,05). All groups had a significant increase in platelet counts at discharge. The groups did not differ for days of hospital stay. Lymphocyte count, NLR and platelet count at the time of admission and discharge are given in Table 3.
The metabolic equivalent of task (MET) scores that reflect the level of physical activity were compared with the days of hospital admission and laboratory results at admission. There was a weak but significant positive correlation between MET scores and lymphocyte percentages (r=0,282, p=0,022) and a weak but significant negative correlation between MET scores and NLR at admission (r=0.264, p=0.032).
Transfer to the ICU was necessary for 3 (4.5%) of the 66 study patients; 67% of these patients were male. One male patient expired in the ICU, while the other 2 patients survived to discharge. All of these patients were physically inactive (C1) and had poor sleep quality (PSQI: 12, 14, 10, respectively). Two of the patients were malnourished (MNA: 11, 12, respectively), and one patient was obese (BMI: 38.6 kg/m2).
Discussion
When COVID 19 patients are examined according to their lifestyles, in the good sleep quality group, the mean NLR at admission was lower and the platelet count was higher than in the poor sleep quality group. It was observed that sleep quality had an effect on platelet count and NLR. The lymphocyte count was lower in malnourished patients. Platelet counts were significantly higher in patients with normal nutritional status. Platelet counts were higher in physically active patients (>3000 MET).
Uslu et al have retrospectively studied 114 patients for their thoracic CT findings and reported typical findings in 41 (35.9%) patients, atypical findings in 3 (2.6%) patients, inconclusive findings in 18 (15.7%) patients, and no pathology in 52 (45.6%) patients. Among 62 patients with CT findings, infiltrates were bilateral in 42 (67.7%) and unilateral in 20 (32.3%) patients [11]. Among our study patients, 58 (90.6%) had bilateral lung infiltrates and 6 (9.4%) had unilateral infiltrates, while 2 patients had no COVID-19 associated findings on chest CT. A high rate of bilateral lung infiltrates was observed among our patients similar to previous reports in the literature.
High (>40 kg/m2) BMI was the second strongest predictor for admission to a hospital after advanced age in the study by Petrilli et al on 4103 COVID-19 patients [12]. The mean BMI of our study patients was 29.59, with 14.4% of the patients having a BMI > 40 kg/m2. One of the three patients who required treatment in the ICU had a BMI of 38.6 and eventually did not survive.
Zuin et al investigated the comorbidities and COVID-19 mortality in their metaanalysis, reporting that hypertension (HT) was the most frequent cardiovascular comorbidity (24.3%), followed by diabetes mellitus with 15.2% and cardiac diseases with 6.2% [13]. In our study, the most frequent comorbidity was hypertension seen in 50% of the patients.
A pilot study on 8 healthy males was conducted by Boudjeltia et al to investigate cardiovascular risks of sleep deprivation. Neutrophil and leucocyte counts were increased with sleep deprivation, which may be associated with higher cardiovascular risk due to activated inflammatory processes [14]. The relationship of poor sleep quality with the recovery of lymphopenia and ICU requirement in COVID-19 patients was investigated by Zhang et al who found higher NLR and lymphopenia that further decreased with poor sleep quality [15]. Liu et al studied the relationship between mortality and platelet counts and emphasized the importance of monitoring platelet counts for COVID-19 prognosis [16]. Platelets have effects on the innate immune system as well as T cell activation and differentiation [17]. In both our sleep quality groups, mean lymphocyte counts significantly increased at the time of discharge. The increase in lymphocyte count was higher, albeit insignificantly, in the good sleep quality group. A significant difference may have not been shown due to the low number of included patients. NLR at admission was higher and platelet count at discharge was lower in the poor sleep quality group.
Satio et al studied the effect of nutrition on immune regulation with 33 female anorexia nervosa patients and reported low lymphocyte and neutrophil counts in these patients along with increased susceptibility to infection [18]. In the study on the prevalence of malnutrition and associated factors in 182 geriatric COVID-19 patients by Li et al, the lymphocyte count at admission was lower in their malnutrition group compared to their normal nutrition group [19]. In the cross-sectional study by Kaya et al on 95 geriatric patients, patients at risk of malnutrition and with malnutrition had significantly higher NLR than patients with normal nutritional status, with a negative correlation between NLR and MNA scores [20]. In our study, the decrease in NLR at the time of discharge was significant for both patients with normal nutritional status and at risk of malnutrition, while the change in NLR was not significant in patients with malnutrition. The change in NLR did not differ between the malnutrition groups. Yoshiuchi et al have studied anorexia nervosa patients and observed a rise in thrombopoietin and thrombocyte levels shortly after recovery of liver functions with proper nutrition [21]. In our study, patients with normal nutritional status had higher platelet counts both at admission and discharge compared to patients at risk of malnutrition.
Campbell et al studied the immunological effects of exercise, reporting the benefits of a physically active lifestyle with reduced bacterial and viral infections and better overall health [22]. In a systemic review of the immune effects of physical exercise by Silveira et al, the rise in neutrophil counts after physical activity was associated with the release of neutrophils from the bone marrow upon stimulation with cortisol [23]. In the study by Furtado et al, they studied the effects of physical activity during and after COVID-19 infection, an it was found that lymphocyte and leukocyte counts were maintained at normal levels with continued physical activity [24]. In all our activity groups, there was a significant rise in lymphocyte counts at discharge. No difference could be shown between lymphocyte counts at discharge between the highly active group and the inactive group, which can be explained by the variability in the duration of COVID-19 infection prior to hospital admission and the low sample size. Hulmi et al. investigated the effects of resistance exercise and protein intake on blood leukocytes and platelets in young and old men; they found that platelet count increased rapidly after high-intensity exercises [25]. In our study, patients with high physical activity (>3000 MET) had significantly higher thrombocyte counts at admission than minimally active patients.
The limitations of our study include its single-center design, lack of a control group with healthy subjects, and its low sample size. Our findings can be confirmed by similar studies designed with larger sample sizes.
Conclusion
In our study on the effect of lifestyle on the course of COVID-19 infection, patients with proper nutrition, good sleep quality, and sufficient physical activity did not require treatment in the ICU. This finding revealed the importance of adopting and maintaining a healthy lifestyle.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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7. Önal HY, Demirci Z. The Role of Nutritional Supplements in the Development and Support of The Immune System. J Health Pro Res. 2020;2(3):137-47.
8. Park BK. The Pittsburg Sleep Quality Index (PSQI) and Associated Factors in Middle-school Students: A Cross-sectional Study. Child Health Nurs Res. 2020;26(1):55-63.
9. Donini LM, Poggiogalle E, Molfino A, Rosano A, Lenzi A, Rossi Fanelli F, et al. Mini-Nutritional Assessment, Malnutrition Universal Screening Tool, and Nutrition Risk Screening Tool for the Nutritional Evaluation of Older Nursing Home Residents. J Am Med Dir Assoc. 2016;17(10):959.e11-8.
10. Lee PH, Macfarlane DJ, Lam TH, Stewart SM. Validity of the International Physical Activity Questionnaire Short Form (IPAQ-SF): a systematic review. Int J Behav Nutr Phys Act. 2011;21(8):115.
11. Uslu H, Tosun M, Doğan S. Thorax Computed Tomography Imaging Findings Of Covid-19 At Kocaeli University. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi. 2021;7(1):78-82.
12. Petrilli CM, Jones SA, Yang J, Rajagopalan H, O’Donnell L, Chernyak Y, et al.Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study. BMJ. 2020;369:m1966.
13. Zuin M, Rigatelli G, Zuliani G, Rigatelli A, Mazza A, Roncon L. Arterial hypertension and risk of death in patients with COVID-19 infection: Systematic review and meta-analysis. J Infect. 2020;81(1):e84-6.
14. Boudjeltia KZ, Faraut B, Stenuit P, Esposito MJ, Dyzma M, Brohée D, et al.Sleep restriction increases white blood cells, mainly neutrophil count, in young healthy men: a pilot study. Vasc Health Risk Manag. 2008;4(6):1467-70.
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16. Liu Y, Sun W, Guo Y, Chen L, Zhang L, Zhao S, et al. Association between platelet parameters and mortality in coronavirus disease 2019: Retrospective cohort study. Platelets. 2020;31(4):490-6.
17. Morrell CN, Aggrey AA, Chapman LM, Modjeski KL. Emerging roles for platelets as immune and inflammatory cells. Blood. 2014;123(18):2759-67.
18. Saito H, Nomura K, Hotta M, Takano K. Malnutrition induces dissociated changes in lymphocyte count and subset proportion in patients with anorexia nervosa. Int J Eat Disord. 2007;40(6):575-9.
19. Li T, Zhang Y, Gong C, Wang J, Liu B, Shi L, et al. Prevalence of malnutrition and analysis of related factors in elderly patients with COVID-19 in Wuhan, China. Eur J Clin Nutr. 2020;74(6):871-5.
20. Kaya T, Açıkgöz SB, Yıldırım M, Nalbant A, Altaş AE, Cinemre H. Association between neutrophil-to-lymphocyte ratio and nutritional status in geriatric patients. J Clin Lab Anal. 2019;33(1): e22636.
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Yildiz Yigit, Nuriye Esen Bulut, Cem Nazikoglu. The effect of lifestyle on the course of COVID-19 infection. Ann Clin Anal Med 2022;13(10):1075-1079
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Predictors of mortality after traumatic splenectomy and factors affecting prognosis
Serdar Oter 1, Metin Yalcin 2
1 Department of Gastroenterological Surgery, Manisa City Hospital, Manisa, 2 Department of General Surgery, Antalya Training and Research Hospital, Antalya, Turkey
DOI: 10.4328/ACAM.21215 Received: 2022-04-27 Accepted: 2022-06-20 Published Online: 2022-06-21 Printed: 2022-10-01 Ann Clin Anal Med 2022;13(10):1080-1083
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 spleen is the second most commonly injured abdominal organ in both penetrating and blunt trauma. Although mortality rates after splenectomy vary according to the indications for splenectomy, they are 0.97-6.04 times higher than in the general population. The aim of this study is to determine the mortality determinants and factors affecting prognosis after traumatic splenectomy.
Material and Methods: A retrospective study was designed. Patients who underwent emergent surgery for traumatic splenectomy in our clinic were evaluated between July 2009 and December 2020
Results: A total of 107 patients were included in the study. The mean age was 30.16 ±12.11 years (min-max: 16-68 years). In the postoperative period, according to the Clavien-Dindo classification, 34 (31. 80%) complications were grade 1-2 and 5 (4.70%) were grade 3 and early mortality was seen in 19 (17.80%) patients. When the data were analyzed, it was found that the development of postoperative complications, the development of complications of 3 or more according to the Clavian- Dindo classification, and the high number of injured organs in addition to spleen injury were found to be statistically significant for worsening prognosis and development of mortality (p<0.0001 for all three factors).
Discussion: Our study has shown that the development of postoperative complications, the development of complications of three or more according to the Clavian- Dindo classification, and the high number of injured organs in addition to spleen injury are poor prognostic factors in determining the prognosis after splenectomy due to trauma and are factors that increase mortality.
Keywords: Traumatic Splenectomy, Predictors, Mortality, Prognosis
Introduction
The spleen is the second most commonly injured abdominal organ in both penetrating and blunt trauma. In 1783, Scottish surgeon John Ferguson performed the first splenectomy for trauma [1]. After that, splenectomy was used as the main surgery for spleen injuries, even if there were minor injuries for years [2]. Spleen injury occurs in approximately 32% of patients with blunt abdominal trauma [3]. The role of the spleen in the immune response has led to greater efforts to protect the spleen after injury [3]. Today, methods such as non-surgical monitoring of the injured spleen, splenorrhaphy or partial splenectomy are used according to the etiology of the injury and the severity of the injury [4, 5]. Preserving spleen function, avoiding sepsis after splenectomy, and preventing complications of thrombosis or laparotomy can be counted among the advantages of spleen preservation [5]. Late intra-abdominal bleeding is the main problem in non-surgical follow-up or after spleen-sparing surgery. Therefore, splenectomy should be considered if a good follow-up cannot be done or the stage of the injury is not suitable for spleen-sparing treatment [4, 5].
Although the mortality rates after splenectomy vary according to the indications for splenectomy, they are 0.97-6.04 times higher than in the general population [5]. Death rates associated with spleen injury in a previous study were 18%; these high death rates were probably secondary to associated injuries and related post-traumatic complications [6, 7, 8].
The aim of this study is to determine the mortality determinants and the factors affecting the prognosis after traumatic splenectomy.
Material and Methods
A retrospective study was designed after receiving the local ethical committee’s approval. Patients who underwent emergent surgery for traumatic splenectomy in our clinic were evaluated between July 2009 and December 2020. The study was approved by the Ethics Committee of the Medical Faculty of … University (Date: 21/06/2021; Decision No: HHRU/21.12.01).
Inclusion criteria: Patients over 16 years of age who underwent emergency surgery for traumatic splenectomy were included.
Exclusion criteria: Elective cases, splenectomy performed for benign reasons, splenectomy due to other cancer involvements, patients who performed splenography or partial splenectomy, patients with immunocompromised status or pregnancy and patients with missing data were excluded.
Open laparotomy was preferred in all operations. All operations were performed with a midline laparotomy incision. After surgery, all patients were vaccinated to prevent encapsulated bacterial infections.
Age, gender, peroperative amount of blood loss, cause of the accident, mechanism of injury, stage of the splenic injury, additional organ injury, number of transfusions, surgical procedure, hospitalization period, complication in the postoperative period, state of the early mortality and cause of early mortality were retrospectively collected and evaluated. Patients who developed complications and mortality after splenectomy were found and the factors affecting mortality and prognosis in these patients were examined.
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 numbers and percentages. Continuous variables were compared using Unpaired – T tests and p values were calculated. Categorical variables were compared using the Fisher exact test and p-value was estimated. The p<0.05 was considered statistical significance.
Results
A total of 107 patients were included in the study. Among these patients, who emergent open splenectomy for splenic injury, males predominated; 92 (86%) were male, 15 (14%) were female. The male to female ratio was 6.13:1. The mean age was 30.16 ±12.11 years (min-max: 16-68 years). Demographic and clinical findings of the patients are summarized in Table 1. The stage of the splenic injury was grade 3 in 17 (48.59%), grade 4 in 55 (51.40%) and grade 5 in 40 (37.38%) patients The mean operative time was 155.60 ± 88.16 (min-max: 80-720) minutes. The median amount of blood loss during the operation was 600 ml (min-max: 200-5000 ml). The median number of transfusions of the erythrocyte suspension was 2 bags (min-max: 0-6 bags). The most common additional organ injury was the left kidney in both blunt and penetrating trauma (Table 2). The mean postoperative hospital stay was 11.65 ± 9.33 days (min-max: 1-57). In the postoperative period, according to the Clavien-Dindo classification, 34 (31. 80%) complications were grade 1-2 and 5 (4.70%) were grade 3, and early mortality was seen in 19 (17.80%) patients. The commonest complication was surgical site infection in 14 cases (13.1%), while atelectasis was observed in 10 cases (9.3%). Forty-nine cases (45.8%) of patients had no complications. All surgical site infections were healed with drainage, dressing of the wound and antibiotics. Postoperative complications are summarised in Table 3. The first 30-day mortality during the postoperative period was 19 (17.80%). The cause of mortality was multi-organ dysfunction syndrome in the postoperative first day in 14 patients, sepsis in 2 patients, massive pulmonary embolism in 2 patients and myocardial infarction in 1 patient.
When the data were analyzed, it was found that the development of postoperative complications, the development of complications of 3 or more according to the Clavian- Dindo classification, and the high number of injured organs in addition to spleen injury were found to be statistically significant for worsening prognosis and development of mortality. (p<0.0001 for all three factors). No statistical significance was found in terms of age, gender, mean amount of bleeding during surgery, mean amount of erythrocyte suspension replaced during surgery, and the effect of operative time on prognosis or mortality. (0.39, 0.46, 0.27, 0.43, 0.74, respectively).
Discussion
The spleen is one of the most frequently injured organs after trauma. The mortality rate after spleen injury has been reported between 7.6%-13% [8,9,10]. This study was designed to determine the factors affecting the prognosis and mortality in patients who underwent post-traumatic splenectomy and development of postoperative complications, the development of complications of 3 or more according to the Clavian- Dindo classification, and the high number of injured organs in addition to spleen injury were found to be statistically significant for worsening prognosis and development of mortality. Our mortality rate was 17.7%.
In the previous study, male dominance was seen in traumatic splenectomy patients [11]. In our study, 92 (86%) of the patients were male, 15 (14%) were female, and the male to female ratio was 6.13:1.
In our study, complications in the postoperative period were seen in 54.20 % of the cases. Our results are similar to those given in the literature [11,12]. Recent literature reported that the most common complication was pneumonia, followed by Surgical site infections. In our study, the results were different from this. The most common complications were surgical site infections, followed by atelectasis and pneumonia [11]
There are articles in the literature suggesting that patients with Grade III spleen injury and traumatic brain injury should undergo splenectomy, since hypotension due to traumatic brain injury will double the mortality [13,14]. In our study, 7 patients had spleen injury and traumatic brain injury, and splenectomy was performed in all these patients.
In the literature, Omer at al. reported that the mortality rate in their study was 7.9%. Our mortality rate was 17.7% [15]. This difference in mortality rate is due to the difference in mortality determining factors in the two study groups. Therefore, risk factors determining mortality were investigated in our study, and the development of postoperative complications, the development of complications of three or more according to the Clavian- Dindo classification, and the high number of injured organs in addition to spleen injury were to be statistically significant for worsening prognosis (p<0.0001 for all three factors).
Limitations of our study; Since it is a retrospective study and a single center experience, the number of cases is low.
Conclusion
Our study has shown that the development of postoperative complications, the development of complications of three or more according to the Clavian- Dindo classification, and the high number of injured organs in addition to spleen injury are poor prognostic factors in determining the prognosis after splenectomy due to trauma and are factors that increase mortality. Since the risk of mortality will increase in patients with these factors, more care should be taken in their management.
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. Dionigi R, Boni L, Rausei S, Rovera F, Dionigi G. History of splenectomy. Int J Surg. 2013; 11(Suppl. 1): 42-3.
3. Amirkazem VS, Malihe K. Randomized clinical trial of ligasure TM versus conventional splenectomy for injured spleen in blunt abdominal trauma. Int J Surg. 2017; 38:48-51.
4. Atiya AM, El Sageer EM. Different modalities in management of splenic trauma. MJMR. 2016; 27:72–83.
5. Rosati C, Ata A, Siskin GP, Megna D, Bonville DJ, Stain SC. Management of splenic trauma: a single institution’s 8-year experience. Am J Surg. 2015; 209(2): 308-14.
6. Kristinsson SY, Gridley G, Hoover RN, Check D, Landgren O. Long-term risks after splenectomy among 8,149 cancer free American veterans: a cohort study with up to 27 years follow-up. Haematologica. 2014; 99(2): 392-8.
7. El Gammala AS, Abo Ghidab AM, Nabila AM. Different treatment modalities in traumatic splenic injuries. Menoufia Medical Journal. 2020; 33(4):1322-7.
8. Uslukaya Ö, Bozdag Z, Gumus M, Turkoglu A, Böyük A, Yılmaz EE, et al. Factors affecting mortality in patients with splenic injuries. Ann Ital Chir. 2018; 89(1):51-5.
9. Johnsen NV, Betzold RD, Guillamondegui OD, Dennis BM, Stassen NA, Bhullar I, et al. Surgical management of solid organ injuries. Surgical Clin. 2017; 97(5):1077-85.
10. Jabbour G, Al-Hassani A, El-Menyar A, Abdelrahman H, Peralta R, Ellabib M, et al. Clinical and radiological presentations and management of blunt splenic trauma: a single tertiary hospital experience. Med Sci Monit. 2017; 23:3383-92.
11. Rode A, Bansod PY, Gaikwad U, Pind VR, Kulkarni TV, Mandhare AV, et al. Clinical review of splenic trauma in central India: a prospective observational study. Int Surg J. 2021; 8(10):2951-5.
12. Cadili A, De Gara C. Complications of splenectomy. Am J Med. 2008;121(5):371-5.
13. Stockinger Z, Grabo D, Benov A, Tien H, Seery J, Humphries A. Blunt Abdominal Trauma, Splenectomy, and Post-Splenectomy Vaccination. Mil Med. 2018; 183(Suppl. 2):98-100.
14. Alabbasi T, Nathens AB, Tien CH. Blunt splenic injury and severe
brain injury: a decision analysis and implications for care. Can J Surg.
2015; 58(3 Suppl. 3): 108–17.
15. Emre A, Sanli AN. Splenectomy indications and postoperative follow-up results of a department of general surgery. Ann Med Res. 2018; 25(2):241-5.
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Serdar Oter, Metin Yalcin. Predictors of mortality after traumatic splenectomy and factors affecting prognosis. Ann Clin Anal Med 2022;13(10):1080-1083
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The effect of perioperative hypotension on perfusion index in infants in cesarean delivery with spinal anesthesia
Erdinç Koca
Department of Anesthesiology and Reanimation, Malatya Training and Research Hospital, Malatya, Turkey
DOI: 10.4328/ACAM.21216 Received: 2022-04-27 Accepted: 2022-06-16 Published Online: 2022-06-20 Printed: 2022-10-01 Ann Clin Anal Med 2022;13(10):1084-1087
Corresponding Author: Erdinç Koca, Department of Anesthesiology and Reanimation, Malatya Training and Research Hospital, Malatya, Turkey. E-mail: drerdinckoca@hotmail.com P: +90 530 223 96 25 / +90 530 223 96 24 F: +90 422 325 34 38 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6691-6711
Aim: The perfusion index (PI) is maintained as the rate of pulsatile blood flow to nonpulsatile flow in the peripheral extremity and is used as a rapid indicator of microcirculatory changes.
Material and Methods: Fifty patients a gestational age of 38-42 weeks and a planned elective cesarean were included in our study. Patients who did not develop hypotension after spinal anesthesia and were not administered ephedrine (Group 1) and newborn patients who developed hypotension and needed ephedrine (Group 2) were divided into 2 groups.
Results: There was no statistical difference in PVI and PI measurements between Group1 and Group 2.
Discussion: Negative effects on PI, PVI and APGAR scores that may develop in the newborn can be prevented with rapid and adequate fluid replacement and appropriate vasoconstrictive treatment.
Keywords: Perfusion Index, Cesarean, Hypotension, Newborn
Introduction
Evaluation of perfusion in peripheric tissues is best achieved through simple and noninvasive monitoring methods, one of which is the PI. When based on the new-generation pulse oximetry signal, PI has been shown to indicate precise and real-time alterations in peripheric blood flow [1]. In addition, the plethysmographic variability index (PVI) allows for continuous, noninvasive dynamic follow-up of circulating blood volume and has been reported to evaluate fluid replacement [2].
Despite the advantages of spinal anesthesia, including speed of administration and effective sensory and motor blockage, hemodynamic instability following such anesthesia for cesarean surgery remains quite a severe complication [3]. The severity and duration of hypotension are more important than the development of hypotension after spinal anesthesia. It has been emphasized in many studies that when hypotension is treated quickly, it does not result in harm to the fetus or affect Apgar scores, but a prolonged period of hypotension reduces uteroplacental blood flow. This causes fetal acidosis and a lower Apgar score is seen. [4].
Ephedrine has been recommended for decreasing the frequency of hypotension [5]. It has direct and indirect action pathways, especially activating beta receptors (β1 and β2). However, it may lead to supraventricular tachycardia, tachyphylaxis, and fetal acidosis [6].
In this study, our goal was to analyze the influence of perioperative maternal hypotension on newborn PI and PVI values.
Material and Methods
Our study was conducted in the Anesthesia Clinic of the XXX Training and Research Hospital, with the approval of the ethics committee in 2021. Fifty patients at 38–42 weeks of gestation and who had planned an elective cesarean were included in our study. Patients requiring emergency surgery, patients above maternal ASA 2 (American Society of Anesthesiology), patients whose newborns showed the presence of congenital disease, patients with newborns with a low Apgar score after birth, and those whose newborn showed the presence of respiratory and/or cardiac anomalies as a result of chorioamnionitis were excluded. The patients were divided into two groups: those who did not develop hypotension after spinal anesthesia and were not administered ephedrine (group 1) and those who developed hypotension and needed ephedrine (group 2). A decrease of more than 30% from the basal value or a decrease below 90 mmHg was considered hypotension. All newborns had 1st and 5th minute Apgar scores recorded, and at the 5th minute after birth, the Masimo Radical 7 (Masimo Corp., Irvine, CA, USA) pulse oximeter probe was attached to the index finger of the right hand (preductal) and protected from light (Figure 1). HR (Heart Rate), SpO2 (peripheral capillary oxygen saturation), PI, and PVI were recorded. Measurements were taken with the above pulse oximeter when the newborn was calm and not crying.
Statistical Method
Data analysis was carried out using the IBM SPSS version 26.0 statistical program (Chicago, IL, USA). Skewness and Kurtosis values were used to test the normality of the data distribution. Descriptive statistics data were presented as means and standard deviations for the quantitative variables. Demographic data of the groups were compared with one-way analysis of variance (one-way ANOVA). Mixed-design ANOVA was employed to analyze significant differences between the groups with repeated measurements. For the sphericity assumption, Mauchly’s test and MANOVA were used. Duncan’s test was chosen for the between-group post-hoc test. Bonferroni adjustment was made for confidence interval correction. Significant differences in group means (PI and PVI) for newborns were evaluated by independent samples t-test. A p-value of <0.05 was accepted as numerically significant.
Results
In our study, 50 newborns delivered by cesarean under spinal anesthesia were included. Of the newborns, 22 were female and 28 were male. The mean week of delivery was 39 in group 1 and 39.04 in group 2. The newborns’ birth weights were 3240 grams in group 1 and 3378.2 grams in group 2. Apgar values in group 1 were calculated as 8.6 at the 1st minute and 9.2 at the 5th minute, and in group 2, they were 8.4 at the 1st minute and 9.2 at the 5th minute. Peripheral SpO2 was measured as 93.28 in group 1 and 93.8 in group 2. When the maternal data were analyzed, the mean age in group 1 was 31.24 years and the mean age in group 2 was 27.84 years; maternal group 1 was measured as PVI 17.52 and PI 2.9 and group 2 was PVI 17 and PI 2.52 (Table 1). There was no statistical difference in PVI and PI measurements between group 1 and group 2 (Table 2) (Figure 2-3). In the measurements, the PVI values of the group that did not develop hypotension were lower than those of the other group. Similarly, the PI values of group 1 were higher than those of group 2. There was no statistical difference in terms of 1st and 5th minute Apgar scores.
Discussion
PI is the rate of pulsatile to non-pulsatile blood flow in the peripheral extremity and is used as a rapid indicator of microcirculatory changes. These parameters provide continuous information about tissue perfusion in a noninvasive manner. Due to its ease of use, it has become the preferred hemodynamic monitoring method in patient follow-up [7].
Kumar and Nadkarni defined alterations in PI values as an outcome of local vasoconstriction (low PI) or vasodilation (increased PI) in the skin [8]. Before the measurement, the newborn was protected from hypothermia and peripheral vasoconstriction was prevented. In particular, lower PI values (≤1.24) have been reported to be a precise indicator for evaluating the seriousness of neonatal pathology. Additionally, primary PI monitoring has been noticed to be beneficial in identifying preterm and term neonates with chorioamnionitis [9]. In our study, we included newborns who did not have any pathology in their follow-ups.
A reduced PI value in the pre-anesthesia period of elective cesarean surgery is a maternal indicator of an increased risk of neonatal morbidity, particularly resulting from early respiratory complications [10]. Increased anxiety is also known to affect vascular tone [11]. We took the PI measurement starting in the 10th minute, during a period when the newborn was calm and no crying was expected. The readings on the device were followed for 10 minutes, and when they stabilized to a certain value, the recording was made. Pathological circumstances, including neonatal sepsis, hypovolemia, and left-to-right shunting congenital heart ailments commonly develop in preterm neonates in the transitional phase and may have a negative effect on microvascular blood flow and cardiovascular coherence in the primary neonatal period [12].
PVI is a beneficial technique due to its advantages, including noninvasiveness, a simple-to-place sensor, and continuous bedside measurement [13]. PVI evaluates rates of nonpulsatile (AC) to pulsatile blood flow (DC) in the capillary bed [7]. A recent article stated that PVI correlates well with cardiac preload indices [14]. It is also a predictor of the dynamic changes in PI that occur in the course of respiratory periods [15].
The most common and undesirable side effect of spinal anesthesia, which is the preferred method of anesthesia in elective cesarean sections, is maternal hypotension. Uterine blood flow reduction, fetal acidosis, neonatal depression, and maternal nausea and vomiting may occur due to hypotension resulting from sympathetic blockade [16]. In our study, a decrease of more than 30% in the basal value or a decrease below 90 mmHg was considered hypotension. When hypotension developed, IV (Intravenous) fluid replacement and IV ephedrine [10 mg] were administered.
It may cause hypotension, sweating, dizziness, nausea, pulmonary aspiration and cardiac arrest in pregnant women after spinal anesthesia. [17]. Hypotension, which can be seen in 80–90% of cesarean sections in which spinal anesthesia is applied, can have harmful effects on the mother and newborn. Despite research and discussions over the last 10 years, hypotension continues to be the most common side effect associated with sympathetic blockade in this type of surgery [4]. Both phenylephrine and ephedrine are employed to control maternal blood pressure during spinal anesthesia in such surgeries. Since there is no phenylephrine in our country, only ephedrine is used. The latter is the preferred vasopressor for maintaining uteroplacental blood flow in obstetric anesthesia and can be used prophylactically or as an IV bolus or IV infusion in case of hypotension [4]. IV bolus ephedrine was administered to our patients who developed hypotension.
Apgar scoring is frequently used to immediately assess the clinical condition of neonates [18]. The scoring, which is carried out at the 1st, 5th, and (infrequently) 10th minute following birth, analyzes the neonate’s cardiac rhythm, respiration, muscle tone, reflex reply, and skin color [19]. Maternal hypotension due to regional anesthesia can influence uteroplacental blood flow, leading to fetal acidosis, asphyxia, and lower Apgar scores [20]. It is preferable to prevent hypotension, which is dangerous for the mother and more so to the child, rather than allowing it to affect the fetus. Blood pressure is commonly ensured in the face of vasodilation, which is induced due to elements other than central neural blockage, via a reflexive rise in cardiac output. However, when spinal-provoked venodilation is present, venous return is decreased to the extent that cardiac output cannot rise and is commonly decreased. The outcome is serious hypotension with lower uteroplacental perfusion and Apgar scores [21]. In their study examining the effect of Mon at al regional anesthesia on newborn Apgar scores, it was determined that the rate of fetal acidosis was higher in the regional anesthesia group, especially in the ephedrine group [22]. In our study, no statistical difference was observed in Apgar scores and PI values between the two groups. Maternal SBP (systolic blood pressure) of 80 mmHg for 5 minutes generally leads to hypoxic fetal bradycardia [23].
In our clinic, starting from the preoperative period in cesarean section surgeries, a preliminary fluid loading with crystalloid and colloid fluids is conducted, and the surgery is performed with spinal anesthesia. When perioperative hypotension occurs, a 10 mg ephedrine IV is administered in repeated doses. In terms of vasopressors, ephedrine (a mixed α- and β-agonist) was formerly proposed as the preferred agent in obstetrics, but there is currently increasing proof that it has the tendency to reduce fetal pH and base surplus [6]. Now, phenylephrine is considered to have a high impact, low placental transmission, and less tendency to suppress fetal pH [24].
Despite its promising results, our study has some limitations, including the lack of long-term PI and PVI monitoring, not checking the blood gas values of the newborns, and the limited number of participants.
Conclusion
In our opinion, similar results for PI, PVI, and Apgar scores between the two groups were caused by preoperative fluid replacement, as well as rapid intervention in maternal hypotension and circulation through uteroplacental autoregulation. We concluded that the adverse effects of maternal hypotension on newborns can be prevented with adequate fluid replacement and appropriate vasoconstrictive treatment.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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3. Klöhr S, Roth R, Hofmann T, Rossaint R, Heesen M. Definitions of hypotension after spinal anesthesia for caesarean section: Literature search and application to parturients. Acta Anaesthesiol Scand. 2010; 54(8): 909-21.
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5. Macarthur A, Riley ET. Obstetric anesthesia controversies: vasopressor choice for postspinal hypotension during cesarean delivery. Int Anesthesiol Clin. 2007; 45(1):115-32.
6. Ngan Kee WD, Khaw KS, Tan PE, Ng FF, Karmakar MK. Placental transfer and fetal metabolic effects of phenylephrine and ephedrine during spinal anesthesia for cesarean delivery. Anesthesiology. 2009; 111(3): 506-12.
7. Chu H, Wang Y, Sun Y, Wang G. Accuracy of pleth variability index to predict fluid responsiveness in mechanically ventilated patients: a systematic review and meta-analysis. J Clin Monit Comput. 2016; 30(3): 265-74.
8. Kumar A, Nadkarni AV. The variability of perfusion index as a new parameter in different types of anaesthesia techniques and its correlation with surgical stress and recovery from anesthesia: an observational clinical study. Journal of Medical Science and Clinical Research. 2017; 5(1): 15196–265.
9. De Felice C, Toti P, Parrini S, Del Vecchio A, Bagnoli F, Latini G, et al. Histologic chorioamnionitis and severity of illness in very low birth weight newborns. Pediatr Crit Care Med. 2005; 6(3): 298–302
10. De Felice C, Leoni L, Tommasini E, Tonni G, Toti P, Del Vecchio A, et al. Maternal pulse oximetry perfusion index as a predictor of early adverse respiratory neonatal outcome after elective cesarean delivery. Pediatr Crit Care Med. 2008; 9(2):203–8.
11. Amiya E, Watanabe M, Komuro I. The relationship between vascular function and the autonomic nervous system. Ann Vasc Dis. 2014; 7: 109-19.
12. Stark MJ, Clifton VL, Wright IMR. Microvascular flow, clinical illness severity and cardiovascular function in the preterm infant. Arch Dis Child Fetal Neonatal Ed. 2008; 93(4): 271-4.
13. Feldman JM, Sussman E, Singh D Friedman BJ. Is the pleth variability index a surrogate for pulse pressure variation in a pediatric population undergoing spine fusion? Paediatr Anaesth. 2012; 22(3):250-5.
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16. Mercier FJ. Fluid loading for cesarean delivery under spinal anesthesia: have we studied all the options. Anesth Analg 2011; 113(4): 677–80.
17. Balki M, Carvalho JC. Intraoperative nausea and vomiting during cesarean section under regional anesthesia. Int J Obstet Anesth. 2005; 14(3): 230-41.
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Effect of obesity on thiol/disulfide balance in patients with polycystic ovary syndrome
Selda Songur Dağlı 1, Bilal İlanbey 2
1 Department of Obstetrics and Gynecology, 2 Department of Medical Biochemistry, Faculty of Medicine, Kirsehir Ahi Evran University, Kirsehir, Turkey
DOI: 10.4328/ACAM.21217 Received: 2022-04-29 Accepted: 2022-06-21 Published Online: 2022-06-22 Printed: 2022-10-01 Ann Clin Anal Med 2022;13(10):1088-1091
Corresponding Author: Selda Songur Dağlı, Department of Obstetrics and Gynecology, Faculty of Medicine, Kirsehir Ahi Evran University, Kirsehir, 40100, Turkey. E-mail: seldasongurdagli@hotmail.com P: +90 542 316 06 25 Corresponding Author ORCID ID: https://orcid.org/0000-0003-4887-4818
Aim: In this study, we aimed to investigate the hypothesis that thiol/disulfide balance is similar in patients with PCOS with and without obesity.
Material and Methods: This was a prospective study. Seventy-eight patients with PCOS were included in the study. A diagnosis of PCOS was made according to the Rotterdam criteria. The patients were divided into two groups as obese [n = 41, body mass index (BMI) ≥30 kg/m²] and non-obese (n = 37, BMI >18.5 and <30 kg/m²).
Results: Native thiol and total thiol values were significantly lower in the oxidative stress test in the non-obese group than in the obese group (p = 0.021 and p = 0.019, respectively). There was no statistically significant difference in other thiol-disulfide parameters between the groups. Luteinizing hormone (r = -0.293, p = 0.09), total thiol (r = -0.321, p = 0.04), native thiol (r = -0.330, p = 0.03) and disulfide (r = -0.272, p = 0.16) rates were found to be statistically significantly negatively correlated with BMI.
Discussion: Obesity in PCOS affects thiol-disulfide hemostasis. There is a negative correlation between BMI and oxidative stress markers.
Keywords: Polycystic Ovary Syndrome, Obesity, Thiol, Oxidative Stress, Body Mass Index
Introduction
Polycystic ovary syndrome (PCOS), one of the most common endocrine disorders of the reproductive age, was first described by Stein and Leventhal in 1935 [1]. The syndrome causes many endocrine and metabolic disorders in the reproductive period and all periods of life. PCOS is a public health problem that also affects a person’s quality of life. Obesity, which is a widespread problem today, often accompanies this syndrome. Different criteria are used to diagnose PCOS, and the prevalence of the disease varies according to the diagnostic criteria. According to Rotterdam criteria, the prevalence of PCOS in Turkey is 19.9% [2].
Oxidative stress increases in PCOS [3]. Redox sensitivity transcription factors regulate cell differentiation and apoptosis. In PCOS, due to the mildly increased inflammatory response, adequate antioxidation cannot be provided, and cellular necrosis develops. In PCOS, which is insulin resistant, insulin receptor substrate decreases and glucose uptake in muscle and adipose tissue is impaired. In cases of increased oxidative stress, intracellular calcium balance is also disturbed, mitochondria failure develops, ATP synthesis is distressed, resulting in follicular collapse. Oxidized proteins lose their function as proteins and can act as proinflammatory mediators. In addition, fatty acids in plasma and organelle membranes are transformed at a higher rate in PCOS. DNA oxidation markers are shown to be high in PCOS.
When DNA oxidation increases and the anti-oxidation mechanism cannot function adequately, transformation into cancer also increases [4].
Oxidative stress is high in obesity. Cytokines that accumulate in adipose tissue cause a proinflammatory reaction, which increases oxidative stress [5].
Thiol-disulfide homeostasis is one of the indicators of oxidative stress.
Native thiol binds with sulfide, oxidizes, and forms disulfide. In response to this, with the work of the antioxidant mechanism, sulfide bonds are separated and turn into native thiol again. The total thiol level is equal to the sum of native thiol and disulfide [6]. In thiol-disulfide tests, native thiol, total thiol, disulfide, disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol ratios are evaluated. Thus, oxidative stress increases with increasing disulfide concentration. Many studies are examining the oxidative stress balance in the current literature. However, a gold standard test has yet to be demonstrated.
In the last few decades, there has been an increase in studies examining oxidative stress levels with thiol-disulfide hemostasis. Erel et al. developed an inexpensive and easy calorimetric method that examined thiol-disulfide hemostasis. This method is frequently used in modern research. In the current literature, studies are examining oxidative stress levels in PCOS. However, the studies examining the effect of obesity on the oxidative stress level in PCOS are not sufficient. We planned this prospective, controlled study to support the literature on this topic.
In our study, we aimed to investigate the hypothesis that thiol/disulfide balance is similar in patients with PCOS with and without obesity.
Material and Methods
Study design
The study population was formed from patients who presented to Kırşehir Training and Research Hospital Gynecology and Obstetrics Outpatient Clinic between March 2020 and September 2020. Seventy-eight patients who were diagnosed with PCOS were included in the study.
Inclusion criteria
The diagnosis of PCOS was made in the presence of at least two of the Rotterdam criteria [7]. Rotterdam criteria: (1) Oligo- or anovulation, (2) Clinically and/or biochemically diagnosis of hyperandrogenism, (3) Polycystic-looking ovaries.
Exclusion criteria
(1) Congenital adrenal hyperplasia, (2) androgen-secreting tumor, (3) Cushing syndrome, (4) prolactinoma, (5) thyroid disorders, (6) known infectious diseases, (7) known chronic inflammatory diseases, (8) pregnancy, (9) chronic systemic disease (such as diabetes mellitus, hypertension, chronic obstructive pulmonary disease, liver or kidney dysfunction), and (10) body mass index (BMI) <18.5 kg/m2.
Sample collection
Gynecologic examinations and height-weight measurements of the included patients were made, BMI calculation weight (kg) / (height) 2 (m2). The patients were divided into two groups as obes (n = 41, BMI ≥30 kg/m²) and non-obese (n = 37, BMI >18.5 and <30 kg/m²) (Organization WHO. Guide for the formulation of a WHO Country Cooperation Strategy. 2014).
Sample preparation and laboratory analysis
Venous blood sampling of the patients was performed on days 3-5 of their spontaneous or induced menstrual cycles.
Hormone analysis
Levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone, and dehydroepiandrosterone sulfate (DHEA-s) were examined in serum using a Cobas e801 analyzer (Roche Diagnostics, Germany). C-reactive protein (CRP) was analyzed using a Cobas c702 (Roche Diagnostics) autoanalyzer. Homeostatic model assessment-insulin resistance (HOMO-IR) was calculated using the following formula: Insulin × glucose / 405 mg/dL.
Thiol- disulfide analysis
Venous blood samples were also centrifuged at 3000 rpm and stored at -80°C until the analysis date. Thiol/disulfide homeostasis was evaluated using the spectrophotometric method developed by Erel et al. [6].
Ethical considerations
This prospective study was planned according to the current Helsinki criteria. Ethical approval for the study was obtained from Kırşehir Ahi Evran University Faculty of Medicine Clinical Research Ethics Committee (Decision number 2020-19/141).
Statistical analysis
Statistical analyses were performed using the SPSS version 25 software package (SPSS In., Chicago, IL, USA). Whether continuous variables had normal distribution was analyzed using the Kolmogorov-Smirnov test, and the homogeneity of variables was analyzed using the Levene test. Student’s t-test was used for the comparison of the groups. Correlations between variables were evaluated using Pearson’s correlation coefficient. P values less than 0.05 were considered statistically significant. Data are given as mean ± standard deviation (SD).
Results
Thirty-seven obese and 41 non-obese patients with PCOS were included in the study. The mean age of the two groups was 23.86 ± 5.00 years for the obese group and 22.00 ± 3.85 years for the non-obes group. The mean BMI was 36.21 ± 5.47 kg/m² in the obese group and 23.85 ± 3.27 kg/m² in the non-obese group.
Comparison of blood values between the two groups is given in Table 1. LH was significantly higher in the non-obese group (p=0.002). HOMA-IR, there was a statistically significant difference between the two groups (p = 0.012). There was no significant difference between FSH, total testosterone, and DHEA-s (p = 0.908, p = 0.105, p = 0.604).
Table 2 shows the thiol-disulfide results of the groups. Native thiol and total thiol values were significantly lower in the oxidative stress test group in the non-obese group than in the obese group (p = 0.021 and p = 0.019, respectively). There was no statistically significant difference in other thiol-disulfide parameters between the groups.
Table 3 shows the results of the correlation analysis of thiol/disulfide values with BMI and hormone parameters. LH (r = -0.293, p = 0.09), total thiol (r = -0.321, p = 0.04), native thiol (r = -0.330, p = 0.03) and disulfide (r = -0.272, p = 0.16 ) rates were found to be statistically significantly negatively correlated with BMI. There was a positive correlation between HOMA-IR and CRP (r = 0.393, P < 0.001) and BMI (r = 0.347, p = 0.002). A negative correlation was found between CRP and total testosterone (r = -0.260, p = 0.22), DHEA-s (r = -0.286, p = 0.012), BMI (r = -0.229, p = 0.045), native thiol (r = -0.229, p = 0.045), disulfide/native thiol (r = -0.260, p = 0.22), disulfide/total thiol (r = -0.286, p = 0.12), native thiol/total thiol (r = -0.237, p = 038).
Discussion
This study compared thiol-disulfide hemostasis and we found that native and total thiol among oxidative stress markers in obese patients with PCOS were lower than in non-obese patients. There was a negative correlation between native thiol, total thiol, and disulfide ratios and BMI.
Özler et al. compared thiol-disulfide homeostasis between two groups with and without obesity in adolescents with PCOS. In this study, native and total thiol levels were significantly lower in patients with obesity, similar to our findings [8]. In addition, in our study in the adult group, disulfide levels were negatively correlated with BMI. In another study, the level of glutathione S-transferases (GSTs) was examined as an oxidative stress test. According to this study, the antioxidant mechanism in adolescents with PCOS is independent of obesity [9]. In our study, there was a significant negative correlation between oxidative stress factors and BMI. Yıldırım et al. compared patients with PCOS and a normal healthy group and concluded that antioxidant markers were higher in the non-obese group [10]. Our study compared obese and non-obese groups with PCOS and we found significant differences only in native and total thiol levels.
PCOS and oxidative stress levels have been evaluated with different tests and different results have been determined. Tola et al. evaluated neopterin (NEO) levels as a stress index in PCOS, and a significant elevation was found [11]. However, Dereli et al. examined serum malondialdehyde levels in patients with PCOS and found no significant difference between the normal population and those with PCOS [12]. Our study found that some antioxidative parameters were low in the obese PCOS group.
CRP increases due to inflammation in PCOS and obesity [13]. Elmas et al. found that CRP was higher in the obese group than in the non-obese group in children [14]. There was a negative correlation between BMI and antioxidant parameters [15]. In our study, we found a similar result in adults with PCOS.
We found that there was a negative correlation between LH and BMI. Pergola et al. stated that the increase in BMI suppressed gonadotropin secretion and had a negative correlation with LH and BMI [16]. Inflammatory factors are activated in PCOS and obesity. Insulin resistance also runs parallel with increasing BMI. Our study showed a positive correlation between HOMA-IR and CRP and BMI, which was consistent with the literature [17, 18].
A standard treatment option for PCOS cannot be offered because its etiopathogenesis has not yet been elucidated. Enlightening this mechanism will increase our treatment success. Oxidative stress may be the underlying disorder of PCOS or the result of the disease. Until the relationship between obesity and PCOS is clarified, larger case series and studies comparing different methods are required.
Limitations
Normal threshold values for thiol-disulfide parameters have not been established yet, and large series studies are needed for this.
Conclusion
Obesity in PCOS affects thiol-disulfide hemostasis. There is a negative correlation between BMI and oxidative stress markers.
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: Financial support for this work was provided by the Kirsehir Ahi Evran University, Turkey (Project number: TIP.A4.18.009).
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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The effect of a noise and light-reducing hat on the comfort and physiologic parameters of the preterm neonates
Özlem Akarsu 1, Serap Balcı 2
1 Department of Pediatric Nursing, Faculty of Health Sciences, Istanbul Medeniyet University, Istanbul, 2 Department of Pediatric Nursing, Florence Nightingale Faculty of Nursing, Istanbul University-Cerrahpasa, Istanbul, Turkey
DOI: 10.4328/ACAM.21219 Received: 2022-04-30 Accepted: 2022-06-08 Published Online: 2022-06-28 Printed: 2022-10-01 Ann Clin Anal Med 2022;13(10):1092-1097
Corresponding Author: Özlem Akarsu, Department of Pediatric Nursing, Faculty of Health Sciences, Istanbul Medeniyet University, Cevizli Campus, 34862, Kartal, Istanbul, Turkey. E-mail: ozlemakarsuu@gmail.com P: +90 539 373 87 13 Corresponding Author ORCID ID: https://orcid.org/0000-0001-7150-7683
Aim: This study was performed to evaluate the effect of hat that reduced noise and light on preterm neonatal comfort and physiologic parameters.
Material and Methods: This randomized controlled experimental study was conducted with 60 preterm newborns aged 32-37 weeks in a neonatal intensive care unit. The hat, which was developed by the researchers, was designed with and without a visor. The newborns were randomly divided into two groups (hat with a visor = 30 newborns, hat without a visor = 30 newborns). Each group also formed its own control group because all parameters in each group were measured before wearing the hat. The comfort of the newborns was evaluated using the “Premature Infant Comfort Scale.” Heart rate, oxygen saturation, and respiratory rate were also measured.
Results: It was found that there was a highly significant difference in terms of mean comfort score, heart rate, oxygen saturation, and respiratory rate of preterm newborns in the groups after wearing the hat compared with before the hat (p < 0.001). There was no significant difference between the groups in terms of comfort score, heart rate, oxygen saturation, and respiratory rate (p > 0.05).
Discussion: The use of the noise and light-reducing hat positively affected the comfort and physiologic parameters of the preterm newborns.
Keywords: Comfort, Hat, Light, Noise, Preterm Newborn
Introduction
Preterm newborns are exposed to high levels of noise and bright light during their stay in the neonatal intensive care unit (NICU) [1-3]. Noise and bright light are sources of stress for the newborn. Increasing stress in preterm newborns causes physiologic and behavioral reactions. They may have problems such as an increased heart rate and blood pressure, increased respiratory rate, decreased oxygen saturation, apnea, bradycardia, increased intracranial pressure, disturbances in sleep-wake pattern, hearing problems, changes in the transition period to oral nutrition, and weight loss. As a result, the comfort level of the preterm newborn decreased [1,3,4].
The American Academy of Pediatrics (AAP) recommends that the noise level in the NICU should be below 45 dBA during the day and 35 dBA at night [5]. However, in studies conducted in NICUs, it has been found that the noise level is well above the recommendations of the AAP [3,6,7]. Lighting is generally kept constant in NICUs, and this situation causes preterm newborns to be exposed to an excessive amount of light. Continuous illumination negatively affects the circadian rhythm of the newborn and causes disruption of the day/night cycle. The sleep quality of the newborn decreases, the duration of deep sleep decreases, and their growth and development, recovery, and hospital discharge processes are negatively affected [7,8]. However, attempts to reduce light and noise in NICUs can prevent these problems. These initiatives include regulation of the physical environment [9,10], use of double-walled incubators [11], incubator covers [12], training of healthcare professionals [6], earmuffs [13,14], light-stimulating decibel meters [15], cyclic lighting [8,16], and silent time applications [17,18]. These interventions reduce bright light and noise-induced stress behaviors in the preterm newborns hospitalized in NICUs, and their comfort levels increase accordingly. It is very important to evaluate and increase comfort in preterm newborns. NICU nurses should implement interventions to increase the comfort of preterm newborns [13,19,20]. Therefore, the aim of this study was to evaluate the effect of a hat developed to reduce noise and light on the comfort and physiologic parameters of the preterm newborn.
Material and Methods
Design
The study was conducted as a randomized controlled experiment designed to evaluate the effect of a hat that reduced noise and light on preterm newborn comfort and physiologic parameters.
Participants
The population of the study was composed of preterm newborns who were hospitalized to the NICU of a training and research hospital between October 2016 and March 2018 and who met the selection criteria. Power analysis was performed using the G*Power (9.1.3.2) program to determine the sample size. Cohen’s effect size coefficients were used. Assuming that the effect size (d = 0.8) of the difference between the comfort level score of preterm newborns before and after using the hat use would be large, according to the calculation made with 5% alpha (two-sided) and 95% power, at least 23 newborns should be included in the study groups. With the suggestion of the statistician, considering that there might be losses during the working process, it was planned to include 30 newborns in each group. Since all parameters in each group were measured before using the hat, each group also formed its own control group. Numbers from 1 to 60 were randomly distributed to two groups through a computer program without repeating the number to determine which newborn would be in which group in the selection of the sample (available at: https://www.randomizer.org/) (Figure 1: Consort Flow Diagram).
The inclusion criteria for the study were as follows: newborns at 32-37 weeks of gestation and the appropriate gestational age (AGA), age 7 days to adapt to the external environment, not taking an analgesic 4 hours before that could affect their comfort, not receiving mechanical ventilation support, no hearing problems, and parental consent. The exclusion criteria were the presence of a congenital anomaly, sepsis or any infection.
Measures
Data were collected using a data collection form, an observation form, the Premature Infant Comfort Scale, pulse oximetry, a decibel meter, a lux meter, and the preterm noise and light-reducing hat. The data collection form developed by the researchers included some descriptive characteristics such as the newborn’s sex, date of birth, gestational week, mode of delivery, weight and height at the time of the study. Observation form developed by the researchers included noise levels outside the incubator, light levels inside the incubator, physiologic parameters and comfort scale total score.
The Premature Infant Comfort Scale (PICS) is used to evaluate the comfort and pain of preterm newborns aged between ≥28 and ≤37 weeks in behavioral and psychological terms. It evaluates seven parameters: alertness, calmness/agitation, crying, physical movement, muscle tone, facial tension, and average heart rate. Each parameter is scored on a 5-point Likert-type scale from 1 to 5. High scores obtained from the scale indicate that the comfort level of the preterm newborn is low [21]. The Turkish validity and reliability study of the scale was conducted and the Cronbach alpha coefficient was found as 0.88 [19]. In our study, the Cronbach alpha coefficient was 0.65 before wearing the hat and 0.70 afterwards. The scale was scored by two independent observers, and the consistency between the mean scores was evaluated using the intraclass correlation coefficient (ICC) (two-way random effect model: consistency). It was found that there was a perfect fit between the comfort scores of the two observers (97.9% and 100%), (p < .001). Only the researcher’s measurement results were used in the study analysis because the reliability level of the inter-observer measurement results was found to be high.
The preterm noise and light-reducing hat, developed by the researchers, is designed to protect the newborn from both sound and light. The hat had flaps to reduce noise, a visor to reduce light, and the hat was made of 100% cotton. There was a fiber in the flap part and a foldable visor in the front. Laces were not used on the hat due to the risk of choking, especially in preterm newborns (Figure 2). For this reason, the flap of the hat was created in three different sizes, taking into account the head circumference measurements, to cover the newborn’s ear. The cotton fabric and fiber used were obtained from a manufacturer of baby clothing that has an international guarantee certificate (Oeko-Tex Standard 100 certificate) to ensure that it did not contain any chemicals that might harm the newborn. The hat was tested by experts in the sound and lighting laboratories of X University Faculty of Engineering. The product received a “utility model” certificate from the Turkish Patent and Trademark Office (Registration Number: 2016/15262, Registration Date: 2017/05/22).
Procedure
Preparation phase:
Descriptive information about preterm newborns was recorded in the data collection form. Working hours were ensured to be the same for all newborns so that the noise and light that the newborns were exposed to would be similar. Feeding, care, and treatment of the newborn were conducted by a NICU nurse between 08.00-08.30. The newborns were observed by the researcher between 09:00 and 11:30 AM. To ensure the stability of the newborns, observation was started half an hour after the care and treatment hours. Preterm newborns were placed in the supine position by nesting in the incubator at the time of the study. The intra-incubator light levels of newborns in both groups were measured.
Before wearing the hat:
Preterm newborns were followed for one hour without a hat. No action was taken during the observation period. At the end of an hour, a video was recorded for 3 minutes just before donning the hat. Comfort levels were evaluated by watching the video recording independently by two observers. Physiologic parameters and noise levels were also recorded on video.
With the hat:
Hats were put on the preterm newborns in both groups for 1 hour. No action was taken during the observation period. At the end of an hour, a video was recorded for 3 minutes while the neonate was wearing a hat. The comfort levels were evaluated independently by two observers by watching the video recording. Physiologic parameters and noise levels were also recorded on video.
Statistical Analysis
The SPSS (Statistical Package for the Social Sciences) 20.0 package program was used for data analysis. The results were evaluated at a 95% confidence interval, and the significance level was p < .05. When evaluating the data, the number, percentage, mean and standard deviation were given in descriptive statistics. Compatibility of numerical variables to normal distribution was evaluated using Skewness and Kurtosis. In testing the homogeneity of the descriptive characteristics of the groups, Yates’s corrected Chi-square test and Pearson’s Chi-square test were used for categorical variables and the independent samples t-test was used for numerical variables. Interobserver agreement of the Preterm Infant Comfort Scale scores was evaluated using Wilcoxon’s signed-rank test and the ICC. The Mann-Whitney U test was used to compare the difference between the comfort scale mean scores of the hat groups with and without visors (for the differences between groups), and the t-test in independent groups was used to compare the averages of physiologic parameters. Wilcoxon’s signed-rank test was used to compare the average scores of the premature newborns in each study group before and after wearing the hat (difference within the group), and the dependent group t-test was used to compare the averages of the physiologic parameters.
Ethical Considerations
Before data collection, ethics committee permission (IRB number: 148 Approval date: 15.07.2016) and institutional permission (No: 30965 date: 11.10.2016) were obtained. Verbal and written consent was obtained from the parents of the newborns included in the study.
Results
There was no significant difference between the groups in terms of descriptive characteristics, light and noise levels (Table 1, p> 0.05).
Comfort levels
Intragroup comparison: It was found that the average post-hat comfort score of preterm newborns in both groups with and without visors was found to be significantly lower than before wearing the hat (Table 2, p< 0.001).
Intergroup comparison: It was found that there was no significant difference between the groups in terms of average comfort scores before and after wearing the hat (Table 2; p> 0.05).
Physiologic measurements
Intragroup comparison: The mean heart rate and respiratory rate of the preterm newborns wearing hats with or without visors were found to be significantly lower than before wearing the hat. The average post-hat oxygen saturation of preterm newborns wearing a hat with or without visors was found to be significantly higher than before wearing the hat (Table 3, p< 0.001).
Intergroup comparison: It was found that there was no significant difference between the groups in terms of physiologic measurements before and after wearing the hat (Table 3, p> 0.05).
Discussion
In the NICU, preterm newborns are exposed to high levels of noise and lighting. In this study, the average noise level outside the incubator was found as 61 dBA before the test and 62 dBA after the test in both groups. In studies measuring noise levels in NICUs, ambient noise levels were found as 60 dBA by Parra et al. [3], 64 dBA by Garrido et al. [22], and 59 dBA by Varvara et al. [7]. Considering our study and other studies, it was determined that the noise levels outside the incubator in the NICU were higher than the level recommended by the AAP. In this study, the average light level inside the incubator was found as 236 lux in the group with the hat with a visor and 241 lux in the group with the hat without a visor. Similar to our study, Varvara et al. [7] found the average light level as 204 lux in their study between 8:00 and 12:00 AM in the NICU. Engwall et al. [23] found the ambient light level at the lowest level was 2 lux and the highest was 615 lux for any intervention in the NICU. As a result of noise and uncontrolled lighting, preterm newborns have physiologic and behavioral reactions due to increased stress [2]. In this study, a hat was developed to reduce the noise and light, which the preterm newborns were exposed to in our NICU. It was observed that the use of hats in preterm newborns was effective in increasing comfort and regulating physiologic parameters.
It was determined that the comfort level of preterm newborns wearing hats with and without visors was significantly greater after wearing the hat (1 hour after the hat was worn) than before (just before the hat was worn). However, there was no significant difference between the groups in terms of comfort levels. It was thought that the increase in comfort level was due to the reduction of noise and light due to wearing the hat, the reduction of the stress experienced by the newborns due to not being touched during observation, and the intact sleep-wake cycle of the newborns. Stokes et al. [20] found that playing music to premature newborns increased their comfort levels. In the study by Kahraman et al. [13], comfort levels in premature newborns in earmuffs, those listening to white noise, and those hearing their mother’s voice were significantly higher than the control group during heel prick. Parallel to these studies, it was proven that the hat, which reduced noise and light, was an effective alternative method for increasing the comfort of preterm babies.
In this study, preterm newborns in the groups with hats with and without visors had lower heart and respiratory rates, and higher mean oxygen saturation after wearing the hat. However, there was no significant difference between the groups in terms of physiologic parameters. Considering these findings, it was seen that the use of hats was effective in reducing heart and respiratory rates and in increasing oxygen saturation. Similar to our study, Khalesi et al. [14] found that newborns who wore earmuffs had significantly lower heart rates and higher oxygen saturations than newborns who did not. In their study, Cardoso et al. [24] found that newborns had lower oxygen saturation and higher heart rates when the noise was highest (61 dBA) compared with when the noise was lowest (58 dBA). These results showed that as the noise and light levels to which the preterm newborns were exposed in the NICU decreased, newborns experienced less stress, and as a result, the physiologic parameters were positively affected.
Limitations
In the study, the noise level and the physiologic parameters of the neonates were evaluated in a single instant. The average of the one-hour follow-up was not calculated, which may have affected the comfort level of the newborns.
Conclusion
It was found that the hat developed to reduce noise and light increased the comfort levels of preterm newborns and was effective in the regulation of physiologic parameters. The hat can be used as one of the initiatives to increase comfort in premature newborns hospitalized in NICUs. Nurses working in NICUs are recommended to evaluate the comfort level of newborns and to plan interventions to increase comfort.
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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Özlem Akarsu, Serap Balcı. The effect of a noise and light-reducing hat on the comfort and physiologic parameters of the preterm neonates. Ann Clin Anal Med 2022;13(10):1092-1097
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Evaluation of the effect of coronary slow flow phenomenon on cardiac functions
Ahmet Barutcu 1, Ercan Akşit 1, Mehmet Arslan 2, Özge Özden Tok 3, Uğur Küçük 1
1 Department of Cardiology, Faculty of Medicine, Canakkale Onsekiz Mart University, Canakkale, 2 Department of Cardiology, Canakkale Mehmet Akif Ersoy State Hospital, Canakkale, 3 Department of Cardiology, Bahcelievler Medical Park Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.21222 Received: 2022-05-10 Accepted: 2022-06-20 Published Online: 2022-06-23 Printed: 2022-10-01 Ann Clin Anal Med 2022;13(10):1098-1102
Corresponding Author: Uğur Küçük, Barbaros Mahallesi, Prof. Dr. Sevim Buluç Sokak, No:2, Canakkale, Turkey. E-mail: drugurkucuk@hotmail.com P: +90 534 591 19 02 Corresponding Author ORCID ID: https://orcid.org/0000-0003-4669-7387
Aim: Although coronary slow flow phenomenon (CSFP) is seen in 2% of patients undergoing coronary angiography, its clinical significance and impact on ventricular function remain controversial. Cardiac magnetic resonance imaging (CMR) is the gold standard for evaluating ventricular function and volumes. In this study, we aimed to assess the impact of CSF on ventricular function using CMR-based deformation imaging.
Material and Methods: This is a cross-sectional study. Twenty-two people were included in the study. Patients with structural heart disease and secondary coronary slow flow were excluded. Twelve subjects with CSFP and 10 subjects with normal flow and normal cardiac function were compared by CMR and CMR strain.
Results: Left ventricle (LV) and right ventricle (RV) functions and volumes were similar. There was no difference between CMR strains in both groups. Furthermore, there was no correlation between age and heart function in patients with CSF.
Discussion: CSF has no or limited impact on cardiac functions. Further long-term prospective studies should be carried out to establish the impact and significance of CSF in patients with CSF.
Keywords: Slow Flow, Strain, Atherosclerosis, Coronary Angiography
Introduction
Coronary slow flow (CSF) is a rare angiographic clinical entity characterized by delayed distal vascular opacification without critical coronary artery stenosis. Microvascular disease has been proposed as a potential pathophysiological mechanism for this angiographic phenomenon and clinical findings [1].
Its incidence was reported to be 2% in patients undergoing coronary angiography. Although various mechanisms have been proposed for the pathogenesis of CSF, the underlying pathophysiology and clinical consequences of CSF are not clearly understood. A study supporting this hypothesis showed histologically small vessel coronary artery disease, myofiber hypertrophy, hyperplastic fibromuscular thickening of small arteries, swelling of endothelial cells, and narrowing of the lumen [2-5].
Similarly, some studies have suggested that CSF is associated with atherosclerosis and even has an early phase, which is only characterized by abnormal resistance of both small vessels and epicardial arteries [6].
However, another study proposed that improper release of vasoconstrictor autacoids such as neuropeptide Y, endothelin-1, and thromboxane A2 could lead the CSF [7]. Despite numerous published papers on the CSF, its clinical significance is still unclear, and the effects of CSF and subsequent inadequate blood supply on myocardial functions are still controversial. Comparative cross-sectional studies with different echocardiographic methods showed signs of early cardiac dysfunction in patients with CSF, but in these studies, conventional echo parameters were similar [8,9].
Cardiac magnetic resonance imaging (CMR) is the gold standard imaging method for ventricular functional assessment. Additionally, a new tool CMR-based deformation imaging ‘Magnetic resonance imaging (MRI) tissue tracking’, facilitates objective detection of wall motion abnormality. In this stuy, we aimed to perform a detailed assessment of the impact of CSF on cardiac function.
Material and Methods
Patient group and study protocol
Catheter laboratory records over the last year were evaluated to identify patients with CSF, and a total of 44 patients were detected. CSF can be a secondary related to many reasons. In our study, we excluded patients with CSF due to secondary reasons. In addition, we excluded patients with other conditions that could affect cardiac functions. Subjects who had structural cardiovascular disease (e.g., Left ventricle (LV) dysfunction, LV hypertrophy, cardiomyopathies, and atherosclerotic coronary artery disease), atrial fibrillation, valvular heart disease, congenital heart disease, pericardial disease, or stage 3– 4 hypertension were excluded from the study. Patients who had a bundle branch block on electrocardiogram, history of previous thoracic surgery, chronic systemic or inflammatory diseases, any form of malignancy and any contraindication to CMR imaging were excluded from the study as well. Finally, 12 patients, aged 24– 60 years were recruited into the study. Ten patients with normal coronary angiography and normal cardiac functions who agreed to participate in the study were enrolled as the control group. This study was approved by the local ethics committee of our hospital and was conducted in accordance with the principles outlined in the Declaration of Helsinki (Protocol no: 2020/05). Informed consent was obtained from all patients enrolled in the study.
TIMI frame count and definition of coronary slow flow
Thrombolysis in Myocardial Infarction (TIMI) frame count method explained by Gibson et al. was used to diagnose CSF. TIMI frame counts were measured by a cardiologist who was blinded to the properties of the patient. In this method, the first frame is formed at the first moment when the opaque matter begins to load in the ostium of the coronary artery. The last frame is decided at the moment when the first bifurcation in the posterior branch of the right coronary artery (RCA) is filled, and the first moment of opacification in the distal bifurcation for the circumflex (Cx) artery and left anterior descending (LAD) artery. Normal valuations when the frame rate of the coronary angiography machine is 30 frames/sec are 20.4±3.0 for RCA, 22.2±4.1 for Cx, and 36±2.6 for LAD. The corrected-LAD (cLAD) value is estimated by dividing the calculated value by 1.7, and the normal valuation for cLAD is 21.1±1.5. The mean TIMI frame count was estimated by adding these three valuations and dividing them by three. Patients with CSF in at least one of the three major coronary arteries were enrolled in the CSF group [10].
CMR protocol
Cine images and LV and RV functional measurement
All patients underwent CMR in a supine position in a 1.5 Tesla MRI scanner (GE Signa Medical Systems). Cardiac gating and triggering were performed via a vector ECG trace triggered on the R wave. The position of the heart was determined by a fast multi-slice, multi-stack survey scan in the transverse, coronal and sagittal planes. Scout imaging trans-axial, coronal, sagittal, these are in general single heartbeat acquisitions acquired in 1 breath-hold. After positioning of the heart in 3 planes, 4 chambers (CH), 2 CH, 3 CH, and short-axis cine stack with 10–12 slices were acquired with a steady-state free precession pulse sequence. The short axis stack covers from base to apex. Each slice location was acquired during breath holding during end-expiration. The shim volume feature was used for optimal image quality.
Placement Long axis images were used for quantitative LV functional assessment using tissue tracking tool. Short axis images were used. LV and right ventricle (RV) volume and ejection fraction measurement Cine images were acquired during a breath-hold. Slice thickness was 6–8 mm, with or without 2–4 mm interslice gaps (to make a total of 10 mm). Temporal resolution was ≤45ms between phases to optimize the evaluation of wall motion. Cardiac functional and volumetric measurements were performed using Circle CVI 42. Left ventricular ejection fraction (LVEF) and right ventricular Ejection fraction (RVEF) were measured from the short-axis cine stack according to the SCMR guideline [11].
Tissue tracking
CMR-based deformation assessment was done using long axis cine images. LV wall motions were assessed in 4 CH 3 CH and 2 CH long axis cine planes were analyzed by an experienced reader using Circle CVI 42 tissue tracking tool. Long axis endocardial and epicardial contours are required in end-diastole for tissue tracking analysis. For the LV, these contours should be traced excluding the papillary muscle and trabeculations in the 2, 3, 4 CH image series. Endocardial contour detection was performed manually on long axis cine images in end-diastolic and and-systolic phases. After tracing the LV endocardial contours, LV long extent border indicator was checked and corrected if needed throughout all cardiac cycles (Figure 1). Global strain values including longitudinal (GLS) and radial LV strain (GRS) parameters were measured.
Statistical analysis
Data were expressed as mean ± standard deviation or as a percentage (number).
The Shapiro-Wilk test was used to evaluate the distribution of continuous variables. Continuous variables were expressed as mean ± standard deviation and categorical variables were expressed as percentages and numbers. The t-test was used to compare normally distributed data. Categorical data were compared with the chi-square test or Fisher’s exact test. Correlation analysis was done with Spearman rank correlation analysis. IBM SPSS Statistics 21 package program was used for data analysis. p <0.05 was accepted as the level of significance.
Results
There were 12 patients with CSF and 10 patients in the control group. An example of tissue tracking in CMR is shown in Figure 1.
The average number of the TIMI frame count is shown in Table 1.
The general characteristics, ventricular volumes and function of the study population were similar as depicted in Table 2. CMR parameters of the CSF group were compared with the control group. All volumetric parameters, masses, LVEF and RVEF were found to be similar in both groups (p > 0.05) (Table 2).
Discussion
In this study, we demonstrated that there is no statistically significant difference between patients with CSF and the normal population in terms of ventricular volumes and ventricular systolic function. In addition, left ventricular longitudinal strains were statistically similar in our study. Also, all values remained within the normal limits. To the best of our knowledge, this is the first detailed CMR study regarding CSF.
Only in a recently published study, the relationship between scar tissue and NT-proBNP was investigated in patients with CSF, but in this study, ventricular functions and volumes were not evaluated [12]. Early ventricular dysfunction was evaluated by various echocardiographic methods in patients with CSF. Although tissue Doppler parameters are lower, LVEF were statistically similar, and mean LVEF was higher than 60% in patients with CSF in previous echocardiographic studies with tissue Doppler [13]. LV strain, which is a more objective and sensitive tool for early identification of ventricular dysfunction, was found to be statistically lower than the normal population in various echocardiographic studies [14]. However, being statistically lower, LV strain values were still within normal limits in all these previous studies. Similarly, ventricular functions of patients were statistically similar in these studies, and the mean LVEF was over 60%.
The superiority of cardiac MR, which is the gold standard imaging modality for ventricular function and volume evaluation, has already been proven. In our study, CMR was used to assess ventricular volumes and functions, whereas CMR based deformation imaging was utilized to evaluate wall motions in a more detailed and objective way (Figure 2). A lot of mechanisms leading to CSF were accused, therefore some pathophysiological mechanism could be more detrimental than others. Of course, all these mentioned studies, including our study are cross-sectional. We thought that the exposure time of CSF could be important for ventricular functions, but there is no correlation between age and ventricular functions in patients with CSF. In addition, there was no negative correlation between the severity of coronary slow flow and ventricular functions. Also, different clinical presentations have also been reported in patients with CSF. CSF has been shown to cause chest pain, myocardial ischemia, prolonged QT interval in various publications. CSF has been reported to rarely cause arrhythmia and sudden death [15-17].
The commonest presentation of CSF was ACS (65%) requiring hospitalization. Mortality was not detected in these CSF patients presenting as an acute coronary syndrome. Different mechanisms have been claimed for CSF, so these different pathogeneses could lead to a heterogeneous effect and heterogeneous presentations. All patients were managed conservatively. As a result, it was concluded that CSF contributes to significant morbidity [18,19].
Although CSF is seen in 2 % of cardiac catheterizations, there is no guideline for the treatment of CSF phenomenon. Also, despite the fact that there are cross-sectional studies on the clinical effect of CSF, there is no long-term clinical follow-up study on CSF. In only one clinical follow-up study about angina and normal epicardial coronary arteries, 21 patients had slow coronary flow. They found that all patients had a good prognosis. In short-term follow-up studies, the treatment efficacy of some medications for symptoms was tested or coronary flow was re-evaluated after treatment. However, ventricular functions have not been evaluated. In addition, symptoms have been shown to be relieved with various medical treatments [20-24].
We speculate that impaired coronary perfusion pressure may cause angina. However, ventricular functions may be preserved because this perfusion pressure disorder is short-lived or coronary slow flow does not impair the basic supply of the ventricle in patients with CSF.
Limitations
Nonetheless, these results must be interpreted with caution and a number of limitations should be borne in mind. The first is the small sample size of our population due to the strict inclusion and exclusion criteria. The second major limitation concerns the unknown exact duration of CSF exposure. Because of local ethic committee disallowance regarding contrast use, we were solely able to use conventional volume and function assessment. As regards wall motion evaluation, tissue tracking tools were utilized. Nevertheless, this is a cross sectional study and the results clearly indicates the relationship, and there is an apparent need for a prospective follow-up study.
Conclusion
As a result of all, we concluded that CSF has no or limited impact on the ventricular volumes and functions. There is no established treatment protocol for CSF and it is generally assumed to have benign long-term outcomes. However, further long-term prospective studies should be carried out to establish the impact and significance of CSF on cardiac volumes and functions.
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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3. Gazi E, Barutcu A, Altun B, Temiz A, Bekler A, Urfali M, et al. Intercellular adhesion molecule-1 K469E and angiotensinogen T207M polymorphisms in coronary slow flow. Med Princ Pract. 2014;23(4):346-50.
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5. Akşit E, Büyük B, Oğuz S. Histopathological changes in myocardial tissue due to coronary venous hypertension. Archives of Medical Science. 2020. doi:10.5114/aoms.2019.91472.
6. Erdogan D, Caliskan M, Gullu H, Sezgin AT, Yildirir A, Muderrisoglu H. Coronary flow reserve is impaired in patients with slow coronary flow. Atherosclerosis. 2007;191(1):168-74.
7. Beltrame JF, Limaye SB, Wuttke RD, Horowitz JD. Coronary hemodynamic and metabolic studies of the coronary slow flow phenomenon, Am. Heart J. 2003;146(1):84-90.
8. Elsherbiny IA. Left ventricular function and exercise capacity in patients with slow coronary flow. Echocardiography. 2012;29 (2):158–64.
9. Nurkalem Z, Gorgulu S, Uslu N, Orhan AL, Alper AT, Erer B, et al. Longitudinal left ventricular systolic function is impaired in patients with coronary slow flow. Int J Cardiovasc Imaging. 2009;25(1):25-32.
10. Gibson CM, Cannon CP, Daley WL, Dodge JT Jr, Alexander B Jr, Marble SJ, et al. TIMI frame count: a quantitative method of assessing coronary artery flow. Circulation. 1996;93(5):879-88.
11. Kramer CM, Barkhausen J, Flamm SD, Kim RJ, Nagel E. Standardized cardiovascular magnetic resonance (CMR) protocols 2013 update. J Cardiovasc Magn Reson. 2013;15(1):91.
12. Candemir M, Şahinarslan A, Yazol M, Öner YA, Boyacı B. Determination of Myocardial Scar Tissue in Coronary Slow Flow Phenomenon and the Relationship Between Amount of Scar Tissue and Nt-ProBNP. Arq. Bras. Cardiol. 2020;114(3):540-51.
13. Baykan M, Baykan EC, Turan S, Gedikli O, Kaplan S, Kiriş A, et al. Assessment of left ventricular function and Tei index by tissue Doppler imaging in patients with slow coronary flow. Echocardiography. 2009;26(10):1167-72.
14. Barutçu A, Bekler A, Temiz A, Kırılmaz B, Yener AÜ, Tan YZ, et al. Left Ventricular Twist Mechanics Are Impaired in Patients with Coronary Slow Flow. Echocardiography. 2015;32(11):1647-54.
15. Alvarez C, Siu H. Coronary Slow-Flow Phenomenon as an Under recognized and Treatable Source of Chest Pain: Case Series and Literature Review. J Investig Med High Impact Case Rep. 2018;6. DOI: 10.1177/2324709618789194.
16. de Lemos JA, Omland T. Angina in Patients with Evidence of Myocardial Ischemia and No Obstructive Coronary Artery Disease in Chronic Coronary Artery Disease: a Companion to Braunwalds Heart Disease. Philadelphia, PA: Elsevier; 2018. p.374-8.
17. Sharif-Yakan A, Divchev D, Trautwein U, Nienaber CA. The coronary slow flow phenomena or “cardiac syndrome Y”: A review. Reviews in Vascular Medicine. 2014 ;2(4):118-22.
18. Saya S, Hennebry TA, Lozano P, Lazzara R, Schechter E. Coronary slow flow phenomenon and risk for sudden cardiac death due to ventricular arrhythmias: a case report and review of literature. Clin Cardiol. 2008;31(8):352-5.
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Ahmet Barutcu, Ercan Akşit, Mehmet Arslan, Özge Özden Tok, Uğur Küçük. Evaluation of the effect of coronary slow flow phenomenon on cardiac functions.Ann Clin Anal Med 2022;13(10):1098-1102
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Fatty acid-binding proteins in the diagnosis and disease severity prediction in pneumonia
Doganay Can 1, Utku Murat Kalafat 2, Melis Dorter 3, Ahmet Erdur 4, Busra Bildik 5, Ramazan Guven 1, Serkan Dogan 2, Basar Cander 2
1 Department of Emergency Medicine, Basaksehir Cam and Sakura City Hospital, Istanbul, 2 Department of Emergency Medicine, University of Health Science, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, 3 Department of Emergency Medicine, Tekirdag Dr.Ismail Fehmi Cumalioglu State Hospital, Tekirdag, 4 Department of Emergency Medicine, Edirne Sultan 1st Murat State Hospital, Edirne, 5 Department of Emergency Medicine, Karabuk University Training and Research Hospital, Karabuk, Turkey
DOI: 10.4328/ACAM.21223 Received: 2022-05-18 Accepted: 2022-07-08 Published Online: 2022-07-20 Printed: 2022-10-01 Ann Clin Anal Med 2022;13(10):1103-1106
Corresponding Author: Doganay Can, Department of Emergency Medicine, Ministry Of Health Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey. E-mail: drdoganaycan@gmail.com P: +90 535 608 56 70 Corresponding Author ORCID ID: https://orcid.org/0000-0002-9544-2340
Aim: Infections of the respiratory tract are important healthcare problems that are one of the main causes of referrals to the emergency department. PSI and CURB-65 are the most common scoring methods globally with proven accuracy and validity through many studies. Fatty acid- binding proteins are member of small cytoplasmic proteins that play a role in the transportation and deposition of lipids almost in all mammalian cells. They are strongly associated with metabolic and inflammatory processes. The aim of the present study was to determine the value of FABP for diagnosis and disease severity in patients diagnosed with pneumonia and to compare the correlation with PSI and CURB-65 scoring systems.
Material and Methods: This prospective and single-cantered study was conducted on patients referring to the emergency department of Istanbul Kanuni Sultan Suleyman Training and Research Hospital who were diagnosed with pneumonia and on healthy volunteers.
Results: FABP level was significantly higher in the patient group when compared with the control group (p: <0.01). FABP level was detected significantly higher in the severe pneumonia group of the binary groups created according to PSI and CURB-65 scoring.
Discussion: As a result of the data obtained in the present study, it was concluded that FABP would be useful for the determination of the diagnosis, disease severity and the decision whether to hospitalize the patient with pneumonia. FABP is an important biomarker that guides the clinician for management of pneumonia patients who refer to the emergency department.
Keywords: Pneumonia, Inflammation, Infection, Biomarker, FABP
Introduction
Respiratory infections, one of the main reasons for presenting to the emergency department, constitute an important health problem. The occurrence of lung infections without recent exposure to hospitals or healthcare units is defined as community-acquired pneumonia (CAP) and considered an important cause of morbidity and mortality. Despite advancements in medical science, CAP-related mortality remains to be the same over the past four decades in the US [1]. Each year over 5 million cases occur in the USA with over 1 million hospitalizations and 60,000 deaths from pneumonia [2]. CAP is the second most common cause of hospitalization and the most common cause of death associated with infectious diseases in the US [3]. It is well-established that the mortality rate increases in the presence of comorbid disorders.
Fatty acid-binding proteins (FABP), which are a part of the cytoplasmic protein group, are strongly associated with metabolic and inflammatory processes. In macrophages, FABPs induce an inflammatory effect via the nuclear factor-κB pathway [4,5]. The present study aimed to investigate the importance of FABP in diagnosing pneumonia and predicting disease severity in patients presenting at an emergency department of a third-line education and research hospital and determine the correlation between PSI and CURB-65 scoring systems.
Material and Methods
Formation of Study Groups
This was a prospective single-center study that was conducted after obtaining approval from the relevant ethics committee of the third-line training and research hospital. For this study, all patients diagnosed with pneumonia in the emergency room were included in the patient group. Age, gender, vital signs, Glasgow Coma Scale scores, medical history, hemogram results, biochemistry and blood gas parameters, PSI and CURB-65 scores, and FABP levels of the patients were recorded.
The patients categorized under Class I and II based on their PSI scores had a low rate of mortality; thus, outpatient treatment was recommended. Accordingly, the patients categorized under PSI Class I and II were included in the PSI mild-pneumonia subgroup, whereas those categorized under PSI Class III, IV, and V were associated with high mortality rates and were recommended to get admitted to the general ward or intensive care unit were included in the PSI severe-pneumonia subgroup. With regard to the CURB-65 scoring system, the patients with a score of 0 and 1, having low mortality rates, and who were recommended to undergo outpatient treatment were included in the CURB-65 mild-pneumonia subgroup, whereas those with a score of ≥2 were included in the CURB-65 severe-pneumonia subgroup.
The patient group included individuals aged ≥ 18 years who were diagnosed with pneumonia in the emergency department, consented to participate, and had no other acute causative factor that could have affected the FABP level.
The control group included individuals aged ≥ 18 years who had no known chronic diseases or signs of active infection, did not have any recent occurrence of (up to 1 week) respiratory infection, and consented to participate.
Exclusion Criteria
Patients aged < 18 years and those who were pregnant, refused to provide consents, and had any causative factor that might affect the FABP level were excluded from the study.
Laboratory Methods
Biochemical analysis
Venous blood samples were collected from the patient and control groups via routine phlebotomy and transferred into 5-ml gel tubes (BD vacutainer SST II Advance, NJ, USA) and 2-ml anticoagulant tubes (K2-EDTA, Becton Dickinson, NJ, USA). Furthermore, arterial blood samples were collected from the patient group and transferred into 2-ml blood gas tubes (Sarstedt Monovette, 2-ml LH) for use during PSI scoring. The samples in the blood gas and anticoagulant tubes were immediately examined. The samples in the gel tubes were used to perform biochemical examinations for scoring, and the remaining samples were stored at room temperature for 20 min and then centrifuged at 3500 rpm for 10 min to obtain serum and plasma samples. At the same time, excess serum and plasma samples were transferred into Eppendorf tubes and immediately frozen at −80oC for further use in enzyme-linked immunosorbent assay (ELISA).
ELISA
The amount of human FABPs was examined in all the samples using the sandwich ELISA method. The Synergy HTX BioTek device (Biotek Instruments, Inc Highland Park, USA), antibodies against human FABP, and ELISA kit of the Bioassay Technology Laboratory company were used. The intra- and interassay coefficients of variation of the kit were <8% and 10%, respectively.
Statistical Analyses
In this study, statistical analyses were performed by first comparing the main groups, i.e., the control and patient groups, and then the PSI and CURB-65 subgroups. Data were analyzed using the Statistical Package for the Social Sciences Version 26.0 (IBM Inc., New York, USA) software program. Mean ± standard deviation and median [interquartile range (IQR)] values were used for representing continuous variables, whereas categorical variables were represented as numbers (percentages). The Mann–Whitney U test was used for performing binary group comparisons of the continuous variables without normal distribution, whereas the Kruskal–Wallis test was used to compare three or more groups and Pearson’s chi-square test was used to compare categorical data. Since the most informative biomarker was FABP, its cutoff level was calculated, and the sensitivity, specificity, and positive and negative predictive values of PSI and CURB-65 were determined and compared. A p-value of <0.05 was considered statistically significant.
Results
As per pairwise comparisons that investigated patient outcomes from the emergency room and FABP levels of the patient group, the median FABP level was 25.135 ng/ml (IQR: 23.477–31.092 ng/ml) in the outpatient group, 29.692 ng/ml (IQR: 28.926–30.999 ng/ml) in the patients admitted to the ward, and 60.14 ng/ml (IQR: 49.592–106.857 ng/ml) in the patients admitted to the intensive care unit. A significant difference was found between the FABP levels of the patients admitted to the intensive care unit and those of the patients admitted to the ward and outpatient group (p < 0.01, p < 0.01, respectively). There was no significant difference between the patients admitted to the ward and the outpatients in terms of FABP levels. Nevertheless, the FABP levels of the patients admitted to the ward were significantly high (p = 0.056) (Table 2).
For differentiating mild and severe pneumonia, the receiver operating characteristic (ROC) curve analysis was used to determine the FABP cutoff level, which helped determine whether inpatient or outpatient treatment should be provided on the basis of PSI scores (Figure 1). Furthermore, ROC curve analysis was used to determine the cutoff level after a significant difference was found between the patient and control groups in terms of plasma FABP levels (p < 0.01) (Figure 1). When 40.333 ng/ml was set as the cutoff plasma FABP level, its sensitivity, specificity and positive and negative predictive values for diagnosis was found to be 44.44%, 97.56%, 95.24%, and 61.54%, respectively.
When 30.002 ng/ml was set as the cutoff plasma FABP level, the sensitivity of plasma FABP level was 70.27%, specificity was 75%, positive predictive value was 92.86%, and negative predictive value was 35.29% for differentiating mild and severe pneumonia using PSI scores.
Discussion
Despite advancements in medical science, antimicrobial agents, and supportive treatment options, pneumonia remains to be an important cause of mortality and morbidity worldwide. While mortality rates associated with many infectious diseases have decreased owing to the aforementioned developments, there has been no decrease in the rate of mortality in patients with CAP over the past four decades.
In a study by Wang et al. that included 36 pediatric patients and 28 controls, the plasma FABP levels were significantly higher in the patient group than in the control group [6]. In the present study, a comparison between the control and patient groups suggested that FABP levels were significantly high in the patient group, which was considered valuable for diagnosis (p < 0.01). In animal studies, the production of cytokines, such as tumor necrosis factor-α, interleukin-1 and -6, and monocyte chemotactic protein-1, was found to be suppressed in the absence of FABP. It was also observed that the production and functioning of proinflammatory enzymes, such as inducible nitric oxide synthase and cyclooxygenase were suppressed [4,5]. These data suggest the fact that FABP could be used as a diagnostic biomarker in patients with pneumonia.
In their prospective observational study published in 2019, Ham et al. compared the ability of PSI and CURB-65 scoring systems and various laboratory parameters in determining the severity of CAP. Leukocyte and platelet counts, C-reactive protein (CRP), and procalcitonin test (PCT) levels did not reveal any significant difference between the two scoring systems [7]. In a study by Menendez et al., CRP levels were significantly different between the two scoring system subgroups [8]. In a study by Thiem et al., which retrospectively examined 391 advanced-age CAP cases in Germany, leukocyte counts and CRP levels were not associated with the subgroups of the scoring systems [9]. A meta-analysis published in 2020 by Ebell et al. compared leukocyte count, CRP levels, and PCT for the diagnosis of CAP. It was suggested that the most accurate results were obtained using the CRP biomarker [10]. These findings suggest that leukocyte count, CRP, and PCT can successfully diagnose CAP and predict survival. Nevertheless, this is not the case when it comes to determining the provision of inpatient or outpatient treatment.
Conclusion
FABP levels were significantly higher in the CURB-65 and PSI severe-pneumonia subgroups (for which inpatient treatment was recommended) than in the CURB-65 and PSI mild-pneumonia subgroups (for which outpatient treatment was recommended) (p: 0.038, p: 0.035). These data suggest that FABP levels can be used as an objective scale in correlation with the scoring systems for determining the provision of inpatient or outpatient treatment. Despite the fact that no severity marker blood parameters in the laboratory findings were suggested in the relevant literature, in the present study, the FABP levels of the patients admitted to the intensive care unit were significantly higher than those of the outpatients and patients admitted to the ward (p < 0.01, p < 0.01, respectively).
A relatively small group of evaluated patients and the fact that long-term mortality rate of the patients was not included in the study data are the limitations of the study.
When compared with PSI and CURB-65 scoring systems, the FABP levels were found to correlate with both the scoring systems in terms of predicting patient outcome. FABP may guide clinicians in diagnosing pneumonia, assessing disease severity, and predicting patient 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. Waterer GW, Rello J, Wunderink RG. Management of community-acquired pneumonia in adults. Am J Respir Crit Care Med. 2011;183(2):157-64.
2. File TM, Marrie TJ. Burden of community-acquired pneumonia in North American adults. Prostgrad Med. 2010;122:130.
3. Xu J, Murphy SL, Kochanek KD, Bastian BA. Deaths: Final Data for 2013. Natl Vital Stat Rep. 2016;64(2):1-119.
4. Storch J, Thumser AE. The fatty acid transport function of fatty acid-binding proteins. Biochim Biophys Acta. 2000;1486(1):28-44.
5. Furuhashi M, Hotamisligil GS. Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets. Nat Rev Drug Discov. 2008;7(6):489-503.
6. Wang WD, Sun YP, Cui XQ. Serum levels of fatty acid-binding protein and brain natriuretic peptide in children with pneumonia complicated by acute congestive heart failure. Zhongguo Dang Dai Er Ke Za Zhi. 2008;10(3):304-6.
7. Ham JY, Song KE. A Prospective Study of Presepsin as an Indicator of the Severity of Community-Acquired Pneumonia in Emergency Departments: Comparison with Pneumonia Severity Index and CURB-65 Scores. Lab Med. 2019;50(4):364-9.
8. Menéndez R, Martínez R, Reyes S, Mensa J, Filella X, Marcos MA, et al. Biomarkers improve mortality prediction by prognostic scales in community-acquired pneumonia. Thorax. 2009;64(7):587-91.
9. [ Thiem U, Niklaus D, Sehlhoff B, Stückle C, Heppner HJ, Endres HG, et al. C-reactive protein, severity of pneumonia and mortality in elderly, hospitalised patients with community-acquired pneumonia. Age Ageing. 2009;38(6):693-7.
10. Ebell MH, Bentivegna M, Cai X, Hulme C, Kearney M. Accuracy of Biomarkers for the Diagnosis of Adult Community-acquired Pneumonia: A Meta-analysis. Acad Emerg Med. 2020;27(3):195-206.
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Doganay Can, Utku Murat Kalafat, Melis Dorter, Ahmet Erdur, Busra Bildik, Ramazan Guven, Serkan Dogan, Basar Cander. Fatty acid-binding proteins in the diagnosis and disease severity prediction in pneumonia. Ann Clin Anal Med 2022;13(10):1103-1106
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Prognostic markers of mortality in patients with methanol poisoning
Ahmet Kayalı 1, Umut Payza 1, Yakup İriağaç 2, Serkan Bilgin 1, Mehmet Göktuğ Efgan 1, Osman Sezer Çınaroğlu 1
1 Department of Emergency Medicine, Izmir Katip Celebi University, Ataturk Training and Research Hospital, Izmir, 2 Department of Medıcal Oncology, Faculty of Medicine, Tekirdağ Namık Kemal University, Tekirdağ, Turkey
DOI: 10.4328/ACAM.21225 Received: 2022-05-11 Accepted: 2022-06-11 Published Online: 2022-06-18 Printed: 2022-10-01 Ann Clin Anal Med 2022;13(10):1107-1111
Corresponding Author: Mehmet Göktuğ Efgan, Department of Emergency Medicine, Izmir Katip Celebi University, Ataturk Training and Research Hospital, 35360, Izmir, Turkey. E-mail: goktugefgan@gmail.com P: +90 232 243 43 43 / +90 546 674 19 70 F: +90 232 243 15 30 Corresponding Author ORCID ID: https://orcid.org/0000-0002-0794-1239
Aim: Methanol is a kind of alcohol, which is used in industry in numerous different products. Methanol intoxication entails high mortality and morbidity rates. In this study, we aimed to investigate the effectiveness of laboratory parameters in determining the severity of exposure in patients presenting with methanol intoxication.
Material and Methods: The study was performed in the university hospital between January 1, 2015, and January 1, 2020. All data were obtained retrospectively from the hospital automation system. Receiver Operating Characteristic (ROC) curve was used to determine ideal cut-off values. A logistic regression model was used to perform univariate and multivariate analyses.
Results: The study included 49 patients and 3 of them were women. Thirty (61%) received both hemodialysis and intravenous ethanol for treatment. Univariate analysis revealed increased mortality in patients with pH below 7.00, HCO3 below 8.40 (mmol/L), lactate 4.35 (mmol/L), glucose 183 (mg/dl) and above, PCO2 42.7 (mmHg), high osmolarity, and a high anion gap. The results of multivariate logistic regression analysis for model 1 is (pH, bicarbonate, lactate, glucose, PCO2, osmolarity, and anion gap); pH <7.00 (OR:0.016, %95 CI <0.01-0.15, p<0.001) and for model 2 is (bicarbonate, lactate, glucose, PCO2, osmolarity, and anion gap); lactate ≥4.35 (OR:31.66, 95% CI 3.25-308.5, p=0.003) and PCO2 ≥42.7 (OR: 7.01, 95% CI 1.12-43.96, p=0.038).
Discussion: Laboratory parameters would predict mortality. PH emerged as a predictive mortality marker, while blood lactate and high partial carbon dioxide pressure were capable of predicting mortality if pH was excluded. Starting on the treatment with clinical diagnoses decreases mortality in methanol intoxication.
Keywords: Methanol, Emergency Department, Prognostic Markers
Introduction
Methanol is a colorless type of alcohol whose odor and taste resemble those of ethanol. It is employed in industry in the manufacture of antifreeze, brake fluids, windshield washer fluids, wallpaper, and window washer fluids [1].
When methanol enters the circulatory system, it is metabolized in the liver by alcohol dehydrogenase (ADH) to formaldehyde, which is then metabolized to formic acid by aldehyde dehydrogenase (ALDH).
Although methanol is not itself toxic, the resulting metabolites can lead to permanent organ damage and death in humans [2]. Pathognomonic findings of formic acid intoxication include petechial bleeding in the occipital, temporal, and parietal cortex, basal ganglia, and pons. Hemorrhagic necrosis and edema are also seen in the thalamus, putamen, globus pallidus, basal ganglia, and cerebral cortex. It also causes visual disorders in association with mitochondrial deterioration and vacuolization in the retinal pigment epithelium, photoreceptor inner segment, and the optic nerve [3].
While methanol intoxications can be accidental, they are frequently observed as a result of the use of methyl alcohol instead of ethyl alcohol in beverage production. Many individuals are affected by the deliberate or accidental consumption of these products [4]. Intoxication is a global health problem, although it is more common in developing countries. Outbreaks involving large numbers of cases involving the consumption of alcohol containing methanol have been reported from Argentina, Norway, the Czech Republic, Libya, and Iran [5-7].
Due to its high mortality and morbidity rates, methanol intoxication requires rapid and effective treatment, which should be initiated in the emergency department [4]. It is difficult to diagnose and determine the severity of intoxication for reasons such as the inability to obtain adequate information due to impaired consciousness, difficulties in measuring blood methanol levels, or because gas chromatography used to measure methanol levels is not available in all hospitals [2-4].
This study investigated the value of laboratory parameters in determining the severity of exposure in patients presenting with methanol intoxication. Our aim was to be able to predict mortality using different models.
Material and Methods
Patients
The study was performed retrospectively in the emergency department of a university hospital in Turkey between January 1, 2015, and January 1, 2020. Forty-nine patients meeting the study criteria and definitely diagnosed by means of gas chromatography were included from the 67 patients presenting due to methanol exposure. Patient data were retrieved and analyzed from the hospital record system. Inclusion criteria were age over 18 and blood gas and biochemistry parameters recorded during presentation to the emergency department. Patients with no heart beat at presentation were excluded.
Approval for the study was granted by the university ethics committee (no. 1058). The study conformed to the provisions of the 1995 Declaration of Helsinki.
Data collection
The arrival symptoms, laboratory test results, treatment administered, and outcomes for the patients included in the study were recorded by examining data from the hospital automation system. Blood gas tests were performed on a RADIOMETER COPENHAGEN ABL 835 FLEX device, while biochemistry parameters were measured with an Abbott kit on an Abbott C 16000 device.
Statistical Analysis
Ideal cut-off values with high sensitivity and specificity in predicting mortality after methanol intoxication were determined using a Receiver Operating Characteristic (ROC) curve. Univariate and multivariate analyses were performed using a logistic regression model. Odds ratios (OR) were reported with corresponding 95% confidence intervals (95% CI), and a p-value of <0.05 was considered statistically significant. Statistical analyses were performed using SPSS version 24 software (SPSS Inc., Chicago, IL, USA).
Results
Forty-nine patients with a mean age of 50.5±14.1 and a median age of 53 (min 16, max 72) years were included in the study. Ninety-four percent (n=46) of the participants were men and 6% (n=3) were women. The median age of the female patients was 39 (min 31, max. 59) years, and the median age of the male patients was 53 (min 16, max 72).
Analysis showed that 46.9% (n:23) of patients arrived in their own vehicles, while 53.2% (n:26) were brought by ambulance. Eleven patients (16%) received hemodialysis only, eight (22%) received intravenous ethanol only, and 30 (61%) received both hemodialysis and intravenous ethanol. Methanol intoxication-related mortality occurred in 14 (29%) patients following emergency department and subsequent stage treatment (Table 1).
Cut-off values predicting mortality for laboratory parameters were determined separately using ROC analysis. Cut-off values were not determined for age (p=0.199), BUN (p=0.382), potassium (p=0.163), chloride (p=0.054), calcium (p=0.765), INR (p=0.982), or ethanol (p=0.974). Other parameters are shown in Table 2.
Univariate analysis revealed greater mortality in patients with PH<7.00 (OR: 0.02 95% CI <0.01-0.15, p<0.001), bicarbonate <8.40 mmol/L (OR: 0.06 95% CI 0.01-0.31, p=0.001), lactate ≥4.35 mmol/L (OR: 52.0 95% CI 5.78-467.48, p<0.001), serum glucose ≥183 mg/dl (OR: 10.59 95% CI 2.40-46.75, p=0.002), PCO2 ≥42.7 mmHg (OR: 14.67 95% CI 3.20-67.18, p=0.001), serum osmolarity ≥293.5 mOsm/kg (OR: 5.46 95% CI 1.40-21.29, p=0.015), and anion gap ≥24.4 mmol/L (OR: 12.38 95% CI 2.76-55.50, p=0.001). No association was observed between mortality and age (p=0.083), type of treatment (p=0.155), or troponin (p=0.147), creatine (p=0.067), or sodium (p=0.091) levels (Table 3).
Modeling established by including pH, bicarbonate, lactate, glucose, PCO2, osmolarity, and anion gap at multivariate logistic regression analysis (model 1) identified pH <7.00 (OR:0.016, %95 CI <0.01-0.15, p<0.001) as a powerful significant predictor in diagnosis for methanol intoxication. Modeling without pH but in which bicarbonate, lactate, glucose, PCO2, osmolarity, and the anion gap were included (model 2) revealed increased mortality in patients with lactate ≥4.35 (OR: 31.66, 95% CI 3.25-308.5, p=0.003) and PCO2 ≥42.7 (OR: 7.01, 95% CI 1.12-43.96, p=0.038)
Univariate analysis of the relationship between mortality and blood and clinical parameters in patients with suspected methanol intoxication revealed an increase in mortality in patients with PH below 7.00 at presentation, HCO3 below 8.40 (mmol/L), lactate above 4.35 (mmol/L), glucose levels of 183 (mg/dl) or above, PCO2 above 42.7 (mmHg), high molarity, and a high anion gap. Mortality was approximately six times higher in patients who started treatment following the determination of blood methanol levels compared to those who started treatment with clinical diagnoses (OR: 6.21 95% CI:1.46-26.43, p=0.014). The multivariate model identified pH below 7.00 alone as a predictive marker, while when pH was excluded, lactate of 4.35 (mmol/L) and above together with PCO2 above 42.7 (mmHg) constituted a predictive model.
Discussion
Despite being a rare cause of presentation to the emergency department, methanol intoxications are a chaotic condition that can lead to significant mortality. Clinical symptoms emerge within approximately four hours after oral intake and can persist for 24-72 hours [1]. Presentations generally involve large numbers of patients arriving within a similar time frame [8]. Delays in the diagnosis of methanol intoxications may occur due to non-specific symptoms being observed, such as severe nausea and vomiting. Late blood methanol level results and delays in diagnosis are associated with increased mortality [9]. In the present study, mortality was approximately six times higher in patients who started treatment as a result of determination of blood methanol levels compared to those who started treatment based on clinical findings and histories (i.v. ethanol and hemodialysis) (OR: 6.21 95% CI:1.46-26.43, p=0.014).
Altered consciousness and vision disorders are symptoms frequently observed following exposure to methanol. Patients generally describe blurred and cloudy vision, double vision, or altered color perception. Narrowing of the visual field may occur, or vision may even be lost entirely. Petechial bleeding in the basal ganglia and pons in autopsy series is pathognomonic. Formic acid has been held responsible for mitochondrial impairment and vacuolization in the retinal pigment epithelium, photoreceptor inner segments, and optic nerve [1,3]. Hovda et al. also reported significant numbers of patients with neurological symptoms and observed higher mortality in the patient groups with accompanying neuropathologies [5]. Shokoohi M et al. described blurred and cloudy vision as the most common presentation symptom, and reported that neurological symptoms, including visual findings, were correlated with the severity of the toxicity [7]. Similarly, in the present study, the most frequent presentations were seen in patients with neurological findings (67%).
Another factor associated with mortality is age, with advanced age and decreased physiological capacity being linked to mortality [5-8]. Chung JY et al. reported that mortality increased in line with age, and implicated age-related impairment of physiological resistance mechanisms and chronic damage resulting comorbid diseases [10]. However, no statistically significant relationship was observed between increasing age and mortality in the present study (OR: 1.05 95CI%: 0.99-1.12, p=0.083).
Cellular and tissue damage due to formic acid results in an increase in breakdown products. Depending on the severity of toxicity, products and waste materials cause remarkable precursor changes in blood gas parameters, without yet causing significant alterations in conventional biochemical markers. The first indications of cellular breakdown are observed in pH, HCO3, PCO2, and lactate, which accumulate with an increase in breakdown with impairment of glucose balance, osmolarity, and an increased anion gap. Methanol is metabolized to formaldehyde by alcohol dehydrogenase (ADH), and formaldehyde is metabolized to the toxic agent formic acid by aldehyde dehydrogenase (ALDH). The accumulation of formic acid results in metabolic acidosis and hypoxia with cytochrome inhibition in mitochondria. Methanol intoxication is therefore essentially linked to metabolic acidosis and hypoxia [11,12]. Coulter C et al. examined laboratory parameters and blood gas in victims of methanol exposure and reported that the evaluation of metabolic acid and hypoxia alone could be used in the prediction of mortality, while other parameters were insufficient in terms of predicting mortality. Those authors reported that pH was the most powerful predictor of mortality, and that mortality increased in case of pH <6.7 [13]. Raido Paasma also emphasized the importance of blood gas analysis and reported that a high osmolar gap and anion gap metabolic acidosis were associated with mortality. pH <6.98 was described as a cut-off value for mortality [4]. Consistent with previous literature, the most powerful determinant of mortality in the present study was also pH, with high mortality being observed at pH values lower than 7.00.
Partial carbon dioxide and bicarbonate are directly linked to pH. An increase in PH resulting from increased anaerobic respiration mechanisms due to mitochondrial damage developing in association with accelerated anaerobic respiration and formaldehyde production in the early period and formic acid leads to a decrease in carbon dioxide and bicarbonate [11,12]. Kadam DB et al. reported pH below 7.3 and HCO3 lower than 20 mEq/L in methanol intoxications. Those authors emphasized that pH and HCO3 decreased in line with the severity of toxicity. Similarly in the present study, and consistent with the previous literature, low HCO3 indicated the severity of toxicity and was one of the early markers [14].
Increased catabolic breakdown with anaerobic respiration, together with acidosis and hypoxia, results in the production of lactate and pyruvate from glucose and alanine without oxygen consumption. The lactate and pyruvate cause lactic acidosis at the cellular level and acidosis and hypercarbia with increased lactate accumulation in tissues. In addition, increasing formic acid and lactate also result in an anion gap [11,12]. Kraut JA emphasized the methanol-induced anaerobic respiration steps and compensation mechanisms, and reported that increased lactic acidosis and hypercarbia, and therefore, an increased anion gap osmolarity, are compatible with the severity of toxicity. Glucose also increased in line with energy production. Those authors also reported that the severity of the anion gap and osmolarity will increase with exacerbation of tissue hypoxia [15]. Although the sensitivity and specificity were low in the present study, PCO2, anion gap, glucose and osmolarity were moderately-highly compatible with methanol toxicity.
This study investigated the clinical and laboratory parameters of patients who presented to the emergency department with methanol intoxication and determined cases that would result in mortality. Univariate analysis revealed increased mortality in patients with low pH, high lactate, high glucose, high PCO2, increased serum osmolality, and an increased anion gap. Multivariate analysis revealed that pH<7 or lactate ≥4.35 mmol/L together with CO2 ≥42.7 mmHg at the time of presentation may represent a predictive marker of mortality.
One of the most important findings of this study is the value of blood gas measurements. Changes in blood glucose levels, liver function tests, electrolytes, and electrocardiograms will be observed with an increase in tissue hypoxia and end-organ damage. However, reactions commencing at the cellular level did not alter the laboratory results in the early period, although blood gas analysis constitutes an earlier response compared to other laboratory parameters.
Limitations
The principle limitation of this study is its retrospective nature. Another limitation lies in the heterogeneous nature of the treatments applied. We do not know which patients achieved idea ethanol levels with ethanol therapy. We recommend that further studies with larger patient numbers be performed investigating factors capable of reducing mortality.
Conclusion
In conclusion, mortality decreased in patients who started treatment based on clinical diagnosis. In addition, our findings show that pH is a predictive marker of mortality, and that if pH is excluded, then high lactate and high partial carbon dioxide pressure can predict mortality in patients presenting with methanol intoxication.
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. Hantson PE. Intoxication aiguë par le méthanol : physiopathologie, pronostic et traitement [Acute methanol intoxication: physiopathology, prognosis and treatment]. Bull Mem Acad R Med Belg. 2006;161(6):425-36.
3. Ferrari LA, Arado MG, Nardo CA, Giannuzzi L. Post-mortem analysis of formic acid disposition in acute methanol intoxication. Forensic Sci Int. 2003;133(1-2):152-8.
4. Paasma R, Hovda KE, Jacobsen D. Methanol poisoning and long term sequelae – a six years follow-up after a large methanol outbreak. BMC Clin Pharmacol. 2009;9:5.
5. Hovda KE, Hunderi OH, Tafjord AB, Dunlop O, Rudberg N, Jacobsen D. Methanol outbreak in Norway 2002-2004: epidemiology, clinical features and prognostic signs. J Intern Med. 2005;258(2):181-90.
6. Zakharov S, Pelclova D, Urban P, Navratil T, Diblik P, Kuthan P, et al. Czech mass methanol outbreak 2012: epidemiology, challenges and clinical features. Clin Toxicol (Phila). 2014;52(10):1013-24.
7. Shokoohi M, Nasiri N, Sharifi H, Baral S, Stranges S. A syndemic of COVID-19 and methanol poisoning in Iran: Time for Iran to consider alcohol use as a public health challenge? Alcohol. 2020;87:25-7.
8. Liberski S, Kaluzny BJ, Kocięcki J. Methanol-induced optic neuropathy: a still-present problem. Arch Toxicol. 2022;96(2):431-51.
9. Aghababaeian H, Araghi Ahvazi L, Ostadtaghizadeh A. The Methanol Poisoning Outbreaks in Iran 2018. Alcohol Alcohol. 2019;54(2):128-30.
10. Chung JY, Ho CH, Chen YC, Chen JH, Lin HJ, Wang JJ, et al. Association between acute methanol poisoning and subsequent mortality: a nationwide study in Taiwan. BMC Public Health. 2018;18(1):985.
11. Barceloux DG, Bond GR, Krenzelok EP, Cooper H, Vale JA; American Academy of Clinical Toxicology Ad Hoc Committee on the Treatment Guidelines for Methanol Poisoning. American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning. J Toxicol Clin Toxicol. 2002;40(4):415-46.
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Download attachments: 10.4328.ACAM.21225
Ahmet Kayalı, Umut Payza, Yakup İriağaç, Serkan Bilgin, Mehmet Göktuğ Efgan, Osman Sezer Çınaroğlu. Prognostic markers of mortality in patients with methanol poisoning. Ann Clin Anal Med 2022;13(10):1107-1111
Citations in Google Scholar: Google Scholar
Is robotic surgery safe in patients with rectum cancer and multiple comor-bidities?
Mustafa Yener Uzunoglu 1, Fatih Altintoprak 2, Enis Dikicier 3, Omer Yalkin 4, Yesim Akdeniz 3, Kayhan Ozdemir 2, Burak Kamburoglu 2, Fehmi Celebi 2
1 Department of General Surgery Bursa City Hospital, Bursa, 2 Department of General Surgery, Faculty of Medicine, Sakarya University, Sakarya, 3 Department of General Surgery, Sakarya University Research and Educational Hospital, Sakarya, 4 Bursa City Hospital, Department of Surgical Oncology, Bursa, Turkey
DOI: 10.4328/ACAM.21226 Received: 2022-05-12 Accepted: 2022-06-21 Published Online: 2022-06-21 Printed: 2022-10-01 Ann Clin Anal Med 2022;13(10):1112-1116
Corresponding Author: Mustafa Yener Uzunoglu, Bursa Şehir Hastanesi, Doğanköy Mahallesi, 16110, Nilüfer, Bursa, Turkey. E-mail: mdyeneruzunoglu@gmail.com P: +90 224 975 00 00 F: +90 224 268 00 62 Corresponding Author ORCID ID: https://orcid.org/0000-0001-8133-2311
Aim: In this article, by combining the facts that the incidence of colorectal cancer accompanied by multiple comorbidities has increased and that robotic surgery is being used increasingly, it was investigated whether robotic surgery applications were reliable in this group of high-risk patients.
Material and Methods: The records of patients with the diagnosis of rectum cancer who un-derwent surgery between January 2011 and January 2019 were reviewed retrospectively. Pa-tients who were older than 65 years, with 2 or more comorbid diseases, with no neoadjuvant treatment protocol in the preoperative period, and with the tumor localization in the middle or distal rectum were evaluated in the study. In terms of the surgical procedure applied, the patients were divided into 3 groups: laparoscopic (L), robotic (R), and open (O) rectal resection.
Results: Of the 86 patients included in the study, 41 patients (47.6%) underwent open surgery (group O), 29 patients (33.7%) laparoscopic surgery (group L), and 16 patients (18.6%) robotic surgery (group R). The two most common comorbidities were diabetes mellitus (DM) (65.5%) and hypertension (56.1%). In this study, there were no differences between our groups in terms of postoperative intensive care requirements and early mortality and morbidity rates.
Discussion: Robotic surgery does not adversely affect early postoperative outcomes and can be safely applied to the patient group at high risk due to the presence of comorbid diseases.
Keywords: Rectal Cancer, Robotic Surgery, Minimally Invasive Surgery, Multiple Comorbidities
Introduction
Minimally invasive approaches, which were included in general surgery in the 1980s, have rapidly become widespread and are the first-choice surgical method in many abdominal surgical procedures today [1]. Especially in the field of colorectal surgery, laparoscopic experiences have increased more rapidly, and prospective studies have shown that the technique is favorable and reliable, with oncologic outcomes similar to open surgery [2].
Because of the presence of laparoscopic surgical experience, the surgeon’s adaptation to robotic surgery has been shorter, and nowadays it is known that the oncologic outcome of robotic surgery is not different from open or laparoscopic surgery [3, 4]. Therefore, is no debate left about the application of laparoscopic or robotic surgery for patients with colorectal cancer, and the field of debate has shifted towards expanding the applicability of these methods.
Due to the development of patient care conditions, patients who were previously in the risk group for open surgery have begun to be assessed as candidates for minimally invasive surgery. While different parameters are included in the definition of patients in the risk group, currently, the presence of chronic co-morbid diseases, especially multiple chronic comorbid diseases, has also been included in the classification criteria of high-risk patients [5].
In this article, by combining the facts that the incidence of colorectal cancer accompanied by multiple comorbidities has increased and that robotic surgery is being used increasingly, it was aimed to investigate whether robotic surgery applications were reliable in these patients evaluated as being in a high-risk group.
Material and Methods
The records of patients with the rectal cancer diagnosis who underwent surgery between Janu-ary 2011 and January 2019 were reviewed retrospectively. Permission for this study was ob-tained from Sakarya University Faculty of Medicine Clinical Research Ethics Committee. Pa-tients who were older than 65 years, with 2 or more comorbid diseases, with no neoadjuvant treatment protocol in the preoperative period, and with the tumor localization in the middle or distal rectum were evaluated within the scope of the study. Patients who undergone surgery for local recurrence, who had a synchronous tumor or other localization of a second primary tumor, who had only one co-morbid disease, had neoadjuvant therapy, who had undergone abdom-inoperineal resection, who had irregular clinical follow-up or had no access, even by telephone, were excluded from the study.
According to the surgical procedure applied, the patients were categorized into three groups: laparoscopic resection (L), robotic resection (R), and open resection (O).
Surgical technique
The dissection was performed from the lateral to the medial in the open surgery group, whereas it was performed from the medial to the lateral in the laparoscopic and robotic surgery groups. The Inferior Mesenteric Vein (IMV) was ligated at the level of the Ligament of Treitz. In the robotic group, stages of IMV ligation and splenic flexure release were completed laparoscopi-cally, and then the robotic system was docked. Distal resection in the laparoscopic and robotic groups was performed using Endo GIA (Endo GIA™ 60 mm Articulating Stapler, Covidien, USA). Proximal resection was performed by electrocautery, and the anastomosis was per-formed intracorporeally following the insertion of the anvil of the circular stapler.
Statistical analysis
The Kolmogorov–Smirnov test was used to determine if the continuous and intermittent numer-ical variables showed normal distribution, and the homogeneity of variances were investigated with the Levene test. Descriptive statistics of continuous and intermittent numerical variables were expressed as mean ± standard deviation or median (minimum–maximum), while categori-cal variables were expressed as number of cases and percentage (%). The significance of the difference between the groups in terms of mean age was assessed using one-way ANOVA, whereas the significance of differences in terms of T-phase, number of lymph nodes, and dura-tion of operation were evaluated using the Kruskal–Wallis test. Analyses of categorical data in cross-tabulations of RxC (if at least one of the categorical variables in the row or column were duplicate outcomes) were performed using Pearson’s Chi-Square or Likelihood-Ratio test. Analysis of the data was performed using IBM SPSS Statistics 17.0 (IBM Corporation, Ar-monk, NY, USA). For p <0.05, the results were considered statistically significant.
Results
Demographic data and preoperative parameters
A total of 252 patients with a rectal cancer diagnosis underwent surgery between the dates men-tioned. In this study, the data obtained from 86 (34.1%) of the 252 patients were evaluated in detail. Of these patients, 34 were female (39.5%) and 52 were male (60.5%). The mean age was 70.3±5.4 years (range: 65-89 years). Forty-one patients (47.6%) underwent open surgery (group A), 29 patients (33.7%) laparoscopic surgery (group L), and 16 patients (18.6%) robotic surgery (group R). BMI values predominantly fell into the range of 25-30 (43%) (mean BMI: 26.30 ± 2.17 kg/m2). When comorbid diseases were evaluated, it was determined that Diabetes Mellitus (65.5%) and Hypertension (56.1%) were the most two common comorbidities. The ASA score was determined as III in 63 patients (73.2%). Tumor localization was determined as middle rectum in 55 patients (64%) and distal rectum in 31 patients (36%) When preoperative staging was assessed, it was determined that 1 patient had intramucosal carcinoma (Stage-0) (1.16%), 37 patients had Stage-1 disease (43.02%) and 48 patients had Stage-2 disease (55.8%). Demographic data and preoperative parameters of all patients are shown in Table 1.
Preoperative and early postoperative parameters
The operation times were 140 (90-270) min in the open group, 200 (170-240) min in the lapa-roscopic group, and 218 (170-330) min in the robotic group. In the laparoscopic surgery group, the operation was continued with open surgery due to presacral bleeding in one patient (3.4%) and obesity in one patient (3.4%). Due to obesity seen in one patient (6.3%) in the robotic group, the operation had to be shifted to open surgery. Protective ileostomy was applied to 51 patients (59.3%), while the remaining 35 patients (40.7%) did not undergo this procedure.
Eleven patients (12.7%) required reoperation in the early postoperative period (bleeding in 6 patients, 6.9%; anastomotic leakage in 5 patients, 5.8%). Four (9.7%) open surgery patients and 2 (6.8%) laparoscopic surgery patients were re-operated on due to hemorrhage. In the re-operations, none of the patients were found to have major vascular hemorrhagic foci, whereas hemostasis was performed in 3 patients (50%) who had minor vascular hemorrhagic foci in the colon mesothelium. No hemorrhagic foci were found in the other 3 patients (50%). In the robot-ic group, there was no requirement for reoperation due to hemorrhage. Four patients (9.7%) in the open surgery group and one patient (3.4%) in the laparoscopic group required reoperation due to anastomotic leakage. During reoperations, anastomosis was halted, and the Hartmann procedure was applied subsequently. In both laparoscopic and robotic groups, endoscopic stent-ing was performed in one patient who was found to have anastomosis.
One patient in the open surgery group (2.4%) who had DVT in the lower extremity underwent medical therapy. DVT was not detected in the minimally invasive surgery groups.
A total of 15 patients (17.4%) were enrolled in postoperative follow-up intensive care (5 of the patients in the open surgery group, 12.1%; 5 of the patients in laparoscopic group, 17.2%; 5 of the patients in robotic group, 31.2%). Thirteen of the 15 patients (86.6%) were hospitalized after a 24-hour intensive care, while 2 patients (13.4%) were in intensive care for more than 24 hours.
A total of 3 patients died within the first 30 days after surgery (among patients in the open sur-gery group, 1 patient (2.4%) died in the first 24 hours due to myocardial infarction, 1 patient (2.4%) died on postoperative day 4 due to massive pulmonary embolism, and 1 patient (2.4%) died due to cardiovascular causes 22 days after hospital discharge).
Superficial wound infections occurred in 15 patients (17.4%) (7 of the patients in open surgery group, 17%; 2 of the patients in laparoscopic group, 6.9%; 1 of the patients in robotic group, 6.2%). Only patients with anastomotic leakage developed deep surgical site infection.
When groups were evaluated for duration of hospital stay, the time was found to be 9.1 days (5-28) in the open surgery group and 6.2 (5-9) and 6.4 (5-11) in the laparoscopic and robotic group, respectively.
The number of lymph nodes dissected was 16 (5-34) in the open surgery group, 14 (7-30) in the laparoscopic group and 15 (8-26) in the robotic group. Preoperative and early postoperative parameters of all patients are shown in Table 2.
Discussion
With the realization of laparoscopic rectal cancer surgery by Dr. Jacobs, the first laparoscopic rectal cancer surgery operations were performed in 1991, and in the following years, this meth-od was shown to be feasible and effective in various prospective studies [6].
Experiences have greatly increased since the early use of robotic methods in rectal cancer sur-gery, and sufficient experience and knowledge have been gained in this area. However, there are still doubts about the use of robotic surgery in patients with advanced age and multiple co-morbidities. The robotic surgery operation time for various procedures has been shown to be longer than open and laparoscopic techniques [7]. However, with the increase in experience and the development of robotic systems, the operation times have come to the point of equalizing with laparoscopic surgery. In the study by Wang et al, it was also indicated that the application of robotic rectal surgery in centers with laparoscopic surgery experience does not differ in terms of operation time [8].
In terms of oncologic results, robotic surgery by colorectal cancer surgeons is now known to be equivalent to open and laparoscopic surgery [4]. In the meta-analysis by Li et al. including 3601 cases and 17 studies, robotic rectal cancer surgery was found to be similar to laparoscopic sur-gery in terms of oncologic and functional outcomes [9]. In the same study, it was found that laparoscopic and robotic surgeries have similar results in terms of circumferential surgical mar-gin negativity, local recurrence, 3-year survival rates, and postoperative complications rates. Staderini et al. reported in their review, examining the results of 3013 patients with moderate and distal rectal cancer, determined that laparoscopic-robotic surgery had similar oncologic out-comes compared to open surgery and lower postoperative complication rates [10]. In our study, oncologic results were found to be similar in all three groups in accordance with the literature.
There are a limited number of studies demonstrating that the use of minimally invasive surgery is safe and feasible in a population of elderly patients with rectal cancer accompanied by system-ic co-morbidities [11]. In this group of patients, there are far fewer studies on the results of ro-botic surgeries. It was reported that robotic surgery is safe in the study by Oldani et al. involv-ing 50 patients over 70 years of age undergoing robotic surgery [12]. The fact that our patients have multiple comorbidities is another aspect compared to the work of Oldani et al. In a study comparing robotic surgery and laparoscopic surgery in patients with rectal cancer in the high-risk group, Fernandez et al. reported that the results of the robotic surgeon were as safe as lapa-roscopy in terms of postoperative complications [13]. In our study, similar oncologic and post-operative results were obtained in accordance with the study by Fernandez et al. Our study dif-fers from the study by Fernandez et al. in that patients who underwent open surgery are also included, and thus we have the feasibility to compare the outcome of the open method with the results of minimally invasive methods involving the combination of laparoscopic-robotic sur-gery [13].
Although laparoscopic and robotic methods indicate that the duration of surgery is equal to the open method in experienced centers, it is a fact that the total duration of anesthesia is longer due to the technical details and preparations in these methods [14] (docking, insufflation, trocar placement, patient position). This difference in time is greater in centers that have not yet com-pleted the learning curve for minimally invasive surgery [15]. The most important factor for the shortening of this training time is experience [16]. Our results were similar to those of experi-enced centers, and the duration of total anesthesia was longer in the minimally invasive surgery group than in the open group. When the laparoscopic and robotic groups were evaluated within themselves, the length of time in the robotic group was not significantly different.
Although the patients in our study had multiple co-morbidities, and the duration of surgery in the robotic surgery group was not statistically significant, there were no differences in postoper-ative intensive care requirement and early mortality rates between the groups. We are of the opinion that this was the most important outcome of our work.
It has been indicated in the literature that there are several determinants for a return to open sur-gery in minimally invasive surgery, and it has been emphasized that factors such as experience, technical obstacles, obesity, and large tumor size are the most important causes [17, 18]. The retrospective nature of the study and the insufficient number of patients involved are the limiting aspects of this study. Minimally invasive methods have proven to be sufficient in the surgical treatment of colorectal cancers.
Conclusion
We are of the opinion that the long operation time in robotic surgery does not adversely affect the outcome in patients who are considered to be in the high-risk group due to the presence of comorbid diseases and that robotic surgery can be applied safely in this patient group.
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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11. Wilks JA, Balentine CJ, Berger DH, Anaya D, Awad S, Lee L, et al. Establishment of a minimally invasive program at a Veterans’ Affairs Medical Center leads to improved care in colorectal cancer patients. Am J Surg. 2009;198(5):685-92.
12. Oldani A, Bellora P, Monni M, Amato B, Gentilli S. Colorectal surgery in elderly pa-tients: our experience with DaVinci Xi® System. Aging Clin Exp Res. 2017;29(1):91-9.
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Mustafa Yener Uzunoglu, Fatih Altintoprak, Enis Dikicier, Omer Yalkin, Yesim Akdeniz, Kayhan Ozdemir, Burak Kamburoglu, Fehmi Celebi. Is robotic surgery safe in patients with rectum cancer and multiple comor-bidities?. Ann Clin Anal Med 2022;13(10):1112-1116
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Clinical evaluation of cerebral MRI findings in children with cerebral palsy
Sevda Canbay Durmaz 1, Ahmet Kağan Karabulut 2, Serdal Güngör 3, Zeliha Fazlıoğulları 2, İsmihan İlknur Uysal 4, Nadire Ünver Doğan 2
1 Department of Anatomy, Institute of Health Sciences, İnönü University, Malatya, 2 Department of Anatomy, Faculty of Medicine, Selçuk University, Konya, 3 Department of Pediatrics, Faculty of Medicine, İnönü University, Malatya, 4 Department of Anatomy, Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey
DOI: 10.4328/ACAM.21228 Received: 2022-05-15 Accepted: 2022-06-21 Published Online: 2022-06-25 Printed: 2022-10-01 Ann Clin Anal Med 2022;13(10):1117-1121
Corresponding Author: Sevda Cabay Durmaz, Department of Anatomy, Institute of Health Sciences, Inonu University, 44280, Malatya, Turkey. E-mail: sevdacnby@hotmail.com P: +90 541 348 50 05 Corresponding Author ORCID ID: https://orcid.org/0000-0002-7792-5306
Aim: In this study, we aimed to investigate the frequency of lesions, which show the hypoxic-ischemic brain damage, their anatomical localization, the timing of the occurrence of the lesions and the causes using the magnetic resonance imaging (MRI) method.
Material and Methods: MRI findings of 150 patient with cerebral palsy (CP) were analyzed. MRI findings, patients’ ages, gender, type of birth, birth ages, relationship of parents, additional diseases to CP and clinical type of CP were evaluated. As a control group, 100 healthy children with normal MRI findings of the same age, their gender, types of birth, birth ages, parents relationship and data were compared with the data of children with CP
Results: When etiological factors of CP and the control group were compared, male children were found to be more affected than female. In the age groups, children aged 1-5 were determined to have cerebral palsy more than in the other groups. Related with CP ethiogenesis, prematurity and low birth weight play important roles. On the other hand, negative hospital conditions during and after the birth as well as the curative effect of rapidly developing medical technologies on the babies with high mortality, also have important effects on CP ethiogenesis.
Discussion: Our results show that there are some similarities and differences between the cerebral palsy group and the controls. It was also determined that the MRI method is important in CP diagnosis. Anatomical localisations of the lesions in the brain support the relevant clinical symptoms and thus play an important role in the differential diagnosis.
Keywords: Cerebral Palsy, Children, Brain Damage, MRI
Introduction
Cerebral palsy (CP) affects various parts of the nervous system that have not yet completed their development, and it is a clinical syndrome characterized by pathologies such as movement and posture disorders, mental retardation (MR), hemiplegia and dysarthria [1].
CP was first defined as spastic rigidity (Little’s Disease]) in 1861 by William John Little (1810-1894), an English orthopedist. William John Little, a very good observer, cited abnormal, difficult and prolonged labor, premature birth and neonatal asphyxia as the cause of the disease. [2]. The definition of CP was first used by William Osler. [3].
Damage to the central nervous system (CNS) in patients with CP causes disorders in the neuromuscular, musculoskeletal and sensory systems. These disorders cause insufficiency in the posture and motor functions of the child. Secondary disorders such as various musculoskeletal deformities and the addition of tertiary disorders to the table with the effect of different mechanisms over time, negatively affect the development and functional independence levels of children [4]. Although the damage itself is not progressive, the consequences of inadequacies and disability can be progressive [5].
CP is one of the most common causes of childhood disability. Since the child with CP develops with a lesion in the CNS, symptoms change throughout life and problems that arise can persist throughout their life [6].
The frequency of CP in our country has been determined as 4.4 per 1000 live births, but specified as 8/1000 in some cases. It is stated as 2-2.5/1000 in Europe and Australia and 1.6/1000 in China [7,8].
There is an increase in the frequency of CP, especially in developed countries. This increase has been observed mainly in spastic and ataxic diplegic cases due to the increased chance of survival of immature and premature infants as a result of medical care and technological developments [9].
It is very important to support clinical findings with radiological methods in the diagnosis of CP. It has been stated that especially magnetic resonance imaging [MRI] has been of a great importance in determining the etiology of CP in recent years [9].
In our study, MRIs of patients diagnosed with CP were examined. MRI findings, age, gender, mode of delivery, birth weight, age at birth, presence of consanguineous marriage, diseases accompanying CP, clinical type of CP were evaluated. Etiological factors of healthy children in the same age group who underwent MRI for any reason but did not have any lesions were evaluated and compared with the data of children with CP. In this direction, our aim is to help determine the frequency, anatomical location, timing and causes of the lesions showing hypoxic-ischemic brain injury.
Material and Methods
In our study, we retrospectively analyzed all data of patients diagnosed with CP who applied to the Pediatric Neurology Outpatient Clinic between January 2008 and April 2012.
Our study was conducted after the approval of the clinical research ethics committee of İnönü University with the research protocol numbered 2012/2.
Our article was produced from master’s thesis at Selcuk University Health Sciences Institute, Department of Anatomy. It was presented as an oral presentation at the 15th National Anatomy Congress.
MRI findings of 150 patients aged 1-16 years were evaluated. In addition, age, gender, birth age, birth weight, mode of delivery, presence of consanguineous marriage, disease accompanying CP, and type of CP were examined.
Age, sex, birth age, birth weight, type of birth, and consanguineous marriage of 100 healthy children who had MRI for any reason at the same age and had no pathology were evaluated and compared with the data of children with CP.
SPSS 15 statistical program was used to evaluate patient and control group data. Data were summarized using mean ± standard deviation values. The Mann-Whitney U, Chi-square and t tests were used for parametric test assumptions, and p< 0.05 was considered statistically significant.
Classified as MRI findings, normal, lesion in the corpus callosum, lesion in lateral ventricles, lesion in the cerebrum (lesion in the right hemisphere, left hemisphere, temporal lobe, occipital lobe lesion), lesion in the cerebellum, periventricular leukomalacia (PVL), lesion in the basal ganglia.
The ages of the patients were taken as years from the date of filling the files. Age groups were classified as the first group between the ages of 1-5, the second group between the ages of 6-10, and the third group between the ages of 11-16.
The time of birth was recorded in weeks. Those born at 37 weeks and later were recorded as term, and those born before 37 weeks were recorded as preterm.
Birth weight was recorded in grams, and babies with a birth weight of less than 1500 g were very low birth weight (VLBW), 1500-2500 g babies with a low birth weight (LDA) and 2500 g-4000 g babies were normal birth weight (NDA) were divided into three groups.
Mode of delivery was recorded as normal vaginal delivery (NVYD), home or hospital, and cesarean section (C/S).
It was recorded whether there was consanguineous marriage or not.
Mental retardation (MR), epilepsy, vision problems, speech problems were recorded as accompanying findings with CP.
The patients were classified as quadriplegic, right hemiplegic, left hemiplegic, diplegic, ataxic, hypotonic and mixed type CP.
Results
In our study, MRI findings of 150 patients with CP, 87 males (58%) and 63 females (42%), were evaluated. The male/female ratio was found to be 1,38.
In the control group, 47 healthy girls and 53 healthy boys were evaluated. The male/female ratio was found to be 0.886.
The ages of the patients were between 1-16. There were 77 patients in the first group, whose ages were 1-5 years (%51,3). There were 39 patients in the second group, whose ages were 6-10 years (%26). There were 34 patients in the third group, whose ages were 11-16 years (%22,6). The mean age in the group with CP was 76.8 ±54.96 months.
In the control group, there were 46 healthy children in the first group with an age range of 1-5 years (%46). The second group, whose age range was between 6-10 years, included 30 healthy children (%30). The third group, whose age range was between 11-16 years, included 24 healthy children (%24). The mean age in the control group was 81.12±45.62 months.
When we evaluated the age of birth in the group with CP, there were 96 patients in the term group who were born at 37 weeks and above (%64), 54 patients (36%) in the preterm group who were born before 37 weeks.
In the control group, there were 88 healthy children in the term group who were born at 37 weeks and above (%88). There were 12 healthy children (12%) in the preterm group who were born before 37 weeks.
There were 42 patients in the very low birth weight (VLBW) group with a birth weight of 1500 g or less (%28). There were 46 patients in the low birth weight (LDA) group birth weight between 1500 g and 2500 g (%30,7). There were 62 patients (41.3%) in the normal birth weight (NBW) group, whose birth weight was between 2500 g and 4000 g.
In the control group, there were 46 healthy children in the low birth weight (LBA) group (%46). There were 54 healthy children (54%) in the normal birth weight (NDA) group (p<0,05).
Sixty-six patients (44%) were born with C/S, 44 patients (29.3%) were born at home with NVYD and 40 patients (26.7) were born in hospital with NVYD.
In the control group, 20 (20%) children were born with C/S; 16 (16%) children were born with NVYD at home, 64 (64%) children were born with NVYD in the hospital.
There was a consanguineous marriage between the parents of 88 patients (58.7%), and in 62 patients (41.3%) there were no consanguineous marriages.
In the control group, there was a consanguineous marriage between the parents of 79 patients (79%), there were no consanguineous marriages in 21 patients (21%) (p<0,05).
Epilepsy was present in 72 (48%) patients, speech problems in 19 (12.66%), visual problems in 10 (6.66%) and MR in 26 (17.3%) patients with CP. There was no accompanying different clinical table in 23 (15.3%) patients with CP.
The clinical CP type of the patients was mostly quadriplegic type CP. There were 82 patients (54.6%) in this group. Twenty-four patients (16%) had hypotonic CP, 8 patients (5.3%) had ataxic CP, 8 patients had mixed CP (5.3%), 13 patients had diplegic type CP (8,6%), there were 6 patients with left hemiplegic type CP (4%), and 9 patients with right hemiplegic type CP (6%).
The Anatomical localization of the lesion in CP cases is given in Table 1.
MRI findings of patients diagnosed with CP were evaluated separately in term and preterm cases. , Frequency and localization of the findings are summarized in Table 1.
Anatomical localization of the lesion in term ve preterm CP cases is given in Table 2.
The distribution of MRI findings of patients with CP by age group is given in Table 3.
Discussion
CP is a non-progressive condition that occurs due to CNS damage or anomaly in the prenatal, natal and postnatal periods, but it can lead to various motor dysfunctions over time [8].
In children, the lesion in the CNS and its clinical reflection may change over time. Especially after birth or in the first months of life, motor, movement and posture anomalies may change over time. In addition, the underlying cause of the clinical finding may not be a lesion in the central nervous system, it can also be an indicator of metabolic disease. In these cases, the diagnosis of CP would be misleading or CP becomes more difficult to diagnose. Therefore, we did not include patients younger than 1- year- old in our study [9].
Prematurity has become an important cause of CP with the development of medical technology and the increased chance of survival of infants at a very young birth age [10]. Pellegrino draws attention to the decrease in mortality in preterm infants and the increase in the rate of CP in preterm infants with the widespread use of intensive care units [11].
In our study, unlike previous studies, we evaluated the birth ages of both children with CP and randomly selected healthy children and compared these data. There was no statistically significant difference between the birth ages of the CP group and the control group, but the number of term babies was numerically higher in the group with CP. This rate was in parallel with other studies conducted in our country. The rate of term babies was found to be 76% in one study and 73.6% in another study [12,13]. These data also draw attention to the fact that the poor care conditions of the baby after birth play a major role in the etiology of CP.
According to studies conducted in our country, it has been determined that between 77.8% and 95.1% of children with CP are born with NVYD [3]. In our study, 44% of the patients were diagnosed with C/S; 29.3% of them were born with NVYD at home and 26.6% of them were born in hospital with NVYD; 55.9% of total CP cases were born with NVYD. In the control group, 21% of the cases had C/S; 64% were born with NVYD in the hospital, and 16% were born with NVYD at home.
In terms of these data, when compared with both the control group and with previous studies, no significant value was found for the mode of delivery among the causes of CP. However, the high rate of birth with C/S in the CP group suggests that there should be any problem in the prenatal mother and baby health and that birth with C/S should be compulsory. One of the reasons for this is that the developing medical technology keeps babies who are difficult to live. Therefore, the problems seen in babies born prematurely with C/S are increasing. The reason for the difference in the literature data is thought to be due to the fact that the studies were conducted in different geographical regions and that each region has different sociocultural and socioeconomic levels.
Epilepsy is one of the most common neurological problems in children with cerebral palsy. According to studies, it is thought to be more common in quadriplegic type CP and CP caused by postnatal reasons [14-16]. In previous studies, the rate of cases with CP with epilepsy ranged from 18% to 60% [17]. In our study, epilepsy was accompanying 48% of the cases with CP. As demonstrated in previous studies, most of our cases with CP in our study were quadriplegic type CP, and the most common accompanying neurological problem was epilepsy.
In our study, unlike other studies, we examined CP in terms of extremity involvement and motor movement limitation in 7 groups: quadriplegic type CP, hypotonic type CP, ataxic type CP, mixed type CP, diplegic type CP, right hemiplegic type CP, and left hemiplegic type CP. In previous studies, CP was grouped as spastic, dyskinetic, ataxic, hypotonic and mixed type and among these, the most common type of CP was reported as the spastic type. In the studies conducted, spastic type CP cases were found at a rate of 77% in the USA, 79% in Sweden, 94% in Northern Ireland, 82% in Norway and 86% in Saudi Arabia [18,19].
Our study was similar to some of the other studies in our country in terms of quadriplegic type SP ratio. However, this rate is quite high compared to studies conducted in developed countries. This may be due to poor maternal care in the perinatal period and exposure of risky, preterm and preterm infants to unfavorable hospital conditions. Even patients with a milder clinical type of CP may become quadriplegic due to all these adverse conditions.
In a study conducted in Germany, PVL was reported as the most common pathological finding with a rate of 56% [20]. In our study, this rate was determined as 22%.
Damages that occur during the maturation and development of the brain cause different pathologies in different parts of the brain. For example, damage in the first 20 weeks of the gestational period usually causes lesions in the cerebellum, damage between 24-34 weeks of gestation causes lesions in the periventricular area and problems occurring after 34 weeks of gestation usually cause lesions in the gray matter [19].
Accordingly, when we separately evaluate the MRI findings in term and preterm infants in the CP group, the most common corpus callosum lesion and PVL were detected in MRI findings.
In a previous study, the most common MRI findings in term babies with CP were found to be cortex-subcortical tissue damage with 44.8%, and PVL with a rate of 16.5%. [20]. In another study, it was emphasized that 43.3% cortex subcortical tissue damage, 16.6% cortical migration anomalies, 10% PVL were the most common MRI findings [14].
Conclusion
In our study, we found that the etiological factors and MRI findings showed some differences from the findings of studies conducted both in Turkey and abroad.
In the etiology of cerebral palsy, it was determined that the negative hospital conditions during and after birth, as well as premature and low birth weight births and the survival of babies who did not have a chance to survive with the developing medical technology were also important. In this case, it was concluded that the frequency or severity of CP could be reduced by raising the standards of delivery rooms and infant intensive care units, by making good pregnancy follow-up and raising the awareness of pregnant women. MRI method has an important place in the diagnosis of CP; the anatomical localization of the lesion formed in the brain overlaps with the clinic and plays a role in the differential diagnosis of the clinical type; It has been understood that it is a mandatory method to be applied in the suspicion of CP.
It is thought that more studies should be done on early detection of the disease, understanding the age limit and the exact causes.
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.21228
Sevda Canbay Durmaz, Ahmet Kağan Karabulut, Serdal Güngör, Zeliha Fazlıoğulları, İsmihan İlknur Uysal, Nadire Ünver Doğan. Clinical evaluation of cerebral MRI findings in children with cerebral palsy. Ann Clin Anal Med 2022;13(10):1117-1121
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Effect of head position during thyroidectomy on cerebral oxygenation and cognition: Prospective observational study
Necla Gülçek 1, Bengü Gülhan Aydın 1, Gamze Küçükosman 1, Özcan Pişkin 1, Rahşan Dilek Okyay 1, Güldeniz Karadeniz Çakmak 2, Hilal Ayoğlu 1
1 Department of Anesthesiology and Reanimation, 2 Department of General Surgery, Faculty of Medicine, Zonguldak Bülent Ecevit University, Zonguldak, Turkey
DOI: 10.4328/ACAM.21230 Received: 2022-05-16 Accepted: 2022-06-21 Published Online: 2022-06-23 Printed: 2022-10-01 Ann Clin Anal Med 2022;13(10):1122-1126
Corresponding Author: Bengü Gülhan Aydın, Department of Anesthesiology and Reanimation, Faculty of Medicine, Bülent Ecevit University, Zonguldak, Turkey. E-mail: bengukoksal@gmail.com P: +90 530 558 30 76 F: +90 372 261 27 68 Corresponding Author ORCID ID: https://orcid.org/0000-0002-7111-8685
Aim: In this study, we aimed to observe the effect of head position during thyroidectomy on carotid artery blood flow, cerebral oxygen saturation (rSO2) and postoperative cognitive dysfunction (POCD).
Material and Methods: Forty patients were included in the study. The time-average velocity (TAV), peak systolic velocity (PSV), end-diastolic velocity (EDV), flow volume (FV), carotid artery diameter (CAD), and resistance index (RI) of the common carotid artery were measured using Doppler ultrasonography when the patient was in supine position before anesthesia, after surgical position (semi fowler position with extension of the neck and head), and before position correction at the end of the surgery. Bilateral rSO2 values were monitored continuously. Cognitive functions were evaluated with the standardized mini-mental test.
Results: At the end of the operation, it was determined that FV, PSV, EDV, CAD and bilateral rSO2 values decreased compared to the initial values (p <0.05). Early and late POCD were found to be 47.5% and 32.5%, respectively. No relationship was found between cerebral desaturation and POCD. It was observed that the decrease in FV might be related to early POCD (p <0.05).
Discussion: The head position caused a decrease in carotid blood flow, and bilateral rSO2, and these outcomes became more pronounced towards the end of the surgery. Although there was a correlation between early POCD and a decrease in FV, there are many factors that might have affected POCD.
Keywords: Cerebral Perfusion, Thyroidectomy, General Anesthesia, Cognition
Introduction
In order to perform surgical procedures more comfortably, the positions given according to the region and type of the operations might cause physiological changes. During thyroid surgery, the semi-Fowler position is defined as a body position at 30° head-of-bed elevation, with the extension of the head and neck in order to reach the mass comfortably. In this position, the main carotid arteries may be exposed to compression as a result of hyperextension of the head and the retraction of the thyroid. In addition to the effect of the position, when vasodilation caused by general anesthesia is added, cerebral hypotension might occur and consequently, cerebral blood flow, cerebral oxygen saturation and cognitive functions might be affected [1,2].
Doppler ultrasonography (USG) is a reliable, non-invasive imaging method used in the examination of carotid arteries with 92.6% sensitivity and 97% specificity [3].
Cerebral oximetry helps predict the cerebral oxygen delivery/consumption ratio in the frontal cortex, a hypoxemia-prone area named the “watershed zone”, which is supplied by the anterior and middle cerebral arteries of the brain. Low intraoperative cerebral oxygen saturation (rSO2) values are reported to be associated with postoperative cognitive dysfunction (POCD) [4,5]. POCD is a common complication after anesthesia and surgery.
We aimed to observe the changes in main carotid artery blood flow measured with Doppler USG and cerebral oxygenation measured with NIRS during head positioning in thyroidectomy and related early and late effects on cognitive functions.
Material and Methods
Study Design and Ethical Consideration
This prospective and observational study (ClinicalTrials.gov: NCT04830293) was carried out in Zonguldak Bulent Ecevit University Hospital, from June 2019 to April 2020 after its approval by the Ethics Committee (Meeting Protocol No. 2019-40-14/02, Date: Feb 14, 2019) and obtaining written consent from the patients. It was conducted with 40 patients who were in the ASA I-II risk group and between the ages of 18-50, who were going to have a total thyroidectomy under general anesthesia. Those with a preoperative standardised mini-mental test (SMMT) [6] score below 23, hemoglobin below 8 g/dl, with a diagnosis of hypertension, hyperlipidemia, pregnancy, diabetes mellitus, cerebrovascular insufficiency, known carotid artery lesion, metabolic diseases, presence of any intracranial pathology, and surgeries exceeding 180 minutes were excluded. In addition to standard monitoring, bispectral index monitoring and bilateral rSO2 monitoring were performed using NIRS technology (O3 TM, Masimo, Irvine, USA). A decrease of more than 20% in rSO2 values compared to the initial value was accepted as intraoperative cerebral desaturation [7], and any decrease in such nature was recorded. After preoxygenation, routine anesthesia induction and maintenance were provided. Hemodynamic data of the patients -such as heart rate (HR), mean arterial pressure (MAP), bilateral rSO2 values and % change were measured at specific time intervals (T0: Before the induction of the anesthesia, T1: 10 minutes post-induction, T2: After positioning for the surgery, T3: 30 minutes post-induction, T4: 60 minutes post-induction, T5: 90 minutes post-induction, T6: 120 minutes post-induction, T7: 150 minutes post-induction, T8: Before the correction of the surgical position). Carotid diameter, PSV, EDV, mean flow velocity, AH, and RI were measured Using doppler USG and recorded for both sides at T0, T2, and T8. The cognitive functions of the patients were evaluated by applying SMMT 24 hours before the operation, at the postoperative 24th hour (early period), and 3 months later (late period). A decrease of ≥2 points compared to the baseline postoperative SMMT score was evaluated as a decrease in cognitive function.
Statistical Analysis
The necessary sample size was calculated using PASS (Power Analysis and Sample Size) 11 software before starting the study. The minimum number of patients to be reached was calculated as 31 as a result of the sample size analysis performed with reference to a 95% confidence interval (CI) and 95% power [8]. Considering a failure rate of 20%-25%, the required sample size was determined as 40 participants. The research data were analyzed using SPSS v.22.0 software. The Shapiro-Wilk was used as the normal distribution test. T-Test, Mann-Whitney U test, Friedman test, Repeated measures ANOVA, Spearman’s correlation analysis, Pearson’s correlation analysis, and ROC analysis were used during the analyses. A p <0.05 value was considered statistically significant. Descriptive statistics were presented as Mean±SD, median, minimum, maximum, and the reference data as n and %.
Results
A total of 40 patients were included in the study. Table 1 presents the sociodemographic characteristics and the surgery and anesthesia times of the patients.
There was a significant difference between the HR, MAP and SpO2 values measured prior to and at certain times during the operation (p <0.001). All measurements were within normal limits. When rSO2 values measured before and at certain times of the operation were examined, it was observed that there was an increase in rSO2 values 10 minutes after induction and a decrease at other times compared to the preoperative time, and there was a significant difference between intraoperative times (p <0.001). Figure 1 presents the distribution of right and left rSO2 values measured before and at certain times of the operation.
The carotid diameter measured at T0 was significantly higher than the values measured at T2 and T8 (p<0.05). The blood-flow volume, PSV, and EDV values at T8 were significantly lower when compared to the value at T0 (p <0.001, p = 0.043, p = 0.001, respectively). In contrast to other findings, pre-induction RI was significantly lower than after the surgical positioning (p = 0.004) and before the correction (p = 0.001).
The early POCD incidence was 47.5% (n = 19), and the late POCD incidence was 32.5% (n = 13). When preoperative, postoperative 24th-hour, and postoperative 3rd-month SMMT values were compared, there was a significant difference (p <0.001). Considering the post-hoc comparisons of the SMMT results, it was found that the preoperative SMMT value was significantly higher than the postoperative 24th-hour and postoperative 3rd-month results (p <0.001), and the 3rd-month was significantly higher than the postoperative 24th-hour value (p = 0.003).
In this study, the incidence of cerebral desaturation was 15% (n = 6). There was no significant correlation between cerebral desaturation and early and late POCD (p = 0.619, p = 0.351, respectively). There was also no significant correlation between anesthesia and the duration of surgery and early and late POCD.
When early POCD and carotid artery Doppler measurement parameters were examined, there was a correlation between the decrease in carotid artery blood-flow volume and early POCD (p <0.05), while there was no significant relationship between late POCD and measurement parameters (Table 2).
Considering the possibility of using Doppler measurements for diagnostic purposes in early POCD, the % of the reduction in carotid artery blood flow volume was determined to be significant. The decision-making power of carotid artery blood flow volume as a diagnostic test was moderate (AUC = 0.717). Figure 2 presents the early impairment ROC analysis areas under the curve.
Table 3 presents the valid values for different cut-off values in terms of carotid artery blood flow volume change. The sensitivity was 73.7% and the specificity was 76.2% for a 53.5% change.
Discussion
In this study, we considered the effects of head and neck extension on carotid artery blood flow, rSO2 and POCD during thyroidectomy. A significant reduction in carotid blood flow and cerebral oxygenation was observed towards the end of the thyroidectomy. Decrease in carotid artery flow volume was determined to correlate with early POCD. However, no relationship was observed between POCD and cerebral desaturation.
Among general surgery patients, those who have undergone neck surgery are at higher risk of cerebrovascular events. These events might appear due to surgical and anesthetic maneuvers. In addition to surgical maneuvers, this increased risk may also be associated with the increased risk of surgical procedures requiring neck hyperextension. Hyperextension may lead to an intimal tear in the carotid artery, thrombus formation, or plaque ulcer caused by turbulent blood flow [9,10].
Especially the middle cerebral artery is an important vessel for cerebral blood flow. Therefore, stretching or narrowing of the carotid and vertebral artery leads to a greatly reduced flow in the middle cerebral artery, globally causing impaired brain perfusion. Siwac et al. [11] evaluated the blood flow changes in cerebral arteries in different head positions and stated that the blood flow velocity in cerebral arteries decreases, although not significantly, while the head and neck are in extension.
In another study, intraoperative rotation and/or extension of the cervical spine was demonstrated to cause a decrease in the mean blood flow rate of the middle cerebral artery by more than 20%, compared to the basal value [12]. Saraçoğlu ve ark. [8] showed that PSV, mean velocity, and blood flow volume in the common carotid artery were found to be significantly decreased compared to the initial values in their study on the effect of cervical extension on cerebral blood flow changes.
In this study, at the end of the operation, common carotid artery diameter, PSV, blood flow volume, and EDV decreased significantly compared to baseline values, while RI increased significantly. Approximately, there was a 9% decrease in PSV, an 18% decrease in EDV, a 35% decrease in flow volume, and a 5% increase in RI, compared to base values. We believe that these changes may have resulted from the mechanical stress caused by the head and neck position to the artery and the impact of general anesthesia on blood pressure, heart rate, cardiac output, peripheral vascular resistance, and arterial compliance.
Postural changes during anesthesia have a complex impact on systemic and cerebral circulation, potentially reducing cerebral blood flow and oxygenation [2]. One of the methods to monitor cerebral perfusion is cerebral oximetry. The normal rSO2 range in unconscious patients is 60%-75% [13]. There are reports that with an increase in cerebral desaturation over 20% compared to the base value in conscious patients, clinical symptoms of presyncope occur, and the highest cerebral desaturation value is 13% in those who do not develop syncope [14]. In this study, a decrease of 20% from the initial value lasting more than 15 seconds was accepted as cerebral desaturation.
Smarius et al. [15] showed that there was a severe cerebral desaturation lasting at least 3 minutes, less than 45%, rare, unilateral due to excessive stretching of the neck as a result of hyperextension applied to the head and neck during cleft palate surgery. They emphasized that there were no neurological sequelae postoperatively in any patients. Although there is no data for rSO2 values on cerebral desaturation threshold, which is severe enough to cause brain damage, animal studies suggest that values below 60% may be associated with medium risk and below 45% with a high risk of damage [16]. Although the definition of cerebral desaturation has changed in studies, the incidence of cerebral desaturation in the sitting position is reported to be between 0-80% [17,18]. Yaman et al. [19] emphasized that there was a significant decrease in cerebral oxygenation after the head and neck position given for thyroid surgery, and no serious cerebral desaturation was observed during the operation. In this study, the incidence of cerebral desaturation was found to be 15%. In this study, there was an increase in rSO2 values after induction, compared to the baseline value. During monitoring, the right and left rSO2 values tended to decrease, the lowest rSO2 values were at the end of the operation, just before the position was corrected, and they were above 60%. We believe that the reason for the increase in rSO2 values after induction is associated with the decrease in cerebral metabolism and oxygen demand due to the anesthetics, and the tendency of intraoperative rSO2 values to decrease results from the decrease in carotid blood flow volume due to the position. The reason for the absence of severe desaturation may be due to the possibility that autoregulation may have continued cerebral blood perfusion with the intracerebral collateral flow, even if the carotid blood flow decreased since the ASA I-II patient groups were included in the study.
Kim et al. [20] evaluated cerebral oxygenation in the beach-chair position and showed that the decrease in hemodynamic data, especially in MAP, was correlated with the decrease in rSO2. In our study, among 6 patients, one-time decreases of 20%-23% in rSO2 values were observed for less than 20 seconds, compared to baseline values. In all 6 patients, MAP was between 50-53 mmHg when rSO2 decreased. To increase cerebral rSO2, oxygen delivery to the brain should be increased. For this purpose, an increase PaCO2, hemoglobin, and/or cardiac output should be considered. To increase MAP, 5 mg of ephedrine hydrochloride was administered iv, since the PVI, BIS, and EtCO2 values were within the normal range. An increase in rSO2 values was observed after ephedrine. Although continuous monitoring of cerebral oxygenation provides interventions to maintain adequate cerebral oxygenation by monitoring rSO2, it is unclear from neuropsychological results whether interventions can improve POCD. Aguirre et al. [21] stated that hypotension in the first five minutes intraoperatively was more pronounced among patients with neurobehavioral disorders than those without. In our study, the relationship between cerebral desaturation and POCD could not be demonstrated. Biedler et al. [22] reported that 25.8% of patients with POCD in the first week, while this rate decreased to 9.9% in the third month. They stated that while older age, longer anesthesia time, low education level, second operation, postoperative infections, and respiratory complications were risk factors for early POCD, only advanced age was the risk factor for late stage POCD. Endocrine disorders and cognitive functions are also linked to each other. In the case of hypothyroidism, in which thyroid hormones are less secreted, slowing of all cognitive functions and distraction might be present [23-25]. However, it is not possible to demonstrate the results as we did not evaluate postoperative thyroid functions in the study There were no participants with advanced age in this study, and the incidence of early POCD was 47.5% and late POCD was 32.5%. It is a possible that the differences in incidence were due to the application of SMMT at different postoperative times, the age distribution, characteristics of the patient population, and the different types of operations they underwent.
Study Limitations
The first limitation of this study is that the postoperative thyroid functions were not evaluated. The second limitation is that the effect of the patient’s position during the operation on cerebral hemodynamics and cognitive function among high-risk patients could not be evaluated.
Conclusion
It was observed that the head position caused a decrease in carotid artery diameter, blood flow velocity and flow volume, and cerebral rSO2. Although it was found that early POCD is correlated with the decrease in carotid artery flow volume, there are many factors that may affect POCD, so other factors need to be investigated. We believe that further studies will prove very useful to demonstrate the effect of head and neck position on carotid artery blood flow, cerebral oxygenation, and POCD, especially for advanced age and high-risk patients with vertebrobasilar insufficiency or intracranial pathologies.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: This research was supported as a part of the Bülent Ecevit University Scientific Research Project.
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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7. Slater JP, Guarino T, Stack J, Vinod K, Bustami RT, Brown JM 3rd, et al. Cerebral oxygen desaturation predicts cognitive decline and longer hospital stay after cardiac surgery. Ann Thorac Surg. 2009; 87(1):36-44
8. Saraçoğlu A, Altun D, Yavru A, Aksakal N, Sormaz İC, Camcı E. Effects of Head Position on Cerebral Oxygenation and Blood Flow Velocity During Thyroidectomy. Turk J Anaesthesiol Reanim. 2016; 44(5):241-6.
9. Selim M. Perioperative stroke. N Engl J Med. 2007; 356(7):706-13.
10. Thompson SK, Southern DA, McKinnon JG, Dort JC, Ghali WA. Incidence of perioperative stroke after neck dissection for head and neck cancer: a regional outcome analysis. Ann Surg. 2004; 239(3):428-31.
11. Siwach R, Kumar S, Kumar M. Assessment of cranial blood flow in cervical spondylosis patients. Indian J Clin Anat Physiol. 2016; 3(4):460-3.
12. Fudickar A, Leiendecker J, Köhling A, Hedderich J, Steinfath M, Bein B. Transcranial Doppler sonography as a potential screening tool for preanaesthetic evaluation: a prospective observational study. Eur J Anaesthesiol. 2012; 29(10):471-6.
13. Kishi K, Kawaguchi M, Yoshitani K, Nagahata T, Furuya H. Influence of patient variables and sensor location on regional cerebral oxygen saturation measured by INVOS 4100 near-infrared spectrophotometers. J Neurosurg Anesthesiol. 2003; 15(4):302-6.
14. Szufladowicz E, Maniewski R, Kozluk E, Zbiec A, Nosek A, Walczak F. Near-infrared spectroscopy in evaluation of cerebral oxygenation during vasovagal syncope. Physiol Meas. 2004; 25(4):823-36.
15. Smarius BJA, Breugem CC, Boasson MP, Alikhil S, van Norden J, van der Molen ABM, et al. Effect of hyperextension of the neck (rose position) on cerebral blood oxygenation in patients who underwent cleft palate reconstructive surgery: prospective cohort study using near-infrared spectroscopy. Clin Oral Investig. 2020; 24(8):2909-18.
16. Hou X, Ding H, Teng Y, Zhou C, Tang X, Li S, et al. Research on the relationship between brain anoxia at different regional oxygen saturations and brain damage using near-infrared spectroscopy. Physiol Meas. 2007; 28(10):1251-65.
17. Murphy GS, Szokol JW, Marymont JH, Greenberg SB, Avram MJ, Vender JS, et al. Cerebral oxygen desaturation events assessed by near-infrared spectroscopy during shoulder arthroscopy in the beach chair and lateral decubitus positions. Anesth Analg. 2010; 111(2):496-505.
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Download attachments: 10.4328.ACAM.21230
Necla Gülçek, Bengü Gülhan Aydın, Gamze Küçükosman, Özcan Pişkin, Rahşan Dilek Okyay, Güldeniz Karadeniz Çakmak, Hilal Ayoğlu. Effect of head position during thyroidectomy on cerebral oxygenation and cognition: Prospective observational study. Ann Clin Anal Med 2022;13(10):1122-1126
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Endoscopy-assisted suturectomy for craniosynostosis treatment: A single-center experience
Harun Demirci 1, Pelin Kuzucu 2, Atilla Kazancı 1, Pınar Özışık 1
1 Department of Neurosurgery, Faculty of Medicine, Ankara Yıldırım Beyazıt Unıversity, Ankara, 2 Clinic of Neurosurgery, Birecik State Hospital, Şanlıurfa, Turkey
DOI: 10.4328/ACAM.21232 Received: 2022-05-17 Accepted: 2022-06-28 Published Online: 2022-07-18 Printed: 2022-10-01 Ann Clin Anal Med 2022;13(10):1127-1130
Corresponding Author: Pelin Kuzucu, Department of Neurosurgery, Birecik State Hospital, Şanlıurfa, Turkey. E-mail: drpelinkuzucu@gmail.com P: +90 505 704 13 38 Corresponding Author ORCID ID: https://orcid.org/0000-0003-0484-3753
Aim: Craniosynostosis is a clinical condition that occurs after premature fusion of fibrous tissue at the suture line. This study aimed to present the management and method of patients with craniosynostosis in our center.
Material and Methods: This study retrospectively reviewed 89 patients who underwent surgery at Ankara City Hospital Children’s Hospital between 2020 and 2021. The age, gender, diagnosis, length of hospital stay, surgical duration, and the amount of needed transfusion of patients were recorded.
Results: Sagittal synostosis was determined in 45 (50.5%) patients, metopic in 32 (36%), coronal in 10 (11.3%), and lambdoid in 2 (2.2%) synostosis. Endoscopy-assisted suturectomy is a safe, easy, and comfortable surgical treatment option for craniosynostosis.
Discussion: Endoscopy-assisted suturectomy is a safe, easy, and comfortable surgical treatment option for craniosynostosis.
Keywords: Endoscopy-Assisted Suturectomy, Craniosynostosis, Sagittal Synostosis, Metopic Synostosis, Coronal Synostosis
Introduction
Craniosynostosis is a clinical condition that occurs after early fusion of fibrous tissue at the suture line [1]. The incidence of craniosynostosis is 1 in 2500 live births. In healthy newborns, rapid brain growth in the first year of life creates a thrust on the skull bones, thus preventing suture fusion [2]. This thrust force cannot be effective in the affected area due to premature suture closure. Visual deterioration and increased intracranial pressure are observed due to growth pattern deterioration in the pathological area [3]. Vault reconstruction surgery (VRS) is traditionally used for craniosynostosis. In our country, this method can be successfully applied in a limited number of health centers. Vault modeling and fronto-orbital advancement surgery have more successful results when performed under 1 year old. However, it carries risks for the age group in the treatment target. The surgical duration, the high risk of blood loss, and the need for intensive postoperative care are the main factors in the limited number of treatment centers. Since 1990, minimally invasive endoscopy-assisted suturectomy (EAS) has been performed. Many studies have reported significant gains in surgical duration, blood loss, and hospital stay. This single-center study aimed to determine the safety of EAS surgery, which can be performed relatively easily compared to VRS and can be performed in many hospitals in our country.
Material and Methods
A retrospective review of 89 patients who underwent surgery in Ankara City Hospital Children’s Hospital from 2020 to 2021 was conducted. Our study was approved by the ethics committee of Ankara Yıldırım Beyazıt University.
Patients’ age at admission and treatment, gender, diagnosis, length of hospital stay, surgical duration, and amount of needed transfusion were noted. The duration of helmet use, which is a complementary postoperative treatment procedure, was determined.
Surgical Techniques
Sagittal Craniosynostosis
All patients were operated on under general anesthesia and were placed on the surgical table in the prone position using soft gel support. 2–3 cm behind the anterior fontanel and 2 cm in front of the lambda, two incision lines of 4 cm were determined, which perpendicularly cut the sagittal suture (Figure 1A,2A). The periosteum between the incision lines was dissected. A 0-degree 4-mm thick endoscopic camera was used (Karl Storz, Germany). The bone bar was removed using Kerrison rongeur, bone scissors, and ultrasonic bone cutters. Barrel osteotomies were performed behind the coronal suture and in front of the lambdoid suture, parallel to the sutures.
Metopic Craniosynostosis
All patients were operated on under general anesthesia and were placed on the surgical table in the supine position using soft gel support. A 3-cm incision was made 2 cm in front of the anterior fontanel to perpendicularly cut the metopic suture (Figure 1A,2B). Periosteal dissection was performed up to the nasion. A 0-degree 4-mm thick endoscopic camera was used (Karl Storz, Germany). A wedge-shaped bone excision was performed posteriorly at the width of the incision line and anteriorly at the width of the nasion region (approximately 0.7 mm).
Coronal Craniosynostosis
All patients were operated on under general anesthesia and were placed on the surgical table in the supine position using soft gel support. A coronal suture was determined. In the middle of the coronal suture line, a 2-cm incision line was determined to perpendicularly cut the suture (Figure 1A,2C). A periosteal dissection was performed up to the anterior fontanel and squamous suture. A 0-degree 4-mm thick endoscopic camera was used (Karl Storz, Germany). A 1-cm wide bone excision was performed from the fontanel to the squamous suture.
Ringer’s lactated solution irrigation and bleeding control were achieved after the bone excision of all patients. Hemostatic agents to stop bleeding were used and the skin was subcuticularly closed.
Results
The treatment was completed in 53 patients, and 36 continue the treatment at various stages. Patients were hospitalized for preoperative preparations the day preoperatively and coronavirus disease-19 tests were studied. Surgery was delayed for 7–10 days due to positive results in 7 patients. Patients whose anesthesia preparations were completed were accepted for surgery. All patients were operated on under general anesthesia. Anesthesia preparation took an average of 23 min. Patients were followed up with bispectral index, which monitors the anesthesia.
Sagittal synostosis was determined in 45 (50.5%) patients, metopic in 32 (36%), coronal in 10 (11.3%), and lambdoid in 2 (2.2%). Of all patients, 59 (66.3%) were males and 30 (33.7%) were females. Male and female made up 27 (60%) and 18 (40%) in sagittal, 28 (87.5%) and 4 (12.5%) in metopic, 4 (40%) and 6 (60%) in coronal, and 0 and 2 (100%) in lambdoid synostoses, respectively. In coronal synostosis, 3 patients were right (30%), 6 were left (60%), and 1 patient was bicoronal (10%) (Table1).
Patients with sagittal synostosis had a mean age at hospital admission of 50 days, mean age at surgery of 94 days, mean surgical duration of 35 min, mean bleeding of 20 ml, mean postoperative hospital stay of 40 h, mean blood replacement of 5 ml/kg. None of the patients needed intensive care. The dural injury occurred in 1 patient, which was repaired by primary suturing. The preoperative cephalic index (medial-lateral length/anterior-posterior length) of the patients was 0.69 on average, whereas 0.83 postoperatively (Figure 1A).
The average helmet use duration postoperatively was calculated as 7.6 months. All patients were measured at 2-week intervals.
Patients with metopic synostosis had a mean age at hospital admission of 38 days, mean age at surgery of 71 days, mean surgical duration of 40 min, mean bleeding of 30 ml, mean postoperative hospital stay of 40 h, and mean blood replacement of 10 ml/kg. None of the patients needed intensive care. The dural injury occurred in 1 patient, which was repaired by primary suturing. Based on the theorem “In triangles, the opposite of the large angle is the large edge,” data after the comparison of the 30-degree diagonal diameter of the lines drawn between the frontal contact points and the midline with the distance between these two points, while the mean before the treatment was 1.74, the average after the treatment was obtained, which was 1.87 (Figure1B). The average helmet use duration postoperatively was calculated as 8.5 months. All patients were measured at 2-week intervals.
Patients with coronal synostosis had a mean age at hospital admission of 61 days, mean age at surgery of 83 days, mean surgical duration was 30 min, mean bleeding was 15 ml, mean postoperative hospital stay was 40 h, and mean blood replacement was 5 ml/kg. None of the patients needed intensive care. The mean diagonal asymmetry of patients preoperatively was 5.3 mm, and the mean diagonal asymmetry at the end of the treatment was 0.9 mm. (Figure 1C) The mean helmet use duration postoperatively was 8.7 months. All patients were measured at 2-week intervals.
Discussion
The emerging results of this study show that EAS is a safe and effective surgical method for patients with craniosynostosis. With the developments in technology, minimally invasive techniques have been applied more frequently in all surgical branches. EAS has become widespread in non-syndromic craniosynostoses [2, 4]. According to a multicenter retrospective study, the length of hospital stay of 933 patients treated with EAS was significantly reduced [5]. This result supports our study results, which revealed a mean postoperative hospital stay of 40 h. Vogel et al. found that the cost of EAS was less than that of VRS [6].
Some studies that use non-invasive ultrasonography revealed a reduced risk of venous embolism in EAS surgeries compared to VRS, which is compatible with the safe surgery doctrine [7, 9].
A cosmetic analysis by Tan et al. for unilateral coronal craniosynostosis revealed no significant difference between dome reconstruction surgery and EAS [10]. In our study, the diagonal diameter difference was significantly reduced.
Сomparison of VRS and EAS surgery performed on metopic synostoses revealed a reduction in blood loss, surgical time, and hospital stay, in line with our study results [11, 12]. Evaluation of cosmetic results by Farber et al. revealed no significant difference between the two methods of frontal deconstruction and expansion [13]. However, an angular increase was seen in the analysis of our series. Garber et al. showed no difference in complications between VRS and EAS surgery for sagittal synostosis [13].
Ghenbot et al. reported no significant difference in the cephalic index results at the end of the treatment [15].
Conclusion
In craniosynostosis treatment, EAS has been an alternative, as described in this and many other studies, as a safe, relatively easy, and comfortable surgery. Dome reconstruction surgery cannot be performed in many health centers due to the absence or insufficiency of pediatric intensive care units and limited anesthesia conditions. Craniosynostosis treatments are thought to be performed in many health centers with the EAS method, which is relatively easier to perform compared to dome reconstruction surgery. Considerably, with the surgical prevalence, helmet service providers will become more widespread and post-op follow-up of patients will be more comfortable for families.
Acknowledgment
We certify that the content of this manuscript, in part or in full, has not been submitted to any other journal in any form, and its publication has been approved by all co-authors. Preparation for publication of this article is partly supported by Turkish Neurosurgical Society.
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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13. Farber SJ, Nguyen DC, Skolnick GB, Naidoo SD, Smyth MD, Patel KB. Anthropometric Outcome Measures in Patients With Metopic Craniosynostosis. J Craniofac Surg. 2017;28(3):713-16. DOI:10.1097/SCS.0000000000003495
14. Garber ST, Karsy M, Kestle JRW, Siddiqi F, Spanos SP, Riva-Cambrin J. Comparing Outcomes and Cost of 3 Surgical Treatments for Sagittal Synostosis: A Retrospective Study Including Procedure-Related Cost Analysis. Neurosurgery. 2017;81(4):680-7. DOI:10.1093/neuros/nyx209
15. Ghenbot RG, Patel KB, Skolnick GB, Naidoo SD, Smyth MD, Woo AS. Effects of open and endoscopic surgery on skull growth and calvarial vault volumes in sagittal synostosis. J Craniofac Surg. 2015;26(1):161-4. DOI:10.1097/SCS.0000000000001236
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Harun Demirci, Pelin Kuzucu, Atilla Kazancı, Pınar Özışık. Endoscopy-assisted suturectomy for craniosynostosis treatment: A single-center experience. Ann Clin Anal Med 2022;13(10):1127-1130
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IL28B rs12979860 and rs8099917 polymorphisms in patients with chronic hepatitis C and non-viral liver disease
Bulent Cakal 1, Bilger Cavus 2, Alp Atasoy 2, Damla Altunok 2, Mehves Poda 3, Mesut Bulakci 4, Mine Gulluoglu 5, Mehmet Demirci 6, Leyla Turker Sener 7, Asli Berru Arslan 8, Filiz Akyuz 2
1 Department of Medical Microbiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, 2 Department of Internal Medicine, Division of Gastroenterohepatology, Faculty of Medicine, Istanbul University, Istanbul, 3 Department of Genetics, Aziz Sancar Institute for Experimental Medical Research, Istanbul University, Istanbul, 4 Department of Radiology, Faculty of Medicine, Istanbul University, Istanbul, 5 Department of Pathology, Faculty of Medicine, Istanbul University, Istanbul, 6 Department of Medical Microbiology, Faculty of Medicine, Kirklareli University, Kirklareli, 7 Department of Biophysics, Faculty of Medicine, Istanbul University, Istanbul, 8 School of Medicine, Istanbul University, Istanbul, Turkey
DOI: 10.4328/ACAM.21274 Received: 2022-06-15 Accepted: 2022-07-28 Published Online: 2022-08-03 Printed: 2022-10-01 Ann Clin Anal Med 2022;13(10):1131-1136
Corresponding Author: Bulent Cakal, Department of Medical Microbiology, Faculty of Medicine, Istanbul University, 34093, Fatih, Istanbul, Turkey. E-mail: bulentcakal@yahoo.com P: +90 532 726 64 54 F: +90 212 414 20 37 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1254-844X
Aim: In this study, we aimed to evaluate the relationship of IL28B rs12979860 and rs8099917 polymorphisms with the clinical, histological and virological outcomes of patients with chronic hepatitis C and non-viral liver disease, and also the treatment responses of patients with chronic hepatitis C, who received direct-acting antiviral (DAA) therapy.
Material and Methods: A total of 142 patients, 59 of whom had chronic hepatitis C, and 83 of whom had liver biopsy for different clinical indications, were included in the study. The IL28B rs12979860 and rs8099917 polymorphism were genotyped using the TaqMan assay.
Results: IL28B rs12979860 CC and IL28B rs8099917 TT were identified as the genotypes with the highest frequency in all patients, and patient groups included in the study. On the other hand, IL28B rs12979860 TT and IL28B rs8099917 GG were the genotypes with the lowest frequency. No significant association was found between IL28B rs12979860 and IL28B rs8099917 polymorphisms and clinical and histopathological outcomes of patients as well as DAA treatment responses in patients with hepatitis C.
Discussion: IL28B rs12979860 and rs8099917 polymorphisms do not affect clinical and histopathological outcomes of patients with chronic hepatitis C and non-viral liver diseases as well as with DAA treatment.
Keywords: Interleukin 28B, Chronic Hepatitis C, Non-Viral Liver Disease, Treatment Response
Introduction
Hepatitis C Virus (HCV) is a substantial public health concern owing to its progressive clinical outcomes with higher morbidity and mortality, such as chronic active hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). HCV infection affects more than 150 million people worldwide. The natural course of chronic HCV infections and host factors of the virus-infected individuals can be determinative of the pathogenesis and progression of the liver diseases with which they are associated. The human immune system can impact the pathogenesis, clinical course, and outcomes of viral and non-viral liver diseases [1,2]. Interferons lambda (IFN-λs; IFNL1-4), classified as type III IFN, is a cytokine that plays a role in the formation of antiviral immune responses, encoded by IFNL3 interleukin 28B (IL28B), which mostly acts on epithelial surfaces [3].
It has been suggested that IL28B rs12979860 and rs8099917 polymorphisms may be associated with spontaneous clearance and clinical and histological outcomes of chronic viral hepatitis caused by HCV. In general, IL28B rs12979860CC and rs8099917 TT genotypes are reported as favorable genotypes due to the reduced risk of advanced liver damage such as HCV-related cirrhosis and HCC, and the positive effects on the clinical course and outcomes of the patients as well. On the other hand, the genotypes characterized by the presence of CT and TT polymorphisms for rs12979860 and TG and GG minor allele polymorphisms for rs8099917 are considered unfavorable genotypes due to their negative effects on the clinical course and outcomes of patients with HCV-related increased risk of cirrhosis, and HCC [4-8]. Some studies have reported that there is no relationship between IL28B rs1297986 and rs8099917 polymorphisms and the virological and clinical outcomes of patients. In addition, they found no correlation between IL28B rs1297986 and rs8099917 polymorphisms and the risk of developing HCV-related cirrhosis and HCC [9-12].
It has been reported that IL28B rs12979860 CC and IL28B rs8099917 TT genotypes are strongly associated with treatment and sustained virologic responses (SVR) in patients with chronic hepatitis C after IFN-based antiviral treatments. However, the data on the effects of IL28B rs12979860 and rs8099917 genotypes on treatment response of patients with chronic hepatitis C receiving direct-acting antiviral therapy (DAA) therapy are limited [5,13].
In addition, it has been suggested that IL28B rs12979860 and rs8099917 gene polymorphisms may have an impact on the formation of non-viral liver diseases, especially non-alcoholic fatty liver disease (NAFLD). However, the data on such a suggestion is quite limited [14-16]. In general, there is no consensus on the relationship between IL28B polymorphisms and liver pathologies that may develop due to viral or non-viral factors. In addition, most studies conducted for this purpose included patients who developed HCV-related cirrhosis and HCC. The data on the association of IL28B polymorphisms with liver histology and clinical and virological characteristics of patients with chronic hepatitis C are limited.
In this study, we aimed to evaluate the IL28B rs12979860 and rs8099917 gene polymorphisms among the patients with chronic hepatitis C and non-viral chronic liver disease and also treatment responses of patients with chronic hepatitis C who received DAAs therapies.
Material and Methods
Ethical approval for the study was provided by Istanbul Medical School Ethics Committee at Istanbul University (No: 2018/895).
Patients: The present study included a total of 142 patients were followed up by the Gastroenterohepatology Department of Istanbul University Istanbul Medical School, 59 for chronic hepatitis C, and 83 whose liver parenchymal biopsy was performed due to different clinical indications other than viral hepatitis agents. Biopsy indications of patients who underwent liver parenchyma biopsy except for viral hepatitis agents consisted of metabolic liver disease 32 (38.5%), cholestatic liver disease 16 (19.3%), elevated liver enzymes unknown of cause 18 (21.7%), elevated autoimmune antibodies 5 (6.0%), cirrhosis 4 (4.8%), vascular liver disorders 4 (4.8%), toxic hepatitis 3 (3.6%), and granulomatous liver diseases 1 (1.2%).
A total of 142 patients, 59 of whom were diagnosed with chronic hepatitis C and 83 with non-viral liver disease, had seronegative hepatitis B virus surface antigen (HBsAg). Anti-HCV antibodies of patients with defined non-viral liver disease were seronegative. All patients were seronegative for human immunodeficiency virus (HIV) antibodies.
Clinical materials: Liver biopsies were performed in the Interventional Radiology Unit of the Radiology Department and in the Gastroenterohepatology Department of Internal Medicine, at Istanbul Medical School. One set of liver-tissue specimens was preserved in Hollande’s fixative and sent to the Pathology Department for evaluation. A second tissue fragment or another biopsy sample was immediately snap-frozen in liquid nitrogen and kept at 80°C before use for genotype analysis.
DNA extraction from liver-biopsy specimens: Total genomic DNA was extracted from each liver-tissue sample using a commercially available kit (QIAamp DNA Mini kit, Qiagen GmbH, Hilden, Germany). Total DNA was purified according to the manufacturer’s recommendations. DNA concentrations were determined using a NanoDrop 2000 spectrophotometer (Thermo Fisher Scientific, USA).
IL28B genotyping: IL28B rs12979860 rs8099917 was typed using the standard TaqMan SNP Genotyping Assay. The allele discrimination plot and results were then generated using StepOne Software (Applied Biosystems, Foster City, CA, USA).
Liver histopathology: Histology of liver biopsy specimens was evaluated in the Department of Pathology of Istanbul Medical School, Istanbul University. Liver biopsy samples were fixated in a formalin solution and stained with Masson’s trichrome. Pathology reports contained histological parameters including fibrosis, portal and lobular inflammation, lobular necrosis, steatosis, cholestasis, and bile duct damage. Inflammation and fibrosis for chronic hepatitis C patients were assessed using the modified Ishak scoring system [17]. Patients were divided into groups in terms of inflammation: minimal/mild (0–7), moderate (8–11), and severe (12–18), and fibrosis: none (0) mild (1), moderate/severe (2–4), and cirrhosis (5–6). NAFLD was defined as the observation of abnormal lipid accumulation (hepatic steatosis) in more than 5% of hepatocytes. NASH was defined as the presence of lobular inflammation together with ballooning (hepatocyte damage) and hepatic steatosis, with or without fibrosis [18]. In histopathological diagnosis, the presence of minimal portal or lobular inflammatory infiltrates, absence of fibrosis, and absence of structural changes was considered non-specific histological findings.
Clinical laboratory data: Demographics and pre-biopsy patient data, including HCV RNA viral load, and HCV genotypes were obtained from patient files or from the hospital’s electronic data management system (Table 1). Viral load of patients with chronic hepatitis C was classified as low (400000 IU/ml) or high (400000 IU/ml), in accordance with Witthöfft et al. [19].
DAA treatment and sustained virologic responses:
Dasabuvir/Ritonavir+Ombitasvir+Paritaprevir treatment was given to 74.50% (38/51) of the patients. Of the remaining patients, 3 received Sofosbuvir+Ledipasvir, 3 received Dasabuvir/Ritonavir+Ombitasvir+Paritaprevir/Ribavirin, 1 Ribavirin/Sofosbuvir+ Ledipasvir, 1 sofosbuvir/ribavirin, and 1 Glecaprevir+Pibrentasvir. Dasabuvir/Ritonavir+Ombitasvir+Paritaprevir treatment was given to 2 of the 4 patients who were found to have treatment failure after interferon (IFN)-based treatment, and Sofosbuvir+Ledipasvir/Ribavirin treatment was applied to the other 2 patients. SVR is defined as undetectable HCV-RNA in serum or plasma 24 weeks after the end of therapy [20]. In order to evaluate the effect of IL28B rs12979860 and rs8099917 polymorphisms on SVR after DAA treatment, 51 patients whose serum HCV RNA results could be obtained at least 24 weeks after treatment were included. Finally, the absence of SVR or a relapse after treatment was defined as treatment failure.
Statistical analysis
Descriptive statistics were used to describe continuous variables (mean, standard deviation). Comparison of two independent and normally distributed variables was performed using the Student’s t-test. Comparison of two independent and non-normally distributed variables was made using the Kruskal-Wallis or Mann-Whitney U test. The independent variable effects on the dichotomous dependent variable were investigated by Logistic Regression Analysis. Analyzes were performed using IBM SPSS Version 25.0 (IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp). Linkage disequilibrium (LD) between pairwise SNPs, was calculated using Haploview software. Hardy-Weinberg equilibrium (HWE), allele frequencies, and genotype distributions were analyzed using the chi-square test. The statistical significance level was determined as 0.05.
Results
Demographic, clinical, and histopathological characteristics of patients
Table 1 summarizes the demographic, clinical, clinical laboratory, and histopathological data of the total 142 patients, 59 of them with chronic hepatitis C, and 83 of them with non-viral liver disease. Histologically, the mean inflammation grade in patients with chronic hepatitis C was 6.00 ± 2.1, and the mean fibrosis stages 2.59 ± 1.13. histopathological diagnoses of 83 patients who underwent liver biopsy for different non-viral clinical indications are summarized in Table 1. Accordingly, the most histopathologically reported finding was liver steatosis, with a total of 33 (39.8%) patients with 22 (26.5%) NASH, and 11 (13.2%) NAFLD.
Genotype and frequency of IL28B rs12979860 and rs8099917
The genotypes and frequencies detected for IL28B rs12979860 and rs8099917 polymorphisms in this study are shown in Tables 2 and 3. IL28B rs12979860 CC (42.37%) and IL28B rs8099917 TT (57.63%) were identified as the genotypes with the highest frequency for chronic hepatitis C patients. IL28B rs12979860 CC (43.37%) and CT (43.37%) and also IL28B rs8099917 TT (63.86%) were identified as the genotypes with the highest frequency for chronic hepatitis C patients. On the other hand, IL28B rs12979860 TT and IL28B rs8099917 GG were the genotypes with the lowest frequency for all patients. No deviation from HWE for rs12979860 and rs8099917 at IL28B gene was found in both patient groups (χ2 tests, p ≥ 0.05).
IL28B polymorphisms in patients with chronic hepatitis C
HCV genotype was 1B in 52 (88.13%) patients with chronic hepatitis C included in this study, 1A in 6 (10.16%) and, 3B in 1 (1.69%) (Table 2). As shown in Table 2, no significant association was found between IL28B rs12979860 and IL28B rs8099917 polymorphisms; and demographic, clinical laboratory, virological including viral genotype and viral loads of chronic hepatitis C patients and as well as histological data including necro-inflammatory activity grade and fibrosis stages of patients.
Association of IL-28B polymorphism and outcomes of DAAs treatment in patients with chronic hepatitis C
In this study, HCV RNA was not detected in serum/plasma samples taken at least 24 weeks after the completion of their treatment in all but one of the patients with chronic hepatitis C who received DAA treatment (Table 2). Treatment failure, characterized by the presence of viral relapse was described in a patient with HCV genotype 1B who had histologically defined cirrhosis. The same patient received Ribavirin/Sofosbuvir + Ledipasvir therapy and subsequently developed hepatocellular carcinoma (HCC).
IL-28B polymorphisms in patients with non-viral liver diseases
Table 3 summarizes the histopathological data of non-viral liver disease patients, as well as their IL28B genotypes and frequencies. Briefly, there was no significant association in 33 (39.8%) patients with histopathological liver steatosis, in 23 (27.7%) patients with non-specific changes, and in 27 (32.5%) patients with liver disease other than the above-mentioned causes in terms of L28B rs12979860 and IL28B rs8099917 polymorphisms.
Discussion
In this study population, the frequencies of IL28B rs12979860 CC and CT and also IL28B rs8099917 TT, described as favorable genotypes, were determined as 61 (%42.96) and 87 (%61.27), respectively. There was also no difference in the frequency distributions of these genotypes between the observed groups (Table 2 and 3). The relationship between polymorphisms near the IL28B gene and occurrence, progression, and outcomes of viral or non-viral liver diseases is quite challenging because of the studied geography, the genetic background of populations, characteristics and extent of patient groups, and other various factors, such as viral factors and so on.
In this study, no relationship was identified between rs12979860 and rs8099917 and histopathological results of patients with hepatitis C, including demographics, virological genotypes, viral loads, and clinical characteristics, including clinical laboratory findings, and HCV-related liver damage stages. It has been reported in some studies conducted for similar purposes that polymorphisms characterized by the presence of T alleles for IL28B rs12979860 and G alleles for rs8099917 were associated with the risk of developing advanced liver damage such as HCV genotype I-related cirrhosis and HCC [6,21,22].
However, the effects of IL28B rs12979860 and rs8099917 polymorphisms on the histological results of patients with chronic hepatitis C may be associated with viral genotypes. In this respect, favorable genotypes, especially IL28B rs12979860CC and rs8099917 TT genotypes, have also been reported that may cause advanced clinical outcomes with HCV other than genotype I, and hepatic damage and adverse effects [23] However, different studies have reported that IL28B rs12979860 and rs8099917 polymorphisms are not associated with HCV-related liver damage and disease progression, regardless of viral genotype [9,12].
It has been revealed in a small number of studies carried out to determine the relationship between IL28B rs12979860 and rs8099917 polymorphisms and viral genotype, viral load, and clinical laboratory data of patients with chronic hepatitis C, that especially IL28B rs12979860 CC genotype may be associated with higher ALT and higher serum HCV RNA levels [9,21]. On the other hand, it was found that IL28B rs12979860 and rs8099917 polymorphisms in patients with chronic hepatitis C were not associated with the demographic HCV genotype of the patients, and liver fibrosis stages. In the same study, they revealed that individuals carrying IL28B rs12979860 TT or CT genotypes have a higher likelihood of developing chronic hepatitis after HCV infection [24].
It has been reported that the presence of the CC genotype and C allele for IL28B rs12979860, and the presence of the TT genotype and T allele for rs8099917 are associated with SVR in IFN-based anti-viral treatments in patients with chronic hepatitis C, regardless of viral genotype. Additionally, it has been reported that the presence of minor alleles T and G, respectively, may be associated with unsuccessful treatment responses [5,6]. Nevertheless, the effect of IL28B polymorphisms on the outcome of patients with hepatitis C receiving DAA therapy is not clear yet. In a study conducted to evaluate such outcomes, IL28B rs12979860 TT genotype and T allele were found to be significantly associated with failure in achieving SVR [25]. The data obtained in this study indicate that IL28B rs12979860 and rs8099917 polymorphisms are not associated with SVR after the DAA treatment.
The results of the limited number of studies to determine the relationship between non-viral chronic liver diseases and IL28B polymorphisms are inconsistent and unclear (20-22). This study suggests that there is no direct relationship between IL28B rs12979860 and rs8099917 polymorphisms and non-viral liver diseases, based on the histopathological data of patients with non-viral liver disease and the IL28B rs12979860 and rs8099917 genotypes and frequency distributions detected in these patient groups.
The limited number of patients with chronic hepatitis C and non-viral liver disease included in this study and the lack of homogeneous distribution between the groups, as well as the low number of patients with advanced liver damage such as HCV-associated cirrhosis, were limiting factors for this study. Hereafter, this study included patients with histologically chronic hepatitis, then advanced liver damage such as HCV-associated cirrhosis and HCC.
Conclusion
It is suggested according to the data obtained from this study that IL28B rs12979860 and rs8099917 polymorphisms are not associated with the clinical and histopathological outcomes of viral hepatitis C and non-viral liver diseases as well nor with DAA treatment responses in patients with hepatitis C.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: This study was supported by the Scientific Research Projects Coordination Unit of Istanbul University with the project number TSA-2018-30611.
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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Bulent Cakal, Bilger Cavus, Alp Atasoy, Damla Altunok, Mehves Poda, Mesut Bulakci, Mine Gulluoglu, Mehmet Demirci, Leyla Turker Sener, Asli Berru Arslan, Filiz Akyuz. IL28B rs12979860 and rs8099917 polymorphisms in patients with chronic hepatitis C and non-viral liver disease. Ann Clin Anal Med 2022;13(10):1131-1136
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Is the presence of tumor cavitation important in stage III lung squamose cell cancer?
Elanur Karaman 1-2, Arife Ulas 1, Arif Hakan Onder 3
1 Department of Medical Oncology, University of Health Sciences, Bursa City Education and Research Hospital, Bursa, 2 Department of Medical Oncology, Medical Park Karadeniz Hospital, Trabzon, 3 Department of Medical Oncology, Antalya Training and Research Hospital, Antalya, Turkey
DOI: 10.4328/ACAM.21300 Received: 2022-07-01 Accepted: 2022-09-12 Published Online: 2022-09-23 Printed: 2022-10-01 Ann Clin Anal Med 2022;13(10):1137-1142
Corresponding Author: Elanur Karaman, Department of Medical Oncology, Medical Park Karadeniz Hospital, Inonu district, Yavuz Selim boulevard, No:190, 61040 Ortahisar, Trabzon, Turkey. E-mail: drelanurkaraman@gmail.com P: +90 506 951 16 60 Corresponding Author ORCID ID: https://orcid.org/0000-0002-4264-8214
Aim: Tumor cavitation is seen most frequently in the lung squamous cell cancer subtype (SCC). We aimed to evaluate the prognostic significance of tumor cavitation at the time of diagnosis and survival in patients with lung SCC.
Material and Methods: Stage I-IV lung SCC patients aged >18 years between 2016-2021 were retrospectively analyzed. The presence of tumor cavitation in the patients and its effect on clinical and prognosis were evaluated. The effects of inflammatory indexes on prognosis were investigated. Progression-Free Survival (PFS) and Overall Survival (OS) times were examined.
Results: Thirty-eight patients with tumor cavitation and 66 without tumor cavitation were examined. The frequency of tumor cavitation in lung SCC was 16.8%. Most of the patients with tumor cavitation consisted of men with large tumor diameter, heavy smokers, and advanced stage. The monocyte- lymphocyte ratio and lactate dehydrogenase levels were lower in those with tumor cavitation (p=0.002, p=0.010). Tumor cavitation significantly reduced OS in Stage III lung SCC (17.83 vs 40.53 months, p=0.016). However, the presence of tumor cavitation did not affect PFS or OS in the whole population (p=0.759, p=0.256). High neutrophil-lymphocyte ratio and advanced stage were independent factors affecting OS (p=0.048, p=0.009).
Discussion: Tumor cavitation is a clinical entity that differs in its biology and clinical course. It is a poor prognostic factor in Stage III lung SCC patients.
Keywords: Tumor Cavitation, Squamous Cell Lung Carcinoma, Inflammatory Score, Prognosis, Survival
Introduction
Squamous cell cancer (SCC) is the most common type of non-small cell lung cancer after adenocarcinoma. Lung SCCs consist of heterogeneous tumors with different biological characteristics and clinical behavior [1,2]. The scarcity of targeting mutations, their histopathological and genetic features and difficulties of diagnosis, cause the prognosis of this patient group to be worse.
Cavitation can be seen in 10-22% of lung cancers [3,4]. Tumor cavitation is thought to be caused by rapid tumor growth and, as a result, insufficient blood flow to the central lesion, ischemia, infection, or the drainage of necrotic material from the bronchi, which occurs with central necrosis [3,5]. Tumor cavitations are large, high-grade, peripherally located tumors that are most commonly seen in lung SCCs [6]. Tumor cavitation causes delay in the diagnosis of cancer in patients, and difficulties in treatment in patients with diagnosis due to complications that develop in the patient.
In the literature, there are conflicting results between tumor cavitation in lung cancer patients and tumor control and survival. We aimed to evaluate the effect of tumor cavitation on prognosis, its relationship with inflammatory indexes, and its effect on Overall Survival (OS) in patients with lung SCCs at the time of diagnosis.
Material and Methods
Squamous cell lung cancers who applied to the Medical Oncology outpatient clinics of two centers between 2016 and 2021 were evaluated retrospectively.
Ethics Statement:
The study protocol was approved by the local ethics committee of the study center (Approval Date: 29.12.2021 No: 2021-24/10).
Inclusion criteria were as follows:
1. Patients over 18 years of age
2. Oncologic treatment applied for lung SCCs
3. Follow-up at least six months
4. Finding hemogram and biochemistry values at the time of diagnosis
5. Evaluation of staging at diagnosis with thorax computered tomography, a fluorodeoxyglucose (FDG)-positron emission tomography (PET CT) and brain magnetic resonance scan.
Exclusion criteria were as follows:
1. The presence of a synchronous or metachronous tumor
2. Using vascular endothelial growth factor treatment
3. The presence of immunosuppresive disease
4. The presence of brain metastasis at diagnosis.
Clinical, demographic, tumor characteristics, primary tumor PET CT the maximum standardized uptake value (SUVmax) level and presence of tumor cavitation in the patients were evaluated. American Joint Committee on Cancer 8th Edition was used for T (tumor), N (lymph node) and M (metastasis) classification in clinical and pathological staging [7]. Primary tumor PET CT Eastern Cooperative Oncology Group (ECOG) level was calculated by taking the highest cavitary-noncavitary metabolic value in the primary tumor. Oncological treatments (surgery, chemotherapy, radiotherapy, immunotherapy) applied for lung SCC were examined.
Assessment of tumor cavitation:
Tumor cavitation was evaluated by a five-year radiologist specialist as an abnormal space in the lung parenchyma containing fluid or air by examining the thorax computered tomography images.
Evaluation of inflammatory markers:
Hemogram and biochemistry analyses at the time of diagnosis were evaluated with xn1000 Sysmex and Cobas-e 801 analytical unit in one center, and with Sysmex xn2000 and Beckman coulter Au5800 in the other center.
Neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), monocyte lymphocyte ratio (MLR), SII-score (SII=Neutrophil × Platelet/Lymphocyte), Hemoglobin Albumin Lymphocyte and Platelet (HALP)-score [hemoglobin(g/L)×albumin(g/L)×lymphocytes(/L)/platelets(/L)] and anemia were examined [8-12]. The presence of anemia was evaluated as <12g/dL in the population consisting of mostly male patients receiving oncological treatment. Receiver Operating Characteristic (ROC) analysis was performed to determine the threshold level of inflamatuar indexes. The threshold values for NLR; 2.1859, PLR; 130.56, MLR; 0.4125, SII-score; 604.65 and HALP-score; 29.1545 were used, respectively.
Survival analyses:
Progression-Free Survival (PFS) was calculated as the time of diagnosis to first progression, and OS was calculated as the time of diagnosis to death or last follow-up.
Statistic:
After the obtained data were coded, they were analyzed using the SPSS program version 22.0. Descriptive statistics of evaluation results: numbers and percentages for categorical variables, median and interquartile range (IQR) for numerical variables. Comparisons of numerical variables between two independent groups; Since the normal distribution condition was not met, it was evaluated with the Mann-Whitney U test. The Chi-square test was used to compare qualitative data. The Kaplan-Meier test was used for survival analysis. Univariate and multivariate Cox-regression analysis was performed to determine Hazard ratios (HRs) and 95% Confidence intervals (CIs). Factors that were determined to be significant only according to the univariate analyzes were then included in the multivariate analyses. Statistical alpha significance level was accepted as p<0.05.
Results
A total of 88 lung SCCs were screened in one of the centers and the data of 40 patients were evaluated within the scope of the study. In the other center, 137 patients with lung SCC were screened and 64 of these patients were included in the study. When patients of the two centers were evaluated, it was seen that 225 (33.9%) of 663 lung cancer patients had lung SCC and TC was observed in 38 (16.8%) patients. In the study, the data of 38 patients with tumor cavitation and 66 patients without tumor cavitation were evaluated.
Ninety (86.5%) patients were male, the mean age was 60.34 ±8.0 (33-76) years. Age, gender, the maximum standardized uptake value (SUVmax) performance status, smoking, comorbidity, TNM stage and primary tumor localization between patients with and without tumor cavitation are shown in Table 1.
There was no significant difference in demographic and clinical characteristics between patients with and without tumor cavitation at diagnosis.
The FDG-PET CT SUVmax level of the primary tumor was 10.17±5.38 (4-31.6). FDG-PET CT SUVmax level did not differ with the presence of tumor cavitation (p=0.316). The mean hemoglobin level in the patients was 11.258±1.73 g/dL (8.8-16.5). When the inflammatory indices between those with and without tumor cavitation were examined, it was observed that MLR and lactate dehydrogenase (LHD) levels were lower in those with tumor cavitation (p=0.002, p=0.010). It was observed that LDH level increased as the stage increased [194 U/L (173-242.5) in Stage I,II; 205 U/L (162.5-323) in Stage III and 375 U/L (192.5-598) in Stage IV, p=0.001].
Twenty-four (23.1%) patients underwent lung surgery. In terms of oncological treatments, six patients (5.8%) underwent surgery only, 20 (19.2%) underwent neoadjuvant/adjuvant chemotherapy±radiotherpy, 24 (23.1%) underwent definitive chemoradiotherapy/radiotherapy, 49 (47.1%) underwent palliative chemotherapy, and five (4.8%) underwent immunotherapy± chemotherapy. 96 (92.3%) patients received chemotherapy.
Local recurrence was observed in 23 (22.1%) patients and distant metastases developed in 55 (52.9%) patients. Second progression was observed in 45 (43.3%) patients. Relapse/metastasis was more common in patients with anemia at diagnosis (p=0.009). In addition, patients with recurrence/metastasis had higher diagnostic LDH levels (p=0.001). The median PFS was calculated as eight months (4.5-11.5) in lung SCCs 13 months (10.5-15.5) in patients with tumor cavitation, and seven months (5.3-8.7) in non-tumor cavitation patients (p=0.759). While chemotherapy was given to 79.4% (62 patients) of the patients who developed recurrence/metastasis, radiotherapy was applied to 12 (15.3%) patients, immunotherapy was applied to nine (11.5%) patients, and lung surgery was applied to five (6.4%) patients. Of the patients who developed relapse, 2.5% (two patients) could not receive treatment.
Fifty-nine (56.7%) patients died. The median OS was 21 months (11.2-30.8) in those with tumor cavitation, and 23 months (13.4-32.6) in those without (p=0.256). In univariate cox-regression analysis, factors that negatively affected OS were ≥65 age, ECOG performance status ≥2, presence of comorbidities, advanced stage, smoking ≥50 pack/year, chemoradiotherapy implementation, high SUVmax at diagnosis, high NLR, PLR, MLR, SII, HALP, LDH levels and presence of anemia (Table 2). In multivariate analysis, high NLR level and advanced stage were found to decrease OS (p=0.048, p=0.009).
When the OS is examined according to the stages, the survival decreased numerically in all stages in those with tumor cavitation (Stage I-II 64 vs 60.8 months p=0.937, Stage III-IV 27.7 vs 17.2 months p=0.017). However, the presence of tumor cavitation was found to significantly decrease OS in Stage III patients (40.53 vs 17.83 months, p=0.016, Figure 1).
When the Stage III patients were examined, it was seen that 60% (6/10) of the patients with tumor cavitation and 77.3% (17/22) of the patients without tumor cavitation had definitive chemoradiotherapy.
The presence of Stage III disease decreased OS in the presence of tumor cavitation (p=0.032).
Discussion
In our study, tumor cavitation was seen with a rate of 16.8% in lung SCCs. Most of the patients with tumor cavitation were men, patients with large tumor diameter, smokers, and advanced stage patients with comorbidities. Presence of tumor cavitation significantly reduced survival in Stage III patients. High NLR level and advanced stage reduced OS in lung SCCs.
Cavitations are abnormal spaces filled with air or fluid in the lung parenchyma. Infections, rheumatological diseases, septic embolism and malignancies play a role in its etiology. In addition, tumor cavitation may develop in oncological treatments. Studies have shown that the risk of tumor cavitation increases in advanced age, male gender, high smoking and advanced stages [13,14]. In our study, the majority of patients with tumor cavitation were male and in advanced stages. The frequency of tumor cavitation in lung SCC patients was similar to the literature. However, there was no statistically significant difference between smoking and the presence of cavitation due to the presence of heavy smoking in the etiology of lung SCCs.
There are conflicting results between the presence of tumor cavitation and prognosis in the literature [6,13,14]. Koladziesjshi et al. and Onn et al. showed that the presence of tumor cavitation negatively affects survival. Also, Singh et al. found that advanced age and tumor cavitation reduced OS in most advanced stage NSCLC patients [6,14,15]. However, there are also studies showing that the presence of tumor cavitation does not affect survival, as in the study of Coffey et al. also reported that tumor cavitation did not affect PFS and OS [4,13,16]. In our study, the presence of tumor cavitation significantly reduced survival in Stage-III patients, most of whom underwent chemoradiotherapy (40.53 vs 17.83 months p=0.016). Topkan et al. found that the presence of tumor cavitation reduced survival in Stage III patients who underwent chemoradiotherapy [17]. In the Phernambucq et al. studies, median OS was decreased in patients with tumor cavitation who received concomitant chemoradiotherapy, but it could not reach statistical significance (9.9 vs 16.3 months, p=0.09) [4]. Considering that definitive chemoradiotherapy is the main treatment in unresectable Stage III patients, it can be hypothesized that chemoradiotherapy may be a poor prognostic in the presence of tumor cavitation.
FDG-PET CT can detect necrosis in the tumor by measuring tissue metabolic activity. Studies have shown that OS decreases when tumor diameter and SUVmax increase in lung cancers [18]. However, Coffey et al. found in their study that the presence of tumor cavitation did not increase SUVmax [16]. In our study, high SUVmax level decreased OS in univariate analysis, but it did not reach significance in multivariate analysis (p<0.001, p=0.058). This situation can be explained by the fact that the cavitary lesions are usually large in volume, and the high SUVmax level measured in living cells due to central tumor necrosis is low due to the large volume.
Tumor cavitation is a marker of necrosis because the risk of infection is increased in patients with tumor cavitation [13]. NLR, PLR, MLR, SII and HALP scores are indexes that reflect the immune response in lung cancer and have prognostic significance [8-12]. In the study of Wang et al. in early stage lung cancer patients, MLR was reported as an independent factor affecting survival [9]. Aduquaye et al. found that high NLR was associated with recurrence-free survival among inflammatory markers in early-stage lung cancer [19]. In a recent study conducted by Winther-Larsen et al. on 5320 stage I-IV non-small cell lung cancer patients, high NLR, PLR and MLR were found to be associated with decreased OS [20]. This is the first study in the literature to show the relationship between cavitary lesions and inflammatory indexes. Contrary to expectations in our study, MLR and LHD levels were found to be lower in patients with tumor cavitation at the time of diagnosis. Although it is known that high LDH concentration has a poor prognostic role in lung cancer, LDH level is affected by many factors [21]. In addition, serum inflammatory markers are thought to be affected by environmental and hereditary factors [22]. However, in our study, high NLR level was found to be associated with reduced OS, as is frequently shown in the literature.
Limitations: The limitations of our study are its retrospective nature and the limited number of patients. Another limitation of our study is the inability to evaluate the formation mechanisms of cavitary lesions or the level of response to treatment.
Conclusion
The presence of tumor cavitation is especially important for lung SCCs. Due to delayed diagnosis and complications, these tumors usually reach large diameters and are caught in advanced stages. In our study, it was shown that tumor cavitation negatively affects the prognosis especially in stage III lung SCCs.
Among the inflammatory indices, high NLR has been shown to decrease survival in lung SCCs. No increase in inflammatory indices was detected in patients with tumor cavitation. This may be due to the inclusion of patients at different stages in the study and other factors affecting inflammatory indices. More comprehensive studies are needed on this subject.
Tumor cavitation differs with its mechanism, biology and clinical course. Care should be taken in the follow-up and treatment planning of these patients, and they should be closely monitored for complications.
Acknowledgment
We would like to thank our teammates for their contributions.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.
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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Association between the atrial septal aneurysm and frequent premature ventricular complexes
Isa Ardahanli 1, Murat Ozmen 2, Onur Akgun 3, Davut Karakurt 4, Rafig Gurbanov 5, Olgica Mihaljevic 6
1 Department of Cardiology, Faculty of Medicine, Seyh Edebali University, Bilecik, Turkey, 2 Department of Cardiology, Erzurum City Hospital, Erzurum, Turkey, 3 Department of Cardiology, Ankara Training and Research Hospital, Ankara, Turkey, 4 Department of Cardiology, Ataturk State Hospital, Sinop, Turkey, 5 Department of Bioengineering, Seyh Edebali University, Bilecik, Turkey, 6 Department of Pathophysiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
DOI: 10.4328/ACAM.21314 Received: 2022-07-15 Accepted: 2022-08-31 Published Online: 2022-09-03 Printed: 2022-10-01 Ann Clin Anal Med 2022;13(10):1143-1147
Corresponding Author: Isa Ardahanli, Pelitözü Location, Fatih Sultan Mehmet Boulevard, No:25/A, 11040, Bilecik, Turkey. E-mail: isaardahanli@gmail.com P :+90 533 576 83 25 F: +90 228 202 33 66 Corresponding Author ORCID ID: https://orcid.org/0000-0002-9309-803X
Aim: Atrial septal aneurysm (ASA) is a rare congenital malformation consisting of excess atrial septal tissue protruding into the right or left atrium and has been described as an association between cardiac arrhythmias. Premature ventricular contractions (PVCs), which are common in the general and patient population, are irregular heartbeats that indicate potential heart diseases. Frequent PVCs can often cause a reversible form of cardiomyopathy. Our study aimed to compare the incidence of frequent PVC with healthy volunteers after 24-hour rhythm Holter monitoring in patients diagnosed with ASA by transthoracic echocardiography (TEE).
Material and Methods: Fifty-eight patients between the ages of 18-65 who applied to our clinic and were diagnosed with ASA in TTE were included in the study. The control group was composed of 58 non-ASA volunteer participants. All participants underwent a complete physical examination and 12-lead surface electrocardiography was performed. All participants, whose clinical indications were met, underwent 24-hour rhythm Holter monitoring. The presence of PVC in more than 5% of all heartbeats in 24 hours in Holter recordings was defined as frequent PVC.
Results: The mean age in the study group was (50.68 ± 11.55) years. Age, gender, and clinical findings were similar in both groups. There was no significant difference between parameters in echocardiographic evaluation. In 24-hour rhythm Holter monitoring, the number of those who met the definition of frequent PVC was higher in the ASA group compared to the non-ASA group (n=17 (29.3%) vs. n=7, (12.1%), p<0.001).Discussion: Our study showed that frequent PVCs were significantly higher in 24-hour ambulatory ECG monitoring in ASA patients compared to the control group. We think that patients with ASA detected on TTE should be examined in terms of arrhythmia and should be aware of the risk of PVC-related cardiomyopathy.
Keywords: Atrial Septal Aneurysm, Frequent Premature Ventricular Complex, Ventricular Arrhythmia
Introduction
Premature ventricular complexes (PVCs) are the most common type of ventricular arrhythmia and are found in most healthy individuals [1,2]. In the absence of structural heart disease, PVC is considered relatively benign. However, in the case of underlying heart diseases such as previous myocardial infarction and heart failure, it may be an indicator of poor prognosis [3,4]. It is known that frequent PVCs can cause cardiomyopathy if not treated. Frequent PVC definitions may differ in the literature [5,6]. In our study, PVC was defined as more than 5% of all QRS complexes on standard 24-hour Holter monitoring.
Atrial septal aneurysm (ASA) is a redundant or saccular deformity of the atrial septum and is associated with increased mobility of atrial septal tissue. ASA is defined as more than a 10 mm extension of septal tissue (typically fossa ovalis) from the plane of the atrial septum to the right or left atrium, or a total extension of 15 mm on the right and left [7]. The prevalence of ASA is 2-3% in the general population [8,9]. The clinical significance of ASA has been associated with an increased prevalence of cryptogenic stroke and other embolic events. Another important clinical finding is that cardiac arrhythmias frequently accompany ASA. It is estimated that the wavy movements of the atrial septum caused by stretching initiate these arrhythmias. Although there are many studies in the literature investigating the relationship between ASA and arrhythmias, there is no study investigating the relationship between frequent idiopathic PVC.
In our study, we aimed to investigate the relationship between ASA and frequent idiopathic PVC with the help of 24-hour rhythm Holter monitoring and to compare it with the non-ASA control group.
Material and Methods
This study was designed as single-center, prospective and observational study. Our study was performed on fifty-eight patients aged between 18-65 years, who applied to the cardiology outpatient clinic between September 2021 and March 2022, and had ASA detected in transthoracic echocardiographic (TTE) imaging. As the control group, age and gender-matched fifty-eight non-ASA participants were included in the study. The study was carried out in accordance with the Declaration of Helsinki. Ethics committee approval was obtained from Bilecik Şeyh Edebali University (Approval number: 050.01.04-95175).
All participants in the study group underwent a complete physical examination and their medical histories were questioned. Clinical, demographic characteristics, and drug use histories were questioned. The obtained data were recorded on a worksheet. Arterial blood pressure measurements were made after at least 10 minutes of rest. Arterial hypertension was defined as repeated blood pressure measurements ≥140/90 mmHg or the use of antihypertensive drugs. Body mass indexes were calculated by measuring height and weight (BMI = kg/m2) and recorded. All participants were informed about the study and their written consent was obtained. Figure 1 shows the image of ASA in TTE.
Criteria for exclusion from the study: • Heart failure with reduced ejection fraction (LVEF ≤ 40%), and heart failure with mid-range ejection fraction (LVEF between 41% – 49%).
• History of previous cardiac surgery.
• Moderate to severe heart valve disease.
• Severe anemia (Hg< 11 gr/dL).
• Patients implanted with ICD, CRT.
• Pulmonary hypertension (sPAP >20 mm-Hg).
• History of antiarrhythmic drug use.
• Advanced chronic obstructive pulmonary disease (COPD) and cor pulmonale.
• History of previous pulmonary embolism.
• Active infection.
• Pregnancy.
• Left bundle branch block (Asynchronous contractions may be confused with arrhythmias).
• Heavy artifact on 24-hour Holter monitoring.
• Poor echogenicity and poor image quality.
Electrocardiographic and transthoracic echocardiographic evaluation
A standard 12-lead superficial ECG was taken in the supine position after rest for at least 20 minutes in the entire study population. ECG recordings were made using the Nihon Kohden (Tokyo, Japan) branded device at a paper speed of 25 mm/s and a voltage of 10 mm/mV. To avoid diurnal variations, we generally evaluated the ECG recordings at the same time (09:00-10:00 AM).
PVC was defined as a wide QRS complex (>120 ms) with abnormal morphology and discordant ST-segment and T wave changes on ECG (Figure 2). Transthoracic echocardiography was performed on all participants in the study group. Echocardiographic examinations were performed in the Department of Cardiology Echocardiography Laboratory using the EPIQ 7 echocardiography device (Philips, Amsterdam, Netherlands). All echocardiographic measurements were performed in the left lateral decubitus position as recommended by the American Society of Echocardiography. Left atrium, ascending aorta diameter, left ventricular end-systolic and end-diastolic diameters, interventricular septum, and posterior wall were measured with parasternal long-axis imaging. Left ventricular ejection fraction was measured with the modified Simpson’s method. ASA was defined as a protrusion of the interatrial septum to the left or right atrium by more than 15 mm along with the cardiac cycle on apical four-chamber imaging [7].
Ambulatory 24-hours rhythm monitoring
All participants in the study group underwent 12-lead 24-hour ambulatory ECG rhythm monitoring (Cardioline S.P.A Walk 400H). Pause, ectopic beat, and all normal beats were manually verified. Artifacts and missing signals for more than 2 hours were defined as insufficient recording and repeated. Frequent VPC was defined as more than 5% of all QRS complexes on standard 24-hour Holter monitoring.
Statistical analysis
All statistical analyses were performed using GraphPad Prism 8.01 (GraphPad Software, San Diego, CA, USA) software. Continuous variables were expressed as mean ± SD and categorical variables were presented as counts and/or percentages. A comparison of parametric values between the two groups was performed through an unpaired t-test (one-tailed). Categorical variables were compared using the chi-square test. P < 0.05 and P < 0.01 were considered as statistical significance. The receiver operator characteristic (ROC) analysis was used to select a cutoff value distinguishing common TB and VPC parameters from aberrant ones in ASA (+) and ASA (-) groups [10]. A tradeoff of sensitivity versus specificity was conceived as a ROC curve. The area under the curve (AUC) of 95% confidence was evaluated, estimating the overall ability of the test to differentiate the ASA (+) group from the control ASA (-) group.
Results
The mean age of the study population was 50.68 ± 11.55 years. The mean age of the ASA(+) and control groups was similar (respectively, 50.53 ± 11.69 years vs 50.83 ± 11.41). The gender numbers of males and females were similar in those with ASA (+). Again, gender distribution was similar in the non-ASA group. Transthoracic echocardiographic measurements of the study population did not differ significantly between the groups. Demographic and clinical characteristics and echocardiographic measurements of the groups are presented in Table 1.
During the study, no patient had a simultaneous atrial fibrillation attack or ventricular tachycardia attack in holter analysis. In the 24-hour ambulatory ECG monitoring, the total heart rate was significantly higher in the group with ASA (121396 ± 26345 (beats/day) vs. 111397 ± 19604 (beats/day), p = 0.0111). In the ASA group, the mean number of PVCs in 24 hours was statistically significantly higher than in the non-ASA group. (2345 ± 399 vs. 1129 ± 291, p=0.0078).
The number of people with frequent PVCs was significantly higher in the ASA + group (n=17 vs n=7, respectively, p <0.0001). In the ROC curve analysis, total beats and PVCs showed significant specificity in the ASA (+) group. The comparative statistical analysis of the groups is shown in Figure 3.
Discussion
The most important novel finding of this study is the statistically significantly increased frequency of idioventricular PVCs in patients with ASA compared to control subjects without ASA. To our knowledge, this is the first study in the literature to investigate the association of ASA with frequent idiopathic PVC using 24-hour rhythm Holter monitoring and compare it with healthy individuals.
PVCs are a type of ventricular arrhythmia that is very common in the general population and rarely gives symptoms unless there is underlying structural heart disease. In the case of underlying structural heart disease, it may be an indicator of poor prognosis [11]. The increase in the frequency of PVC causes cardiomyopathy and increases mortality due to all causes [12,13].
It has been reported in previous studies that ASA, which is a congenital cardiac defect and can often be diagnosed with TTE, is associated with many clinical conditions. These include atrial septal defect, patent foramen ovale, mitral valve prolapse, stroke, and cardiac arrhythmias [14-16]. The relationship between ASA and cardiac arrhythmias has been reported in some previous studies. Russo V et al. reported in their study that P wave dispersion was significantly longer in ASA patients compared to the control group and that atrial electromechanical delay may have a role in ASA [17]. Unlike our study, this study was designed only for paroxysmal supraventricular arrhythmias. Morelli et al showed increased episodes of arrhythmia during a 24-hour Holter in their study of twenty ASA patients. In the study, it was shown that all patients with ASA were accompanied by one or more of any type of arrhythmia. PVC was detected in 12 patients (60%) [18]. However, as it is known, in the 24-hour rhythm holter, rare PVC can be found in up to 75% of even normal individuals. Unlike this study, we evaluated those with frequent PVC (>5% PVC of all heartbeats). In addition, the population constituting our study group was higher in number.
In a study examining patients with paroxysmal and persistent AF, it was reported that IAS had structural anomalies at a rate of 43%, and approximately 59% of them had ASA [19]. In another recent study investigating the relationship between ASA and arrhythmia, atrial premature complexes and supraventricular tachycardia were found to be significantly increased in patients with ASA. Again in this study, it was reported that PVCs were observed significantly more. While it was approximately 5% in ASA patients, this rate was 2% in the healthy group [20]. In our study, the PVC rate was found to be higher in ASA patients. The reason for this difference may be that most of the individuals participating in the study did not use 24-hour Holter recording in the evaluation of arrhythmia. In addition, in our study, those who had PVC more than 5% of all beats in 24-hour Holter recordings (frequent PVC) were included in the study.
The pathophysiological mechanisms of cardiac arrhythmias due to structural abnormalities of the interatrial septum are not yet clearly known. However, some studies in the literature have focused on investigating the underlying mechanism. Mitrofanova et al. reported in their study in 40 postmortem patients that the interatrial septum had atypically shaped muscle fibers composed of working cardiomyocytes [21]. According to the results of this study, we can think that atypical myocytes with conduction system characteristics are located in the interatrial septum, which is effective in the development of arrhythmia. Again, it is a possible pathophysiological mechanism that can induce arrhythmogenesis by irritating the surrounding tissues as a result of the physical movement of the aneurysmatic tissue during the cardiac cycle. As a matter of fact, in a recent case report, it was reported that a large ASA protruding into the left atrium contacted the back of the left atrium along with the cardiac cycle and induced tachycardia
[22]. In addition to mechanical irritation of the interatrial septum, another reason why arrhythmias are often seen together in ASA may be accompanied by genetic mutational damage.
Conclusion
As a result, we found that idiopathic frequent PVCs were more common in patients diagnosed with ASA in TTE than in the age- and the sex-matched healthy control group without ASA. We think that patients with ASA detected on echocardiography should be followed closely regarding ventricular arrhythmias. In addition, further experimental and large-scale clinical studies are required to elucidate the possible pathophysiological mechanisms of PVC being observed more frequently in ASA patients.
Limitations
Our study has some limitations. The main limitation was that the study was single-center and only TTE was used in the diagnosis of ASA. The transesophageal echocardiographic evaluation may be required in suspicious cases that cannot be detected in TTE. Another limitation was the use of only 24-hour rhythm Holter monitoring for the diagnosis of frequent PVCs due to the design of the study. With the help of electrophysiological studies, the number of patients diagnosed with frequent PVC could be higher.
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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Nutritional status of patients with heart failure
Esma Asil 1, Emine Yıldız 2
1 Department of Nutrition and Dietetics, Faculty of Health Sciences, Ankara University, Ankara, Turkey, 2 Department of Nutrition and Dietetics, Faculty of Health Sciences, East Mediterranean University, Gazimagusa, Turkish Republic of Northern Cyprus
DOI: 10.4328/ACAM.21327 Received: 2022-07-20 Accepted: 2022-08-22 Published Online: 2022-08-29 Printed: 2022-10-01 Ann Clin Anal Med 2022;13(10):1148-1152
Corresponding Author: Esma Asil, Ankara Üniversitesi, Sağlık Bilimleri Fakültesi, Fatih Cd., Keçiören, Ankara, Türkiye. E-mail: energin@health.ankara.edu.tr P: +90 533 699 44 89 Corresponding Author ORCID ID: https://orcid.org/0000-0003-0809-4008
Aim: This study aims to evaluate and compare the nutritional status of patients with heart failure (HF) and coronary artery disease without HF.
Material and Methods: The study included 33 HF patients and 33 patients without HF coronary artery disease . The nutritional status of participants was evaluated with anthropometric measurements and Nutritional Status Control (CONUT). The obtained data were analyzed with the SPSS program.
Results: It was determined that most of the individuals participating in the study were overweight or obese (HF=66.7%, without HF=75.8%), and when the body fat percentage was classified, the majority of them were in the unhealthy class (HF=81.8%, without HF=63.6%). In addition, individuals in both groups were considered at high risk of chronic disease according to their waist circumference, waist-hip ratio, and waist-to-height ratio. Although the handgrip strength of individuals with heart failure was not statistically significant, it was lower than in the other group (p>0.05). It was determined that the mean CONUT score of individuals with HF was significantly higher (p<0.05), and the score increased with the increase in New York Heart Association (NYHA) class.
Discussion: In this study, it was determined that the risk of malnutrition in individuals with HF is higher than in the other group. It is known that the symptoms that occur with the progression of heart failure negatively affect the nutrition of patients. For this reason, it is essential to follow up on the nutritional status of HF patients by evaluating their nutritional status from the time of diagnosis.
Keywords: Heart Failure, Nutrition Status, CONUT
Introduction
Heart failure is defined as a structural or functional cardiac disorder in which the heart does not deliver enough oxygen to meet the metabolic needs of the tissues, despite normal or only increased filling pressures. The functional classification prepared by the NYHA is used to classify the disease according to symptoms and severity [1].
Nutritional deficiencies and weight loss are prevalent in individuals diagnosed with HF disease, and involuntary weight loss develops in most patients [2]. The European Society of Cardiology (ESC) defines cachexia as the involuntary loss of ≥6% of total body weight in the last 6–15 months, not related to edema [1]. It is known that cardiac cachexia that develops in patients affects the course of the disease and accelerates cardiac death [3]. Therefore, nutritional intervention has an important place in the treatment of HF patients. One of the most important causes of weight loss and cachexia observed in patients is insufficient intake of various nutrients and dietary energy [2,4]. This situation shows the necessity of evaluating and following the nutritional status of the patients.
Body mass index (BMI) is frequently used in assessing body weight because it is a practical and straightforward method. However, studies showed that BMI alone is insufficient in evaluating nutritional status in HF patients [5,6]. In a study, it was found that even in individuals who were considered normal or overweight according to BMI, there was nutritional deficiency according to arm muscle area, skinfold thickness, and albumin level [6]. Therefore, the nutritional status of patients with heart failure should be evaluated with other anthropometric measurements, such as skinfold thickness or waist circumferences [6-7].
Various screening and evaluation tools and risk indices can be used to evaluate the nutritional status of these patients [8]. CONUT (Controlling Nutritional Status), calculated by albumin, lymphocyte, and cholesterol values, is one of the screening tools which is suitable for use in HF patients [9].
In this study, it was aimed to evaluate and compare the nutritional status of patients with HF and coronary artery disease without HF.
Material and Methods
This study was conducted with 33 patients (M=21, F=12) diagnosed with heart failure by the physician and 33 coronary artery patients (M=28, F=5) in a similar age group without HF diagnosis. The heart failure group included 12 systolic heart failure patients with ejection fraction (EF) ≤35% and class I according to NYHA functional classification, 13 in class II, and eight patients in class III. Patients admitted to the hospital due to Acute Coronary Syndrome in the last three months, hospitalized with decompensated HF, or diagnosed with HF with preserved ejection fraction were not included in this group. Individuals who were not diagnosed with chronic heart failure had normal left ventricular ejection fraction (LVEF), but were diagnosed with coronary artery disease, were included in the study as the control group.
In individuals included in both the case and control groups,
1. Glomerular Filtration Rate was >30,
2. There was no diagnosis of Type 1 or Type 2 Diabetes Mellitus,
3. The condition of not having a by-pass in the last three months was sought.
Individuals who applied to Hacettepe University Medical Faculty Hospital Cardiology Department polyclinic between March 2014-May 2015 and agreed to participate in the study were included. The EF of the coronary artery patients included in the study was re-checked by the physician before the study, and the presence of HF was eliminated.
Before the study, ethics committee approval was obtained from Hacettepe University Ethics Committee (10.01.2014-16969557-25). The “Informed Consent Form”, that explained the purpose and practices of the research, was read to the individuals who agreed to participate in the study. General information of the participants was recorded using the questionnaire form prepared by the researchers.
Anthropometric Measurements
Using this technique, height, body weight, handgrip strength, waist and hip circumference, triceps, biceps, subscapular, and suprailiac skinfold thicknesses of the participants were measured. BMI was calculated and classified as <18.5 underweight, 18.5-24.99 normal weight, 25.0-29.99 overweight, and ≥30.0 obese (available at: https://apps.who.int/iris/handle/10665/63854).
Waist circumferences were classified as ≥94 cm and ≥80 cm at risk in men and women, respectively, and ≥102 cm and ≥88 cm as high risk. The waist-hip ratio was interpreted as 0.90 in men and above 0.85 in women (available at: https://www.who.int/publications/i/item/9789241501491).
The ratio between measured waist circumference and height was evaluated according to the classification developed by Ashwell et al. [10]. Accordingly, it was classified as <0.4 attention, 0.4-0.5 appropriate, 0.5-0.6 consider action, and >0.6 take action. The body composition of the patients was determined by the “Durnin and Womersley” body fat and lean tissue mass equation and the Siri equation. The body fat percentage of male participants ≤5 was considered unhealthy (very low), 6-15 (low), and 16-24 (high) were considered acceptable, and ≥25 was considered unhealthy (very high). The reference values used for women in the body fat percentage classification are ≤8, 9-23, 24-31, and ≥32, respectively [11].
Evaluation of Nutritional Status
The Nutritional Status Control-CONUT, which was developed to evaluate the nutritional status of HF patients in the clinic, was calculated from albumin, lymphocyte, and cholesterol values [9]. The first validity study of this scoring method was carried out in 2005, and it was shown that it gave results compatible with proven techniques. The obtained CONUT score is classified as 0-1 normal nutritional level, 2-4 mild, 5-8 moderate, and 9-12 severe nutritional deficiency [12].
Statistical analysis
SPSS 21.0 package program was used in the analysis of the data. From the answers given by the subjects to the questionnaire, mean ± standard deviation was given for the continuous variables. The Chi-square test was used to investigate the relationships between qualitative variables. Differences between group values of continuous variables were analyzed with the t-test and statistical significance level was accepted as p<0.05.
Results
Thirty-three patients with a diagnosis of HF with a mean age of 62.7±9.7 years and 33 patients diagnosed with any other coronary artery disease (CAD) other than HF with a mean age of 62.9±6.3 years participated in the study. It was found that 90.9% of individuals with heart failure were married, 39.4% were university,18.1% were high school graduates, and only 18.2% were working. All participants in the other group were married, 57.5% of them were university and 15.2% were high school graduates. The number of employed participants was significantly higher in the non-HF group (63.6%, p<0.05).
In Table 1, the mean values of the anthropometric measurements of the individuals are given. The mean triceps skinfold thickness (SFT) of men with HF was significantly higher, and the hip circumference of women was lower (p<0.05).
It was determined that 28.8% of the participants in the study had normal body weight, and there were no underweight individuals. 66.7% of individuals with heart failure and 75.8% of the other group were overweight or obese (Table 2). When the body fat percentage was classified, it was seen that the majority of them were in the class considered unhealthy (HF=81.8%, without HF=63.6%). In addition, it was found that the risk of chronic disease was higher in both groups according to waist circumference, waist-hip ratio, and waist-height ratio.
In Table 3, the average CONUT score and the nutritional status classifications were given. The mean CONUT score of patients with HF was significantly higher than in those without HF (p<0.05). It was determined that 39.4% of patients with HF and 21.2% without HF who participated had a mild nutritional deficiency.
In Figure 1, the nutritional status of patients with HF was given according to the NYHA class. With the increase in the NYHA class, the proportion of patients with mild nutrition deficiency also increased (p<0.05). It was determined that 62.5% of the patients in class 3 had nutritional deficiencies.
Discussion
Nutritional deficiency and cachexia are frequently seen in patients with advanced HF. This situation causes the progression of the disease and increases mortality [3,8]. This study determined that 39.4% of HF patients had moderate nutritional deficiency according to the CONUT score (p>0.05), and the mean score was higher than in the other group (p<0.05) (Table 3). In the study of Nakagomi et al. [13], a CONUT score of 3 and above was associated with cardiac events. Therefore, although the results of the nutritional classifications between the two groups are not statistically significant, they are clinically meaningful. Nutritional deficiencies are more common as symptoms of the disease progression in heart failure patients [8]. Contrary to the literature [14], the number of patients with NYHA class I and II in whom HF symptoms did not develop much was high in this study. However, it was determined that the percentage of participants with mild nutrition deficiency also increased with increasing the NYHA class in patients with HF (Figure 1). Although the nutritional deficiency found in this study is lower than in the literature, the possibility of developing nutritional deficiency with the increase in the severity of the disease should not be ignored.
BMI is frequently used in the clinical assessment of body weight and monitoring of nutritional status. In this study, although the difference between the two groups was not statistically significant, the mean BMI value of individuals with HF was higher (p>0.05) (Table 1). However, as the edema that develops with the progression of the clinical-stage masks weight loss, the evaluation with BMI alone gives erroneous results, especially in patients with advanced HF [9].
In a study conducted by Gastelurrutia et al. [6], at the end of the anthropometric and biochemical evaluation of individuals with a ≥BMI 25, it was understood that nutritional deficiency was more common in this group. A recent study has shown that skinfold thickness or equations based on skinfold thickness are more effective than BMI in evaluating patients with HF [5]. Zuchinal et al. [15] found that triceps skinfold thickness was a strong independent predictor of all-cause mortality in HF. In this study, the rate of patients who were overweight or obese according to BMI, was lower in HF patients. However, when the body fat percentages of the participants were calculated using skinfold thickness measurements, it was found that the number of individuals with a very high body fat percentage, in contrast to BMI, was higher in the group with HF (HF=81.8%; without HF= 63.6%) (Table 2). The increase in adipose tissue in response to muscle loss in HF patients who reduce physical activity due to limited effort capacity is thought to be one of the reasons for this situation.
Obesity is one of the risk factors in the etiology of HF. However, in recent years, studies have shown that high BMI reduces the risk of mortality in patients with HF [16,17]. In a study that followed heart failure patients for ten years, it was determined that a BMI below 23.8 kg/m2 increases the risk of mortality [17], and in another study, non-ischemic HF patients with a BMI of 30-34.9 have a longer life expectancy [16]. For this reason, the Heart Failure Society of America recommends 5-10% weight loss only in HF patients with a BMI of 35 and above [18]. This situation, which is called the obesity paradox, is supported by various studies. However, it should not be forgotten that in addition to the body weight and BMI classification of individuals, body composition is also crucial for the prognosis of the disease. Abdominal obesity has an important place in both coronary artery disease’s etiology and life span. It was known that abdominal obesity is an independent risk factor for mortality in patients with HF [19]. In this study, it was found that the risk of chronic disease was relatively high in both groups according to the waist circumference, waist-hip ratio, and waist-to-height ratio (Table 2).
Handgrip strength is used practically in the clinic to evaluate the general condition of muscle mass. In recent years, it has been understood that there is a relationship between handgrip strength and, cardiovascular diseases [20]. In the PURE (Prospective Urban Rural Epidemiology) study, it was determined that the average handgrip strength value of the participants was 30.6kg and that the handgrip strength was inversely related to cardiovascular disease and cardiovascular deaths [20]. A study evaluating the risk of chronic HF (CHF) with handgrip strength showed that CHF is 1.35 times higher in individuals with low handgrip strength [21]. The relationship between handgrip strength and the risk of developing heart failure is very important [22]. In addition, low handgrip strength and high adipose tissue are also independent risk factors for mortality [23]. In this study, it was found that the handgrip strength was lower, and the body fat percentage was higher in patients with HF. In order to increase the quality and duration of life in patients, these two risk factors that increase the risk of both cardiovascular and all-cause mortality should be eliminated as soon as possible.
Limitation
Nutritional deficiencies are common in patients with advanced HF. However, in this study, both the small sample size and the high number of people with class 1 and 2 HF caused the general nutritional status of the patients to be better than expected. Therefore, the nutritional status of HF patients should be determined by prospective studies to be conducted with a larger sample. Comprehensive assessments will allow the creation of a tailored nutrition program for HF patients.
Conclusions
In this study, it was determined that individuals with HF have a higher risk of malnutrition than the other group. It is known that the symptoms that occur with the progression of heart failure adversely affect the patients’ nutritional status. For this reason, the course of the disease must evaluate the nutritional status of HF patients from the time of diagnosis and follow up with the patient. Preventing involuntary weight loss in individuals with heart failure, creating an exercise and nutrition plan that will help reduce adipose tissue and increase muscle mass will help improve the patient’s quality of life and duration.
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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Esma Asil, Emine Yıldız. Nutritional status of patients with heart failure. Ann Clin Anal Med 2022;13(10):1148-1152
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The role of neutrophils and platelets on the development and enlargement of jaw cysts
Fatma Doğruel 1, Canay Yılmaz Asan 1, Ahmet Emin Demirbaş 1, Mehmet Amuk 2
1 Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Erciyes University, Kayseri, 2 Department of Oral and Maxillofacial Radiolog, Private Dental Clinic, Samsun, Turkey
DOI: 10.4328/ACAM.21336 Received: 2022-08-01 Accepted: 2022-09-05 Published Online: 2022-09-13 Printed: 2022-10-01 Ann Clin Anal Med 2022;13(10):1153-1157
Corresponding Author: Fatma Dogruel, Department of Oral and Maxillofacial Surgery, Erciyes University, 38039 Kayseri, Turkey. E-mail: fdogruel@gmail.com P: +90 352 207 66 66 F: +90 352 438 06 57 Corresponding Author ORCID ID: https://orcid.org/0000-0002-4290-2737
Aim: The aim of this study was to compare the circulatory inflammatory cells in peripheral blood tests of patients with odontogenic cysts and healthy subjects and the effect of these markers between the development and enlargement of cysts.
Material and Methods: Ninety-eight patients with an odontogenic cyst in the maxillofacial region (Group 1) and 102 healthy subjects as control (Group 2) were included in the study. White blood cell count, neutrophil count, lymphocyte count, platelet count, neutrophil to lymphocyte ratio (NLR), mean platelet volume (MPV), and platelet to lymphocyte ratio (PLR) were compared between groups. In addition, the correlation of these markers with volume of the cysts was determined.
Results: Fifty-six radicular cysts, 34 dentigerous cysts, and 8 odontogenic keratocysts were observed in Group 1. Lymphocyte count, platelet count, and MPV were statistically higher in Group 2 (p<0.05). The optimum cut-off level for MPV was detected as 8.7 according to the ROC analysis (Sensitivity: 85, Specificity: 80). The median cyst volume was 4663 mm3 (min: 1213 max: 48553) and cyst volume was not different according to the type of the cyst (p=0.063). A positive and significant correlation between neutrophil count and PLR with cyst volume was observed (p=0.023, p=0.007)
Discussion: This study considered the effect of circulatory inflammatory cells on the pathogenesis of jaw cysts. Lower platelet counts and MPV may have an essential role in the development of cystic jaw lesions and higher circulating neutrophils may be associated with an expansion of the cysts.
Keywords: Odontogenic Cysts, Neutrophil, Platelet
Introduction
Odontogenic jaw cysts are common pathological destructive lesions in the maxillofacial region and are composed of an epithelial tissue wall and fluid content [1]. The most common odontogenic cystic lesions are radicular cysts, dentigerous cysts, and odontogenic keratocysts. The odontogenic keratocyst, which has been termed previously as a “keratocystic odontogenic tumor”, was reintroduced as a cystic lesion in the 2017 World Health Organization (WHO) classification [2]. The exact mechanism of growth and enlargement of cystic lesions is still controversy but it is reported that local immunological responses play a role in the pathogenesis of these lesions [3]. T-lymphocytes, macrophages, plasma cells, mast cells, and many other cytokines are associated with cellular immune response and the modulation of inflammatory process [4]. However, neutrophils, lymphocytes, and platelets (PLT) are key players in the systemic and local inflammatory response [5]. Mean platelet volume (MPV), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) are useful biomarkers reflecting systemic inflammation and can be obtained from peripheral blood samples easily and without additional costs [6]. These markers are also associated with the development of many tumoral lesions, such as breast, gastrointestinal, oral cancer, and the survival characteristics and prognosis of these diseases [7]. The impact of the local inflammation and immune response is well known regarding cystic lesions but it is unclear what the effect of these markers is on cyst development and prognosis. Suzuki M. investigated the transporting mechanism of cystic lesions and it was found that cyst fluid contains similar ingredients with serum and lymphocytes, and segmented polymorphs existed more in cyst fluid than in serum, and they modulate the protein components of cyst fluids with active diffusion [8]. To the best of our knowledge, circulatory inflammatory cells and ratios have not been evaluated in patients with odontogenic cysts in comparison with healthy patients. Our hypothesis is that circulatory cells such as neutrophils, lymphocytes, platelets and their ratios in cyst patients could be different from healthy patients, and this could be used as a diagnostic marker in cyst patients. Therefore, the aim of this study was to compare inflammatory cells in peripheral blood tests, NLR, PLR, and MPV values in patients with odontogenic cysts and healthy subjects and the relationship of these markers between cyst type, development, and enlargement.
Material and Methods
Patient Selection
The study included 98 patients with odontogenic cysts in the maxillofacial region, who were operated under general anesthesia due to gagging reflex, dental phobia, and lack of cooperation during surgery with local anesthesia, and pre-operative blood tests were performed for the evaluation of the patients before surgery in the Oral and Maxillofacial Surgery Department. Approval from the local Ethics Committee was obtained (approval number: 2018/178). For a control, 102 patients were examined. The control group included patients who had radiological images and treated because of tooth extraction, pre-prosthetic surgery, dental implant or any other reason and had no cystic lesions in maxilla or mandible. All radiological and clinical examinations were performed by the same radiologist and surgeon. Patients with signs of infection in the maxillofacial region because of impacted teeth, pericoronitis or any other reasons were not included due to the effect on blood parameters. Patients with signs of any systemic infection, systemic diseases such as autoimmune diseases, allergies, concomitant drug use, and pregnant and lactating women were excluded from the study. Blood samples were drawn and collected into Tripotassium EDTA based tubes by hematology laboratory staff, stored at 4° C and assessed by a Sysmex K-1000 auto analyzer within 30 minutes of sampling. Platelets, white blood cells (WBC), neutrophils, lymphocyte counts and percentages were determined using a blood counter ADVIA 2120 Hematology System (Siemens AG, Eschborn, Germany).
Data collection
Data were collected from the preoperative blood tests of the patients. Clinical data about gender, age, affected region, and histopathological diagnosis of cysts were also compared.
Cone Beam Computed Tomography (CBCT) Images and Volumetric Analysis
CBCT images were obtained from the patients for detailed examination before surgery. All CBCT images were obtained with a New Tom 5G unit (QR, Verona, Italy) using standard mode with a 12 × 8 cm field of view (FOV) and a small voxel size of 250 μm3. Additionally, the CBCT unit itself modulated kilovolt (kV) and mill ampere (mA), depending on the patient. Axial slice thickness was set at 0.25 mm. All images were recorded in DICOM format and reconstructed in Simplant Pro 16 (Materialize NV, Leuven, Belgium) software. The contours of the cysts were determined for measurement of the volume of the cysts from the CBCT. Afterwards, air values were thresholded to reveal the volume value of the cysts. The drawing / delete mask and segmentation wizard techniques were used (Figure 1).
Standardization was achieved by keeping the threshold values constant in all individuals. Cyst images were examined by threshold and masking without loss of axial, coronal, and sagittal sections. The three-dimensional shaping of the cysts and the values of the volume were recorded as mm3.
Statistical Analysis
A sample size of 90 for the cyst group was calculated with power analysis. The data normality was assessed using a histogram, q-q plots, and the Shapiro-Wilk test. Variance homogeneity was examined using the Levene test. To compare the differences between groups, a two-sided independent samples t-test or the Mann-Whitney U test was applied. The Spearman test was used for correlation analysis. Moreover, receiver operating characteristics curve analysis (ROC) was applied to assess the predictive effect of markers on cyst development and volume. The area under the ROC curve was calculated with a 95% confi-dence interval. The Youden index was used to identify the optimal cut-off value. Sensitivity, specificity, as well as positive and negative predictive values were calculated with 95% confidence intervals based on the identified cut-off value [9]. Data values were expressed using mean ± standard deviation, median (1st-3rd quartiles), or frequencies (percentages). TURCOSA (Turcosa Analytics Ltd. Co., Turkey, www.turcosa.com.tr ) software was used for statistical analysis and a p- value less than 5% was considered statistically significant.
Results
A total of 200 patients with blood tests were evaluated. Ninety-eight patients were included in the cyst group (Group 1) and 102 patients were included in Group 2 as controls. 54% of all patients were women (n=108) and 46 % were men (n=92). The mean age of all patients was 27 (min: 14, max: 71) years. There was no statistical relationship between age and any of the blood parameters (p>0.05). In Group 1, 56 radicular cysts, 34 dentigerous cysts and 8 odontogenic keratocysts were observed. 54% (n=53) of the cysts were in the maxilla and 46% (n=45) were observed in the mandible. Median lymphocyte count, platelet count and MPV were statistically higher in Group 2. The optimum cut-off level for MPV was detected as 8.7 according to the ROC analysis (Sensitivity: 85, Specificity: 80) (Table 1, Figure 2).
The patients in Group 2 had an MPV value of 8.7 and higher. Median neutrophil count and NLR were higher in Group 1 but the difference was not significant. All results of the blood tests are summarized according to patients in Table 2.
Platelet count and MPV were statistically higher in all women (n=108; p=0.014, p<0.001). MPV and NLR were different according to gender in Group 1. MPV was significantly higher in women (p=0.049) and NLR was higher in men (p=0.021). According to the type of the cyst, only lymphocyte count was significant between groups. Lymphocyte count was statistically lower in patients with odontogenic keratocysts and higher in those with dentigerous cysts (p=0.039) (Table 3).
The median cyst area was 1983,5 mm2 (min: 923,22-max: 15797) and the median cyst volume was 4663 mm3 (min: 1213-max: 48553). Cyst volume was not different according to localization of the cyst in the maxilla or mandible and type of the cyst (p=0.920, p=0.063). Spearman’s correlation coefficients for neutrophil count, PLR, and cyst volume were obtained. A positive and statistically significant correlation between neutrophil count and PLR with cyst volume was observed (p=0.023, p=0.007) (Figure 3).
Discussion
Cystic lesions are most common treated pathologies in oral and maxillofacial surgery practice. It was reported that men are more affected by odontogenic cysts than women [1]. Radicular cysts are the most commonly seen form of these lesions [10]. The underlying mechanism of cysts is the persistent exudation of large numbers of immunocompetent cells, such as macrophages, lymphocytes, plasma cells, and leucocytes [11]. Studies in the literature stated that more lymphocytes and segmented polymorphs existed in cyst fluid than in serum and a part of the protein components of cysts are emitted as immunoglobulin by lymphocytes [8]. T- and B- lymphocytes were found a major inflammatory infiltrate of radicular cysts and have an important role in cell-mediated mechanisms in chronic inflammation [12]. Cyst development is a result of an inflammatory process in the periapical tissues and humoral and cellular immune responses play a role in the pathogenesis of these lesions [13].
Various biomarkers of humoral immune response, such as lymphocyte count, platelet count, WBC, NLR, PLR, MPV, and C reactive protein have been developed to investigate the effect of several diseases, and changes of these parameters are useful in the prognosis of many malignancies [5,13].
Neutrophils play a critical role in the progression of cancer by enhancing the proliferation, invasion and metastases via the release of cytokines. In addition, lymphocytes can eliminate cancer cells by inhibiting tumor cell proliferation and migration. High levels of lymphocyte counts were reported to be associated with a better prognosis in many types of cancer [14]. For this reason, the balance between these cells is crucial in the pathogenesis of cancer [15].
Since the relationship between chronic inflammation and carcinogenesis was reported, various studies have been focused on the role of inflammation on tumor generation, distant metastases, and prognosis [7,16]. NLR has been reported in hepatocellular carcinoma and preoperative elevated NLR was associated with a worse survival rate [17].
NLR and platelet counts are useful and PLR seems to play an important role in tumor progression. Platelets induce an epithelial/ mesenchymal transition, and the interaction between tumor cells and platelets promotes distant metastases of tumors [18].
NLR and PLR had been evaluated in patients with oral squamous cell carcinoma and it was observed that high PLR and NLR are associated with shorter survival rates [13]. Similarly, it was reported the association of high pretreatment NLR and PLR levels with poor prognosis of paranasal sinus cancer [6]. Considering the similarities between the mechanisms that are effective in the development of cysts and tumor pathogenesis, investigation of inflammatory markers in the circulation can be helpful in elucidating the effect of a humoral immune response on the pathogenesis of cysts.
Most of the studies about the effect of inflammatory cells are associated with oral cancers and metastasis of solid tumors and there are few studies about other diseases seen in the maxillofacial region. NLR was found as a useful prognostic marker for high risk of multiple recurrences in patients with adenoid cystic carcinoma [19].
It was reported in the literature that severe periodontitis was found to be associated with high platelet counts [20,21]. To the best of our knowledge, there is no study about the association between maxilla-mandibular cystic lesions and blood cells. For this reason, systemic inflammatory markers were evaluated in patients, who had radicular, dentigerous, or odontogenic keratocysts, and their relation was detected with cyst development and volume for the first time in this study. According to the results, lymphocyte count, platelet count, and MPV were statistically higher in healthy patients. These results are similar to other studies on the pathogenesis of tumors. Therefore, it can be thought that lower lymphocyte counts, which are interacting with increasing neutrophil counts, may be associated with cyst formation. Higher platelet count and MPV were also found in healthy patients in this study and MPV could be used as a diagnostic tool in cyst patients.
MPV is an indicator of platelet activation and reflects platelet production and stimulation [22]. It was reported that the size of circulating platelets is dependent on the intensity of systemic inflammation. High-grade inflammation attends a decrease of MPV, possibly due to the increased migration to the inflammatory site and high consumption of platelets at the sites of inflammation. Another statement of decreased MPV in inflammatory conditions states that the excessive production of pro-inflammatory cytokines and acute phase reactants have an impact on the size of platelets via interfering with megakaryopoiesis and the following release of small-sized platelets from the bone marrow [23]. The findings suggest that MPV was related with the inflammatory status of patients with cystic lesions. According to the ROC analysis in the present study, MPV had a high sensitivity (85%) and specificity (80%) for the evaluation of cyst pathogenesis and lower MPV values (optimum cut off: 8.7) and was found to be associated with cyst formation.
CBCT examination of cystic lesions is a feasible method for the evaluation of extension and growth in three dimensions. Kauke et al. reported that volumetric analysis of tumors by image segmentation is a precise technique [24]. They analyzed the volumetric size differentials of periapical cysts, dentigerous cysts, and keratocysts. Their results indicated that the mean volumetric extent of keratocysts is significantly higher compared to other lesions [24]. Gomez et al. found that 19% of jaw cysts exceed a volume of 10000 mm3 and they suggested a close clinic-radiologic examination of lesions with sizes exceeding a value of 3000 mm3 [17]. Higher cyst volume was seen in a keratocyst and the lowest was dentigerous cyst. Keratcyts can achieve great intraosseous volumes, most likely by multidimensional infiltration of bone [24]. According to the results of present study, it was found that volumes of cystic lesions were not different according to the type of cyst and 30% of all lesions exceed a volume of 10000 mm3 (p=0.063). The relatively low sample size for keratocysts is the limitation of present study. The main reason of the low sample size is that the patients treated under general anesthesia were included in the present study, and the patients treated in local theatre were excluded due to the absence of the result of blood panels.
In addition, to the best of our knowledge, this is the first report, which evaluates the correlation between inflammatory markers and the volume of cysts. The authors concluded that neutrophil count and PLR have a positive correlation with cyst volume. Neutrophils may migrate to the cyst area where the inflammation is intense. This may result in an increase in circulating neutrophil production from the bone marrow and decrease in lymphocyte count. For this reason, PLR can increase due to the circulating lower lymphocyte count. It can be thought that this sequential process might be effective in the enlargement of cysts. Circulatory cells may have a potential role in this process. However, the exact mechanisms under the cyst formation and expansion are still unclear and could not be explained only by these results.
Conclusion
The present study, to the best of our knowledge, the first report in the literature, which considers the effect of circulatory inflammatory cells on the pathogenesis of jaw cysts. Odontogenic cysts are highly associated with systemic inflammatory conditions and immunological responses. Lower platelet count and MPV may play a critical role in the development of cystic lesions and neutrophils may play a role in the expansion of the cysts. Further clinical studies with more patients are needed for results that are more accurate.
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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Fatma Doğruel, Canay Yılmaz Asan, Ahmet Emin Demirbaş, Mehmet Amuk. The role of neutrophils and platelets on the development and enlargement of jaw cysts. Ann Clin Anal Med 2022;13(10):1153-1157
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Effect of vitamin D deficiency on ocular blood flow
Ayşe Güzin Taşlıpınar Uzel 1, Özlem Ünal 2, Demet İyidoğan 3, Elif Şimşek Ürer 4, Nagihan Uğurlu 5, Mehmet Murat Uzel 6
1 Department of Ophthalmology, Faculty of Medicine, Ufuk University, Ankara, 2 Department of Radyology, Ankara State Hospital, Ankara, 3 Antalya Dünya Göz Hospital, Antalya, 4 Samsun Physical Therapy and Rehabilitation Hospital, Samsun, 5 Department of Ophthalmology, Faculty of Medicine, Yıldırım Beyazıt University, Atatürk Education and Research Hospital, Ankara, 6 Department of Ophthalmology, Faculty of Medicine, Balikesir University, Balikesir, Turkey
DOI: 10.4328/ACAM.21343 Received: 2022-08-05 Accepted: 2022-09-21 Published Online: 2022-09-29 Printed: 2022-10-01 Ann Clin Anal Med 2022;13(10):1158-1161
Corresponding Author: Ayşe Güzin Taşlıpınar Uzel, Department of Ophthalmology, Faculty of Medicine, Ufuk University, Dr. Rıdvan Ege Hospital, Ankara, Turkey. E-mail: agtaslipinar@gmail.com P: +90 312 204 40 00 Corresponding Author ORCID ID: https://orcid.org/ 0000-0002-0079-5179
Aim: In this study, we aimed to evaluate the effects of vitamin D deficiency (VDD) on retrobulbar blood flow in healthy eyes.
Material and Methods: In this prospective study, thirty eyes of 30 patients with VDD (Group 1) and 25 eyes of 25 individuals without VDD (Group 2) were included. The peak systolic flow velocity (PSV), end-diastolic flow velocity (EDV) and vascular resistance index (RI) were obtained from the ophthalmic artery (OA) with color doppler imaging. Multiple linear regression was performed for the covariate-adjusted comparison.
Results: Mean ages were 37.83±9.89 years in Group 1 and 35.32±9.61 years in Group 2, (p = 0.347). Mean values of serum 25(OH)D3 level were 11.38 ± 3.85 ng/dl in Group 1 and 26.80 ± 10.03 ng/dl in Group 2 (p < 0.001). PSV and EDV were significantly higher in Group 2 than in Group 1 (p<0.001, p=0.001, respectively). RI was slightly higher in Group 1 than in Group 2, but this difference was not statistically significant. In multivariate linear regression, PSV and EDV were positively correlated with OPP, and negatively affected by the presence of VDD.
Discussion: VDD can be an important factor in reducing ocular blood flow.
Keywords: Vitamin D Deficiency, Color Doppler Imaging, Retrobulbar Blood Flow, Ophthalmic Artery, Multiple Linear Regression
Introduction
Vitamin D is well known for its role in calcium and phosphorus metabolism, which are important in regulation of the musculoskeletal system [1]. However, its effects on cell proliferation and differentiation, apoptosis, immunity, and angiogenesis have recently been studied [2]. Vitamin D deficiency (VDD) is also associated with cardiovascular diseases [3]. The inhibitory effects of vitamin D on the renin-angiotensin-aldosterone system (RAAS) and its protective effects on the vessels are among the physiopathological mechanisms explaining this association [4]. Additionally, due to the effects of vitamin D on arterial compliance and endothelium, arterial stiffness increases and blood flow is affected in VDD [5].
Recent research on the effect of VDD on eye disorders has established a link between the severity of diseases such central retinal vein occlusion, glaucoma, uveitis, diabetic retinopathy, and age-related macular degeneration and VDD [6-9]. Although the underlying mechanism is not fully known, VDD has been shown to affect retinal and choroidal microvasculature in healthy individuals [10, 11]. It is unclear whether these changes are the result of a specific local effect or a general decline in ocular blood flow. Changes in ocular perfusion also play an important role in the pathogenesis of many ocular diseases [12,13]. Therefore, the effect of VDD on blood flow is an issue that needs to be emphasized in order to understand its effect on ocular diseases.
The aim of the study is to evaluate the effects of VDD on ophthalmic artery (OA) by measuring the peak systolic flow velocity (PSV), end-diastolic flow velocity (EDV) and vascular resistance index (RI) in healthy eyes.
Material and Methods
This prospective study was conducted between March 2016 and May 2016 at Ankara Atatürk Training and Research Hospital in accordance with the tenets of the Declaration of Helsinki. The protocol was approved by the Yildirim Beyazit University Ethics Committee. Informed consent was obtained from all individual participants included in the study.
Serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations were measured by high-performance liquid chromatography. Vitamin D levels below 20 ng/ml were considered as VDD (Group 1), according to the guidelines of the U.S. Institute of Medicine [14]. Healthy volunteers whose serum vitamin D levels were above 20 ng/ml were included as a control group (Group 2). Patients younger than 18 years or with a history of ocular trauma and intraocular surgery, uveitis, glaucoma and retinal pathologies, systemic disease, smoking and/or current pregnancy were excluded from the study.
All participants underwent a complete ophthalmological examination, including measurement of intraocular pressure (IOP) with a Goldmann applanation tonometer.
The weight and height of the participants were appropriately measured by the same device for all cases. After obtaining body weight (in kilograms) and height (in meters) values, BMI was calculated using the weight/height2 (kg/m2) formula.
All patients rested for half an hour and, caffeinated beverages and alcohol consumption were questioned before measurements of arterial blood pressure (BP), and color Doppler imaging was performed. BP was measured using a sphygmomanometer. Mean arterial pressure (MAP) was calculated as follows: 1/3 systolic BP + 2/3 diastolic BP. Similarly, mean ocular perfusion pressure (OPP) was calculated as 2/3 MAP – IOP.
Retrobulbar blood flow was measured with a high-frequency linear probe (12-17 MHz) on an Aplio 500 ultrasound machine (Toshiba Medical Systems, Co., LTD, Otawara, Japan). After applying a sterile gel to the outside of the eyelid of the patient lying in the supine position with his eyes closed, a gray scale examination followed by a color Doppler imaging examination was performed without applying pressure. A radiologist, who was blinded to the vitamin D levels of the participants, took measurements from OA at the same time of day. Measurements were made at an angle set parallel to the direction of blood flow and, the peak systolic flow velocity (PSV) and end-diastolic flow velocity (EDV) were evaluated. The vascular resistance index (RI) was calculated by using the formula of RI=(PSV-EDV)/PSV. [14] The right eyes of the participants were analyzed.
A priori power analysis using PASS 11 (Power and Sample Size Calculation Software, Version 11) revealed that we required to enroll at least 25 eyes for each group in the study. In the present study, 30 eyes were included in the study group and 25 eyes in the control group and, accordingly, the power of the study was 82.3%.
Data were analyzed using the SPSS software (version 21; International Business Machines Co., Armonk, NY). The variables were presented as mean and standard deviation. The normality of all data was evaluated with the Shapiro-Wilk test. Differences between the groups were analyzed with the independent samples t-test. Multiple linear regression was performed for the covariate-adjusted comparison. P values < 0.05 were accepted as statistically significant.
Results
The mean age was 37.83±9.89 years in Group 1 and 35.32±9.61 years in Group 2 (p=0.347). The gender ratio was also similar between the groups (18/12 in group 1, 16/9 in group 2, p=0.491).
The mean serum 25(OH)D3 levels were 13.52±6.88 ng/ml and 24.08±7.14 ng/ml in Group 1 and Group 2, respectively (p <0.001). BMI was slightly higher in Group 1 (26.20±1.74 kg/m2) than in Group 2 (25.36±1.77 kg/m2), but this difference was not statistically significant (p=0.084).
As shown in Table 1, OPP did not differ between groups (p=0.163), but PSV and EDV were significantly higher in Group 2 than in Group 1 (p<0.001, p=0.001 respectively). RI was slightly higher in Group 1 than in Group 2, but this difference was not statistically significant.
The multivariate linear regression analysis between ocular perfusion parameters and demographic variables, OPP, BMI and presence of VDD is presented in Table 2. No correlation was found between gender, BMI, and ocular perfusion parameters, but age showed a statistically significant correlation with PSV, EDV and RI. While PSV and EDV were positively correlated with OPP, they were negatively affected by the presence of VDD.
Discussion
The present study revealed that ocular perfusion is negatively affected in presence of VDD. Other related factors with EDV and PSV are age and OPP.
The role of VDD in many diseases associated with vascular pathologies has been studied. Especially, relationship between VDD and cardiovascular diseases has been demonstrated. Kendrick et al. reported that patients with VDD had more angina, myocardial infarction and heart failure [15]. In recent years, studies have shown that VDD is associated with many eye diseases. Kim et al. have reported that low serum vitamin D status is associated with increased glaucoma risk in females [8]. Studies have shown that VDD accelerates the development of neovascularization and proliferative retinopathy in patients with type 2 diabetes mellitus [16, 17]. Parekh et al. have shown a correlation between reduced serum vitamin D levels and risk for early age-related macular degeneration [18]. A meta-analysis found a trend for late AMD among patients with VDD. [7]. In elderly patients without macular dysfunction, VDD is also associated with thinning of macular thickness [19].
In our study, we found that the blood flow decreased significantly in the group with VDD. One of the underlying mechanisms may be RAAS activation. It has been shown that vitamin D modulates RAAS. Renin expression was significantly increased in vitamin D receptor knock-out mice and suppressed in wild type mice after injecting 1.25 (OH)2D [20]. Activation of RAAS leads to severe vasoconstriction. Another factor can be acceleration of atherosclerosis due to VDD. VDD has been associated with increased pro-inflammatory cytokines such as TNF-α, interleukin (IL) -6 and interleukin-1beta (IL-1β), which predisposes to the development of atherosclerosis [21]. This condition is associated with atherosclerosis. In addition, vitamin D has been shown to reduce the risk of atherosclerosis by decreasing endoplasmic reticulum stress and oxidative stress, and thus has a protective effect on endothelial cells [22]. VDD increases arterial stiffness and atherosclerosis and also affects blood flow [5]. Influence of changes in ocular blood flow in the occurrence and progression of these diseases might suggest that VDD worsens these diseases by affecting ocular blood flow. Both changes in structure of artery and its regulation affect arterial stiffness and blood flow.
Vascular function varies with aging and may affect the retrobulbar blood flow. The most important cause of altered vascular function in elderly individuals is impaired endothelial function [23]. In addition, atherosclerosis, which increases with age, is another important factor [24]. Another result of our study is that low OPP values reduce retrobulbar blood flow. Low OPP is thought to be a risk factor for glaucoma [25]. However, it is not clear which mechanism causes this. In particular, low perfusion in the optic nerve head may increase glaucomatous damage.
This is the first study to evaluate the effects of VDD on ocular perfusion. However, there were some limitations in our study. We carried out the study in the spring to evaluate average levels of serum vitamin D. However, cross-sectional measurement of vitamin D levels might be misleading when assessing VDD. Fluctuation of level of serum vitamin D in a year or throughout years might cause different effects on ocular blood flow. Cohort studies in which vitamin levels are monitored for longer periods are needed, and assessment of vitamin D levels in different seasons might also be beneficial in evaluating the effects of VDD.
Conclusion
The relationship between VDD and various eye diseases has been frequently investigated in recent years. Ocular perfusion reduction in VDD may be an important factor in the emergence or aggregation of these diseases.
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. Nebbioso M, Buomprisco G, Pascarella A, Pescosolido N. Modulatory Effects of 1,25-dihydroxyvitamin D3 on Eye Disorders: A Critical Review. Critical Reviews in Food Science and Nutrition. 2017; 57(3):559-65.
3. Cosentino N, Campodonico J, Milazzo V, De Metrio M, Brambilla M, Camera M, et al. Vitamin D and Cardiovascular Disease: Current Evidence and Future Perspectives. Nutrients. 2021;13(10):3603
4. De la Guía-Galipienso F, Martínez-Ferran M, Vallecillo N, Lavie CJ, Sanchis-Gomar F, Pareja-Galeano H. Vitamin D and cardiovascular health. Clin Nutr. 2021;40(5):2946-57.
5. Lee JH, Suh HS. Association of serum 25-hydroxy-vitamin D Concentration and arterial stiffness among Korean adults in single center. J Bone Metab. 2017;24(1):51-8.
6. Epstein D, Kvanta A, Lindqvist PG. Vitamin D Deficiency in Patients with Central Retinal Vein Occlusion: A Case Control Study. Curr Eye Res. 2017;42(3):448-51.
7. Ferreira A, Silva N, Furtado MJ, Carneiro Â, Lume M, Andrade JP. Serum vitamin D and age-related macular degeneration: Systematic review and meta-analysis. Surv Ophthalmol. 2021;66(2):183-97.
8. Kim HT, Kim JM, Kim JH, Lee MY, Won YS, Lee JY, et al. The Relationship between Vitamin D and Glaucoma: A Kangbuk Samsung Health Study. Korean J Ophthalmol. 2016;30(6):426-33.
9. Tecilazich F, Formenti AM, Giustina A. Role of vitamin D in diabetic retinopathy: Pathophysiological and clinical aspects. Rev Endocr Metab Disord. 2021;22(4):715-27.
10. Icel E, Ucak T, Ugurlu A, Erdol H. Changes in optical coherence tomography angiography in patients with vitamin D deficiency. Eur J Ophthalmol. 2022; DOI: 10.1177/11206721221086240.
11) Vural E, Hazar L, Çağlayan M, Şeker Ö, Çelebi ARC. Peripapillary choroidal thickness in patients with vitamin D deficiency. Eur J Ophthalmol. 2021;31(2):578-83.
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13. Shab GB, Sharma S, Mehta AA, Goyal RK. Oculohypotensive effect of angiotensin-converting enzyme inhibitors in acute and chronic models of glaucoma. J Cardiovasc Pharmacol. 2000; 36(2):169-75.
14. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011; 96(1):53-8.
15. Kendrick J, Targher G, Smits G, Chonchol M. 25 Hydroxyvitamin D deficiency is independently associated with cardiovascular disease in the Third National Health and Nutrition Examination Survey. Atherosclerosis. 2009;205(1):255-60
16. Mohammadian S, Fatahi N, Zaeri H, Vakili MA. Effect of vitamin d3 supplement in glycemic control of pediatrics with type 1 diabetes mellitus and vitamin d deficiency. J Clin Diagn Res. 2015; 9(3):5-7.
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18. Parekh N, Chappell RJ, Millen AE, Albert DM, Mares JA. Association between vitamin D and age-related macular degeneration in the Third National Health and Nutrition Examination Survey, 1988 through 1994. Arch Ophthalmol. 2007; 125(5):661-9.
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Ayşe Güzin Taşlıpınar Uzel, Özlem Ünal, Demet İyidoğan, Elif Şimşek Ürer, Nagihan Uğurlu, Mehmet Murat Uzel. Effect of vitamin D deficiency on ocular blood flow. Ann Clin Anal Med 2022;13(10):1158-1161
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Relationship between diabetic retinopathy and liver enzyme activities
Cenk Zeki Fikret 1, Ceylan Bal 2, Nil Irem Ucgun 3, Filiz Yildirim 4
1 Department of Ophthalmology, Ankara City Hospital, 2 Department of Medical Biochemistry, University of Yıldırım Beyazıt, Ankara City Hospital, 3 Department of Ophthalmology, University of Health Science, Ankara City Hospital, 4 Department of Internal Medicine, Polatlı Duatepe Government Hospital, Ankara, Turkey
DOI: 10.4328/ACAM.21347 Received: 2022-08-08 Accepted: 2022-09-17 Published Online: 2022-09-21 Printed: 2022-10-01 Ann Clin Anal Med 2022;13(10):1162-1165
Corresponding Author: Nil Irem Ucgun, Department of Ophthalmology, Ankara Sehir Hastanesi, Universiteler Mahallesi 1604. Cadde No: 9, Cankaya, Ankara, 06800, Turkey. E-mail: niliremucgun@yahoo.com.tr P: +90 542 697 69 33 Corresponding Author ORCID ID: https://orcid.org/0000-0002-2665-3355
Aim: In this study, we aimed to examine the relationship between diabetic retinopathy and liver enzyme activities in patients with type 2 diabetes mellitus.
Material and Methods: Thirty-eight eyes with proliferative diabetic retinopathy were included in our study. Twenty-five eyes with idiopathic epiretinal membrane were included in the control group. There was no difference between the two groups in terms of age and gender. Undiluted vitreous samples (0.1 ml) of all patients were collected at the beginning of vitreoretinal surgery and stored at -80°C until analysis. Vitreous and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma glutamyl transpeptidase (GGT) levels of all patients were analyzed. Serum glucose, HbA1C, glomerular filtration rate (GFR) levels were also analyzed.
Results: Serum glucose and HbA1c levels were higher in the diabetic patient group (p<0.001). Serum GFR values were lower in the diabetic patient group (p<0.005). Vitreous AST levels were higher in the diabetic patient group (p=0.037). However, serum AST, ALT, ALP and GGT levels were not different between the two groups (p>0.05). There was a positive correlation between serum AST and vitreous AST levels (p=0.01). Serum GFR levels were also correlated with serum ALT levels (p= 0.034).
Discussion: Although serum levels of liver enzyme activities are within normal limits in patients with diabetes mellitus, an increase in vitreous AST levels may occur. AST may be an indicator of retinal damage in diabetic retinopathy.
Keywords: Diabetic Retinopathy, Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Gamma-Glutamyl Transpeptidase
Introduction
Hyperglycemia in Diabetes Mellitus plays an important role in the pathogenesis of retinal microvascular damage. Many metabolic pathways have been implicated in vascular damage caused by hyperglycemia. Dilatation of retinal blood vessels and blood flow changes occurs in the early stages due to hyperglycemia. Pericyte loss develops secondary to pericyte apoptosis due to high glucose levels in later stages. Diabetic retinopathy is an important microangiopathic complication of diabetes mellitus [1]. However, diabetic microvascular pathologies can affect all organs and tissues in the body, such as kidney and liver.
Diabetic microangiopathy of the liver is also one of the common pathologies in diabetic individuals. Coexistence of diabetes mellitus and liver dysfunction has been reported. Hepatomegaly and increased activity in liver enzymes may occur as a result of hepatocellular glycogen accumulation. However, there are limited studies examining the role of liver dysfunction in the pathogenesis of diabetic retinopathy [2,3]. Non-alcoholic fatty liver disease (NAFLD) describes a state of fat accumulation in the liver irrelevant to excessive alcohol consumption or other causes of secondary hepatic steatosis. Obesity, diabetes and insulin resistance are often present in the etiology of NAFLD. NAFLD is present in 75% of individuals with type 2 diabetes mellitus (T2DM). It has been reported that serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT) are significantly increased in diabetic patients with liver dysfunction secondary to diabetes mellitus [4-6].
In this study, we aimed to examine the relationship between diabetic retinopathy and liver enzyme activities in patients with type 2 diabetes mellitus, who do not have hepatobiliary disease.
Material and Methods
Thirty-eight eyes of 38 patients with Type 2 Diabetes Mellitus who were operated for complications of proliferative diabetic retinopathy were included in our study. Twenty-five eyes of 25 patients who were non-diabetic and operated for idiopathic epiretinal membrane were included in the control group.
Undiluted vitreous fluid samples (0.1 ml) were obtained from 25 non-diabetic eyes with idiopathic epiretinal membrane and 38 proliferative diabetic retinopathy eyes at the beginning of the pars plana vitrectomy. All vitrectomies were performed by one author (NIU). Samples were stored at -80°C until analysis.
The blood samples were taken after overnight fasting. Samples are centrifuged at 3000 rpm and stored at -20°C until analysis time.
Biochemical variables including ALT, AST, ALP, GGT and glucose were analyzed photometrically on the Siemens Advia 1800 device (Siemens Healthcare, Erlangen, Germany). HbA1c is measured with capillary electrophoresis method (Sebia Capillarys 2 Flex Piercing). Glomerular filtration rate (GFR) was estimated according to the CKD-EPI formula.
Patients with the following conditions were excluded: a history of ocular trauma, intraocular surgery, ocular inflammatory diseases, glaucoma, alcohol consumption, viral hepatitis or malignancies. All participants in our study were tested for hepatitis B and hepatitis C, and individuals with positive tests were excluded from the study.
Written informed consent was obtained from all patients. This study was performed in accordance with the Declaration of Helsinki, and the Ankara City Hospital Ethics Committee approved the protocol for the study (E1-22-2614).
Statistical analysis
Descriptive statistics were calculated using SPSS version 22 (Statistical Package for the Social Sciences, Chicago, IL, USA). Coherence to the normal distribution analysis was made by using the Kolmogorov-Smirnov test. Variables with non-normal variables were presented as median (min-max). The Mann-Whitney U test was used to find the difference of the patient group from the control group. Spearman’s correlation was used to find the correlation among the parameters. All results were accepted statistically significant at p<0.05.
Results
There was no difference between the two groups in terms of age and gender.
Patient and control group parameters are available in Table 1. Serum glucose and HbA1c parameters were higher in the diabetic patient group. GFR values were lower in the diabetic patient group. Vitreous AST levels were higher in the diabetic patient group (Figure 1). However, there was no difference between the 2 groups in terms of serum AST, ALT, ALP and GGT levels.
A positive correlation was found between serum AST and ALT levels (p=0.000). There was a positive correlation between serum AST and vitreous AST levels (p=0.01). Serum ALP levels were correlated with vitreous GGT values (p=0.03). Serum GGT levels correlated with serum ALT (p=0.047) and ALP (p=0.011) levels. Serum GFR (p=0.000) and ALT (p=0.003) levels were negatively correlated with age. Serum GFR levels were correlated with glucose (p=0.00) and HbA1c (p= 0.008). Serum GFR levels were also correlated with serum ALT levels (p= 0.034).
Discussion
ALT, AST, ALP and GGT are commonly used diagnostic tests to evaluate liver function. Complications of diabetes may include liver dysfunction and may cause other pathologies. The effect of liver dysfunction in the pathogenesis of diabetic complications should not be underestimated.
The expression of ALP in the neurosensory retina and optic nerve head (especially choriocapillaris, small blood vessels, capillaries and pia mater) can be considered an important and hitherto unrecognized mechanism controlling blood flow. The presence of ALP in surgically excised pathological neofibrovascular tissues in eyes with proliferative diabetic retinopathy suggests that it may be effective in etiopathogenesis [7]. However, in our study, we found that serum and vitreous ALP levels were not different in diabetic patients and control groups.
GGT is an important enzyme in glutathione metabolism, which is an essential cellular antioxidant. Glutathione metabolism has effects on oxidative stress and lipid deposition in the retina. Increased levels of GGT were observed in diabetic patients [8]. Divya et al. found that the serum GGT concentration were significantly elevated in diabetic patients with retinopathy compared to the patients without retinopathy. They reported that high GGT levels may be a marker for diabetic retinopathy [9]. Arkkila et al. reported that serum GGT levels increased depending on the diabetic retinopathy stage. However, they did not detect any difference in ALT and ALP levels [3].
Mainali et. al. also reported high levels of serum aminotransferases in patients with diabetic retinopathy [10]. According to Atli et al. they did not detect a difference in serum ALT levels, but they reported that AST levels were lower in patients with proliferative diabetic retinopathy [11].
Itoh et al. reported that serum AST levels were lower in PDRP patients than in NPDR patients. They also found a negative correlation between vitreous VEGF levels and serum AST levels [12].
Osuna et al. examined the ALT, AST and GGT levels in the vitreous, and found that ALT levels increased in the vitreous of postmortem patients with heavy alcohol consumption [13].
We found that vitreous AST levels were higher in the diabetic patient group. However, there was no difference between the two groups in terms of serum AST, ALT, ALP and GGT levels.
We also found a correlation between serum GFR levels and serum ALT levels. In this situation, it can be thought that liver and kidney functions may affect each other. Mo et al. reported that ALT and AST levels increased in patients with decreased GFR levels [14]. Screening for retinal vascular changes could help in prognostication and risk-stratification of patients with diabetic kidney disease [15]. There is a relationship between diabetic retinopathy and the severity of diabetic kidney disease. The relationship between microvascular pathologies caused by diabetes in the liver and diabetic retinopathy has not yet been determined. Current studies and our knowledge of the etiopathogenesis of diabetes mellitus show that there may be a relevancy between retinal and liver pathologies.
AST is an enzyme found in the mitochondrial matrix, however, it is tightly associated with mitochondrial membranes. It is reported that AST is located in important tissues such as liver, brain and heart muscle. The increase in serum AST is due to many causes such as liver, brain, and myocardial damage [16,17]. Most of the AST activity in the retina is in the outer plexiform and photoreceptor inner segments. AST activity decreases secondary to retinal ischemia, and atrophy develops in the outer plexiform and photoreceptor inner segments of the retina [18].
Conclusion
The increase in vitreous AST levels without an increase in serum AST level, which we found in our study, suggests AST transition from damaged retinal cells to the vitreous. Further studies are needed to confirm whether AST is an indicator of retinal damage in diabetic retinopathy.
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. Wang W, Lo ACY. Diabetic Retinopathy: Pathophysiology and Treatments. Int J Mol Sci. 2018;19(6):1816.
2. Harrison SA, Brunt EM, Goodman ZD, Di Bisceglie AM. Diabetic hepatosclerosis: diabetic microangiopathy of the liver. Arch Pathol Lab Med. 2006;130(1):27-32.
3. Arkkila PE, Koskinen PJ, Kantola IM, Rönnemaa T, Seppänen E, Viikari JS. Diabetic complications are associated with liver enzyme activities in people with type 1 diabetes. Diabetes Res Clin Pract. 2001;52(2):113-8.
4. Zhang M, Li L, Chen J, Li B, Zhan Y, Zhang C. Presence of diabetic retinopathy is lower in type 2 diabetic patients with non-alcoholic fatty liver disease. Medicine (Baltimore). 2019;98(18):e15362.
5. Zhang X, Ji X, Wang Q, Li JZ. New insight into inter-organ crosstalk contributing to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Protein Cell. 2018;9(2):164-77.
6. Lv WS, Sun RX, Gao YY, Wen JP, Pan RF, Li L, et al. Nonalcoholic fatty liver disease and microvascular complications in type 2 diabetes. World J Gastroenterol. 2013;19(20):3134-42.
7. Zeiner J, Losenkova K, Zuccarini M, Korhonen AM, Lehti K, Kauppinen A, et al. Soluble and membrane-bound adenylate kinase and nucleotidases augment ATP-mediated inflammation in diabetic retinopathy eyes with vitreous hemorrhage. J Mol Med (Berl). 2019;97(3):341-54.
8. Gasecka A, Siwik D, Gajewska M, Jaguszewski MJ, Mazurek T, Filipiak KJ, et al. Early Biomarkers of Neurodegenerative and Neurovascular Disorders in Diabetes. J Clin Med. 2020;9(9):2807.
9. Divya R, Ashok V. Evaluation of serum gamma glutamyl transferase levels as a marker of oxidative stress in type 2 diabetes patients with and without retinopathy. MedPulse Int J Physiol. 2019;9:30–4.
10. Mainali A, Uprety N, Adhikari P, Pathak UN. Serum aminotransferases level in patients with type 2 diabetes mellitus attending a tertiary care center, Kathmandu. Nepal Med Coll J. 2018; 20(4): 178-82.
11. Atlı H, Onalan E, Yakar B, Duzenci D, Dönder E. Predictive value of inflammatory and hematological data in diabetic and non-diabetic retinopathy. Eur Rev Med Pharmacol Sci. 2022;26(1):76-83.
12. Itoh K, Furuhashi M, Ida Y, Ohguro H, Watanabe M, Suzuki S, et al. Detection of significantly high vitreous concentrations of fatty acid-binding protein 4 in patients with proliferative diabetic retinopathy. Sci Rep. 2021;11(1):12382.
13. Osuna E, Pérez-Cárceles MD, Moreno M, Bedate A, Conejero J, Abenza JM, et al. Vitreous humor carbohydrate-deficient transferrin concentrations in the postmortem diagnosis of alcoholism. Forensic Sci Int. 2000;108(3):205-13.
14. Mo Z, Hu H, Du X, Huang Q, Chen P, Lai L, et al. Association of evaluated glomerular filtration rate and incident Diabetes Mellitus: A secondary retrospective analysis based on a Chinese cohort study. Front Med (Lausanne). 2022;8:724582.
15. Gupta M, Rao IR, Nagaraju SP, Bhandary SV, Gupta J, Babu GTC. Diabetic Retinopathy Is a Predictor of Progression of Diabetic Kidney Disease: A Systematic Review and Meta-Analysis. Int J Nephrol. 2022;2022:3922398.
16. Sookoian S, Pirola CJ. Liver enzymes, metabolomics and genome-wide association studies: from systems biology to the personalized medicine. World J Gastroenterol. 2015;21(3):711-25.
17. McKenna MC, Hopkins IB, Lindauer SL, Bamford P. Aspartate aminotransferase in synaptic and nonsynaptic mitochondria: differential effect of compounds that influence transient hetero-enzyme complex (metabolon) formation. Neurochem Int. 2006;48(6-7):629-36.
18. Endo S, Ishiguro S, Tamai M. Possible mechanism for the decrease of mitochondrial aspartate aminotransferase activity in ischemic and hypoxic rat retinas. Biochim Biophys Acta. 1999;1450(3):385-96.
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Cenk Zeki Fikret, Ceylan Bal, Nil Irem Ucgun, Filiz Yildirim. Relationship between diabetic retinopathy and liver enzyme activities. Ann Clin Anal Med 2022;13(10):1162-1165
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Delayed cholecystectomy after cholecystostomy versus early cholecystectomy in acute cholecystitis
Alparslan Şahin, Kemal Arslan
Department of Surgery, University of Health Science, Konya City Hospital, Konya, Turkey
DOI: 10.4328/ACAM.21351 Received: 2022-08-09 Accepted: 2022-09-12 Published Online: 2022-09-19 Printed: 2022-10-01 Ann Clin Anal Med 2022;13(10):1166-1170
Corresponding Author: Alpaslan Sahin, Department of Surgery, University of Health Science, Konya City Hospital, Adana Cevre Yolu, 42020, Konya, Turkey. E-mail: drasahin@gmail.com P: +90 532 136 90 22 F: +90 332 324 18 54 Corresponding Author ORCID ID: https://orcid.org/0000-0001-5707-1203
Aim: In this study we aimed to compare early laparoscopic cholecystectomy and delayed laparoscopic cholecystectomy after percutaneous cholecystostomy for acute cholecystitis with respect to operative characteristics, complications and hospital stay.
Material and Methods: A total of 225 files of patients who admitted to the hospital with acute calculous cholecystitis were retrospectively analyzed. Patients who underwent open cholecystectomy, delayed cholecystectomy, who refused surgical treatment, or there was a lack of data were not included in the study.
Results: Seventy-eight patients who underwent early laparoscopic cholecystectomy [EC group], and 61 patients who underwent delayed laparoscopic cholecystectomy after percutaneous cholecystostomy [DC group] were included in this study. There were no differences between genders or BMI- associated comorbidities between the two groups. The median age was 60 [29-81] in the EC and 75 [56-87] in the DC groups. Age and ASA scores were significantly higher in the DC group [p <0.05]. The operation times in the EC and DC groups were 67.78 [±12.66] and 62.50 [±12.56] minutes, respectively, and were significantly longer in the EC group [p <0.05]. Converted open procedure, another complication and mortality were not different between boths groups. Hospitalization time was longer in the EC group [3.95 ±1.49 vs. 2.16 ±1.28, p<0.001].
Discussion: In the treatment of acute calculous cholecystitis for patients who are not suitable for early surgery, delayed laparoscopic cholecystectomy after percutaneous cholecystectomy does not increase surgical complications, hospital stay, and mortality.
Keywords: Acute Cholecystitis, Percutaneous Cholecystostomy, Laparoscopic Cholecystectomy, Delayed Laparoscopic Cholecystectomy
Introduction
Cholelithiasis, one of the most common diseases of the digestive system, and occurs in 10-20% of adults, and its incidence increases with age [1, 2]. Laparoscopic cholecystectomy [LC] has become the gold standard in the surgical treatment of cholelithiasis due to shorter hospitalization, faster recovery, and postoperative complications than open cholecystectomy.
LC has recently become the first choice in the treatment of acute cholecystitis [3-6]. However, the severity of acute cholecystitis ranges from mild to moderate to severe [7]. According to the Tokyo guidelines, patients with acute cholecystitis can be treated with early cholecystectomy or percutaneous cholecystostomy, with medications and delayed cholecystectomy [8,9]. For patients with stage I and some stage 2 acute cholecystitis, early laparoscopic cholecystectomy may be the most appropriate treatment. Percutaneous cholecystostomy may be appropriate for patients with Stage II or III acute cholecystitis if surgery is at risk due to comorbidity and advanced age [10-14]. The cholecystostomy tube can be removed in about four weeks. Elective laparoscopic cholecystectomy can be planned in about 6 to 8 weeks [15].
There are limited data in the literature regarding the perioperative outcomes of delayed laparoscopic cholecystectomy after percutaneous cholecystostomy for acute cholecystitis. The purpose of the present study was to compare delayed laparoscopic cholecystectomy after percutaneous cholecystostomy versus early laparoscopic cholecystectomy in Acute Cholecystitis.
Material and Methods
The study was conducted in the Department of General Surgery of a tertiary reference hospital. University of Health Sciences Hamidiye Scientific Research Ethics Committee approved the study protocol [number 17/2, dated July 01, 2022]. Written informed consent was obtained from all participants. This study complies with the 1964 Declaration of Helsinki and its subsequent amendments and ethical standards.Between January 2012 and December 2017, the data of 225 patients hospitalized with a diagnosis of acute calculous cholecystitis were retrospectively analyzed.
The following TG13 criteria were used for the diagnosis of acute cholecystitis.
A. Local signs of inflammation etc.
1. Murphy’s sign, 2. RUQ mass / pain / tenderness
B. Systemic symptoms of inflammation etc.
1. Fever, 2. Elevated CRP, 3.Raised WBC count
C. Imaging findings
The criteria for imaging findings characteristic of acute cholecystitis:
Suspected diagnosis: One item in A + one item in B
Definite diagnosis: One piece in A + one item in B + C
Acute calculous cholecystitis was staged according to ASA scores and TG13 criteria, and the treatment strategy was determined [9]. Patients who decided to have laparoscopic cholecystectomy were operated on within the first 72 hours. The Tokyo severity criteria guidelines for acute cholecystitis are presented in Table 1.
Abdominal ultrasonography, complete blood count, prothrombin and partial thromboplastin times, the international normalized ratio [INR], and platelet counts were determined for patients undergoing percutaneous cholecystostomy due to advanced ASA score or stage III acute cholecystitis. Those with INR <1.5 and platelet count >100.000/ml were considered suitable for percutaneous treatment. All percutaneous treatment procedures were performed under local anesthesia with USG and fluoroscopy.
Percutaneous cholecystostomy patients were discharged from the hospital after their septic condition improved. Percutaneous cholangiography was performed at the end of 3-4 weeks to check whether the cystic duct was intact. Percutaneous drains of the patients with the entire cystic duct were removed. The draining of the patients whose cystic duct was not intact in the cholangiography was left in place for 6-8 weeks and was removed during the operation. Percutaneous cholecystostomy patients were re-consulted by anesthesiologists at the end of the 6-8th week, and a laparoscopic cholecystectomy was performed.
Demographic characteristics of the patients, acute cholecystitis levels according to TG13 severity scores, ASA scores, treatment methods, length of hospital stay, duration of surgery, intraoperative complications, additional surgical interventions, morbidity and mortality were recorded.
Data Entry and Statistical Analysis
The Kolmogorov-Smirnov normality test was performed to select statistical methods. If no normality assumption occurred in any of the groups, nonparametric test methods were preferred. The Mann-Whitney U test was used to compare the variables obtained from the measurements between the two groups, and chi-square and Fisher exact tests were used to compare the categorical variables.
Group comparison results related to the research and other demographic features were presented through a ratio of qualitative variables and the averages of quantitative variables. These quantities were interpreted with p-values, which are expressions of statistical significance. The Social Sciences Statistical Package [SPSS], version 17.0 [SPSS Inc., Chicago, IL, United States of America] program was used to conduct statistical analysis of the research, and p <0.05 was accepted as the statistical significance limit.
Results
Between January 2012 and December 2017, a total of 225 patients with acute calculous cholecystitis, according to TG13 criteria, were hospitalized. The study did not include 43 patients who underwent delayed laparoscopic cholecystectomy, seven patients who underwent open cholecystectomy, 12 patients whose files were missing, 14 patients who refused surgical treatment, and 10 patients for other reasons [feasibility, 61.8%] [139 of 225]. Thus, 78 patients who underwent early laparoscopic cholecystectomy [EC group], and 61 patients who underwent delayed laparoscopic cholecystectomy after percutaneous cholecystostomy [DC group] were included in this study. The study flow diagram is shown in Figure 1.
Of the 139 patients included in the study, 77 [55.4%] were women, and 62 [44.6%] were men. There was no difference between the two groups [p> 0.05] in terms of gender, BMI, and associated comorbidities. The median age was 60 [29-81] years in the EC group and 75 [56-87] years in the DC group. Age and ASA scores were significantly higher in the DC group [p <0.05]. Demographic data are shown in Table 2.
The operation time in the EC and DC groups were 67.78 [±12.66] and 62.50 [±12.56] minutes, respectively, and was significantly longer in the EC group [p <0.05]. In the EC group, eight [10.3%] laparoscopic procedures were initiated but converted to the open method due to difficult dissection. Six [7.7%] patients underwent cholecystectomy, and 2 [2.6%] had a partial cholecystectomy. In the postoperative period, one [1.3%] patient was detected to have the Bismuth Type II injury; a hepaticojejunostomy was performed and discharged without any problems. Postoperative bleeding occurred in two [2.6%] patients, and superficial surgical area infection developed in 3 [3.8%] patients and they were treated conservatively. Two [2.6%] patients died in the early postoperative period due to comorbid diseases. In the DC group, 3 [4.9%] patients’ laparoscopic procedures were initiated but converted to the open method due to a difficult dissection. Three [4.9%] patients developed bronchopneumonia, and one [1.6%] patient developed deep vein thrombosis and recovered with medical treatment in the postoperative period. Five [8.2%] patients died due to associated comorbidities. There was no statistically significant difference in operations that were converted to the open procedure, complications, and mortality between either of the groups, except bronchopneumonia [p> 0.05]. Bronchopneumonia was detected significantly more in the percutaneous cholecystectomy group. Hospitalization time was longer in the EC group [3.95 ±1.49 vs. 2.16 ±1.28, p<0.001]. Surgical features and complications are shown in Table 3.
Discussion
The standard treatment of symptomatic cholelithiasis is laparoscopic cholecystectomy [2]. Laparoscopic cholecystectomy is also used in the treatment of acute calculous cholecystitis. Recent studies have shown that the operation can be performed with equivalent or improved morbidity, mortality, and length of stay, as well as a similar conversion rate to open cholecystectomy [3, 5, 16]. However, concerns remain among surgeons about catastrophic complications and biliary system injury. It has been reported that partial cholecystectomy can be performed in acute cholecystitis since severe inflammation does not allow safe dissection of hilar structures. However, this procedure is not always reliable, and publications show that acute cholecystitis develops again [17]. For patients who are not medically suitable for surgery due to the severity of their illness, advanced age, or medical comorbidities, biliary decompression is achieved by percutaneous cholecystostomy and is planned for operation after stabilization. Laparoscopic cholecystectomy, assuming that the medical suitability is improved, can be scheduled 6-8 weeks after percutaneous cholecystostomy [18]. Percutaneous cholecystostomy is a life-saving procedure in severe acute cholecystitis. However, the definitive treatment of these patients is laparoscopic cholecystectomy and concerns among surgeons continue with regard to delayed laparoscopic cholecystectomy after percutaneous cholecystostomy, because of the difficulty of dissection and, the risk of injury in the biliary tract.
In this study, we investigated the effect of performing percutaneous cholecystostomy for acute cholecystitis on the operative outcomes of delayed laparoscopic cholecystectomy. The present study shows that early laparoscopic cholecystectomy and percutaneous cholecystostomy were able to improve cholecystitis sepsis in all of the patients quickly, and the mortality rates did not show any difference. The patients treated with percutaneous cholecystostomy were older than patients in the early laparoscopic cholecystectomy group. This is an expected outcome, and similar results were also presented by other studies [18, 19]. Furthermore, in this study, patients with percutaneous cholecystostomy had higher ASA scores than patients who underwent early laparoscopic cholecystectomy, which was not a surprising result. This is because, according to the criteria of TG13, it recommends avoiding laparoscopic cholecystectomy and minor interventions, such as percutaneous cholecystostomy, for patients with a high ASA score [10]. Other studies have shown that patients undergoing early cholecystostomy have a higher ASA score than patients undergoing percutaneous cholecystostomy [12, 20, 21].
In our study, the duration of surgery was shorter in patients who underwent laparoscopic cholecystectomy after percutaneous cholecystectomy. Our results are similar to other studies, where the operation time was also shorter among patients that underwent delayed laparoscopic cholecystectomy after percutaneous cholecystostomy [22, 23]. Difficulty in laparoscopic cholecystectomy is due to inflammation and edema of the dissection in Calot’s triangle dissection. The dissection becomes more comfortable with reduced inflammation and edema in this area within 6-8 weeks following a percutaneous cholecystostomy. In early laparoscopic cholecystectomy, we evaluated the longer operation time as being a difficult dissection due to inflammation in the acute phase.
In our study, laparoscopic to open conversion rates for patients in the EC group were higher than in the DC group [10.3% vs. 4.9%]. However, this was not statistically significant [p =0.68]. These results show that the laparoscopic cholecystectomies planned after percutaneous cholecystostomy do not increase the risk of conversion to an open procedure. Kim et al. reported that patients’ early laparoscopic cholecystectomy had a higher conversion frequency rate to open surgery was associated with delayed cholecystectomy after percutaneous cholecystostomy [22].
A study by Sippey et al. found that 7242 patients who underwent emergency cholecystectomy for acute cholecystitis who were converted to open procedure had advanced age and higher BMIs as risk factors [24]. In their prospective and multicentric study, Navez and colleagues were able to start the operations in 1015 of 1089 [93.2%] acute cholecystitis patients as a laparoscopic procedure, and out of them, 116 patients [11.4%] who underwent laparoscopic surgery required conversion to an open method. However, in other studies, the rate of conversion to an open procedure was higher in patients undergoing a percutaneous cholecystostomy [25]. Our research assumed that the reason for this was surgical intervention after waiting at least six weeks, and inflammation around the gallbladder decreased.
Departmental instructions state that the delayed period is at least 6-8 weeks, as practiced bymany authors who adopt the prolonged time interval to surgery. The purpose and rationale for percutaneous cholecystostomy are to relieve symptoms and improve acute cholecystitis sepsis with a less invasive method than medicine. This is achieved by reducing gallbladder distension through percutaneous cholecystostomy under local anesthesia. In addition, antibiotics and fluid therapy are applied and oral nutrition is stopped. Thus, time is obtained to optimize and prepare critical patients with acute cholecystitis for elective surgery instead of emergency surgery who are not otherwise suitable for surgery. The treatment strategy for patients with acute cholecystitis may differ in various centers, where the most common application is that patients with a comorbid disease and stage II acute cholecystitis and patients with stage III acute cholecystitis, according to TG13 criteria, are not suitable for surgery. Percutaneous cholecystostomy can be applied o prepare for surgery in the treatment of these patients.
Frequently performed with ultrasound guidance under local anesthesia with some sedation, percutaneous cholecystostomy can be a temporizing measure by draining the infected bile—percutaneous drainage results in an improvement in symptoms and physiology. In patients with cholecystostomy tubes, when fluoroscopy shows a patent cystic duct, the cholecystostomy tube can be removed after 3 to 4 weeks. Thus, cholecystectomy is determined by the patient’s ability to tolerate surgical intervention and allow a delayed laparoscopic cholecystectomy 6 to 8 weeks after medical optimization.
In our study, patients who underwent early laparoscopic cholecystectomy due to acute cholecystitis were found to have significantly longer hospitalization [3.95 ±1.49 vs. 2.16 ±1.28 days]. A survey conducted by El-Gendi et al. found hospitalization times to be five times shorter in delayed laparoscopic cholecystectomy after percutaneous cholecystostomy, compared to early cholecystectomy for acute cholecystitis [10]. This period should be considered as a very different entity when viewed socially. As these patients were hospitalized twice, both in our study and in other studies, this seems to be a contradictory determination. Our hypothesis is whether the surgeon will be apprehensive of the surgery to be performed on patients who have previously undergone percutaneous cholecystostomy. It is a matter of whether it is more difficult compared to early surgery. Our study showed that the laparoscopic cholecystectomy performed after percutaneous cholecystostomy for acute calculous cholecystitis is not a difficult procedure with the duration of surgery, the rate of conversion to open surgery, and the length of hospital stay.
The limitations of our study are that it is a retrospective study and is performed only in a single center. However, it should be appreciated that continuous research will not be straightforward due to the nature of the study subject.
Conclusion
In the treatment of acute calculous cholecystitis for patients who are not suitable for early surgery, delayed laparoscopic cholecystectomy after percutaneous cholecystectomy, is an effective treatment method.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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7. Hirota M, Takada T, Kawarada Y, Nimura Y, Miura F, Hirata K, et al. Diagnostic criteria and severity assessment of acute cholecystitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg. 2007; 14(1):78-82.
8. Strasberg SM. Clinical practice. Acute calculous cholecystitis [published correction appears in N Engl J Med. 2008;359(3):325. N Engl J Med. 2008;358(26):2804-11.
9. Yamashita Y, Takada T, Strasberg SM, Pitt HA, Gouma DJ, Garden OJ, et al. TG13 surgical management of acute cholecystitis. Tokyo Guideline Revision Committee. J Hepatobiliary Pancreat Sci. 2013; 20(1): 89-96.
10. El-Gendi A, El-Shafei M, Emara D. Emergency Versus Delayed Cholecystectomy After Percutaneous Transhepatic Gallbladder Drainage in Grade II Acute Cholecystitis Patients. J Gastrointest Surg. 2017; 21(2): 284-93
11. Alvino DML, Fong ZV, McCarthy CJ, Velmahos G, Lillemoe KD, Mueller PR, et al. Long-Term Outcomes Following Percutaneous Cholecystostomy Tube Placement for Treatment of Acute Calculous Cholecystitis. J Gastrointest Surg. 2017; 21(5):761-9.
12. Pavurala RB, Li D, Porter K, Mansfield SA, Conwell DL, Krishna SG. Percutaneous cholecystostomy for high-risk patients with acute cholecystitis. Surg Endosc. 2019; 33 (10): 3396-403.
13. Sanjay P, Mittapalli D, Marioud A, White RD, Ram R, Alijani A. Clinical outcomes of a percutaneous cholecystostomy for acute cholecystitis: a multicentre analysis. HPB (Oxford). 2013;15(7):511-16.
14. Zeren S, Bayhan Z, Koçak C, Kesici U, Korkmaz M, Ekici MF, et al. Bridge treatment for early cholecystectomy in geriatric patients with acute cholecystitis: Percutaneous cholecystostomy. Ulus Travma Acil Cerrahi Derg. 2017; 23(6):501-6.
15. Jang WS, Lim JU, Joo KR, Cha JM, Shin HP, Joo SH. Outcome of conservative percutaneous cholecystostomy in high-risk patients with acute cholecystitis and risk factors leading to surgery. Surg Endosc. 2015;29(8):2359-64.
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Alparslan Şahin, Kemal Arslan. Delayed cholecystectomy after cholecystostomy versus early cholecystectomy in acute cholecystitis. Ann Clin Anal Med 2022;13(10):1166-1170
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Efficacy of ultrasound-guided percutaneous drainage in the treatment of psoas abscess
Alperen Kayalı 1, Selen Beyazıt 1, Fatma Öztürk Keleş 1, Tayibe Bal 2, Ayça Seyfettin 3, Mustafa Uğur 4
1 Department of Radiology, Hatay Mustafa Kemal University, School of Medicine, Hatay, 2 Department of Infection Disease and Clinical Microbiology, Hatay Mustafa Kemal University, School of Medicine, Hatay, 3 Department of Radiology, Osmaniye State Hospital, Osmaniye, 4 Department of General Surgery, School of Medicine, Hatay Mustafa Kemal University, Hatay, Turkey
DOI: 10.4328/ACAM.21364 Received: 2022-08-20 Accepted: 2022-09-20 Published Online: 2022-09-25 Printed: 2022-10-01 Ann Clin Anal Med 2022;13(10):1171-1175
Corresponding Author: Alperen Kayalı, Department of Radiology, School of Medicine, Hatay Mustafa Kemal University, Hatay, 3140, Turkey. E-mail: alperenkayali@gmail.com P: +90 0326 229 10 00 / +90 0533 251 97 65 F: +90 0326 221 33 20 Corresponding Author ORCID ID: https://orcid.org/0000-0002-9862-8925
Aim: In this study, we aimed to evaluate the efficacy of ultrasound-guided percutaneous drainage applied to cases determined with psoas abscess, and to investigate predisposing factors and micro-organisms causing the disease.
Material and Methods: Twenty-eight patients were examined, including 15 males and 13 females, aged 22-87 years, who underwent ultrasound-guided percutaneous drainage. Predisposing factors for the development of psoas abscess, the need for an additional surgical procedure after percutaneous abscess drainage, length of stay in hospital after the procedure, complications, and agent micro-organisms were evaluated. The efficacy of percutaneous drainage in the treatment was investigated.
Results: The most common agents were determined to be Staphylococcus aereus, Escherichia coli, and Mycobacterium tuberculosis. Primary psoas abscess was determined in 6 (21.4%) patients and secondary psoas abscess in 22 patients. In cases with secondary psoas abscess, skeletal origin predisposing factors (spondylodiscitis, history of abdominal or vertebral surgery) were seen to most often play a role in the etiology. In 20 of the 22 (78.5%) patients with secondary psoas abscess, effective treatment was applied with antibiotherapy and percutaneous drainage. The mortality rate was 10.7%.
Discussion: Low morbidity and mortality rates are the greatest advantages of percutaneous drainage. Although CT has emerged as a better diagnostic method for psoas abscess, ultrasound-guided percutaneous drainage has the advantages of easy availability, low cost, and it does not contain radiation. Ultrasound-guided percutaneous drainage is an effective and reliable method in the treatment of psoas abscess.
Keywords: Percutaneous Drainage, Abscess, Psoas Abscess, Tuberculous Abscess
Introduction
Psoas abscess is a relatively uncommon pathology. Although there are no clear data about the incidence, studies have reported a prevalence of 1-10/100,000 per year [1, 2]. Psoas abscess is classified as primary when it occurs with hematogenous spread, and secondary if the infection is spread to adjacent surrounding tissues. The etiology shows variability according to whether the disease is primary or secondary and geographic location. [3]. Back pain and fever are among the most common symptoms [1]. Although back pain, fever, and restricted movement form a classic triad, it is seen in very few patients [4].
Computed tomography (CT) is important in diagnosis and is accepted as the basic imaging method for diagnosis as it is helpful in revealing the underlying cause (inflammatory bowel disease, diverticulitis), especially in acute patients [5]. Magnetic resonance imaging (MRI) plays a major role in showing the spread of infection to the spinal canal and bone marrow [6, 7].
Recent studies have reported mortality rates of2.3%-12% [1, 4]. There are differences in mortality data because of the relative rarity of the disease, the variability of factors playing a role in the etiology, and the generally low number of patients in studies in the literature.
Antimicrobial treatment is usually combined with percutaneous or surgical drainage in the treatment of the disease [4]. Antibiotic treatment alone is insufficient [3]. Compared to surgical drainage, percutaneous drainage has the advantages of a shorter stay in hospital, fewer complications, and lower mortality rates, so it has become the currently preferred treatment method [8].
The aim of this study was to evaluate the efficacy of the percutaneous drainage procedure applied under ultrasound guidance to patients determined with psoas abscess and to investigate the predisposing factors and micro-organisms causing the disease.
Material and Methods
After ethical approval this retrospective, observational study included 28 patients determined with psoas abscess who were treated with ultrasound-guided percutaneous drainage in the interventional radiology unit between 2016 and 2021. Informed consent was not obtained because of the retrospective design of the study. The patient data were obtained retrospectively from the medical records in the hospital information system, in respect of demographic characteristics, predisposing factors for the development of psoas abscess, the need for the additional surgical procedure after percutaneous abscess drainage, length of stay in hospital after the procedure, complications, and agent micro-organisms.
The drainage procedure was applied to all the patients in the interventional radiology unit under local anaesthetic and ultrasound guidance (HI-VISION Avius, Hitachi Aloka Medical, Tokyo, Japan). Under ultrasound guidance, the abscess pouch was entered with an 18 gauge needle and a 10cc sample was taken for microbiological examination. Then, an 8-12 Fr pigtail catheter (Skater, Argon Medical Devices, USA) was placed with the help of a 0.035-inch guidewire. The size of the pigtail catheter was selected according to the viscosity of the abscess material. After appropriate placement of the pigtail catheter, the abscess content was aspirated. It was then irrigated with saline and left for free drainage until the color of the content became clear.
In the follow-up of the patients, the drain was irrigated with saline several times a day and daily monitoring was applied. When the daily drainage amount fell to <10cc, and no residual collection was observed in the psoas on follow-up images, the pigtail catheter was removed. At 7-10 days after removal of the catheter, patients were checked with imaging methods in respect of recurrence (Figure 1).
Results
Twenty-eight patients were examined, including 15 males and 13 females with a mean age of 53.2±20.0 years (range, 22-87 years), who underwent ultrasound-guided percutaneous drainage of a psoas abscess. The epidemiological characteristics of the cases, the risk factors that could have played a role in the development of psoas abscess, and the abscess localization are shown in Table 1.
Unilateral abscess was determined in 23 cases (left psoas in 13 patients, right psoas in 10 patients) and bilateral psoas abscess was present in 5 cases (Table 1). Abscesses were evaluated as primary psoas abscesses in 6 (21.4%) patients and secondary psoas abscesses in 22 (78.6%) patients. In the etiology of the cases with secondary psoas abscess, predisposing factors of skeletal origin most often played a role (12 patients, 42.8%). Vertebral osteomyelitis/discitis in 7 patients (39.2%), vertebral surgery history in 4 patients (14.2%) and sacroiliitis in 1 patient (3.5%) were observed as skeletal predisposing factors. Other predisposing factors of secondary psoas abscess included gastrointestinal causes in 5 patients (17.8%) and genito-urinary causes in 2 patients (7.1%). In the cultures of the samples taken from the patients, the most frequently isolated agents were determined to be Escherichia coli in 6 patients (30%), Mycobacterium tuberculosis in 4 patients (20%), and Klebsiella species in 5 patients (25%). No production was determined in the cultures of 10 patients.
Of the 28 patients with catheter placement, surgery was applied to 7, of which only 3 were operated on for abscess treatment (Table 2). Of the total patients, mortality developed in 5, 2 of which had undergone surgery after percutaneous drainage (Table 3). Psoas abscess was treated effectively with antibiotherapy and percutaneous drainage in 22 of 28 patients (78.5%). The mortality rate was 10.7%. The mean duration of drainage was 17.14 days (range, 3-37 days) and the mean length of stay in the hospital was 16.9 days (range, 2-56 days).
The catheter became dislodged in 3 patients, so the position was revised. Other than these patients, no major complication associated with the procedure was observed in any case.
Discussion
Psoas abscess generally manifests with non-specific symptoms such as pain, fever, and restricted movement [1]. Despite the application of the necessary treatments, it is a disease which can have a mortal course. There are no definitive data about mortality rates but it has been reported as between 2.3% and 12% in recent literature [1, 4]. This wide range of differences in mortality rates can be attributed to the relative rarity of the disease, the variability of factors playing a role in the etiology, and the generally low number of patients in studies in the literature. In the current study, the mortality rate was found to be 10.7%. Mortality risk factors include high creatinine level, advanced age, cardiovascular disease, bacteremia, and E.coli production in culture [9, 10]. Consistent with the literature, 3 of the exitus patients in the current study had a significant elevation in serum creatine levels followed by acute renal failure.
It has been said that generally, approximately 30% of cases comprise primary psoas abscess [11]. Staphylococcus aureus (S. aureus) is the most common agent in primary psoas abscess [1]. In the current study, 21.4% of the cases were patients with primary psoas abscess. The agent of secondary psoas abscess can show variability according to geographical location and underlying predisposing factors. If there is an abdominal pathology as an underlying factor, such as inflammatory bowel disease, E.coli is most often seen as the agent [9, 12]. In countries where tuberculosis is frequently seen, Mycobacterium tuberculosis has been reported to be the most common agent [13]. Moreover, several studies in recent years have reported bone origin infections as the cause of secondary psoas abscess and S. aureus as the most responsible associated agent [1, 3, 9]. In 9 of the patients with secondary PA in the current study, there was no culture production, and in the rest, the most common agents were E.coli, Mycobacterium tuberculosis, and Klebsiella species.
Percutaneous drainage or surgical drainage methods are used together with antibiotherapy in PA treatment. The place of antibiotherapy alone is a matter of debate, especially in large abscesses. In a previous study it was reported that of 13 patients receiving antibiotic treatment, 11 required a second treatment [2].
The application of percutaneous drainage under imaging guidance, which is a less invasive method, has currently increasing widespread use, and a study in 2015 reported that percutaneous drainage was applied to approximately 82% of all intra-abdominal abscesses [14]. In a study [15] in which 260 patients were applied with percutaneous drainage and 240 with open surgery for intra-abdominal abscess, the mortality rates of the open surgery cases were found to be higher (14.6% vs. 4.2%) and the length of stay in hospital was longer (28.1 vs. 13.5 days). In the same study, the success rates were reported as 69% for percutaneous drainage and 62% for open surgery [15]. In another study that compared the efficacy of open surgery and percutaneous drainage for psoas abscess, the mortality rates were reported as 3% for percutaneous drainage and 22% for open surgery [2]. Percutaneous drainage methods have started to be be the first choice in the treatment of psoas abscess [8]. A success rate of 82.7% has been reported in another study that investigated the efficacy of percutaneous drainage [16]. In the current study, the success rate of percutaneous drainage in the treatment of psoas abscess was 78.5%, which supports the above-mentioned data.
Percutaneous drainage is generally applied under CT or ultrasound guidance. The majority of the studies in the literature have reported CT -guided percutaneous drainage in the treatment of psoas abscess, and those studies have emphasized the high success rate of the treatment, low recurrence rates and short length of hospital stay [17,18]. While a broader anatomic dominance can be achieved with a CT-guided procedure, there are the disadvantages of high cost and the content of ionising radiation. In the current study, the procedure was applied under ultrasound guidance to all the patients, and just as under CT guidance, a low complication rate and high success rate were obtained.
Conclusion
In conclusion, the results of this study demonstrate that ultrasound guided percutaneous drainage is an effective and reliable method in the treatment of psoas abscess. Low morbidity and mortality rates are the greatest advantages of percutaneous drainage. Although CT is known to be a better diagnostic method for psoas abscess, ultrasound guided percutaneous drainage has the advantages of easy availability, low cost, and does not contain radiation.
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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Alperen Kayalı, Selen Beyazıt, Fatma Öztürk Keleş, Tayibe Bal, Ayça Seyfettin, Mustafa Uğur. Efficacy of ultrasound-guided percutaneous drainage in the treatment of psoas abscess. Ann Clin Anal Med 2022;13(10):1171-1175
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Frequency of cervical hpv in women with COVID-19 infection
Yunus Emre Purut 1, Fedi Ercan 2, Mehmet Murat Isikalan 3, Gulchin Babayeva 4
1 Department of Obstetrics and Gynecology, Van Training and Research Hospital, Van, 2 Department of Obstetrics and Gynecology, School of Medicine, Adnan Menderes University, School of Medicine, Aydin, 3 Department of Obstetrics and Gynecology, School of Medicine, Adiyaman University, School of Medicine, Adiyaman, 4 Department of Obstetrics and Gynecology, Private Hospital at Gaziosmanpasa, Istanbul, Turkey
DOI: 10.4328/ACAM.21366 Received: 2022-08-22 Accepted: 2022-09-24 Published Online: 2022-09-28 Printed: 2022-10-01 Ann Clin Anal Med 2022;13(10):1176-1179
Corresponding Author: Fedi Ercan, Department of Obstetrics and Gynecology, Adnan Menderes University, School of Medicine, Aydin, Turkey. E-mail: fediercan@gmail.com P: +90 505 895 53 09 Corresponding Author ORCID ID: https://orcid.org/0000 0003 2175 5405
Aim: At the beginning of 2020, the Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus emerged in China. While there are several studies currently being performed to investigate the multi-organ symptoms of COVID-19 infection, significant attention has yet to be paid to its presence in the cervix. This article aims to establish a medical hypothesis of its association with HPV infection as well as the potential impact of COVID-19 infection on the female genital tract.
Material and Methods: This prospective cohort study was performed in … Research and Training Hospital between January 1 and July 30, 2020. Cervicovaginal samples (co-test) were taken at the gynecological oncology unit, and both HPV screening and Pap smear were studied with the liquid-based method. Two groups of patients who were confirmed by PCR test to have had COVID-19 infection in the last 6 months and patients who did not have a history of infection were included in the study.
Results: A total of 310 participants were evaluated in the study. Of these participants, 30 (9.7%) were confirmed to have undergone COVID-19 by PCR test. There was no significant difference between the total positive smear results in both groups. However, the rate of HPV-16 positive patients was significantly higher in the COVID-19 group (2.5% vs 10.0%, p=0.027).
Discussion: As a result, COVID-19 infection may increase the frequency of HPV-16. Apart from this, it can be said that this increase is not reflected in the frequency of cervical cytopathology.
Keywords: Cervical Cancer Screening, Co-Test, Coronavirus, COVID-19, HPV, SARS-CoV-2
Introduction
Viral diseases constitute serious public health problems all over the world. In the last eighteen years, worldwide viral outbreaks have been reported, such as the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) in 2002 and the Middle East Respiratory Syndrome Coronavirus (MERSCoV) in 2012. At the beginning of 2020, the SARS-CoV-2 virus and the Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 emerged in China. This clinical condition was officially reported by the World Health Organization on the last day of 2019. However, it was understood that traces of a viral infection were present as of November 2019 and were defined as “pneumonia of unknown etiology” [1, 2]. Although governments around the world have implemented many precautions, the number of cases has increased day by day. Health organizations are coordinating data and issuing recommendations and guidelines to reduce and eliminate the effects of the pandemic worldwide. However, there is still much research to be done on the precise etiopathogenetic mechanisms and the many complications caused by COVID-19 infection.
Although the virus is caught through the upper respiratory tract and causes serious illness in the lower respiratory tract, there is evidence to support its effects on many organs and systems. Differently from the respiratory system, it has been shown that SARS-CoV-2 genetic material is detected in blood and plasma samples and spreads to the hematological system [3, 4]. It has been shown to spread throughout the body by this way and has effects on the kidneys, liver, heart, brain and gastrointestinal system [5-10].
The relationship between COVID-19 infection and the female genital system has not yet been clearly demonstrated. However, some indications are present. In a study investigating the presence of COVID-19 in semen and conducted among 38 men, the presence of SARS-CoV-2 was shown in 15.8% of them [11, 12]. Although the percentage is not relatively high and the physiology of the male reproductive system is different from that of women, a virus predominantly found in the respiratory system appears to affect semen. Therefore, the possibility of its presence in the cervical tissue seems plausible.
HPV creates unique effects on the cervical epithelium, unlike other parts of the female genital tract. The first of these is the trigger effect that may be on carcinogenesis. The cervix is the most clearly known part of the female genital tract system affected by the virus [13].
While there are several studies currently being performed to investigate the multi-organ symptoms of COVID-19 infection, significant attention has yet to be paid to its presence in the cervix. There is a study conducted on 35 patients by Cui et al. In this study, the presence of SARS-CoV-2 in the genital tract was not demonstrated in any of the patients diagnosed with COVID-19. However, this study is dated March 2020. However, after this date, the epidemic spread all over the world, but observational studies involving more patients on this subject have not been published. Except for the presence of this virus in the genital tract of patients with active COVID-19 infection, there has been no literature study on the presence of HPV and subtype analysis in women who have had this infection. HPV genetically has little in common with coronaviruses, but may have common features in terms of transmission process or lifecycle. Moreover, the rate of HPV infection in the cervical epithelium of women with COVID-19 infection and women who do not have this infection is unknown. This may be important given the immunosuppressive effect of HPV. Studies examining the detection of genetic material of SARS-CoV-2 in cervical cytology samples are insufficient. In this study, the frequency of infection with HPV within the scope of the cervical screening program in women who had COVID-19 infection compared to women who did not have this infection, and if related, which subtypes were observed and cervical cytopathological changes were investigated. In case of positivity of one of the high-risk HPV types, patients underwent colposcopy and the results of this pathology were compared among the patient groups. This article aims to establish a medical hypothesis of its association with HPV infection as well as the potential impact of COVID-19 infection on the female genital tract.
Material and Methods
This prospective cohort study was performed in … Research and Training Hospital between January 1 and July 30, 2020. The study protocol was approved by our Ethics Committee (Ethics Committee number 2020-13). The study represents a subgroup of sample collected from patients who applied to our center for co-testing (HPV test with cervicovaginal smear application) within the scope of the routine cervical cancer screening program of the Ministry of Health of the Republic of Turkey. Cervicovaginal samples (co-test) were taken at the Van Research and Training Hospital gynecological oncology unit, and both HPV screening and Pap smear were studied with the liquid-based method. Smear results and HPV results were evaluated by the gynecological oncology unit. In our study, all patients with high-risk HPV positivity underwent colposcopy by the same gynecologist oncologist. During colposcopy, 3% acetic acid was used and an average of 2 cervical biopsies were taken. Each patient was informed before the procedure. After the cervix was treated with 3% acetic acid, the transformation zone was examined with a colposcope. A Tischler punch biopsy sample was taken from abnormally observed areas (such as acetowhite area, coarse punctuation area, mosaic pattern, etc.) and sent to the laboratory on the same day.
Two groups of patients who had confirmed COVID-19 infection by PCR test within the last 6 months and patients who did not have a history of infection were included in the study. Informed consent was obtained from all participants before the study commenced. Women aged 18-65 years, without HPV DNA positivity in cervicovaginal smear examination, without cervical cancer and cervical preinvasive lesion history, who did not receive HPV vaccine and who did not have immunodeficiency were included in the study. Grand multiparous patients were excluded from the study. In the study, the group with COVID-19 infection was made up of women who did not have active COVID-19 infections, who had fully recovered and had completed the quarantine period. Patients who met the inclusion criteria during the study period and patients who agreed to participate in the study were consecutively included in the study.
HPV positivity and HPV subtype were determined by co-test for both groups. In addition, those with negative smear results, Atypical Squamous Cells of Undetermined Significance (ASCUS), Low-Grade Intraepithelial Lesion (LSIL), High-Grade Squamous Intraepithelial Lesion (HSIL) and Atypical Squamous Cells-Cannot Exclude High-Grade Squamous Intraepithelial Lesion (ASC-H) were reported. Colposcopy results were divided into 4 groups as Normal/chronic cervicitis, Cervical Intraepithelial Neoplasia (CIN1), Cervical Intraepithelial Neoplasia (CIN2), and Cervical Intraepithelial Neoplasia (CIN 3).
Statistical analysis
All data collected for statistical analysis were analyzed with the Statistical Package for the Social Sciences, version 23, SPSS Inc., Chicago, IL (SPSS). Age was given as mean ± standard deviation, median (minimum, maximum), while categorical variables were given as numbers (%). When comparing the age variable that matches the normal distribution with the Student T-test, the Chi-square test was used to evaluate the categorical data. The statistical significance level was taken below 0.05.
Results
A total of 310 participants were evaluated in the study. Smoking and the number of pregnancies showed a homogeneous distribution among the groups. Of these participants, 30 (9.7%) were confirmed to have undergone COVID-19 by PCR test. In the control group, there were 280 (90.3%) participants without a history of COVID-19. Age values of the groups showed homogeneous distribution (p=0.363). There was no significant difference between the total positive smear results of both groups.
However, the rate of HPV-16 positive patients was significantly higher in the COVID-19 group (2.5% vs 10.0%, p=0.027). There was no significant difference between the groups in the positivity rates of HPV-18 and other HPV types (Table 1). Colposcopy was performed on all patients with positive high-risk HPV. In the comparison of the pathologies of the groups after colposcopy, no significant difference was found between chronic cervicitis, CIN1, CIN2 and CIN3 (p=0.564) (Table 2).
Discussion
As the virus continues to spread worldwide, it is important to understand the consequences of SARS-CoV-2 infection. SARS-CoV-2 has been previously detected in the throat, anal swabs, urine and tears [12]. However, few reports have been submitted on the isolation of the SARS-CoV-2 virus directly in the female genital tract [14]. In these reports, it was emphasized that the virus could be detected in cervicovaginal secretions and therefore the necessary precautions should be taken in the gynecological examination. It is also suggested that an ulcerated lesion in the vulva and the isolation of SARS-CoV-2 RNA from this lesion may cause ulcerative lesions in the genital tract. It is clear that there is strong evidence pointing to multi-organ involvement of COVID-19. Since its effect has been shown for multiple organs, it would be reasonable to assume its potential effect on the female genital system as well. Although it has not been shown to be found directly in the cervical epithelium, its isolation in the cervicovaginal secretion may be an indirect indicator of this condition. In addition, although it has not been shown to cause a direct lesion in the cervix, the isolation of SARS-CoV-2 RNA in an ulcerated lesion in the vulva suggests that it may potentially cause a macroscopic or microscopic lesion in the cervix [14].
On the other hand, HPV can be considered the most common sexually transmitted infection in terms of prevalence in the general population [15]. Both heterosexual and homosexual HPV transmission is possible through penetrating and even non-penetrating sexual contact. Most infected men and women do not show clinically significant signs or symptoms [16]. The reported frequencies of low- and high-risk HPV subtypes are similar for women. Skin or mucosal microlesions allow infection of normal cells in the basal epithelial layer with HPV.
SARS-CoV-2 isolation from the cervix during the COVID-19 infection has not yet been performed. However, the potential for SARS-CoV-2 to infect the cervical epithelium may also increase the risk of HPV infection. The increase in co-test HPV positivity in patients with COVID-19 infection may confirm this situation. However, in this study, the frequency of positive HPV was not different in women who had COVID-19 infection compared to women who did not. On the other hand, when HPV subtype analysis was performed, the frequency of HPV-16 was found to be significantly higher in women who had COVID-19 before. This shows that the frequency of cervical HPV-16 positivity in a woman who has had a previous COVID-19 infection is increased compared to other HPV subtypes.
However, in order to be able to link this situation to the previous COVID-19 infection, there is a need to define the physiopathological mechanisms that can explain the increase in the frequency of cervical infection with HPV in patients with COVID-19 infection. A prospective observational study on the detection rates of SARS-CoV-2 genetic material in cervical cytology is also ongoing [17]. Clinical cervical specimens from this study will be immersed in a bottle containing collection fluid (Hologic). The cytological material will then be analyzed for the presence of COVID-19 genetic material by storing the cells for a long time and, in the case of positive results, HPV typing will also be performed to detect potential correlations between SARS-CoV-2 infection and HPV infection.
With a study of this design, it may be possible to confirm the increased frequency of HPV-16 that we found in patients with COVID-19 infection. In addition, there have been observations that patients with known HPV infection later infected with COVID-19 may cause progression in cervical pathology [17]. The progression of known HPV positivity to CIN 1 lesion on colposcopy after COVID-19 infection for a patient without cervical lesion has led to the observation that there may be a correlation between HPV and COVID-19 infection. However, case-based observations are not sufficient to confirm this hypothesis. These observations need to be confirmed by randomized or cohort studies. Potentially, the mechanism of this situation may not be related to SARS-CoV-2 infection itself, but to impaired immune system, which is already considered a known factor for the occurrence of cervical pathology.
However, our study does not provide information to explain this situation. Because this study was conducted between 2 groups of women who did not have a history of HPV before. For this reason, it does not have a design to explain the progression of the current HPV infection in cervical pathology. The general methodology of the study is that the effect of having a COVID-19 infection on the immune system makes it predispose to HPV infection and if it does, which types cause an increase in frequency.
If, as in this study, COVID-19 infection causes an increase in HPV-16 prevalence, it would not be an exaggeration to conclude that patients exposed to SARS-CoV-2 virus should be followed up more regularly to optimize early detection of cervical premalignant lesions. This may be due not only to the general effects that COVID-19 may have on the female immune system, but also to some unknown interactions between the two viruses.
Our study has some shortcomings. In our study, the number of patients who had COVID-19 was less than the control group. In addition, COVID-19 is an infection that can be transmitted asymptomatically, and the history of COVID-19 infection was only verbally questioned, and serological confirmation was not provided that this infection was not experienced before. This can be a confounding factor. The potential correlation between COVID-19 infection and HPV infection can be demonstrated by planning randomized studies with larger numbers of patients in which confounding factors are eliminated. Due to the limited number of cases, this study is insufficient to strongly demonstrate this relationship.
On the other hand, this study is the first in the literature to identify a correlation between the two viruses in terms of the unknown effects of SARS-CoV-2 on the genital tract. This may encourage other researchers to increase their interest in demonstrating the relationship between HPV and SARS-CoV-2.
Conclusion
COVID-19 infection may increase the frequency of HPV-16. Apart from this, it can be said that this increase is not reflected in the frequency of cervical cytopathology. However, it is highly probable that this is due to the short-term nature of the study. Again, the COVID history does not seem to be a factor affecting the colposcopy results in our study. The colposcopy results of patients with and without COVID-positive HPV can be evaluated according to their HPV types, and the number of patients and groups can be compared, but this is the subject of another study.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Download attachments: 10.4328.ACAM.21366
Yunus Emre Purut, Fedi Ercan, Mehmet Murat Isikalan, Gulchin Babayeva. Frequency of cervical hpv in women with COVID-19 infection. Ann Clin Anal Med 2022;13(10):1176-1179
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