June 2023
Comparison of ureterorenoscopy (URS) procedure performed under general and spinal anesthesia in ureteral stones
Selahattin Celikkaya 1, Bulent Ozturk 2, Hakan Ozkardes 3
1 Department of Urology, Ankara Pursaklar State Hospital, Ankara, 2 Department of Urology, Faculty of Medicine, Baskent Universty, Konya, 3 Department of Urology, Faculty of Medicine, Baskent Universty, Ankara, Turkey
DOI: 10.4328/ACAM.21443 Received: 2022-10-14 Accepted: 2023-03-20 Published Online: 2023-04-27 Printed: 2023-06-01 Ann Clin Anal Med 2023;14(6):478-482
Corresponding Author: Selahattin Celikkaya, Department of Urology, Ankara Pursaklar State Hospital, 06145, Pursaklar, Ankara, Turkey. E-mail: scelikkaya81@gmail.com P: +90 532 543 15 55 Corresponding Author ORCID ID: https://orcid.org/0000-0003-0895-1639
This study was approved by the Ethics Committee of Başkent University Medical School (Date: 2012-01-01, No: KA12/01)
Aim: The objective of this study was to evaluate records of the patients who underwent ureterorenoscopy under general and spinal anesthesia and to determine whether the type of anesthesia affected the success of the operation and complications.
Material and Methods: Medical records of 1548 patients who underwent ureterorenoscopy [URS] were retrospectively reviewed for 10 years. Patients were divided into two groups according to the type of anesthesia as general anesthesia and spinal anesthesia groups. Routine monitoring was performed in the operating. Two groups were compared in terms of demographic data, preoperative, operative and postoperative characteristics.
Results: The mean age was statistically significantly higher in the general anesthesia group [49.57±15,31] compared to the spinal anesthesia group [47.21±13.19] [p<0.01]. There was a significant difference between the groups in terms of ASA class and stone size, while no significant difference was found in terms of previous ESWL application and stone laterality. The use of DJS was significantly less in the spinal anesthesia group compared to the general anesthesia group [p<0.001]. The use of lithotripsy was significantly more common in the spinal anesthesia group [p<0.001]. Length of stay in hospital was statistically significantly shorter in the spinal anesthesia group [p<0.001].
Discussion: Operation time and length of stay in the hospital were shorter in the spinal anesthesia group. Catheter use was less in the spinal anesthesia group. Spinal anesthesia can be readily used in URS procedures regardless of stone size.
Keywords: Ureteral Stone, Ureterorenoscopy, Stone-Free, General Anesthesia, Spinal Anesthesia
Introduction
Urinary system stone disease [USD] is among the most important diseases that directly affect the quality of life. Stones can form anywhere in the proximal urinary tract in the presence of congenital urogenital abnormalities, urinary obstruction, or infection [1]. USD is a very frequent disease with a life-time-risk of about 10 – 15 % in industrialized countries [2]. It has been reported that the prevalence of urinary system stone disease varies between 1% and 20% [3]. The prevalence of stones in males was 1.5 times higher than in females.
The incidence of USD depends on many factors including geographical, climatic, hereditary, ethnic and nutritional status. Infectious causes, anatomic anomalies, and drug use also may play a role in stone formation [4-6]. Mostly asymptomatic stone formation occurs within the renal pelvic system, the typical clinical manifestation results when these stones enter and consequently obstruct the ureter.
Today, many methods are used in the treatment of USD, including Extracorporeal shock wave lithotripsy [ESWL], percutaneous nephrolithotomy [PCNL], ureteroscopy, open surgery and laparoscopy. In light of the innovations made in the field of endourology and the endoscopic experience gained by surgeons, open surgery has become a less preferred method in the treatment of USD. Open stone surgery has been rendered obsolete in most situations, being surpassed by antegrade and retrograde endoscopic techniques, as well as ESWL [7, 8]. Open surgery is preferred in only 1-5.4% of urinary stone cases [9, 10]. Today, ESWL and transurethral ureterorenoscopy [URS] come to the fore in the treatment of ureteral stones. However, ESWL has both a long treatment process and the need for additional treatment. Therefore, its priority in the treatment of ureteral stones is controversial [11, 12]. Treatment of ureteral stones using URS is the primary treatment option for all ureteral stones, especially middle and lower ureteral stones, stones for which ESWL has failed, or depending on patient preference [13, 14]. Today URS is commonly performed under general anesthesia. The European Association of Urology guideline recommends ureterorenoscopy be performed under general anesthesia [15, 16]. In ureterorenoscopy, anaesthesiologists prefer regional anesthesia to avoid complications due to general anaesthesia, while surgeons prefer general anaesthesia to avoid ureteral trauma [17, 18]. However, studies that compared these two anesthesia techniques are limited. The objective of this study was to evaluate records of the patients who underwent ureterorenoscopy under general and spinal anesthesia and to determine whether the type of anesthesia affected the success of the operation and complications.
Material and Methods
Medical records of 1548 patients who underwent URS due to USD in the urology clinics of the Baskent University Ankara and Konya Research Centers for 10 years were retrospectively reviewed. Patients aged >18 years who underwent URS under general or spinal anesthesia were included in the study. Patients aged under 18 years, those who underwent additional surgery at the same session, pregnant women, patients with kidney or ureter anomalies and those with missing data were excluded from the study.
Patients were divided into two groups according to the type of anesthesia as general anesthesia and spinal anesthesia groups. Induction and intubation were performed with 2 mg/kg propofol and 0.1 mg/kg vecuronium bromide. The maintenance was made with 50% N2O and propofol perfusion. Routine monitoring was performed in the operating room.
Patients in the spinal anesthesia group were given a sitting position, and following sterilization, a 25 G needle was entered at the level of L4-L5 in the midline and spinal anesthesia was achieved using 2 mL 0.5% hyperbaric bupivacaine. The patients were then given the supine position. Anesthesia level of the patients was evaluated with the pin-prick test. In addition, 2.5 mg i.v. midazolam was administered for sedation.
The URS Procedure
Intravenous cephalosporin was administered prophylactically before the operation to the patients who underwent general anesthesia and spinal anesthesia. After the appropriate position and cover, a 10 F feeding tube was placed in the bladder, the bladder was entered with the ureteroscope under the guidance of the feeding tube, and the localization and characteristics of the orifice were evaluated.
A 9.5 F Storz [Storz/Germany] ureteroscope was used for ureteroscopy. If the ureteral orifice was of appropriate width, the ureter was accessed. The ureter was accessed with the help of a guide wire when access to the ureter was not possible. A Stone Cone [Cook Medical Co] was placed proximal to the stone in patients whose stone was predicted to be able to migrate proximally. While some of the stones were directly extracted with stone forceps, pneumatic lithotripsy [ELMED vibrolith, 0311VB257] device and 3-4 F rigid probes were used to break the large stones.
Lithotripsy was performed until the stones were broken into very small pieces and broken completely. Large pieces were removed with stone forceps or a basket, while small pieces were left to pass. It was evaluated whether the stone was completely broken or not, by controlling the ureter by passing to the proximal part of the stone and using a scopy in doubtful cases. Double J stent [DJS] was not routinely used after ureterorenoscopic lithotripsy. 6F-26 cm double J was used in cases where there was severe damage or perforation of the mucosa, and in patients who had a large number of residual stone fragments and were thought to cause problems in spontaneous passing. DJSs were removed after 2-4 weeks.
Data evaluation
Two groups were compared in terms of demographic data, preoperative, operative and postoperative characteristics. Demographic data included age and gender. Preoperative characteristics included a history of ESWL [цhether ESWL was applied before URS], stone localization [upper ureter, middle ureter, lower ureter], laterality [right, left], stone size [millimetres and ASA scores]. Operative characteristics included operation time [minutes], use of catheter during URS [basket, stone cone, catheter free], method used in stone extraction [lithotripsy vs extraction] and use of DJS following URS. Postoperative characteristics included operation outcome [stone free, residual fragments], postoperatively used analgesics [NSAIDs, narcotic analgesic], length of stay in hospital [days] and postoperative complications.
Postoperative complications were grouped according to the Clavien classification. Among the complications; nausea, postoperative fever and headache were evaluated as Clavien I, pyelonephritis and thromboembolism as Clavien II and ureteral avulsion and perforation as Clavien III.
Statistical analysis
Power analysis was performed for pre-evaluation of biostatistics before the study. Since categorical variables were also included in the power analysis, the required sample size was determined as 228 individuals in each category and at least 456 individuals in each group. According to the power analysis, the power of the test was expected to be 0.801545. The normality of continuous variables was evaluated with the Shapiro-Wilk test, and the homogeneity of the group variances was checked with Levene’s test. Since the assumptions of the parametric tests were not met, the Mann-Whitney U test was used to compare the medians of two independent groups. Results were expressed as mean±standard deviation and median value, min.-max. and interquartile range [IQR]. Categorical data were analyzed with Fisher’s Exact Test and Pearson’s Chi-square test. p<0.05 values were considered statistically significant. Data obtained in this study were evaluated using the SPSS version 17.0 [SPSS, Social Package for Social Sciences, IBM Inc., Chicago, IL, USA] software.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
A total of 1305 patients who underwent URS and met inclusion criteria were included in the study. Of these, general anesthesia was performed in 461 [35.3%] and spinal anesthesia in 884 [64.7%] patients. The mean age was statistically significantly higher in the general anesthesia group [49.57±15,31] compared to the spinal anesthesia group [47.21±13.19] [p<0.01]. In the general anesthesia group, 314 [69.5%] patients were male and 138 [30.5%] patients were female. In the spinal anesthesia group, 568 [67%] were male and 280 [33%] were female. No significant difference was found between the groups in terms of gender [p=0.383].
Considering preoperative characteristics, there was a significant difference between the groups in terms of ASA class and stone size, while no significant difference was found in terms of previous ESWL application and stone laterality (Table 1).
Comparison of operative characteristics according to the types of anesthesia is given in Table 2.
Comparison of the postoperative characteristics between the groups is given in Table 3.
Whether stone localization affects the outcomes of URS according to the type of anesthesia was evaluated. In the patients with upper ureter stones, stone free rate was significantly higher in the spinal anesthesia group [p<0.05]. Operation time and length of stay in hospital were higher in the general anesthesia group with upper ureter stones [both, p<0.01].
In the patients with middle ureter stones, the stone size was significantly greater in the spinal anesthesia group [p<0.01]. Operation time and length of stay in hospital were higher in the general anesthesia group with middle ureter stones [both, p<0.01].
In the patients with lower ureter stones, the stone size was significantly greater in the spinal anesthesia group [p<0.01]. Operation time and length of stay in hospital were higher in the general anesthesia group with middle ureter stones [both, p<0.01].
Discussion
Majority of stones in the urinary system are ureter stones. The aim of the treatment of ureteral stones is to ensure that the patient is completely stone free with minimal complications. Today, ESWL and USR are commonly used for this purpose. URS is preferred in the treatment of all ureter stones and especially middle and lower ureter stones in the cases where ESWL fails and depending on the patient’s preference.
USR is usually performed under general anesthesia. The purpose of performing URS with general anesthesia is to keep the patient still, to provide breath control and thus to reduce the risk of ureteral injury. The use of spinal anesthesia in URS is becoming widespread due to the reduction of hospital stay, reduction of postoperative analgesic use and complications, early oral feeding, less neurological complications and less risk of anaphylaxis due to the anesthetic agent used. In the present study, we compared preoperative, operative and postoperative characteristics of USR procedure under general and spinal anesthesia.
In our study the mean age was 49.57 years in the general anesthesia and 47.21 years in the spinal anesthesia group. Our findings are in the range specified in the literature [17,19,20].
In our study, the mean stone size was 10.94± 4.42 mm in the general anesthesia and 9.8±3.20 in the spinal anesthesia group, without significant difference between them [p=0.161]. Cai et al. found the stone size as 11.45 ± 3.49 mm in the general anesthesia and 11.11 ± 2.89 in the spinal anesthesia group [p=0.286] [20]. In a study by Topaktas et al., the mean stone size was 11.1 ±2.1 in the general anesthesia and 10.1 ±2.2 in the spinal anesthesia group [19]. In a study by Bosio et al. with 234 patients who underwent URS under spinal anesthesia, the stone size was 13.5 ± 6.6 mm [21].
Operation time and length of stay in the hospital are two important characteristics of USR procedures. Cai et al. compared the effects of general, spinal and epidural anesthesia on surgical outcomes during flexible URS for single stone removal surgeries. They found that the lithotripsy time [p=0.359], operation time [p=0.449], intraoperative complications [p=0.058], and length of hospital stays [p=0.057] of patients were similar among anesthesia groups [20]. In our study, operation time and length of stay in hospital were significantly shorter in the spinal anesthesia group [both, p<0.001]. In the study by Bosio et al. the mean operation time was 76.9 ± 34.6 min [21]. In a study by Topaktas the mean operation time was similar between the general and spinal anesthesia groups. Patients were discharged on the same day of surgery [19]. The differences among the studies might result from our higher number of patients included.
Another important indicator of procedural success is stone free rate. In the present study, stone-free rate was found as 75% in the general anesthesia and 79% in the spinal anesthesia groups. In the study by Cai et al. stone-free status was reported as 88% with general anesthesia and 85% with spinal anesthesia [20].
Ureter stone laterality may affect the treatment outcome [22]. In our study, 54.5% of the stones were on the right side and 45.5% were on the left side in the general anesthesia group and 52.7% on the right side and 47.3% on the left side in the spinal anesthesia group. In the study by Topaktas, 53.1% of the stones were on the right side and 46.8% were on the left side in the general anesthesia group and 52.5% on the right side and 47.5% on the left side in the spinal anesthesia group [19]. Laterality of the stones in our study was consistent with the other studies.
Stone location is one of the important factors affecting the surgical procedure. In the present study, the rate of stones in the lower ureter was higher in both general and spinal anesthesia groups [p<0.001]. In a study by Oztekin et al., there was no significant difference between the stone localization in both groups [p=0.965] [17]. It can be explained by a small number of patients in their study.
Postoperative complications were measured using Clavien classification. In our study no significant difference was found between the groups in terms of Clavien classes. Similarly, Cai et al. reported no significant difference between the general, spinal and epidural anesthesia group in terms of postoperative Clavien classification except for nausea and vomiting that were significantly more common with general anesthesia [20] [p=0.013].
Study Limitations
The major limitations of this study are its retrospective design and being conducted in a single center. In addition, comorbidities could not be studied. Finally, we could not compare our results exactly due to the scarcity of studies on this issue. However, the number of patients in our study was relatively large. Given the limited number of studies on this topic, we believe that our findings will be guiding for future more comprehensive multi-center studies.
Conclusion
Despite stone size being greater in the spinal anesthesia group, URS outcomes and postop complications were similar between the two groups. Operation time and length of stay in hospital were shorter in the spinal anesthesia group. Catheter use was less in the spinal anesthesia group. Spinal anesthesia can be readily used in URS procedures regardless of stone size. However, further comprehensive randomized controlled prospective studies are needed to support these findings.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Selahattin Celikkaya, Bulent Ozturk, Hakan Ozkardes. Comparison of ureterorenoscopy (URS) procedure performed under general and spinal anesthesia in ureteral stones. Ann Clin Anal Med 2023;14(6):478-482
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Pudendal nerve block effect on post-operative urinary catheter-related bladder discomfort after robot-assisted radical prostatectomy
Ahmet Keles 1, Tibet Erdogru 2, Rahmi Onur 3
1 Department of Urology, Faculty of Medicine, Istanbul Medeniyet University, Prof Dr. Süleyman Yalçın City Hospital, 2 Department of Urology, UroKlinik Robotic and Laparoscopic Urology Center, 3 Department of Urology, Faculty of Medicine, Marmara University School of Medicine, Istanbul, Turkey
DOI: 10.4328/ACAM.21505 Received: 2023-01-12 Accepted: 2023-03-12 Published Online: 2023-03-29 Printed: 2023-06-01 Ann Clin Anal Med 2023;14(6):483-487
Corresponding Author: Ahmet Keles, Department of Urology, Faculty of Medicine, Istanbul Medeniyet University, 34720, Kadıköy, Istanbul, Turkey. E-mail: drkeles2009@yahoo.com P: +90 505 395 49 37 F: +90 212 596 67 82 Corresponding Author ORCID ID: https://orcid.org/0000-0001-5436-1803
This study was approved by the Ethics Committee of Marmara University Faculty of Medicine (Date: 2020-12-05, No: E-70737436-050.01.04-2000324126)
Aim: In this study, we aimed to evaluate the effect of bilateral pudendal nerve block (PNB) on the prevention of catheter-related bladder discomfort (CRBD) in men undergoing robot-assisted radical prostatectomy (RARP).
Material and Methods: A total of 83 patients who had previously undergone RARP and were catheterized by a 20Fr urethral catheter were evaluated. Between December 2017 and January 2020, retrospective data of 75 eligible patients were examined in two groups: as receiving bilateral pudendal nerve block (PNB) or not receiving as the control group. Under fluoroscopic view and digital rectal guidance, mixture a of 8 ml of Bupivacaine 0.5% and 40 mg of methylprednisolone (total 10 ml) was injected by a spinal needle at each side for PNB. Pain assessment, CRBD severity, and degree of discomfort experienced were evaluated using the self-reported questionnaires and the Wong-Baker FACES (WB-FACES) scale immediately after the procedure and at postoperative 1, 2, 6, and 12th hours.
Results: No perioperative or postoperative complication related to the intervention was found in this retrospective data. Patients in the PNB group had statistically significantly lower CRBD values and lower WB-FACES scores compared to the control group (p<0.05) immediately after surgery and post-operatively. Furthermore, patients showed significant improvement, as assessed by the responses given to self-reported questionnaires, postoperatively.
Discussion: Bilateral PNB performed immediately after completion of RARP significantly decreased CRBD. This intervention may help improve patient comfort, decrease analgesic use, and reduce hospital stays after RARP.
Keywords: Catheter-Related Bladder Discomfort, Pudendal Nerve Block, Robot-Assisted Radical Prostatectomy
Introduction
Since its introduction, robot-assisted radical prostatectomy (RARP) has been widely used in the surgical treatment of prostate cancer in men due to its long-term documented advantages. These include shorter duration of hospitalization, decreased postoperative pain, rapid recovery of continence, and earlier removal of the urethral catheter. However, catheter-related bladder discomfort (CRBD) is still a common and distressing symptom, especially during the postoperative period, even in patients undergoing RARP [1,2].
CRBD is defined as discomfort in the suprapubic area, a burning sensation or pain within the urethra or penis commonly associated with an urge to void and an increased frequency of urination [3,4]. It was postulated that CRBD may be due to irritation of the urothelium caused by the friction between the catheter and the epithelium [5]. This leads to involuntary bladder contractions through the activation of type three muscarinic receptors, thereby increasing acetylcholine release; it then causes involuntary detrusor contractions [5,6]. Previously, anticholinergics, analgesics, gabapentin, pregabalin, and several anesthetics, such as ketamine and dexmedetomidine, have been used in the management of CRBD [5,7-10]. However, it should be acknowledged that these drugs need to be repeatedly administered and they are not devoid of side effects, such as dry mouth, cognitive dysfunction in elderly patients, constipation, sedation, blurred vision, headache, insomnia, nausea, and vomiting [8-13].
Recently, pudendal nerve block (PNB) has been successfully used for analgesia after several surgical procedures, such as labor, vaginal interventions, sphincter injections, surgeries, and pudendal neuralgia [1]. It has been shown that the branches of the sacral somatic nerves form the afferent nerves of the urethra and bladder triangle; in males, they also provide sensation to the penis [14-15]. In an autopsy series, the terminal branch of the pudendal nerve was shown to be innervating the membranous urethra in more than half of the cases [16]. Considering the physiological role of pudendal innervation, we hypothesized that CRBD can be prevented by PNB. CRBD was prevented by PNB with ropivacaine in a trial of 94 male patients undergoing elective prostate surgery [1]. In another series of 175 patients undergoing transurethral resection of a prostate or bladder tumor, postoperative PNB decreased the incidence and severity of CRBD for the first 12 hours postoperatively [5]. The purpose of this study is to retrospectively evaluate the use of bilateral PNB to prevent CRBD and to determine its efficacy in men undergoing RARP.
Material and Methods
Study design and population
This study was conducted according to the principles of the Declaration of Helsinki, and written informed consent was obtained from all participants. The data were extracted from the hospital’s electronic database after approval by the Research Ethics Committee (Approval number: E-70737436-050.01.04-2000324126). The trial is a single-center study that aimed to evaluate the efficacy of bilateral PNB in relieving CRBD and its role in patients’ perception of pain and other catheter-related problems. The data of 83 patients undergoing RARP were collected. There was no randomization before data collection. We routinely performed RARP without bilateral PNB in our initial practice, and then we started to apply the block later on in other patients. All RARP procedures were performed by an experienced surgeon at a single robotic surgery center. All the patients received a 20-Fr Foley catheter with a balloon volume inflated to 15 mL. The patients were randomly divided into two groups: those receiving bilateral PNB (PNB group) and those not receiving bilateral PNB (control group). Patients with a history of bupivacaine allergy or a contraindication to steroid use were excluded from the study.
Bilateral PNB procedure
Using the fluoroscopic (with the cranially oblique angle) view of the pelvic region and after placing the index finger on the rectum, the ischial spine (IS) and sacrospinous ligament (SSL) were palpated. The IS was located using the index finger; then, under fluoroscopic guidance, a 10–12 cm length spinal needle was inserted percutaneously through the perineum until it reached the IS and the SSL. Next, a mixture of 8 ml of bupivacaine 0.5% and 40 mg of methylprednisolone (total of 10 ml) was injected into each side for PNB beneath the IS and SSL where the pudendal neurovascular bundle was localized.
Assessments
CRBD was assessed at 0 h (just after the patients were transferred to the PACU) and at 1, 2, 6, and 12 hours postoperatively. The discomfort was graded as described previously: no discomfort, “mild” when reported by patients only on questioning, “moderate” when reported by patients on their own without questioning and not accompanied by any movement or response, and “severe” when reported by patients on their own with accompanying behavioral responses, such as moving, a strong vocal response, or an attempt to remove the catheter [17]. We also used the Wong-Baker FACES (WB-FACES) pain rating scale, in which each of the six faces represents a person who has no pain (hurt), a little pain, a bit more pain, moderate pain, significant pain, and severe pain, respectively.
We further assessed CRBD by asking four additional questions: “Q1: Do you feel any pain in your penis?”; “Q2: Do you feel the catheter in your penis?” “Q3: Do you have an urgency to urinate?”; and “Q4: Do you have any urge to urinate, but are unable to do so?” The answers were classified into four categories as described previously (none, mild, moderate, or severe).
Statistical analysis
Statistical analysis was performed using SPSS version 21.0 (IBM Inc., Chicago, IL, USA). The independent samples t-test was used to compare demographic data. The data were expressed as mean + standard deviation (SD) or as a percentage (number). The ISUP grades as well as the answers to the four other questions related to catheter discomfort were compared using Chi-square and Mann-Whitney U tests. A p -value of less than 0.05 was considered statistically significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Between December 2017 and January 2020, data from a total of 83 patients were examined. Three patients from the PNB group and five from the control group were excluded from the study because they could not complete the questionnaires fully or clearly. Therefore, the postoperative data of 75 men were examined for the final analysis. There were no perioperative or early postoperative complications related to the intervention. Table 1 shows the demographic and clinical findings of the patients in both groups. No statistically significant difference was observed between the two groups concerning any of the parameters (P > 0.05). Similarly, no significant difference in ISUP degrees was found between the two groups in the final histopathological examination (P = .824).
Patients in the PNB group had no CRBD or mild CRBD at all the studied time intervals. Immediately after the procedure and postoperatively at 1 h, the patients in the control group had moderate to severe CRBD (Figure 1); the patients who received PNB had moderate CRBD to a lesser degree only immediately after RARP and at 1 h postoperatively. None of the patients in the PNB group had severe CRBD. The severity of CRBD between the two groups was only comparable at 6 h postoperatively (Figure 1).
The WB-FACES pain rating scale scores showed a statistically significant difference between the PNB and control groups. All the patients showed decreased scores immediately after PNB and had low scores until 12 h postoperatively. The scores for the WB-FACES scale were significantly lower in the PNB group than in the control group at all time points (Figure 2).
Table 2 shows the details of the responses to other specific questions related to pain in the penis, feeling of incomplete emptiness, urgency, and the inability to urinate. A significantly higher proportion of patients in the PNB group experienced no or mild discomfort from the catheter immediately following the intervention as well as up to 12 hours later (P =0.002). The most bothersome complaints in the control group were pain in the penis and a sense of incomplete emptiness (Q4: Do you have any urge to urinate but are unable to do so?) The patients continued to have catheter-related discomfort 12 hours postoperatively (Table 2).
Discussion
RARP has been shown to have many advantages for both the surgeon and patients in the treatment of prostate cancer [2]. However, urinary catheterization is also essential with RARP, and CRBD remains a problem for patients, especially on the first postoperative day. It has been postulated that CRBD develops due to stimulation of the urethra by the catheter, stimulation of the trigone area by catheter balloon, afferent discharge and release of acetylcholine, detrusor muscle contraction, and release of inflammatory mediators, such as prostaglandins [18]. Considering these pathophysiological routes, several agents have been used to alleviate CRBD. These include antimuscarinics, gabapentin, pregabalin, anesthetics, such as ketamine and d-dexmedetomidine, tramadol, paracetamol, non-steroidal anti-inflammatory analgesics, and butylscopolamine [5,7,8,10,17].
Although it is known that patients often tolerate the aforementioned pharmacological agents, several side effects need to be considered. These include the anticholinergic side effects of antimuscarinics, a higher incidence of sedation by tramadol and ketamine, the use of increased doses of antiepileptics, such as pregabalin and gabapentin, and repeated administration of drugs [17]. To avoid these limitations, different interventions have been described in the literature. Weinberg described the use of a dorsal penile nerve block to prevent CRBD, but it failed to prevent or reduce the discomfort in that study’s cohort [4]. Recently, bilateral nerve-stimulator-guided PNB has been applied to relieve CRBD in male patients undergoing lower urinary tract surgeries [5]. In the present study, we performed bilateral PNB using fluoroscopy in patients undergoing RARP, and we demonstrated that bilateral PNB significantly reduced or prevented postoperative CRBD.
It was previously reported that CRBD may be resistant to conventional analgesics since it has a different underlying mechanism [10]. As previously mentioned, considering the possible side effects of several pharmacological agents, PNB for analgesia due to CRBD can be a better alternative. PNB has been safely and effectively used for analgesia for labor during vaginal delivery, vaginal repair, sphincterotomy, and the treatment of pudendal neuralgia [19-21]. In 53% of the autopsy series, the terminal branch of the pudendal nerve was shown to innervate the membranous urethra; thus, it is not surprising that PNB has a strong analgesic effect when injected on either one or two sides [16]. In their randomized, parallel-controlled, double-blinded, single-center study, Xiaoqiang et al. evaluated the efficacy of bilateral PNB in 178 men undergoing lower urinary tract surgeries [5]. Bladder discomfort and postoperative pain were the primary outcomes, and they reported that the incidence of postoperative CRBD at 30 min, 2 h, and 8 h was significantly lower in the PNB group than in the control group [5]. In our study, the WB-FACES scale scores were significantly lower in the PNB group in comparison to the control group at all time points. This long-lasting effect may be related to the surgical technique. We performed RARP through abdominal laparoscopic ports, and Foley catheter insertion was the only urethral intervention. In contrast, Xiaoqiang et al. performed prostate or bladder tumor surgeries via the trans-urethral route [5].
In another attempt to prevent or alleviate CRBD after RARP, Weinberg et al. performed a dorsal penile block of bupivacaine in 56 men and used a placebo in 60 patients [4]. They found no difference between the groups concerning reported CRBD or bladder spasm-associated discomfort at any of the measured time points. Despite its prospective, randomized, double-blind design, that study was estimated to be underpowered to detect statistically significant differences, and the pain-rating scales were vulnerable to biases inherent in the questionnaires that were used [4]. Moreover, the hypothesis of pain reduction and CRBD by blockage of dorsal penile block may not be sufficient since innervation of the bladder and urethra is more complex. Considering that the branches of the sacral somatic nerves form the afferent nerves of the urethra and bladder triangle, which are derived from the second to fourth sacral roots, the pudendal nerve seems to have proximity and direct innervation to the male urethra and/or external sphincter [14,15]. Thus, bilateral PNB can be expected to be an effective anesthetic technique, especially for interventions of the lower urinary tract, including urinary catheterization.
In our series, we observed either no CRBD or mild CRBD in patients undergoing bilateral PNB at all time intervals, and none of the patients in the intervention group showed severe CRBD. This efficacy might be related to blockage of the inter-related innervation routes of the pudendal nerve as well as our strategy to combine bupivacaine and a low dose of methylprednisolone.
Discomfort at the injection site is the most common side effect of PNB. It may also be associated with local anesthetic side effects, allergic reactions, an extension of the anesthesia effect to the sciatic nerve region, sciatic fossa hematoma, and rarely, infection and abscess [5]. More serious side effects, such as pudendal nerve damage or structural injury of the organs in the proximity of the pudendal nerve, such as the bladder and rectum, occur rarely. One should also note the potential for pudendal artery puncture and subsequent intravascular injection of local anesthetics, which can cause systemic local anesthetic toxicity and potentially be fatal [22]. Our cohort observed no side effects, and we believe that fluoroscopic identification of several landmarks in patients with dorsal lithotomy positions provided better access and complication-free injection.
Our study has several limitations. First, we analyzed retrospectively collected data. Initial data belonged to the patients who had not received bilateral PNB. Thus, true randomization was not possible. Moreover, there was no initial blind randomization, all the analyses were performed at one robotic surgery center, and fixed doses of a combination of bupivacaine and methylprednisolone were used. Second, the role of bilateral PNB could have been compared to other types of urological procedures. Third, we did not assess the efficacy of bilateral PNB beyond 12 hours postoperatively. However, it was previously shown that the use of long-acting local anesthetics in PNB can last more than 10 hours [5]. Thus, we tested the analgesic effect of bilateral PNB in both the PNB intervention and control groups and found a head-to-head comparison for at least 12 hours.
Conclusion
Bilateral PNB with a combination of bupivacaine and methylprednisolone effectively reduces or prevents pain and CRBD ) in men undergoing RARP compared to the control patients (no PNB injection.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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2. Ficarra V, Novara G, Artibani W, Cestari A, Galfano A, Graefen M, et al. Retropubic, laparoscopic, and robot-assisted radical prostatectomy: a systematic review and cumulative analysis of comparative studies. Eur Urol. 2009;55(5):1037-63.
3. Park JY, Hong JH, Yu J, Kim DH, Koh GH, Lee SA, et al. Effect of Ketorolac on the Prevention of Postoperative Catheter-Related Bladder Discomfort in Patients Undergoing Robot-Assisted Laparoscopic Radical Prostatectomy: A Randomized, Double-Blinded, Placebo-Controlled Study. J Clin Med. 2019;8(6):759.
4. Weinberg AC, Woldu SL, Bergman A, Roychoudhury A, Patel T, Berg W, et al. Dorsal penile nerve block for robot-assisted radical prostatectomy catheter related pain: a randomized, double-blind, placebo-controlled trial. Springerplus. 2014;3:181.
5. Xiaoqiang L, Xuerong Z, Juan L, Mathew BS, Xiaorong Y, Qin W, et al. Efficacy of pudendal nerve block for alleviation of catheter-related bladder discomfort in male patients undergoing lower urinary tract surgeries: A randomized, controlled, double-blind tria.. Medicine (Baltimore). 2017;96(49):e8932.
6. Andersson KE, Wein AJ. Pharmacology of the lower urinary tract: basis for current and future treatments of urinary incontinence. Pharmacol Rev. 2004;56(4):581-631.
7. Bala I, Bharti N, Chaubey VK, Mandal AK. Efficacy of gabapentin for prevention of postoperative catheter-related bladder discomfort in patients undergoing transurethral resection of bladder tumor. Urology. 2012;79(4):853-7.
8. Agarwal A, Gupta D, Kumar M, Dhiraaj S, Tandon M, Singh PK. Ketamine for treatment of catheter related bladder discomfort: a prospective, randomized, placebo-controlled and double blind study. Br J Anaesth. 2006;96(5):587-9.
9. Srivastava VK, Agrawal S, Kadiyala VN, Ahmed M, Sharma S, Kumar R. The efficacy of pregabalin for prevention of catheter-related bladder discomfort: a prospective, randomized, placebo-controlled double-blind study. J Anesth. 2015;29(2):212-16.
10. Kim HC, Lee YH, Jeon YT, Hwang JW, Lim YJ, Park JE, et al. The effect of intraoperative dexmedetomidine on postoperative catheter-related bladder discomfort in patients undergoing transurethral bladder tumour resection: A double-blind randomised study. Eur J Anaesthesiol. 2015;32(9):596-601.
11. Agarwal A, Raza M, Singhal V, Dhiraaj S, Kapoor R, Srivastava A, et al. The efficacy of tolterodine for prevention of catheter-related bladder discomfort: a prospective, randomized, placebo-controlled, double-blind study. Anesth Analg. 2005;101(4):1065-67.
12. Agarwal A, Dhiraaj S, Pawar S, Kapoor R, Gupta D, Singh PK. An evaluation of the efficacy of gabapentin for prevention of catheter-related bladder discomfort: a prospective, randomized, placebo-controlled, double-blind study. Anesth Analg. 2007;105(5):1454-7.
13. Agarwal A, Yadav G, Gupta D, Singh PK, Singh U. Evaluation of intra-operative tramadol for prevention of catheter-related bladder discomfort: a prospective, randomized, double-blind study. Br J Anaesth. 2008;101(4):506-10.
14. Robert R, Labat JJ, Riant T, Louppe JM, Hamel O. Le nerf pudendal: morphogenèse, anatomie, physiopathologie, clinique et thérapeutique [The pudendal nerve: clinical and therapeutic morphogenesis, anatomy, and physiopathology]. Neurochirurgie. 2009;55(4-5):463-9.
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Ahmet Keles, Tibet Erdogru, Rahmi Onur. The impact of bilateral pudendal nerve block on post-operative urinary catheter-related bladder discomfort after robot-assisted radical prostatectomy. Ann Clin Anal Med 2023;14(6):483-487
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Relationship between prediabetic conditions and microalbuminuria
Gulbin Seyman Cetınkaya, Yusuf Uzum
Department of Internal Medicine, Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey
DOI: 10.4328/ACAM.21506 Received: 2022-11-27 Accepted: 2023-01-13 Published Online: 2023-01-18 Printed: 2023-06-01 Ann Clin Anal Med 2023;14(6):488-493
Corresponding Author: Yusuf Uzum, Department of Internal Medicine, Katip Celebi University, Ataturk Training, and Research Hospital, Izmir, Turkey. E-mail: yusufuzum@gmail.com P: +90 536 665 87 86 / +90 232 244 44 44 Corresponding Author ORCID ID: https://orcid.org/0000-0001-5027-1827
This study was approved by the Ethics Committee of Izmir Katip Celebi University (Date: 2021-03-24, No: 0121)
Aim: Microalbuminuria is an expected predictor of renal and cardiovascular diseases and even mortality. In this study, it was aimed to elucidate the effect of microalbuminuria with albumin creatinine ratio in pre-diabetic patients and to follow patients for a period of 2 years.
Material and Methods: In this prospective study, we have enrolled 90 patients, including n=30 impaired glucose tolerance (IGT), n=30 impaired fasting glucose (IFG), and n=30 in the control group. The diagnosis of IGT has been established via 75 gr glucose loading. The enrolled patients have been followed up every 6 months for a period of 2 years prospectively. The renal function tests, insulin levels, body mass indexes, uric acid levels, CRP levels, and urinary ACR levels were recorded and monitored every 6 months, and annual data were noted. Individuals who developed diabetes during follow-up were recorded and their treatments were initiated.
Results: After a two-year follow-up of the patients, 46.7% (n=14) of patients with impaired glucose tolerance (IGT) had impaired glucose tolerance again, while 13.3% (4 individuals) had impaired fasting glucose and 23.3% (n=7) had normal glucose tolerance and 16.7% (n=5) had diabetes. Similarly, impaired fasting glucose was observed in 66.7% (n=20) of patients with impaired fasting glucose (IFG) at the beginning, while impaired glucose tolerance was observed in 6.7% (n=2) and 23.3% (n=7) had normal glucose tolerance and 3.3% (n=1) had diabetes.
Discussion: Regarding the outcomes of this study, it can be concluded that the prevalence of microalbuminuria has been observed to be higher in pre-diabetic situations such as IFG and IGT. Although both IFG and IGT have the progression potential towards diabetes, IGT should be considered a more serious condition.
Keywords: Microalbuminuria, Pre-Diabetes, Renal Impairment, Diabetic Nephropathy
Introduction
Diabetes mellitus is an emerging health issue with increasing prevalence all over the world, especially due to the increase in type 2 diabetes (type 2 DM). Diabetic nephropathy is one of the major complications of diabetes that outrageously increases cost of care. As the progression of diabetes continues, diabetic renal disease will account for >50% of patients in dialysis units [1].
Additionally, the prevalence of undiagnosed diabetes or prediabetes is considerably high in chronic renal diseases. Cross-sectional studies show that prediabetes is associated with chronic renal failure (CRF), but it is not known whether it will predict CRF in people who do not progress to diabetes. Prospective studies have not demonstrated that prediabetes is an independent risk factor for albuminuria or the frequency of CRF. It is thought that prediabetes may be a causal factor for the development of CRF [2, 3].
The American Diabetes Association (ADA) recommends 24-hour urine microalbumin testing as the gold standard for nephropathy screening in diabetic patients [4]. However, difficulties in collecting urine for 24 hours showed that spot urine albumin to creatinine ratio (ACR) measured in diabetic patients can be utilized in the detection of nephropathy in diabetic patients [5]. However, the validity of ACR in spot urine in prediabetic patients has not yet been clearly demonstrated. The prevalence of microalbuminuria and macroalbuminuria for both types of diabetes is 30-35% [6].
Albuminuria (albumin to creatinine ratio) or urinary albumin excretion (UAE) should be analyzed 5 years after the diagnosis of type 1 diabetes or at puberty and should be checked at the time of diagnosis and annually thereafter in type 2 diabetes mellitus. The first-morning (or spot) urine is preferred in the analysis of albumin creatinine ratio. It has been stated that rather than progressing to microalbuminuria or macroalbuminuria, the change in UAE must be taken into account [7].
Normoalbuminuria is defined as <30mg/g ACR in the first-morning (or spot) urine and <30 mg/day UAE, <20 µg/minutes UAE rate in a 24-hour period. Microalbuminuria is defined as 30 – 300 mg/g ACR in the first-morning (or spot) urine and 30 – 300 mg/day UAE, 20 – 200 µg/minutes UAE rate in a 24-hour period. Macroalbuminuria or clinical albuminuria is defined as >300 mg/g ACR in the first-morning (or spot) urine and >300 mg/day UAE, >200 µg/minutes UAE rate in a 24-hour period. The clinician should bear in mind that heavy exercise, infection, fever, congestive heart failure, hypertension, and remarkable hyperglycemia might elevate UAE. Nephropathy screening tests should not be performed until these problems are solved or controlled. In order to establish a diagnosis of MAU 2 of 3 laboratory results should indicate higher values [8].
Melsom et al. (2016) reported 1261 nondiabetic patients followed for 5.6 years [9]. In their study, prediabetes was also observed in the early stages of diabetes as well as glomerular hyperfiltration and albuminuria have been shown to be associated with the development of diabetes [9]. The measurement of microalbuminuria to investigate early-stage nephropathy in adults eGFR needs to be calculated. In addition, eGFR can be calculated from the MDRD, CKD-EPI, or Cockcroft-Gault formulas by measuring the serum creatinine level [9, 10].
To monitor the progression of diabetic nephropathy in patients who develop microalbuminuria, the urine albumin/creatinine ratio should be measured more frequently. Nephropathy is one of the most important causes of morbidity and mortality in adult diabetic patients. Patients with persistent microalbuminuria have a high risk of retinopathy, therefore fundus examination should be performed more closely [11].
The inhibition of the renin angiotensin system plays a major role in the prevention of glomerular hypertension and hyperfiltration thus reducing albuminuria and kidney damage. These renal protective effects are mainly due to the vasodilator effect on efferent glomerular arterioles and as a result attributed to a decrease in glomerular pressure. In patients with microalbuminuria, it is appropriate to use an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) to help prevent progression to macroalbuminuria [12].
Glycemic and blood pressure control, treatment of dyslipidemia, and smoking cessation are essential to prevent the progression of nephropathy. In addition, weight loss may play an important role in preventing DRD and slowing its progression. Renal replacement therapy should be applied when end-stage renal failure develops [13].
In this study, it was aimed to elucidate the effect of microalbuminuria with albumin creatinine ratio in pre-diabetic patients and to follow the patients for a period of 2 years. In this follow-up period, patients with microalbuminuria will be compared with pre-diabetic patients without microalbuminuria and it will be investigated whether microalbuminuria is a risk factor in pre-diabetic patients.
Material and Methods
In this prospective study, we have enrolled 90 patients, including n=30 patients with impaired glucose tolerance (IGT), n=30 patients with impaired fasting glucose (IFG), and n=30 in the control group. The diagnosis of IGT has been established via 75 gr glucose loading in individuals who have been admitted to the outpatient clinic of our institution. The study has been approved by the Ethics Committee and was conducted according to the Guidelines of the Declaration of Helsinki. Informed consent has been obtained from all participants.
The enrolled patients have been followed up every 6 months for a period of 2 years prospectively. The renal function tests, insulin levels, body mass indexes, uric acid levels, CRP levels, and urinary ACR levels were recorded and monitored every 6 months, and annual data were noted. Individuals who developed diabetes during follow-up were recorded and their treatments were initiated.
Inclusion Criteria
The inclusion criteria were as follows: results of glucose tolerance test (GTT, 75 g), and IFG≥ 100mg/dL. IGT was defined as between 140-199 mg/dL of serum glucose after two-hour oral 75 g glucose consumption.
Exclusion Criteria
The exclusion criteria were hypertension, heart failure, patients with overt diabetes that would cause microalbuminuria, renal failure, pre-existing proteinuria, recent urinary tract infection. Patients who had been using corticosteroids, spironolactone, ACE inhibitors, and ARBs were excluded from the study.
Statistical Analysis
Patient data collected within the scope of the study were analyzed with the IBM Statistical Package for the Social Sciences (SPSS) for Windows 23.0 (IBM Corp., Armonk, NY) package program. Frequency and percentage were given for categorical data, and median, minimum, and maximum descriptive values for continuous data. For comparisons between groups, the Mann Whitney U-Test was used for two groups, the Kruskal Wallis H-Test for more than two groups, and the Pearson Chi-square Test was used to compare categorical variables. The results were considered statistically significant when the p-value was less than 0.05.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Within the scope of the study, the evaluation was made on 90 patients, including n=30 impaired glucose tolerance (IGT), n=30 impaired fasting glucose (IFG), and n=30 in the control group. According to the initial evaluations, there was no statistically significant difference between the three groups in terms of gender (p>0.05). Age, body mass index (BMI), initial laboratory parameters of FBG, PPBG, HBA1C, insulin, BUN, uric acid, urine albumin, urinary creatinine, ACR, and CRP values were found statistically significant between the groups (p<0.05) (Table 1). When the age distribution of the groups, BMI, FBG, HBA1C, insulin, BUN, uric acid, and CRP values were examined, it was seen that the values were higher in the IGT and IFG groups compared to the control group.
The demographic, baseline, and second-year laboratory parameters distribution of 30 patients with impaired glucose tolerance (IGT) and 30 patients with impaired fasting glucose (IFG) included in the study are shown in Table 2. When the table was examined, it was seen that there was a statistically significant difference between the two groups in terms of demographic data, age, and BMI (p<0.05). There was a significant difference between the two groups in PPBG, HBA1C, insulin, urine albumin and ACR parameters (p<0.05).
It was noteworthy that the initial laboratory results of patients with impaired glucose tolerance were higher than those of individuals with impaired fasting glucose. In the second-year laboratory data, significant differences were observed in other parameters other than urine albumin, which were significant in the initial laboratory data such as PPBG, HBA1C, insulin, urine albumin, and ACR (p<0.05). It was observed that the laboratory results of patients with impaired glucose tolerance were higher than the laboratory results of individuals with impaired fasting glucose. These parameters showed significant differences in laboratory parameters in the second year.
After a two-year follow-up of the patients, 46.7% (n=14) of patients with impaired glucose tolerance (IGT) had impaired glucose tolerance again, while 13.3% (4 individuals) had impaired fasting glucose and 23.3% (n=7) had normal glucose tolerance and 16.7% (n=5) had diabetes. Similarly, impaired fasting glucose was observed in 66.7% (n=20) of patients with impaired fasting glucose (IFG) at the beginning, while impaired glucose tolerance was observed in 6.7% (n=2) and 23.3% (n=7) had normal glucose tolerance and 3.3% (n=1) had diabetes (Figure 1).
Discussion
The prevalence of impaired glucose tolerance worldwide has been stated as 6.7% in the International Diabetes Federation (IDF) atlas (2015). It is estimated that 318 million people are presumed to be pre-diabetic and this number is predicted to reach 481 million people in 2040. The frequency of pre-diabetes increases with age. The main differences between IFG and IGT can be elaborated as IGT is associated with peripheral insulin resistance (skeletal muscle), while IFG is associated with increased gluconeogenesis. In combined situations, hepatic and extrahepatic insulin resistance and increased gluconeogenesis persist. Isolated first phase insulin secretion defect (early phase) is observed in IFG, while both the first (late phase) and the second phase release defect is associated with IGT [14]. IGT is more closely related to future diabetes and the coexistence of IFG and IGT doubles the risk. IGT has been correlated with increased cardiovascular risks and microvascular complications such as retinopathy and neuropathy [15].
The rate of progression to diabetes from IFG and IGT within 3-5 years is 25% [16]. On the other hand, glucose tolerance remains the same in 50% of the individuals, while 25% returns to normal. Those with additional diabetes clinical risk factors (obesity, family history) have a higher risk of developing diabetes. Additionally, the annual risk of conversion of impaired glucose tolerance to diabetes is 3-11%, while the lifetime risk of type 2 diabetes varies up to 50% [17]. The conversion of pre-diabetes to diabetes in different genetic characteristics is reported as 114.4 versus 2.3/1000 people [18]. In our study half of the patients (46.7%) with IGT had no change in their status in the second year, while 16.7 of them have progressed to diabetes. Additionally, 66.7% of patients with impaired fasting glucose (IFG) at the beginning remained the same within 2 years, while impaired glucose tolerance was observed in 6.7%, 23.3% had normal glucose tolerance and only 3.3% had diabetes.
Prediabetes is a major risk factor for diabetic chronic renal failure (CRF). The vast majority of newly diagnosed diabetic patients will develop CRF despite optimal treatment. Pre-diabetes is about twice as common as diabetes, affects 20-35% of adults, and progresses to diabetes after 10 years in approximately 45-50% of individuals. Cross-sectional studies show that prediabetes is associated with CRF, but it is not known whether it will predict CRF in people who do not progress to diabetes.
Previous literature has reported that approximately 1/3 of newly diagnosed diabetics already have kidney damage, indicating a very early onset of renal failure. In the meta-analysis by Echouffo-Tcheugui et al. (2016), 9 cohort studies evaluating a total of 185.452 patients, the relative risk for the development of CRF in prediabetics was found to be 1.11 (CI 951.02 -1.21) [19].
In this current study, we have investigated the effect of microalbumin¬uria with albumin to creatinine ratio in pre-diabetic patients and followed up the patients for a period of 2 years with respect to control group. In this follow-up period, patients with microalbuminuria were compared with pre-diabetic patients without microalbuminuria, and whether microalbuminuria is a risk factor in pre-diabetic patients was investigated.
Similar studies have been published previously elaborating microalbu¬minuria in prediabetic subjects. Franciosi et al. found that microalbuminuria was present in 6.9%, 5.6%, and 4.3% in IFG, IGT, and control groups, re¬spectively [20]. Tapp et al. have reported that the prevalence of microalbuminuria was 8.3% in IFG, 9.9% in IGT, and 4.3% in the control group [21]. It should be kept in mind that different values could be attributed to geographical demographics and laboratory methods. However, it is evident that urine albumin was significantly higher in patients with IFG and IGT.
The association between IFG and microal¬buminuria has been introduced by Meigs in Framingham Offspring Study (2002) two decades ago [22]. Bahar et al. (2013) published an important article emphasizing that the prevalence of microal¬buminuria in the IGT group was higher than in the IFG group, and IGT was identified as the most important risk factor for microalbuminuria [23]. Our results were in line with these studies and we have found that the laboratory parameters of patients with impaired glucose tolerance were higher than those of individuals with impaired fasting glucose. These differences such as PPBG, HBA1C, insulin, urine albumin, and ACR were significantly persistent in the second year. It was observed that the laboratory results of patients with impaired glucose tolerance were higher than the laboratory results of individuals with impaired fasting glucose. These parameters showed significant differences in laboratory parameters in the second year.
The main limitation of this study could be attributed to its relatively small sample size. Additionally, the ideal follow-up period should have been at least 5 years in order to accurately observe the development of diabetes and microalbuminuria in renal functions. All the individuals have been performed OGT at the diagnosis stage however, this test had not been re-performed annually.
Since there are few studies emphasizing renal dysfunction that can develop in prediabetic patients, this may be an advantage of this research. Increasing the widespread use of microalbuminuria for the predictive purpose was the main focus of this study leveraging a cost-effective test that can be performed in each hospital in the detection of renal injury that may develop in prediabetic patients. In addition, as in other studies requiring follow-up, the fact that during the two years of follow-up period enabled patients to display a more conscious and careful attitude may be another strength of this study.
Conclusion
Regarding the outcomes of this study, one can conclude that the prevalence of microalbuminuria has been observed higher in pre-diabetic situations such as IFG and IGT. Although both IFG and IGT have the progression potential towards diabetes, IGT is considered a more serious condition.
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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The relationship between depression and vitamin D levels in the geriatric population
Çiğdem Cindoğlu 1, Burcu Beyazgül 2, Şenay Koçakoğlu 3
1 Department of İnternal Medicine, 2 Department of Public Health, 3 Department of Famıly Medıcıne, Faculty of Medicine, Harran University, Sanliurfa, Turkey
DOI: 10.4328/ACAM.21550 Received: 2022-12-13 Accepted: 2023-04-05 Published Online: 2023-04-11 Printed: 2023-06-01 Ann Clin Anal Med 2023;14(6):494-497
Corresponding Author: Çiğdem Cindoğlu, Department of İnternal Medicine, Faculty of Medicine, Harran University, Sanliurfa, Turkey. E-mail: ccindoglu@gmail.com P: +90 505 228 13 75
Corresponding Author ORCID ID: https://orcid.org/0000-0002-1805-6438
This study was approved by the Ethics Committee of Harran University, Faculty of Medicine (Date: 2020-03-09, No: 76244175-050.04.04)
Aim: The aim of this study is to evaluate the frequency of depression and vitamin D deficiency and the relationship between them in the geriatric population.
Material and Methods: A cross-sectional and prospective study was carried out with 92 patients. Elderly patients who applied to the Internal Medicine Polyclinic of Harran University Hospital between October 2020 and July 2021, agreed to answer the GDS questionnaire and whose vitamin D levels were checked during examinations were included in the study.
Results: Of the 145 participants, 91 (66.8%) were women and 54 (37.2%) were men, with a mean age of 72.8 ± 6.2 years. According to the GDS results, the mean depression score of the participants was 6.3 ± 3.5. Depression was present in 64.1% (n= 93) of the participants, and 72.5% of these 93 depressed patients were women. When the relationship between depression status and socio-demographic variables was examined, it was found that depression was significantly more common in those with poor income and living in large families (p < 0.05).
Discussion: According to the findings of this study, vitamin D deficiency can be regarded as a comorbidity of depression, and early detection and management of vitamin D deficiency and depression will improve both individual and public health.
Keywords: Geriatric, Depression, Vitamin D Deficiency, Elderly
Introduction
Adults aged 65 years and over are generally included in the elderly population. Depression in the elderly is an important public health problem due to its high prevalence, clinical consequences, and complications [1,2]. In 2014, it was reported that 8% of the population in Turkey is 65 years of age or older, and this rate is estimated to reach 10.2% in 2023, 20.8% in 2050, and 27.7% in 2075 [3]. In this group, symptoms should be carefully questioned, and depression should be diagnosed as early as possible. However, due to decreased daily activity and comorbidities in the elderly, depression symptoms, such as weight loss, low energy, and changes in appetite and sleep, might be overlooked. The Geriatric Depression Scale (GDS) is an instrument used to identify depression by identifying symptoms of depression and dementia in the elderly [4,5]. Vitamin D deficiency, which is also common in the elderly due to environmental and physiological changes, is an important public health problem in all age groups worldwide [6]. In the last decade, studies have focused on the effects of vitamin D on psychiatric disorders, especially depression. The results of some of them suggest that there is a significant relationship between them, and that the treatment of vitamin D deficiency may have positive effects on the development and treatment of depression [7-9].
Receptors and metabolites of vitamin D were shown in the cerebrospinal fluid, prefrontal cortex, and limbic system. Findings related to the central nervous system suggest that vitamin D, an important neurosteroid hormone, may play a role in emotional and cognitive functions [10-12].
Problems related to both depression and vitamin D deficiency are common in society and in the rapidly increasing elderly population. This study was planned to investigate the frequency and relationship between depression and vitamin D deficiency in the geriatric population in Turkey.
Material and Methods
A cross-sectional and prospective study was carried out among 92 patients. The elderly patients who applied to the Internal Medicine Polyclinic of Harran University Hospital between October 2020 and July 2021, who agreed to answer the GDS questionnaire and whose vitamin D levels were checked during examinations were included in the study. The GDS and a questionnaire created by the researchers were presented using a face-to-face survey method to collect data. The vitamin D values of the participants were obtained from the hospital data system. Vitamin D deficiency is accepted as “severe” for values below 10 ng/mL; between 10 and 20 ng/mL as “mild deficiency” and between 20 and 30 ng/mL as “insufficiency”, ≥30 ng/Ml as “normal” [20]. The study was approved by the Ethics Committee of Harran University, Faculty of Medicine (approval no 76244175-050.04.04; dated 09.03.2020), and informed consent was obtained from all participants.
The Geriatric Depression Scale
The GDS is a 30-item scale developed by Yesavage et al. in 1983 [13]. A Turkish validity and reliability study of the 15-item short-form version of the scale for use with elderly populations was conducted by Durmaz et al. in 2018. The GDS-short form consists of 15 questions and is answered with “Yes” or “No”. GDS- short form total score is 15. Depression levels are defined as “normal” for scores between 0-4, between 5 -8 as “mild”, between 9-11 as “moderate”, and between 12-15 as “severe” [14].
Statistical analysis
A pilot study was conducted to calculate the number of participants. In the pilot study, the short-form GDS was administered to the participants, and it was determined whether they were depressed according to the prediction score. The total number of participants who underwent GDS was 145. However, vitamin D analyses of 53 participants could not be performed due to external factors, including analyzer failure. Correlation analyses were performed with the measured vitamin D levels of 92 participants. The vitamin D levels were 20.6 ± 7.5 ng/mL in depressed patients and 13.3 ± 15.4 ng/mL in non-depressed patients. The sample size was calculated using these values and the G-power method. SPSS version 22.0 software (IBM Statistical Package for Social Sciences, IBM Corporation, NY, USA) was used. The significance level was accepted as p < 0.05. The Kolmogorov–Smirnov test was performed to evaluate the suitability of the data for normal distribution. Frequency, mean, and standard deviation values were calculated to determine the distribution, and chi-square and Student’s T tests were used for depression and the variables whose effects were assessed.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Of the 145 participants, 91 (66.8%) were women and 54 (37.2%) were men, with a mean age of 72.8 ± 6.2 years. Other demographic details were as follows: 30.6% of the participants were literate and 69.4% were illiterate, 69% were married and 60.1% lived with an extended family, 22.4% had a low income, and 80% were using prescribed pharmaceuticals due to some diseases.
According to the GDS results, the mean depression score of the participants was 6.3 ± 3.5. Depression was present in 64.1% (n= 93) of the participants, and 72.5% of these 93 depressed patients were women. When the relationship between depression status and socio-demographic variables was examined, it was found that depression was significantly more common in those with poor income and living in large families (p < 0.05). The relationship between the other variables and depression is shown in detail in Table 1.
Vitamin D levels were below the normal range of 90.9% in the study participants: 32.7% showed severe deficiency, 42% showed mild deficiency, and 15.3% showed insufficiency. The correlation of deficiencies with GDS scores is shown in Table 2. Vitamin D levels were lower in the depressed elderly, but there was no significant difference between the depressed and non-depressed groups (p = 0.85) (Table 3).
Discussion
Depression is a psychiatric disorder that is common among geriatric patients and can reduce their quality of life, increasing morbidity and mortality. Vitamin D, an important neurosteroid hormone, may have an impact on depression, so many researchers have focused on its potential effects on the geriatric population. According to this study, which evaluated the relationship between depression and vitamin D in the elderly, it was determined that depression was increased in the elderly population, especially among women, and that vitamin D levels were lower than the ideal range. However, the relationship between the level of vitamin D and depression was not significant.
Depressive disorders and symptoms affect 10% of geriatric individuals. A meta-analysis revealed that the rate of major depressive disorders was higher in women (5.8%). In our study, the rate of depression in women was 70.3%, which was higher than in men [15].
It has been observed that due to low D vitamin levels, a decrease in physical-mental performance and an increase in the incidence of falls, and also fracture risk occur [16,17].
A study from Korea reported an increased rate of deficiency of vitamin in the geriatric population up to 60%. Several studies reported the association of vitamin D with many chronic and autoimmune diseases, malignancy and depression. There is also strong evidence that it is associated with cognitive disorders [18,19].
Several studies have also revealed a significant relationship between depression [20,21].
However, according to the results of Toffanello et al.’s study, there was no significant relationship, and vitamin D deficiency showed no direct effect on the onset of late-life depressive symptoms [22].
The differences in the socio-demographic characteristics of participants and some problems affecting vitamin D synthesis, such as nutrition, sun exposure diversity in the elderly, and kidney function disorders in older ages can cause the difference between study results on this issue. In the selection of participants and the problems affecting vitamin D synthesis, such as nutrition, sun exposure diversity in the elderly, and kidney function disorders in older ages.
Conclusion
The elderly were found to have higher rates of depression in this study. Although vitamin D deficiency was more common in elderly patients who were depressed, there was no significant relationship between them. According to the findings of this study, vitamin D deficiency can be regarded as a comorbidity for depression, and early detection and management of vitamin D deficiency and depression will improve both individual and public health.
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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Çiğdem Cindoğlu, Burcu Beyazgül, Şenay Koçakoğlu. The relationship between depression and vitamin D levels in the geriatric population. Ann Clin Anal Med 2023;14(6):494-497
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The distinctive role of systemic immune-inflammatory parameters in gestational trophoblastic diseases
Levent Ozgen
Department of Gynecological Oncology Surgery, Faculty Of Medicine, Uludag University, Bursa, Turkey
DOI: 10.4328/ACAM.21576 Received: 2023-01-05 Accepted: 2023-02-07 Published Online: 2023-04-04 Printed: 2023-06-01 Ann Clin Anal Med 2023;14(6):498-501
Corresponding Author: Levent Ozgen, Department of Gynecological Oncology Surgery, Faculty Of Medicine, Uludag University, Gorukle, Bursa, Turkey. E-mail: drozgenl@yahoo.com P: +90 534 795 98 77 F: +90 224 295 50 00 Corresponding Author ORCID ID: https://orcid.org/0000-0003-0070-2646
This study was approved by the Ethics Committee of Health Science University Bursa Yüksek İhtisas Training and Research Hospital (Date: 2022-09-14, No: 2011-KAEK-25)
Aim: In this study, we aimed to distinguish molar pregnancies from healthy pregnancies with the parameters that make up simple hematological tests that can be easily applied in the routine and to increase diagnostic sensitivity.
Material and Methods: This retrospective cohort study was conducted between January 2018 and September 2022 at the University Hospital Gynecology Clinic.The study included 80 partial hydatidiform moles (PMH), 45 complete hydatidiform moles (CMH) and 50 healthy pregnant women. Before surgical curettage in molar pregnants and in routine antenatal examinations in healthy pregnant women, white blood cell (WBC) counts, neutrophil (NC) counts, lymphocyte (LC) and platelet counts (PLT), red cell distribution width (RDW), mean platelet volume (MPV), platelet distribution width (PDW), hemoglobin (Hb) and fibrinogen results were recorded. The Neutrophil-lymphocyte ratio (NLR), Platelet-lymphocyte ratio (PLR) and systemic immune-inflammatory index (SII) were calculated based on the results of complete blood count.
Results: WBC [8.5±2.30] vs [10.2±5.6]103/mm3, NC [6.05±5.56] vs [7.5±6.05]103/mm3, PDW [16.59±0.9] vs [16.87±0.75]% in PMH and CMH groups, respectively and NLR [3.23±2.4] vs [3.61±3.1], Fibrinogen [354±79]vs[347±82 ] mg/dl and SII [689.2±76.1] vs [701.16±52] were measured. These parameters were found significantly higher in molar pregnancy group then the controls. However, MPV [10.4 ± 0.1]fL and RDW [14.5 ±1.21] % values were significantly higher in healthy pregnancies than in molar pregnancies (p<0.05 for two parameters).
Discussion: A higher inflammatory response is observed in molar pregnancies than in healthy pregnancies due to uncontrolled trophoblastic growth. Accelerating the diagnosis of GTD allows for early treatment with simple prognostic variables available from the measurement of peripheral blood cells.
Keywords: Blood Cells, Mole Hydatiform, Trophoblastic Disease
Introduction
Gestational trophoblastic diseases (GTD) are a group of diseases that develop as a result of abnormal fertilization and are characterized by abnormal, excessive proliferation of trophoblasts. It has a wide range from a hydatidiform mole that originates from the placenta and may result in spontaneous resolution to life-threatening choriocarcinoma [1-3]. Hydatidiform mole (HM) is the most common form of GTD. It consists of two clinical forms that differ from each other in different cytogenetic, histological, clinical and prognostic features: PHM with 1-4% less invasion and malignant potential, and CMH with 15-20% higher risk of invasion and malignancy [4].
Progress in ultrasonographic imaging (USI) and easier and more sensitive measurement of beta human chorionic gonadotropin (β-hCG) levels have facilitated the diagnosis of molar pregnancy. The characteristic USI for CMH is in the first trimester; It is a “snowstorm”-looking placenta formed by vesicles formed as a result of hydropic swelling of the chorionic villi in the absence of fetal tissue and amniotic sac. The characteristic USI for PMH is a large placenta with a “Swiss cheese” appearance, with focal cystic spaces in the placental tissues. Despite all these findings, it is difficult to diagnose with only USI and β-hCG in early pregnancy [5,6]. GTD includes trophoblastic diseases with varying degrees of malignant potential. GTN can occur after molar or non-molar pregnancies. Today, it is the most cured gynecological malignancy, and programmed follow-up is critical in the management of the disease [4].
New parameters such as NLR, PLR, which are formed by formulating simple blood count parameters (CBC), which are various non-invasive markers, have started to be used as systemic immune response markers (SIR) in most pathological inflammations and malignancies [7,8]. In various studies, it has been shown that decidual trophoblastic cells behave like cancer cells due to their proliferative, migratory and invasive properties and share the same common molecular features. Inflammation brought about by angiogenesis, invasion, and metastasis leads to lymphocytosis, neutrophilia, thrombocytosis, and lymphocytopenia [9,10].
The aim of the study to explain the pathophysiological mechanisms of molar pregnancy with parameters that can be easily applied in routine and simple hematological tests and to increase its diagnostic sensitivity in distinguishing it from healthy pregnancies.
Material and Methods
The study was carried out at the University Hospital Gynecology Clinic between January 2018 and September 2022. A total of 125 patients aged between 18-45 years, who were followed up and treated for the diagnosis of mole hydatidiform (PMH: n=80; CMH: n=45) and 50 healthy first trimester pregnant women were included in the study. Study inclusion criteria were defined as positive pregnancy test, gestational age of<12 weeks, healthy singleton pregnancy, final pathology result, CMH and/or PMH, respectively. Pregnant women with an ectopic pregnancy, a history of chronic systemic disease, disorders in bleeding parameters, using anti-inflammatory drugs, and those with a positive result for malignancy were excluded from the study. Mole hydatidiform pregnancy was diagnosed by pathological examination of curettage material. Demographic characteristics and CBC parameters of the patients were recorded at their first hospitalization before vacuum curettage. NLR, PLR and SII were calculated according to laboratory results (NLR = neutrophil count/lymphocyte count ratio; PLO =platelet count / lymphocyte count ratio; SII = platelet count x neutrophil count / lymphocyte count ). This study was approved by the institutional review board (2011-KAEK-25 2022/09-14 ).Written informed consent was obtained from all participants.
Statistical Analysis
SPSS (ver.23) program was used for statistical calculations. Statistical comparisons between groups were performed using the Student’s t-test and the Mann-Whitney U test. Descriptive data were expressed as mean values and standard deviation. The statistical significance level was accepted as 0.05.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
In the group of 125 molar pregnancies included in the study, 80 patients had PMH (66.6%) and 45 patients (33.4%) had CMH final pathology results. Arh (+) was the most common blood group in 32.4% of the patients, and ARh (-) was the least common blood group in 1.5% of the patients. Only in CMH patients, the pre-curettage β-hCG level was statistically significantly higher (p=0.087). There was no statistically significant difference between molar pregnancy groups in terms of demographic characteristics (p<0.05) (Table 1).
WBC [8.5 ± 2.30] vs [10.2±5.6]103/mm3, NC [6.05±5.56] vs [7.5±6.05] 103/mm3, PDW [16.59±0.9] vs [16.87±0.75] % in PMH and CMH groups, respectively and NLR [3.23±2.4] vs [3.61±3.1], Fibrinogen [354 ±79]vs [347±82 ] mg/dl and SII [689.2±76.1] vs [701.16±52 ] were measured. These parameters were found significantly higher in molar pregnancy group then the controls. However, MPV[10.4±0.1] fL and RDW[14.5±1.21 ]% values were significantly higher in healthy pregnancies than in molar pregnancies (p<0.05 for two parameters). There was no statistical difference between the 3 groups in terms of Hb,PLT, LC and PLR (p>0.05 for all parameters (Table 2).
Discussion
Molar pregnancies and gestational trophoblastic neoplasia (GTN) originate from placental trophoblasts. After excessive abnormal uncontrolled proliferation and invasion of these trophoblasts, GTN occurs [1,2,10]. Decidual implantation, myometrial invasion and abnormalities in immunological tolerance are also blamed in the etiology of GTN. The pathophysiological mechanism underlying molar pregnancies is still unclear. In CMH, lack of villous trophoblast development and defective placentation due to endovascular trophoblastic invasion may lead to inadequate development of the placental decidual interface. However, the presence of maternal genome in PMH may be a reason for adequate interaction between trophoblasts and the decidual layer, according to CMH. This may be due to an inadequate inflammatory response to enhanced trophoblastic invasion in GTD [11,12].
MPV and PDW, indicative of early platelet activation, and platecrit have been associated with conditions with thrombosis and inflammation. The increase in these values is associated with ongoing inflammation. Interpretation of MPV and PDW together is much more effective in the evaluation of platelet activation. Increased platelet count and aggregation allow the tumor to escape from the immune response [13]. With increased inflammatory response and abnormal syncytiotrophoblast activation, dilutional thrombocytopenia due to increased intravascular volume and increased MPV and PDV values are seen in preeclampsia, hyperemesis gravidarum and GTD, which are placental invasion anomalies compared to healthy pregnancies [14]. While leukocytosis develops as a result of the ongoing inflammatory process, adhesion molecules are released into the circulation as a result of this activation and various immune mediators become evident during pregnancy from implantation. Eskicioglu et al. in their study between women with molar pregnancies and women with healthy pregnancies, found decreased PDW levels and WBC values, and found no difference in platelet and MPV values. These results has been atributed due to the loss of cytotrophoblast invasion in complete molar pregnancies [15]. Unlike this study, Aiob et al. in their study comparing molar pregnancy and missed abortion, observed a higher neutrophil level in molar pregnancies [16]. We also found a statistically significant increase in WBC and NC in the molar pregnancy group in this study. This increase was not significant between partial and complete molar pregnancy subgroups. This result suggests that molar pregnancies may cause a higher inflammatory response due to continued trophoblastic growth. In the study by Yayla et al. in which they compared molar pregnancies and healthy pregnancies, they found low MPV, PDW, WBC and an increase in NC, similar to our study [17].
Another marker used in the clinic RDW is a parameter that shows the distribution of erythrocyte volume; it has been shown to increase as a result of defective erythropoiesis, increased inflammation, or hemolysis. Zhang et al. stated an increase in RDW and platelets in invasive moles and attributed the increase in these parameters, which increased in the inflammatory circulation, to the primary immune response secondary to changes in the hemopoietic activity in the bone marrow [18]. In this study, however, there was no significant difference in platelet count between molar pregnancy and healthy pregnancy, while RDW value was found to be low in molar pregnancies, unlike this study.
The neutrophil- to- lymphocyte ratio is a quick and simple test to reach the result, which is accepted as a marker of the body’s immune response to foreign agents. Various studies have reported increased NLR as a predictor of outcomes in trophoblastic endometrial precancerous and cancerous lesions with abnormal uterine bleeding [19]. Guzel et al. suggested that NLR was higher in women who developed invasive moles than in women who did not, and could be used as a biomarker of invasion in GTD [20]. Genc et al. also found NLR to be statistically significantly higher in the molar pregnancy group in their study on hydatidiform mole, healthy pregnancy and non-pregnant gynecology groups [21]. In the current study, we found that the NLR value was higher in the molar pregnancy group compared to the healthy pregnancies, but we did not find a statistically significant difference between the groups in another marker, PLR.
SII, which is another recent new inflammatory index, calculated from platelet, neutrophil and lymphocyte counts, is a much more important marker in demonstrating inflammation and immune response compared to PLR and NLR. Studies have shown that high SII values are associated with disease severity and poor prognosis in many diseases and malignancies [22]. In this study, we found that the SII value is significantly higher in molar pregnancies than in healthy pregnancies, especially in complete moles. The increase in this parameter is the immune response of blood cells to physical stress in molar pregnancies; oxidative stress and inflammation can cause such systemic consequences.
Conclusion
There are few studies that have examined inflammatory markers that make up the parameters of the CBC with a sufficiently large number of cases of GTD. The significant differences in PDW and MPV, which are indicators of platelet activation in the current study, suggest that molar pregnancies require less PLT activation compared to intrauterine pregnancy requiring adequate and healthy endometrial invasion. At the same time, high leukocyte counts, NLR and SII values we detected in molar pregnancies indicate an increased inflammatory response in the etiopathogenesis of GTD. With simple prognostic variables available from CBC counts widely available in clinical practice, even in countries with limited health resources around the world, accelerating the diagnosis of GTD could enable early diagnosis and treatment, while at the same time preventing female deaths and adverse outcomes.
The main limitations of this study are its single-center, retrospective design and relatively small sample size.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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8. Stojkovic Lalosevic M, Pavlovic Markovic A, Stankovic S, Stojkovic M, Dimitrijevic I, Radoman Vujacic I, et al. Combined diagnostic efficacy of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV) as biomarkers of systemic inflammation in the diagnosis of colorectal cancer. Dis Markers. 2019; DOI:10.1155/2019/6036979.
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The effect of pregnancy-related urinary incontinence on incidence and quality of life
Fatih Şahin 1, Erhan Aktürk 1, Ramazan Adan 1, Simten Genç 1, Veli Mihmanlı 1, Arzu Yurci 2, Fatma Nur Çetinkaya 1, Neslihan Bademler 1, Tuğba Salman 1
1 Department of Obstetrics and Gynecology, Prof. Dr. Cemil Taşçıoğlu City Hospital, 2 Department of In Vitro Fertilization, Bahcelievler Memorial Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.21587 Received: 2023-01-12 Accepted: 2023-04-05 Published Online: 2023-04-27 Printed: 2023-06-01 Ann Clin Anal Med 2023;14(6):502-506
Corresponding Author: Tuğba Salman, Department of Obstetrics and Gynecology, Prof. Dr. Cemil Taşçıoğlu City Hospital, Sisli, Istanbul, Turkey. E-mail: tugbasalmann@gmail.com P: +90 543 540 78 02 Corresponding Author ORCID ID: https://orcid.org/0000-0002-5955-007X
This study was approved by the Clinical Research Ethics Committee of Istanbul Prof. Dr. Cemil Taşcıoğlu City Hospital (Date: 2022-11-28, No: 319)
Aim: In this study, we aimed to determine the incidence of urinary incontinence during pregnancy and to evaluate its effects on quality of life.
Material and Methods: The study was designed as a cross-sectional descriptive study. The University of Michigan Incontinence Symptom Index (M-ISI) questionnaire was administered to 549 pregnant women who applied to the antenatal outpatient clinics of Prof. Dr. Cemil Taşcıoğlu City Hospital between December 2022 and January 2023. Descriptive statistical methods were used to evaluate percentages (%), means (standard deviation (SD)), and medians ((25th and 75th percentiles) (minimum and maximum)). A p-value of <0.05 was considered statistically significant.
Results: Urinary incontinence was observed in 56.1% of the 549 pregnant women included in the study. Mixed urinary incontinence was most common in the third trimester (p=0.001). The mean BMI of pregnant women with stress urinary incontinence was higher than that of continent pregnant women (p=0,001). According to the M-ISI questionnaire, the severity and bother scores of pregnant women with urinary incontinence were higher than those of the continent group (p=0,001).
Discussion: Urinary incontinence is common during pregnancy and negatively impacts the quality of life of pregnant women. Our primary outcome was that urinary incontinence was observed in 56.1% of pregnant women. Our secondary outcome was that according to the M-ISI questionnaire, the bother scores of pregnant women with urinary incontinence were higher than those of the continent group, thus negatively impacting the quality of life of incontinent pregnant women.
Keywords: Urinary Incontinence, Pregnancy, Quality Life, Stress Incontinence
Introduction
Urinary incontinence is one of the major problems that a woman may face throughout her life. In pregnancy, the quality of life of women is affected by the addition of urinary incontinence on top of the unique problems of pregnancy. It affects the quality of life of approximately 54.3% of pregnant women, including physical activity, travel, social relationships, and emotional status [1].
Stress, urge and mixed components can be seen in involuntary urinary incontinence. Studies have shown that stress urinary incontinence (SUI) is the most common among pregnant women [2]. Although the true prevalence is still unknown, the prevalence of SUI varies between 18.6% and 75% in the literature [3]. Pregnancy is one of the major risk factors for SUI among young women. Weakness in pelvic floor muscles (PFM), urethral hypermobility and urethral sphincter insufficiency play a role in the pathophysiology of SUI. Changing hormonal status during pregnancy is also effective in the development of SUI. In summary, urinary incontinence may develop as a result of the effect of changing hormones during pregnancy, relaxation in the pelvic muscles and ligaments, compression of the growing uterus on the bladder in the following weeks, and engagement of the fetal head in the last trimester.
Although the prevalence of stress urinary incontinence increased from the 1st trimester to the 3rd trimester, in a study conducted, serious disturbing urge urinary incontinence (UUI) symptoms were observed in 16.9% of pregnant women [4]. Despite this, the quality of life of pregnant women was not affected much in some publications, this may be due to the fact that urge symptoms are not severe, or the fact that pregnant women consider urinary incontinence as a natural part of pregnancy [5].
In studies, pregnant women with urinary incontinence have lower quality of life scores than those without urinary incontinence [avaible at: https://onlinelibrary.whiley.com], and this situation becomes more severe with the progression of the gestational week. Scales specifically developed to differentiate urinary incontinence type, such as the Questionnaire for Urinary Incontinence Diagnosis (QUID), cannot evaluate quality of life scores. International Consultation on Incontinence Questionnaire (ICIQ) evaluates both quality of life and urinary incontinence type, but does not identify its severity with urinary incontinence type [6]. The Michigan Incontinence Symptom Index (M-ISI) scale, whose reliability and validity has been proven for both clinical and research use, was used in this study. We aimed to evaluate the incidence of urinary incontinence and its effects on quality of life in our clinic regarding this situation that pregnant women may encounter.
Material and Methods
This study was conducted as a descriptive and cross-sectional study to examine the effect of urinary incontinence on quality of life according to trimesters of pregnancy. The universe of the research was comprised of pregnant women who applied to the antenatal outpatient clinic of Istanbul Prof. Dr. Cemil Taşcıoğlu City Hospital. The research was carried out between December 2022 and January 2023. The data were collected by the researcher through face-to-face interview technique in a suitable environment in the antenatal outpatient clinic. The average completion time was 15 minutes to fill out the forms. Women with a singleton pregnancy over the age of 18 were included in the study after voluntary consent and signatures were obtained. Pregnant women with active urinary tract infection, pregnant women with no fetal heartbeat during control or in utero mort fetus (IUMF), pregnant women carrying a fetus with a congenital malformation, pregnant women with severe cardiopulmonary disease, kidney disease, liver disease, cerebrovascular disease and serious comorbidities were excluded from the study. Data such as age, height, weight, gravidity, parity, gestational week of the patients were recorded in the case report forms. The Michigan Incontinence Symptom Index (M-ISI) questionnaire consisting of 10 questions was applied to pregnant women. The M-ISI is a Likert-type scale to evaluate its effects on urinary incontinence and quality of life. The scale has ten items divided into 4 parts: SUI (items 1-3), UUI (items 4-6), pad use (items 7 and 8), and irritating effect area (items 9 and 10). Responses to each item range from 0 to 4, with higher values representing more symptoms and more bother [7].
This study investigated the difference in the prevalence of urinary incontinence among trimesters in four different groups: no incontinence, stress incontinence, urge incontinence, and mixed incontinence. The prevalence of incontinence in nulliparous and multiparous pregnant women was also investigated. The BMI (mean (SD)) and M-ISI questionnaire severity and bother scores were compared between the four previously mentioned groups. This study was approved by the Istanbul Prof. Dr. Cemil Taşcıoğlu City Hospital Clinical Research Ethics Committee on November 28, 2022 with approval number 319. In addition, written permission and informed consent were obtained from the pregnant women. The study was conducted in accordance with the Principles of the Declaration of Helsinki.
Statistics
A priori power analysis was conducted using G*Power version 3.1.9.7 to determine the minimum sample size required to test the study hypothesis [8]. Results indicated the required sample size to achieve 80% power for detecting a medium effect, at a significance criterion of α = .05, was N = 159 for [One way ANOVA]. Thus, the obtained sample size of N = 549 is adequate to test the study hypothesis. All analysis was performed using SPSS software (Statistical Package for the Social Sciences, version 16.0, SPSS Inc., Chicago, IL, USA). The Kolmogorov-Smirnov test was used to evaluate the eligibility of the data to normal distribution. Descriptive statistical methods were used to evaluate frequency, percentage, mean (standard deviation (SD)), median ((25th and 75th percentiles) (min and max)) when appropriate. The Chi-square test was used for categorical variables. Student’s t-test and Mann-Whitney U test were used to compare mean values between two independent groups depending on the results of the the Kolmogorov-Smirnov test. One-Way ANOVA and Kruskal Wallis tests were used to compare means between three independent groups. A P-value of <0.05 was considered statistically significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Of the 549 pregnant women included in the study, 43.9% did not have urinary incontinence; 56.1% had urinary incontinence; 9.5% of the pregnant women in the study had stress incontinence, 23.5% had urge urinary incontinence, and 23.1% had mixed type urinary incontinence.
Pregnant women were divided into four groups: no incontinence, stress incontinence, urge incontinence, and mixed incontinence. The difference between the groups was statistically significant (p=0.001). The results are summarized in Table 1.
Subgroup analysis was performed with the Bonferroni correction. Among continent pregnant women, there was statistically significant difference between the first and third trimesters (p=0.001) and the second and third trimesters (p=0.001). The difference between three trimesters was not statistically significant in terms of stress incontinence. There was a statistically significant difference between the first and third trimesters (p=0.001) and the second and third trimesters (p=0.001) regarding urge incontinence. Differences between the first and second trimesters (p=0.004), first and third trimesters (p=0.001) and second and third trimesters (p=0.001) were significant regarding mixed incontinence.
The mean BMI (mean(sd)), was investigated in the 4 previously mentioned groups. The mean BMI of continent pregnant women was 26 (3.9). Statistical differences in BMI were significant among incontinence groups (p=0.001). The mean BMI in pregnant women with stress incontinence was 28.57 (4.06), in pregnant women with urge incontinence it was 26.7 (3.8), and in pregnant women with mixed type incontinence it was 27.5 (4.3). In the subgroups analysis using the Tukey test, there was a difference in BMI between continent pregnant women and those with stress incontinence (p=0.001). There was a statistically significant difference in terms of BMI between continent pregnant women and pregnant women with mixed type incontinence (p=0.004). The difference in terms of BMI between pregnant women with stress and urge incontinence was also statistically significant (p=0.025).
Of the 549 pregnant women included in the study, 39.2% were nulliparous (n:215) and 60.8% were multiparous (n:334); 54% of nulliparous pregnant women were continent and 46% of them had incontinence; 37.4% of multiparous pregnant women were continent and 52.6% of them had incontinence. There was a statistically significant difference in the frequency of incontinence between nulliparous and multiparous pregnant women (p=0.001).
When looking at the bother and severity scores of pregnant women with incontinence compared to continent pregnant women, it was found that the severity scores for incontinence in pregnant women with urinary incontinence [8.51(5.88)] were higher than in the continent group [1.88(2.14)] (p=0.001). When evaluating bother scores, the scores in the incontinent group [0.95(1.65)] were higher than in the continent group [0.08(0.48)] (p=0.001). The results are summarized in Table 2.
There were statistically significant differences in severity scores (p=0.001) and bother scores (p=0.001) among the four groups. The incontinence severity and bother scores for the four groups are summarized in Table 3.
Discussion
Urinary incontinence is a medical condition that poses a problem among women in society. In addition to the specific problems of pregnancy, the quality of life of pregnant women is seriously affected by the addition of involuntary urinary incontinence. The incidence of urinary incontinence in pregnancy, for which we sought an answer in our study, differs in various studies. In a study, the prevalence of urinary incontinence during pregnancy was observed to reach up to 58%, and stress urinary incontinence was observed most frequently during pregnancy [https://www.ics.org/publications/ici_6/Incontinence_6th_Edition_2017_eBook_v2.pdf]. On the other hand, women with urinary incontinence during pregnancy seem to be at higher risk for postpartum urinary incontinence compared to continent women during pregnancy [10]. In our study, urinary incontinence was observed in 56.1% of pregnant women who applied to our antenatal outpatient clinic. Despite everything, it was observed that urinary incontinence experienced during pregnancy decreased within the first year after delivery [11]. In a meta-analysis, the prevalence of SUI during pregnancy was found to be between 18.6% and 60%. Physiological weight gain during pregnancy, the effect of the growing uterus on the pelvic floor muscles, and hypermobility of the urethra due to the engagement of the fetal head pressing on the bladder play a role in the pathophysiology of stress urinary incontinence in pregnancy [12]. During antenatal exams for women planning pregnancy, certain precautions can be taken by questioning symptoms of urinary incontinence. A study conducted in 2022 discovered that the strongest predictor for experiencing incontinence during pregnancy was a history of urinary incontinence before pregnancy [13]. In another study, it was observed that a majority of nulliparous women with incontinence also had urine leakage before pregnancy and most of them ignored the symptoms of incontinence [14]. In our study, urinary incontinence before pregnancy was not questioned.
In terms of preventing urinary incontinence during pregnancy, addressing modifiable risk factors can contribute positively to the process. These recommendations include quitting smoking before pregnancy, aiming for ideal weight before pregnancy, and performing low intensity exercises [15]. However, the focus should be on pelvic floor muscle training. A meta-analysis revealed that engaging in prenatal exercise, including pelvic floor muscle training, decreased the likelihood and severity of experiencing urinary incontinence (UI) both during pregnancy and after giving birth [16]. Pelvic floor muscle training (PFMT) should be regularly included in women’s exercise routines [17].
In another study investigating the risk factors for urinary incontinence during pregnancy, it was found that later gestational age increased stress and urge urinary incontinence [18]. The study found that full-time work increased the occurrence of urge incontinence during pregnancy [18]. Contrary to this study, in our study there was no difference in stress incontinence between trimesters; but there was an increase in urge incontinence and mixed incontinence cases as the trimesters progressed. Other studies have supported the contribution of increased BMI to the pathogenesis of stress urinary incontinence [19]. In our study, the average BMI (mean (sd)) of pregnant women with stress incontinence was found to be higher than that of continent pregnant women (p=0.001).
In the studies conducted so far on “urinary incontinence and quality of life during pregnancy”, the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) was used to determine the amount of urine loss (none, small, moderate, large amount) [20]. Studies have shown that in pregnant women with urinary incontinence, urine leakage occurs in small amounts (drops or just a little, more like a trickle, more than a trickle) [21]. In our study, the number of pads used to protect against wetness was evaluated minimally based on the Michigan University Incontinence Symptom Index questionnaire. Based on the M-ISI questionnaire, the average number of pads used was 1.55 (SD:1.28) when the incontinence group was taken as the base.
Urinary incontinence (UI) can significantly impact quality of life. Clearly defining and quantifying bother will assist researchers in selecting the appropriate measurement tools and interpreting the results [22]. There are publications in the literature that argue that urinary incontinence affects the quality of life either slightly or seriously. A study found that the quality of life of pregnant women was either not affected or only minimally affected by urinary incontinence [7].
In another similar study, minor bother in the quality of life of pregnant women was found to be due to the tendency to view urinary incontinence as a natural part of pregnancy or a natural result of birth [5]. As far as we know, the University of Michigan Incontinence Symptom Index (M-ISI) questionnaire was applied to pregnant women for the first time in our study. In our study, the M-ISI questionnaire, which allows for the separate evaluation of urinary incontinence severity and bother scores, showed that the severity and bother scores of pregnant women with urinary incontinence were higher than those of the continent group (p=0.001), respectively. The bother scores of pregnant women with mixed incontinence were higher than those of pregnant women with stress and urge incontinence (p=0.001). There are publications available that support the negative impact of urinary incontinence on pregnant women, similar to the results of our study [22]. Larger, multicenter studies on UI during pregnancy should be conducted, evidence-based guidelines suitable for use by pregnant women should be developed, and the effects of preventive interventions (e.g. kegel exercises) before pregnancy and during pregnancy should be investigated.
Conclusion
In our study, the primary outcome showed that urinary incontinence was detected in 56.1% of pregnant women. Urinary incontinence during pregnancy is common and affects the quality of life of pregnant women.
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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Fatih Şahin, Erhan Aktürk, Ramazan Adan, Simten Genç, Veli Mihmanlı, Arzu Yurci, Fatma Nur Çetinkaya, Neslihan Bademler, Tuğba Salman. The effect of pregnancy-related urinary incontinence on incidence and quality of life. Ann Clin Anal Med 2023;14(6):502-506
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The use of ultrasound in the assessment of difficult laryngoscopy in children
Mustafa Emrah Yüksek, Lütfiye Pirbudak, Elzem Sen, Mehmet Mustafa Anlaş
Department of Anesthesiology and Reanimation, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
DOI: 10.4328/ACAM.21606 Received: 2023-01-20 Accepted: 2023-02-25 Published Online: 2023-03-06 Printed: 2023-06-01 Ann Clin Anal Med 2023;14(6):507-511
Corresponding Author: Elzem Sen, Department of Anesthesiology and Reanimation, Faculty of Medicine, Gaziantep University, 27310, Gaziantep, Turkey. E-mail: drelzemsen@gmail.com P: +90 532 784 21 51 F: +90 342 360 39 98 Corresponding Author ORCID ID: https://orcid.org/0000-0003-3001-7324
This study was approved by the Ethics Committee of Gaziantep University (Date: 2020-01-15, No: 2019/463)
Aim: In this study, we aimed to investigate whether ultrasound anatomic measurements of the airway prior to anesthetic administration could be used as a predictive standard for difficult intubation in children undergoing surgery under general anesthesia.
Material and Methods: This observational study included 100 patients with an ASA I-III risk score between the ages of 0-6, whose operation was planned under general anesthesia. Age, height, body weight, Cormack-Lehane Classification and distance from skin to pre-epiglottic space (EPI), distance from skin to thyroid cartilage (TC), distance from skin to the anterior commissure (VCA) of vocal cord, distance from skin to posterior commissure (VCP) of the vocal cord and distance from skin to the hyoid bone (HYO) was recorded. These parameters were studied to examine the relationship between the classification of Cormack-Lehane.
Results: Cormack Lehane classification Grade III and above were determined in 9 (9%) patients. There was a statistically significant relationship between intubation difficulty and distance from skin to the thyroid cartilage.
Discussion: The ultrasound parameters we studied, with the possible exception of TC, which was not compared to any other anatomical, radiological or surface anatomy measurement, are virtually useless in predicting intubation difficulty in 0 – 3 years.
Keywords: Ultrasound, Cormack–Lehane Classification, Pediatric Difficult Intubation
Introduction
In the pediatric population, ‘intubation time’ and ‘airway security’ are critical due to the anatomic and physiologic characteristics. In pediatrics, a smaller lung volume, and functional residual capacity in particular, considerably reduce apnea tolerance. Despite optimal preoxygenation of sufficient duration to prevent desaturation in children, no “safety period” can be established even for short-lasting apnea events [1,2].Although measurement of anatomic structures and various scoring systems can be used, the Cormack–Lehane (CL) classification system has proven to be the best method for describing difficult intubation. CL classification has therefore become a standard for the investigational description of difficult laryngoscopy in anesthesia [3-5]. But although it is the standard for describing difficult intubation, it cannot be used in the preoperative evaluation as it is too invasive for a conscious patient [6].
Airway assessment by ultrasound is an important non-invasive, cost-effective, and instructive method. Although it has not yet been established as a standard method for assessing the airway of patients, it has great potential in the prediction of difficult airway [7]. However, there is a paucity of information focusing specifically on such methods in pediatric population where equipment, technique, and challenges are different [8].
In the present study, the aim was to investigate whether ultrasound anatomic measurement of the airway prior to anesthetic administration could be used as a predictive standard for difficult intubation in children undergoing surgery under general anesthesia.
Material and Methods
The study was conducted after obtaining written informed consent from the parents after the approval of the local ethics committee (2019/463) and in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki revised in the year 2000.
A total of 100 patients who were aged 0–6 years, included in ASA (American Society of Anesthesiologists) classification groups I–III, and scheduled for endotracheal intubation under general anesthesia prior to elective surgery were included in the study. Patients without parental consent, with significant airway malformations, with head and neck deformities were excluded from the study. All tests and endotracheal intubation attempts in the study were performed by the same surgeon with four years of experience.
Demographic characteristics recorded in the preoperative evaluation were age, sex, body weight, weight percentile, height, and body mass index (BMI). For all patients whose difficult intubation was assessed with CL classification and ultrasound, the distances between the pre-epiglottic space and the skin (EPI), between the thyroid cartilage and the skin (TC), between the anterior commissure of the vocal cord and the skin (VCA), between the posterior commissure of the vocal cord and the skin (VCP), and between the hyoid bone and skin (HYO) were measured in centimeters. Ultrasound examinations were performed using a GE LOGIQ e (GE Healthcare, USA) ultrasound scanner.
Midazolam at a dose of 0.02 mg/kg was administered intravenously to all patients as premedication before surgery. After the patient was taken to the operating room, standard monitoring (ECG, pulse oximetry, non-invasive arterial blood pressure) was performed. During induction, bolus doses of 0.5–1 µg/kg of fentanyl and 1-2 mg/kg of propofol were administered intravenously. After establishing that the patient was able to be ventilated with an appropriate mask, rocuronium was administered intravenously at 0.6 mg/kg in order to induce muscle relaxation. Laryngoscopy was initiated 2–3 minutes after the administration of rocuronium.
Under ventilation with a mask, the neck was brought into extension for measurement. A hockey stick probe (8–16 MHz) placed transversely in the submandibular region of the patient was moved in the transverse plane from cranial to caudal without changing its position. Distances between the hyoid bone and the skin (HYO), between the pre-epiglottic space and the skin (EPI), between the thyroid cartilage and the skin (TC), between the anterior commissure of the vocal cord and the skin (VCA), and between the posterior commissure of the vocal cord and the skin (VCP) were measured in centimeters and recorded.
Direct laryngoscopy was performed with Macintosh blades 0, 1, or 2. The condition of the vocal cords was assessed through their laryngoscopic appearance using CL classification. Patients were intubated and any complications during laryngoscopy were recorded.
In accordance with the CL classification system, if the glottis was completely visible, the patient was evaluated as grade I; if it was partially visible, they were evaluated as grade II; if only the epiglottis was visible, they were evaluated as grade III; and if even the epiglottis was not visible, they were evaluated as grade IV. Intubation was considered difficult if the CL test was grade III and IV despite appropriate head and neck position and the use of a laryngoscope blade.
Statistical analysis
The IBM SPSS Statistics 22 (IBM SPSS, Turkey) program was used for statistical analysis. The G Power program was used for power analysis. The conformity of numerical variables with the normal distribution was examined using the Shapiro-Wilk test. In the analysis of the study data, in addition to descriptive statistical methods (mean, standard deviation, median, frequency), the Student’s t-test was used to compare normally distributed parameters between two groups, while the Mann-Whitney U test was used to compare non-normally distributed parameters between two groups. When comparing three independent groups, an ANOVA test was used for normally distributed numeric variables, while the Kruskal-Wallis and Dunn’s tests were used for non-normally distributed variables. ROC analysis was performed to determine the threshold for significant levels. The MedCalc package program version 19.2.1 was used for ROC analysis. A p-value of less than 0.05 was accepted as significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
The study was conducted on 100 patients aged 0 to 6 years, including 68 (68%) boys and 32 (32%) girls. Of the patients with difficult intubation, seven (77.8%) were male and two (22.2%) were female. Sixty patients were classified as being ASA I (60%), 30 as ASA II (30%), and 10 as ASA III (10%). The C–L classification was grade I in 34 cases, grade II in 57 cases, and grade III in nine cases. There were no grade IV cases. As grades III and IV were considered difficult intubation, difficult intubation was noted in nine patients (9%), while there was no unsuccessful intubation.
The mean age of the patients was 2.1±1.44 years, mean body weight was 11.72±4.56 kg, mean height was 86.62±17.92 cm, and weight percentile was 41.96±28.95. Two of the cases were in the 3% percentile (1.9%), 12 were in the 5% percentile (11.5%), 12 were in the 10% percentile (11.5%), four were in the 15% percentile (3.8%), 16 were in the 25% percentile (15.4%), 26 of them were in the 50% percentile (25%), 14 of them were in the 75% percentile (13.5%), 12 were in the 85% percentile (11.5%), and two were in the 90% percentile (1.9%).
In the study parameters of the cases, VCA was determined as 0.49±0.06 cm, VCP as 1.41±0.17 cm, HYO as 0.54±0.11 cm, TC as 0.42±0.09 cm, and EPI as 1.9±0.22 cm, as the mean values of measurement. When we compared them, evaluated these parameters against one another in ratios, the mean value of VCA/VCP was 0.35±0.05, EPI/VCA was 3.93±0.46, and EPI/VCP was 1.36±0.46 (Table 1).
The mean age of the patients with difficult intubation was 1.88±1.22 years, the mean body weight was 10.83±4.16 kg, the mean height was 83.22±16.99 cm, and the weight percentile was 28.89±17.09.
In accordance with their CL classification, the cases were divided into two groups: difficult and simple intubation. There was no statistically significant relationship between intubation difficulty and VCA, VCP, HYO, EPI, EPI/VCP ratio, and EPI/VCA ratio (p>0.05). There was a statistically significant relationship between intubation difficulty and TC (p<0.05). There was a statistically significant relationship between intubation difficulty and VCA/VCP ratio (p<0.05) (Table 2).
The statistical sensitivity of TC was 77.78%, its specificity was 72.53%, and its cut-off value was 0.38 cm. The statistical sensitivity of the VCA/VCP ratio was 66.67%, its specificity was 82.42%, and its cut-off value was 0.31 cm (Figure 1).
Discussion
The aim of the present study was to investigate whether ultrasound anatomic measurement of the airway prior to anesthetic administration could be used as a predictive standard for difficult intubation in children undergoing surgery under general anesthesia.
Skilled airway management is the cornerstone of high-quality anesthesia management. Airway complications remain a common cause of anesthesia-related complications in children because of their unique anatomy and physiology [9]. In a retrospective study of 11,219 pediatric patients undergoing general anesthesia with endotracheal intubation, the rate of difficult direct laryngoscopy (CL grades III and IV) was 1.35%. The rate of direct difficult laryngoscopy was highest in children younger than 1 year old (0.7% in children older than 1 year vs. 4.7% in children younger than 1 year). Other predictors of difficult intubation were being classified as ASA III or IV, having a higher Mallampati score (if available), a lower body mass index, and a history of oromaxillofacial or cardiac surgery [10]. Valois-Gomez et al. reported that the incidence of intubation difficulty was 1.2% in a sample of 484 children aged 0 to 8 years [11]. In a prospective multicentre study by Fiadjoe et al., difficult tracheal intubation occurred in 2–5 per 1000 pediatric anesthesia cases [12].
Many different airway measurements have been used to predict difficult laryngoscopy in children. In a study on the airway of children younger than 5 years undergoing cardiac catheterization, it was concluded that body mass index, lower lip-to-chin distance (LCD), and thyromental distance (TMD) could be used to predict difficult laryngoscopic view. In the same study, the incidence of difficulty in viewing the larynx was 4% [13]. However, our study found a higher rate than these studies, with an incidence of 9% for difficulty in viewing the larynx.
It is critical to assess and recognize the potential for difficult airway prior to any procedure so that appropriate equipment and resources are available. For this reason, it has been emphasized that the relationship between various sonographic parameters and difficult airway should be investigated using point-of-care ultrasound (POCUS) for airway evaluation [14].Ultrasound has many advantages in upper airway imaging; it is safe, fast, portable, and accessible. It provides real-time static and dynamic images of various clinical indications of airway management [15].
In a study on 130 adult patients, Parameswari et al [16]. found that an ultrasonographically-measured distance between the epiglottis and the skin, based on CL classification, was the most sensitive (75% sensitivity) and the most specific (63.6% specificity) parameter in predicting difficult laryngoscopy. In a study on 301 patients, Falcetta et al [17] measured anterior cervical soft tissue thickness with ultrasound at two levels (thyrohyoid membrane [epiglottic area] and vocal cords [entry of the larynx]) on adult patients and found a high correlation between pre-epiglottic tissue thickness at the level of the thyrohyoid membrane and CL classification in predicting limited/difficult intubation. The fact that we have not come across any significant findings in the epiglottis region can be explained by the fact that our study was performed on pediatric patients.
In a pilot study conducted with 51 adult patients, Adhikari et al. [18] demonstrated that sonographic measurements of anterior neck soft tissue thickness at the level of the hyoid bone and thyrohyoid membrane can be used to discriminate between difficult and easy laryngoscopy, by comparing the anterior neck soft tissue thickness measured at the level of the hyoid bone and thyrohyoid membrane against CL classification. The present study demonstrated a statistically significant correlation between the difficulty of intubation and the distance between the thyroid cartilage and the skin.
In their study on 72 patients, Gupta et al. [19] found that the PES/EVC (pre-epiglottic space/distance between the epiglottis and the vocal cord) value was positively correlated with CL classification. In a study conducted with 100 patients, Reddy et al [3] showed that when measurements are taken using ultrasonography and based on CL classification, the PES/EVC value has a low-to-moderate predictive value in predicting difficult intubation. The sensitivity of the PES/EVC value was 1.2%, its specificity was 86.7%, its positive predictive value was 33.3, and its negative predictive value was 13.4%. There was a statistically significant relationship between intubation difficulty and the VCA/VCP ratio in this present study. However, we believe that there is room for more studies in this field as the results and anthropometric measurements of ultrasound studies are influenced by various parameters such as race and geography.
Conclusion
In this present study, TC and the VCA/VCP ratio were found to have a statistically significant relationship with CL classification. However, due to the multiple anatomic factors involved in difficult intubation and the lack of an ideal prediction test, an unexpectedly difficult airway should always be considered. Radiographic examination of the anatomy of the region, a method which has recently gained importance, can help predict difficult intubation during physical examination. The ultrasound parameters we studied, with the possible exception of TC, which was not compared to any other anatomical, radiological or surface anatomy measurement, are virtually useless in predicting intubation difficulty in 0 – 3 years.
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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Mustafa Emrah Yüksek, Lütfiye Pirbudak, Elzem Sen, Mehmet Mustafa Anlaş. The use of ultrasound in the assessment of difficult laryngoscopy in children. Ann Clin Anal Med 2023;14(6):507-511
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Relationship between fluid restriction compliance and trait mindfulness among patients receiving hemodialysis treatment
Canan Demirci
Department of Nursing, Akdagmadeni School of Health, Yozgat Bozok University, Yozgat, Turkey
DOI: 10.4328/ACAM.21616 Received: 2023-01-24 Accepted: 2023-03-12 Published Online: 2023-03-29 Printed: 2023-06-01 Ann Clin Anal Med 2023;14(6):512-516
Corresponding Author: Canan Demirci, Department of Nursing, Akdagmadeni School of Health, Yozgat Bozok University, 66300, Yozgat, Turkey. E-mail: canan.karadas@yobu.edu.tr P: +90 546 133 19 89 Corresponding Author ORCID ID: https://orcid.org/0000-0002-3364-6276
This study was approved by the Ethics Committee of Yozgat Bozok University (Date: 2021-03-10, No: 2017-KAEK-189_2021.03.10_04)
Aim: This study aimed to examine the relationship between fluid restriction compliance and the level of mindfulness in patients with HD.
Material and Methods: This cross-sectional and correlational study was conducted on 119 patients receiving HD therapy between January and July 2022. Data were collected via the “Patient identification form”, the “Fluid control in hemodialysis patients scale (FCHPS)”, and the “Mindfulness scale (MS)”. Descriptive statistics and Spearman correlation analysis were used in the evaluation of the data.
Results: The median age of the patients was 62.0 (50-70) years in the study. The majority of them were married (84.9%) and 78.2% of them were living in the center of the district. The median amount of fluid withdrawn in the last session was 3000 (2300-4000) cc. while the median FCHPS score was 52.0 (48.0-56.0); the median MS score was 60.0 (52.0-68.0). There was a weak, positive correlation between FCHPS and MS scores (r: 0.260; p=0.04).
Discussion: Fluid management goal is to preserve fluid volume and electrolyte composition in the body. However, patients may face many symptoms caused by improper management. The results of this study showed that the patients had moderate fluid restriction compliance and level of mindfulness, and a weak positive correlation was found. In other words, as mindfulness level increases, fluid restriction compliance increases. Managing fluid-electrolyte balance and increasing the self-awareness of patients are core steps in HD treatment for health workers. Mindfulness-based interventions for improving mindfulness may be implemented in clinical practice for better fluid management.
Keywords: Chronic Renal Failure, Fluid Restriction, Hemodialysis, Mindfulness, Nursing
Introduction
Chronic renal failure is a significant health problem and its incidence is increasing worldwide [1]. Renal replacement therapies such as hemodialysis (HD), peritoneal dialysis, and kidney transplantation are used to treat end-stage renal failure, an irreversible process. Among these treatments, HD is the most commonly used life-prolonging treatment. HD therapy is a process in which substances that cannot be removed from the blood are transferred into the dialysis fluid through a semi-permeable membrane [2]. HD therapy includes two important steps: fluid and food restriction and the regular removal of waste metabolites from the blood by dialysis [3]. A successful HD therapy requires patients to comply with the prescribed drugs, dialysis regimen, and food and fluid restrictions [4]. Failure to comply causes an increase in HD-related complications and health expenses and may lead to a decrease in quality of life and survival [5,6]. Studies in the literature often report that patients have difficulty complying with fluid restrictions [7-9]. Chironda et al. (2017) stated that non-compliance with fluid restriction in patients receiving HD therapy varies between 10-74% [10]. Education level, gender, diet compliance and therapy might affect compliance with fluid restriction [3,9,11].
Non-compliance with fluid restriction can be tested by measuring the weight gain (interdialytic weight gain [IDWG]) between two dialysis sessions or indirectly with scales that evaluate the patient’s compliance with fluid restriction [3]. IDWG is higher than it should be in most patients receiving HD therapy [7,10]. Clinical conditions such as fluid overload and life-threatening pulmonary edema may occur as a result of non-compliance with fluid restriction. Therefore, it is essential to evaluate the fluid compliance of HD patients and the factors affecting this compliance. In addition to patient training, it has been noted in the literature that complementary integrative approaches also improve patients’ fluid compliance [12-15]. In studies on mindfulness, a mind-body practice included in complementary integrative approaches, HD patients reported improvements in their symptoms [12,15,16]. Mindfulness is a mind and body practice that involves focusing on one’s immediate experiences and observing one’s inner states. Nejad et al. (2018) reported improvement in anxiety, depression, and sleep disorder symptoms following a mindfulness intervention in their study [17]. In a study conducted by Adamoli et al. (2020), HD patients stated that their stress levels decreased and their quality of life and their compliance with fluid and diet restrictions increased with a mindfulness intervention [18]. A systematic review reported that there was a positive correlation between the predisposition to mindfulness and the development of positive health outcomes in patients receiving a mindfulness intervention [19]. For these reasons, the current levels of mindfulness of patients should be evaluated before practicing mindfulness-based interventions, and the relationship of this current level of mindfulness with expected health outcomes should be examined. In the literature, many mind-body approaches have been implemented to improve the symptoms of HD patients, and the potential positive effects of these practices have been reported [12,15-18]. On the other hand, no study has examined the state mindfulness of patients and the compliance of dialysis patients with fluid and diet restrictions. This study thus aimed to examine the relationship between the compliance of HD patients with fluid restrictions and their level of mindfulness. Research questions aimed in the study were as follows:
1. What is the level of mindfulness in HD patients?
2. What is the level of fluid restriction compliance in HD patients?
3. Does the level of mindfulness affect fluid restriction compliance in HD patients?
Material and Methods
The research had a cross-sectional and correlational design. The research was carried out between January and July 2022 in three state HD centers in a city located in the middle center of Turkey. The population of the research consisted of 157 patients aged 18 and over, who had no cognitive disability preventing communication, and who received treatment in the HD unit. In the power analysis, it was found that a minimum of 115 patients should be included in the study with a confidence interval of 95% and a significance level of 5%. Eight patients were away and continued their treatment in another province; eight patients refused to participate in the study; seven patients had cognitive problems; five patients had hearing impairment and communication problems; three patients had language problems; seven patients withdrew from the study before the survey was completed. Therefore, a total of 119 patients were included in the study.
Research data collection tools: Within the scope of the research, the “Patient Identification Form”, “Fluid Control in Hemodialysis Patients Scale (FCHPS)”, and “Mindfulness Scale (MS)” were applied to the participants.
Patient Identification Form: This form, which was created by reviewing the studies in the literature, consists of a total of 13 questions regarding characteristics such as age, gender, height, weight, marital status, education level, income status, comorbid chronic diseases, time of starting HD, amount of IDWG, and frequency and duration of HD [6,10,14,16].
Fluid Control in Hemodialysis Patients Scale (FCHPS): The FCHPS was developed by Coşar and Pakyüz (2016) and consists of three subscales and 24 items that evaluate “knowledge, attitude, and behavior” [20]. The items are ranked on a three-point Likert-type scale (“agree” = 3 points; “unsure” = 2 points, and “disagree” = 1 point). Items 6, 7, 18, 19, 20, 21, 22, 23, and 24 are reverse-scored. The score obtainable from the scale ranges between 24 and 72. A high score indicates that patients have a high level of compliance with fluid control. The Cronbach alpha value of the scale was found to be 0.88. In the present study, the Cronbach alpha value of the FCHPS was 0.606.
Mindfulness Scale (MS): This scale was developed by Brown et al. (2003) and measures the general tendency of individuals to be aware of their immediate experiences in daily life [21]. The scale consists of 15 items that are ranked on a six-point Likert-type scale (“almost always”, “often”, “sometimes”, “rarely”, “quite rarely”, “almost never”). High scores indicate high levels of mindfulness. The Turkish validity and reliability study of the scale was conducted by Özyesil et al. (2011) and the Cronbach alpha value was found to be 0.80 [22]. In the present study, the Cronbach alpha value of the MS was 0.831.
Research data collection: Data collection forms were filled in face-to-face by reading out to the patients by the researcher to decrease contamination. Other Covid-19 precautions were taken by the researcher by keeping social distance and wearing masks.
Bias: Cross-sectional studies are known to be prone to selection bias depending on the study sample participation. Thus, for this study, the author aimed to recruit all patients attending HD units who met the inclusion and exclusion criteria. Another source of bias was the evaluation of findings. This bias was minimized by having an independent statistician for analyses of the study findings.
Research data analysis: The size of the study sample was larger than 50, thus, the normality distribution of the data was analyzed with the Kolmogorov-Smirnov test. Since the data did not fit the normal distribution, non-parametric tests were used for the analysis of the data. Descriptive statistics (median, interquartile range, and frequency) were used in the evaluation of the socio-demographic data. Spearman’s correlation analysis was performed to determine the relationship between the MS and MS and FCHPS scores. The p-value was taken as p<0.05 in the study.
Ethical aspect of research: Ethical approval was obtained from the non-invasive clinical research board to conduct the study (Decision number: 2017-KAEK-189_2021.03.10_04). Institutional permissions were received from the City Provincial Directorate of Health in order to carry out the research. Informed consent was obtained from participating patients. Moreover, permission was received from the authors of the scales used in the study. All the principles of the Declaration of Helsinki were followed.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Socio-demographic and Clinical Characteristics of the Participants
A total of 119 HD patients were included in the study. The median age of the patients participating in the study was 62.0 (50-70) years. Of the participants, 56.3% were male, more than half were primary school graduates (58%), the majority were married (84.9%). 78.2% of the participants were living in the center of the district. The median BMI of the patients in the study was 25.78 (22.65-30.12). While 32.7% of them were of a normal weight, 32.8% were overweight. 87.4% of the patients stated that they had at least one chronic disease other than CRF: hypertension was the most common, with 81.5%, while diabetes mellitus was the second most common, with 53.8%. The patients had been using 4 (3-6) drugs per day (Table 1).
In terms of the clinical characteristics of the patients, the patients had been diagnosed with end-stage renal disease for 7 (3-12) years and had been receiving HD therapy for 4 (2-8) years. Seven of these patients had been diagnosed with end-stage renal disease in the past year. 61.3% of the patients started to receive HD therapy at the same time as the diagnosis of the end-stage failure. The median amount of fluid withdrawn in the last session was 3000 (2300-4000) cc. Furthermore, 37.0% of the patients reported that they complied with the diet for CRF “frequently”, 28.6% reported that they “always” did, while 11.8% reported that they “never” did (Table 2).
Scale Scores and Correlation
As shown in Table 3, the median FCHPS score was 52.0 (48.0-56.0); the median scores on the subscales were 19.0 (17-20) for knowledge, 24.0 (21.0-26.0) for behavior, and 10.0 (9.0-13.0) for attitude. It was seen that the level of compliance with fluid restriction of the patients was moderate. The median MS score was 60.0 (52.0-68.0), and the level of mindfulness of the patients was found to be moderate.
There was a weak, positive correlation between FCHPS and MS scores (r: 0.260; p=0.04). A weak, positive correlation was determined between the MS score and the scores on the knowledge (r: 0.283; p=0.02) and attitude (r: 0.200; p=0.029) subscales of the FCHPS, whereas there was no correlation with the score on the behavior subscale (r: 0.087; p=0.347) (Table 3).
Discussion
The current research evaluated the relationship between fluid restriction compliance and the level of trait mindfulness in HD patients. The findings of the study showed that the patients’ levels of fluid restriction compliance and mindfulness were moderate. It was observed that there was a weak, positive correlation between the patients’ level of fluid restriction compliance and their mindfulness. Accordingly, it was concluded that patients’ fluid restriction compliance increased as their level of mindfulness increased. When the literature was examined, study author could not find any studies focusing on the relationship between trait mindfulness and fluid restriction compliance. It is possible that there is no study on this subject in the literature. Therefore, it is challenging to discuss the findings of the study in light of the literature. In studies found in the literature, these studies have focused on the relationship between mindfulness and anxiety and depression in HD patients, or the effects of mindfulness-based practices on stress, anxiety, and quality of life [23,24]. These studies emphasized that high levels of mindfulness or the use of mindfulness-based interventions are effective in reducing stress, anxiety and depression, and in improving quality of life. Fluid restriction creates the most stress in HD and makes it difficult to comply with the treatment [11]. It was thought that mindfulness, which has been reported to have a stress-reducing effect, may have an effect on increasing the compliance of patients. With the increase in the level of mindfulness, the person can monitor their mood and attention while focusing on the immediate moment. Self-acceptance, part of mindfulness, can make it easier for people to accept the situation they are in and cope with this challenging situation. Thus, individuals can improve their self-management of their health. From this perspective, it is possible to increase the compliance of HD patients with fluid restriction by increasing their levels of mindfulness, or by applying interventions to promote the development of mindfulness.
When the correlation between the MS and the subscales of the FCHPS was examined positive correlation was found with the knowledge and attitude subscales. This correlation may explain the intention to comply with fluid restriction in patients with high levels of mindfulness. However, there was no statistically significant correlation between mindfulness and the behavior subscale of the FCHPS. This may be due to the presence of various sub-factors in the development of behavioral changes in HD patients. For example, considering the literacy status of the patients included in the study, it was seen that more than half of them had only a primary education level or below, and that some of them were illiterate. In addition, the onset of HD and the diagnosis of CRF were simultaneous in more than half of the patients, and only about one-third reported that they always complied with the diet for HD. The quantity of fluid withdrawn from the patients in the last session was found to be high. When all these findings were examined together, it was concluded that the compliance of patients with fluid restriction may have been adversely affected. Studies in the literature have reported that there is no correlation between low education level and fluid restriction compliance; however, being female, being single, complying with the diet, and having a low IDWG fluid level were reported to positively affect compliance with fluid restriction [3,9,11]. Ozkan ZK et al. (2019) stated that nurses and healthcare staff have already given information on fluid/salt restriction to HD patients in their study [9]. Therefore, patients have received high scores in information on fluid/salt restriction and statistical differences were not found. These findings support of the current study findings.
Strengths and limitations
This study has some limitations. As a cross-sectional study, it does not examine the cause-effect relationship. Thus, it is recommended to carry out longitudinal studies on this subject. Since the study sample consisted of patients receiving HD treatment in the center of the district, and the specific status of HD patients and the long course of treatment may affect variables, the results should only be generalized with care. Although the size of the sample was appropriate for this target population (n=119), the results of this study cannot be generalized to all HD patients in Turkey.
Conclusion
Management of fluid-electrolyte balance and increasing self-awareness of HD patients are core steps in HD treatment. The results of this study found out that HD patients had moderate levels of trait mindfulness and fluid restriction compliance and that there was a weak, positive correlation between these parameters. Mindfulness may be effective in increasing the compliance of HD patients with fluid restriction. Although there are many factors influencing fluid restriction compliance, mindfulness could be an important part of nursing management for proper fluid restriction. However, further interventions and information are needed in order to change patients’ behaviors to comply with fluid restriction. For this reason, it is recommended that future studies evaluate other factors that may affect the levels of mindfulness and compliance with fluid restriction in HD patients. It is also recommended that similar studies be performed in other cultures and populations focusing on different dimensions of compliance with fluid restriction and other factors possibly affecting this, such as seasonal changes.
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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Etiological changes of maxillofacial trauma admitted to the emergency department
Cüneyt Arıkan, Ejder Saylav Bora
Department of Emergency Medicine, Izmir Ataturk Research and Training Hospital Izmir, Turkey
DOI: 10.4328/ACAM.21621 Received: 2023-01-27 Accepted: 2023-04-05 Published Online: 2023-04-11 Printed: 2023-06-01 Ann Clin Anal Med 2023;14(6):517-520
Corresponding Author: Ejder Saylav Bora, Department of Emergency Medicine, Izmir Ataturk Research and Training Hospital Izmir, Turkey. E-mail: ejdersaylav@gmail.com P: +90 532 450 78 55 Corresponding Author ORCID ID: https://orcid.org/0000-0002-2448-2337
This study was approved by the Ethics Committee of İzmir Katip Çelebi University (Date: 2022-04-21, No: 0216)
Aim: Maxillofacial trauma (MFT) is one of the most common causes of trauma-related admissions to the emergency department (AS). The aim of this study is to determine the etiological, clinical and demographic characteristics, morbidity and mortality rates of MFT cases admitted to the emergency department.
Material and Methods: Patients aged 18 years and older who underwent maxillofacial (MF) imaging with computed tomography (CT) were included in this retrospective cross-sectional study. The aim of this study is to determine the most common injuries in MFT cases and their relationship with the trauma mechanism. In addition, surgical intervention, morbidity and mortality rates were calculated.
Results: Of the 458 cases included in the study, 72% were male. The most common trauma mechanisms are assault (41%) and fall (32%), respectively. The most frequently injured tissues and organs were soft tissues (42%) is nasal cartilage (21%). It was found that the risk of intracranial pathology increased 23.5 times in patients with frontal bone fractures compared to those without.
Discussion: MFT traumas are important both cosmetically and because surgical intervention cannot be performed everywhere. We should pay attention to the early diagnosis and treatment of frontal bone fractures, which are the most common causes of trauma depending on years and state policies. Future studies will provide clearer data on this subject.
Keywords: Maxillofacial Trauma, Emergency Department, Etiology
Introduction
Maxillofacial trauma (MFT) is one of the most common causes of trauma-related admissions to the emergency department [1,2]. Traffic accidents, beatings, falls and contact sports are the most common causes of maxillofacial trauma [3–6], and the male population is more frequently exposed to MFT [7] .
The head and neck region contains many structures necessary for life that perform complex functions such as speech, vision, swallowing and smell, and has a great aesthetic importance [8]. Emergency physicians should be careful in terms of other accompanying major traumas and complications that may occur in the management of patients with MFT. Deficiencies in the diagnosis and treatment of facial fractures can cause deformity, chewing difficulties, paresthesia, visual disturbances, and death [8–11]. The vascularization of the facial area is intense, and arterial bleeding can quickly result in massive blood loss. Segmented fractures may cause airway obstruction, orbital traumas may cause extraocular muscle squeezing, ischemia, and permanent vision loss [12]. Apart from the medical complications that may occur in acute and chronic periods, severe mental state disorders can also be observed [13,14]. Early evaluation and intervention in MFT can significantly reduce morbidity and mortality [6].
The aim of this study is to determine the etiological, clinical and demographic characteristics, morbidity and mortality rates of MFT cases admitted to the emergency department.
Material and Methods
Study design and settings
This retrospective cross-sectional study was carried out in the emergency clinic of a third-level hospital in the province of Izmir in western Turkey. After obtaining approval from the local ethics committee (Decision No: 0216 Date: 21/04/2022), patients who applied to the adult emergency service with 35-40 thousand trauma patients annually between ‘June 1 – September 30, 2021’ due to MFT were analyzed retrospectively.
Study population
Among the patients admitted to the emergency department due to trauma, patients aged 18 years and older who underwent maxillofacial (MF) imaging with computed tomography (CT) were included in the study. Non-traumatic cases and patients with missing data were excluded from the study. A total of 458 cases were included in the study.
Data collection and processing
Age, gender, type of trauma, injured tissues, organs and bones, need for surgical intervention, developing complications, accompanying intracranial or cervical injury, morbidity, hospitalization and patient outcomes were analyzed from the medical records of the cases. Trauma mechanisms included motor vehicle accidents, assaults, falls, gunshot injuries, and others. Injured tissues and organs included eye-eyelids, tear ducts, nasal cartilage, facial nerve and soft tissues, and bone structures, orbital, nasal, maxilla, mandible, zygoma and frontal bone. It was recorded whether airway obstruction, septal hematoma, bleeding, soft tissue infection and meningitis developed as complications.
Outcome measures
This study aims to determine the most common injuries in MFT cases and their relationship with the trauma mechanism. In addition, surgical intervention, morbidity and mortality rates were calculated.
Data analysis
IBM SPSS Statistics 28 (SPSS Inc., Chicago, USA) program was used for data analysis. Descriptive statistics are presented with frequency, percentage, mean and standard deviation values. Whether the data conformed to the normal distribution was evaluated using the Shapiro-Wilk test, skewness- kurtosis values, and Q-Q plots. Univariate regression analysis was performed to determine the relationship between the type of bone fracture as a result of maxillofacial trauma and surgical intervention and intracranial pathology. All parameters found to be statistically significant in Univariate regression analysis were evaluated in multinomial logistic regression analysis. A p-value of <0.05 was considered significant. All statistics were done at a 95% confidence interval.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Of the 458 cases included in the study, 72% (n=328) were male. The mean age of men (40±17) was lower than women (48±23), and there was a statistically significant difference between them (p<0.001). The most common trauma mechanisms were assault (41%), falls (32%) and motor vehicle accidents (17%). Age and trauma mechanisms by gender are presented in Table 1. The most frequently injured tissues and organs were soft tissue (42%), nasal cartilage (21%), and eye-eyelid (13%), the most common fractures of the bones were nasal (50%), maxillary (25%), and orbital (24%). Surgical intervention was performed in 18% of the cases. In addition, 8.7% of the cases had intracranial pathology and 2.2% had cervical spine pathology. The most common complications were bleeding (19%) and septal hematoma (5.2%). Although soft tissue infection occurred in 2.2% of the cases, meningitis did not develop in any of them. Among other complications, airway obstruction was seen in 5 (1.1%) cases, and facial nerve damage was seen in 2 (0.4%) cases. Loss of function developed in 58 (13%) cases, and cosmetic damage remained in 167 (36%) cases. The hospitalization rate was 11%, the intensive care unit admission rate was 3.5%, and the mortality rate was 0.4%. Tissue, organ and bone types injured due to MFT, accompanying pathology, complications, treatment and morbidity rates are shown in Table 2.
The relationship between fractured bone type and surgical intervention and intracranial pathology was investigated. Univariate regression analysis revealed a statistically significant relationship between all bone fractures and surgical intervention. However, in the multinomial logistic regression analysis, frontal, zygoma, and maxilla fractures were found to be confounding factors. It was found that the surgical risk increased 3 times in those with mandibular fractures, 2.5 times in those with orbital fractures, and 1.9 times in those with nasal fractures. The results of the multinomial logistic regression analysis are presented in Table 3. When the relationship between intracranial pathology and bone fractures was examined, it was seen that there was a statistically significant relationship with orbita, maxilla, zygoma and frontal bone fractures according to univariate regression analysis. No significant relationship was found with nasal and mandible fractures. Orbital, maxilla and zygoma fractures were found to be confounding factors in the multilogistic regression analysis. It was found that the risk of intracranial pathology increased 23.5 times in patients with frontal bone fractures compared to those without (Table 3).
Discussion
As in the world, the most common cause of young deaths in our country is traffic accidents, assault, etc., judicial events. Since we are the only public institution in our city for emergency response related to maxillofacial trauma, patients in this category come to our hospital from all districts.
İrkören et al. [15] and studies in the literature [1,3,12] show parallelism with the gender analysis of patients who applied to the emergency department of our hospital with MFT. Applications of male patients were 2.5 times higher than those of females. In the evaluation made for the trauma mechanism for MFT, dominance is often observed in those who come with the complaint of beating. Although MFTs due to falling with the second frequency are common, the difference in the male-female ratio is preserved in all species.
Unlike the results of our study, Şimşek et al., in their study conducted in 2020, reported that the most common reason for patients presenting with MFT was falling, and the second most common cause was assault [16]. The most important reason why the data differed from our study may be that the geographical location of the province where the hospital is located is in a mountainous area. In support of this idea, the demographic data and trauma types of the nasal USG study performed by Çağlar et al. [17] in patients with maxillofacial trauma and the data of our study can be shown.
Bamjee et al. [18] , Schaftenaar et al. [19] , Erol et al. [20] reported in the data of their studies that the most common reason for application of patients with MFT was traffic accidents, followed by applications after assault. This situation differs from our study. Seasonally, this study also shows that the incidence of MFT cases is higher in summer remains statistically similar. The change in trauma types can be considered a result of the increase in the frequency of traffic controls in our country. This suggests that the socio-economic decline in the country is inversely proportional to the increase in battering incidents.
In the evaluation made among the types of broken bones in MFT, in accordance with the literature [21], it was found that nasal bone fracture was most oftenobserved. Secondly, maxilla fracture is frequently observed, and the third is the accompanying orbital fracture. As can be expected, bone fractures also change with the change in the frequency of trauma type. Although in previous studies, mandible fractures were most frequently detected in the 1st or 2nd row , which were most commonly seen in traffic accidents, more minor bone fractures were observed in our study.
Considering that 1 out of 5 maxillofacial trauma patients underwent surgical intervention, MFTs constitute an important workload for hospitals. The most surgically risky bone fractures are nasal, mandible and orbital bones. These results are similar to DeAngelis et al. [22]
Although frontal bone fractures are less common, they are the most risky condition for intracranial pathologies accompanying maxillofacial fractures. From an anatomical point of view, this is the expected result.
Conclusion
MFT traumas are important both cosmetically and because surgical intervention cannot be performed everywhere. We should pay attention to the early diagnosis and treatment of frontal bone fractures, which are the most common causes of trauma depending on years and state policies. Future studies will provide clearer data on this subject.
Limitations
This study was retrospective and determined for the presence of cosmetic damage, and the data were taken from the patient file, consultation and surgery notes. No face-to-face interviews were conducted with the patients. In addition, the high number of patients were referred to our hospital from another center.
Acknowledgment
We would like to thanks Dr. Fatih Esad Topal for his contributions to the study and also to Dr. Hüseyin Acar for his support in the development of our statistical 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.
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Download attachments: 10.4328.ACAM.21621
Cüneyt Arıkan, Ejder Saylav Bora. Etiological changes of maxillofacial trauma admitted to the emergency department. Ann Clin Anal Med 2023;14(6):517-520
Citations in Google Scholar: Google Scholar
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Prevalence of persistent apical periodontitis in patients with root canal-filled teeth: A cone-beam computed tomography study
Bertan Kesim 1, Fatma Akkoca 2
1 Department of Endodontics, Faculty of Dentistry, Nuh Naci Yazgan University, Kayseri, 2 Department of Dentomaxillofacial Radiology, Faculty of Dentistry, Dokuz Eylul Universitesi, Izmir, Turkey
DOI: 10.4328/ACAM.21634 Received: 2023-02-02 Accepted: 2023-04-05 Published Online: 2023-04-15 Printed: 2023-06-01 Ann Clin Anal Med 2023;14(6):521-524
Corresponding Author: Fatma Akkoca, Department of Dentomaxillofacial Radiology, Faculty of Dentistry, Dokuz Eylul Universitesi, Izmir, Turkey. E-mail: fatmaakkoca92@gmail.com P: +90 507 267 15 01 Corresponding Author ORCID ID: https://orcid.org/0000-0002-4522-656X
This study was approved by the Ethics Committee of Nuh Naci Yazgan University (Date: 2022-04-21, No: 2022/8769)
Aim: Apical periodontitis is the inflammatory destruction of periradicular tissues that occurs gradually over time, primarily originating from invading bacteria in the root canal system and initiated by the release of bacterial products. In this study, the prevalence of post-treatment apical periodontitis was assessed with cone-beam computed tomography imaging and the effects of tooth-level and patient-level factors that may predict the failure of root canal treatment were investigated in a Turkish subpopulation.
Material and Methods: Our study included 305 cone-beam computed tomography images of patients (153 males, 152 females aged 18 to 78 years) [Mean ± standard deviation (SD) = 39.2 ± 17.6].
Results: Post-treatment apical periodontitis prevalence was 83.3% and was more common in the premolars (9.5%), the mandible (11.8%), and the left side of the jaw (11.8%).
Discussion: This study showed a high prevalence of post-treatment apical periodontitis in a Turkish subpopulation even in cases in which the quality of root canal filling appeared to be sufficient radiologically. Cone-beam computed tomography is one of the most sensitive imaging techniques for the detection of apical periodontitis.
Keywords: Apical Periodontitis, Cone-Beam Computed Tomography, Root-Canal Filling
Introduction
Apical periodontitis (AP) is an inflammatory destruction of the periradicular tissues that occurs progressively over time, primarily originating from invading bacteria in the root canal system and initiated by the release of bacterial products [1]. It is well known that there is a healing response and tissue repair in the wounded periapical area if adequate root canal treatment (RCT) is performed [2], but this may not be the case in all cases. More recent studies show a remarkably high prevalence of AP in root canal-treated teeth [3-5]. Persistent AP lesions alone or when coupled with other predisposing factors may lead to tooth loss [6]. Besides, an increasing number of studies have shown that there has been mounting evidence of a bidirectional relationship between AP and systemic diseases [7]. This is consistent with the concept that endodontic infections affect systemic health, and systemic diseases similarly impact the pathogenesis of AP.
Post-treatment AP may be associated with many factors [8]. In previous studies, the effects of tooth-level factors (position, tooth type) [9, 10] and patient-level factors (gender, presence of systemic diseases) [11, 12] on the prevalence of post-treatment AP have been investigated. In this study, it was assumed that as patient-level risk factors, the presence of diabetes, cardiovascular diseases, and hematological disorders may interfere with the periapical healing in root-canal filled teeth.
Cone-beam computed tomography (CBCT) imaging has become a reliable diagnostic tool in pathologies of periradicular tissues and also provides three-dimensional views of the root canal system. In two-dimensional imaging, detailed assessment can not be carried out based upon a single view, due to structural superimpositions. Correspondingly, previous studies showed that CBCT has the highest sensitivity and diagnostic accuracy for detecting AP lesions [13, 14]. Therefore, in this study, CBCT images were utilized to evaluate the prevalence of AP in root canal-treated teeth.
Cross-sectional studies can be very helpful in ascertaining the true prevalence of specific diseases that are common in the population but whose effects are unknown or underestimated [3]. By assessing the current prevalence of AP in individuals with root canal-treated teeth, clinicians can be informed about possible contributing factors associated with post-treatment AP, also healthcare providers may be encouraged to set standards enhancing the procedural quality of RCT. In this study, the prevalence of post-treatment AP was investigated with CBCT examination and the effects of tooth-level and patient-level factors on RCT outcome were evaluated in a Turkish subpopulation. The null hypothesis of this study was that both tooth level and patient level factors did not contribute to differences in the success of the RCT.
Material and Methods
Sample selection
The study was conducted at the Oral and Maxillofacial Radiology Department, Nuh Naci Yazgan University and included 305 CBCT images of patients (153 males, 152 females) between 18 and 78 years [Mean ± standard deviation (SD) = 39.2 ± 17.6] that were taken between January 2020 and April 2022. This study was approved by the Ethics Boards and Commissions of Nuh Naci Yazgan University, Kayseri, Turkey (2022/18).
Inclusion and exclusion criteria
The study was conducted with CBCT images taken from patients over the age of 18 between 2020-2022. Teeth with apical periodontitis, which have radiologically adequate coronal restorations and also have radiologically adequate root canal fillings according to criteria established in a previous study were evaluated [15].
CBCT images of patients with poor image quality, artefacts, and patients younger than 18 years of age were not included. In addition, CBCT images of teeth with radiologically inadequate upper restoration and teeth with radiologically low-quality root-canal fillings were excluded from this study.
Image acquisition
The 3D digital imaging system (KaVO OP 3D Pro, PaloDEx Group Oy, Tuusula, Finland) with a fixed protocol and parameters was used for acquiring CBCT images. With the tomographic KaVO OP 3D Pro CBCT scanner the following parameters were utilized to obtain the images used in this study: (i) exposure setting of 90 kV, 8 mA, (ii) Exposure time- 17.5-26.9 s, (iii) 13×15 cm of field of view (FOV), and (iv) voxel size-0.320 mm. All CBCTs were taken for the purpose of a dental check-up. In this research, these CBCT images were not specifically taken for the examined endodontically treated teeth.
Image evaluation
OnDemand 3D Imaging Software (Cybermed, Seoul, South Korea) was used for the image reconstruction and measurements. First, the images were reconstructed in sagittal, axial, and coronal planes and furthermore, multiplanar reconstruction (MPR) was performed for a comprehensive view of the root canal system. The MPR was performed by navigating through the coronal-apical direction and then in the apical-coronal direction. During the 3D inspection if the images of one of the three planes (sagittal, axial, coronal) were unclear, the actions were repeated.
Statistical analysis
The collected data were analyzed using SPSS (Version 22.0, IBM Corporation, New York, USA) for Windows. The association between risk factors [gender, type of teeth (premolar/molar), jaws (maxillar/mandibular), location of teeth (right/left) the presence of systemic diseases (cardiovascular, hemophilia, and diabetes mellitus) and apical periodontitis were determined using Chi-square test. The statistical level of significance was set with a p-value of 0.05.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Reliability-inter and intra‑examiner
There inter-examiner agreement (Kappa ≥ 0.85) was excellent for the presence/absence of AP and was moderate for the presence/absence of endodontically treated teeth associated with AP (Kappa < 0.75). There was excellent intraexaminer reliability for both the first and second examiners with Kappa scores of ≥ 0.88; ≥ 0.97, respectively, with regard to assessing AP in non-treated and previously root canal-treated teeth.
When the data were analysed according to systemic diseases, no apical periodontitis cases were found in hemophilia patients.
In Table 3, the effects of gender, age, CVS, and DM variables on AP were investigated. Variables with a p-value of <0.25 in Table 1 were evaluated with multiple binary logistic regression analyses. In order to determine the final model (Final Model), variables that are not statistically significant were removed from the model with the Backward Wald elimination method. As a result, the CVS variable was found to be effective on the network. The presence of CVS reduces the risk of AP occurrence by 4,310 times. This result can be considered incidental.
Discussion
The focal infection theory was an exaggerated concept, which has been put forward in the early 1900s [16], claiming a causal relationship between oral infections and systemic diseases and building consensus in medicine in the 1920s without adequate testing [17]. Recently, as a result of the widespread application of root canal therapy and advances in diagnostic imaging, it has been revealed that the prevalence of apical periodontitis after RCT is higher than expected [3, 5, 12]. If undiagnosed, the local effects of AP are at worst limited to tooth loss [6], but in many studies, it has been reported that untreated AP may contribute to low-grade systemic inflammation in the body [18-20]. AP is an inflammatory disease that affects the supporting tissues of the apical part of the tooth root, usually asymptomatic, diagnosed by radiological examination [21]. In the present study, the prevalence of persistent AP was assessed
in a Turkish subpopulation and its relationship with systemic diseases was evaluated using CBCT.
Post-treatment AP was observed in at least one tooth in 83.3% of the patients, which is a very high prevalence. Siqueira et al. [4] observed AP in 29% of teeth with adequate root canal treatment and coronal restoration in their study on periapical radiographs. Kirkevang et al. [22] in their study with conventional radiography in the Danish population, have found the prevalence of AP to be 31.2% in teeth with adequate root canal filling and coronal restoration. Al-Omari et al. [10] conducted a study with panoramic radiography and reported that in 72.4% of endodontically treated teeth, endodontic treatment was inadequate and apical periodontitis was observed in 87.0% of them. Kalender et al. [23] examined adequately treated root canal-filled teeth with periapical and panoramic radiographs and they detected AP in 26.6% of them. The reason for this significantly higher rate in our study may be related to the population difference and may be aroused from the fact that CBCT is much more sensitive in the diagnosis of AP. Abella et al. [13] found a significantly higher prevalence rate of AP lesions detected by CBCT and emphasized the key clinical features of CBCT in the diagnosis. Dutra et al. [14] investigated the sensitivity of imaging methods in diagnosing AP and stated that CBCT scans gave excellent accuracy.
According to Al-Omari et al. [10], AP is more frequent in maxillary teeth compared to mandibular teeth. In this study, the prevalence of AP was found to be higher in the mandible (11.8%) than maxilla (4.9%). Alternative imaging techniques, treatment modalities, and conducting studies in different populations may explain the controversial results. Also in the same study, Al-Omari et al. [10] found no association between AP and gender. In our study, there was no statistical difference between the genders regarding the prevalence of post-treatment AP. In this regard, our findings are compatible with Al-Omari et al’s work. Although there was no significant difference in our study, AP was more common in females (84.9%) compared to males (81.7%).
There are reports in the literature suggesting that there is a potential relationship between systemic diseases (cardiovascular diseases, diabetes, blood disorders, etc.) and the pathogenesis of AP [7, 24, 25]. While acknowledging that systemic diseases have an increasing effect on the possibility of post-treatment AP, in their systemic review, Aminoshariae et al. concluded that the available scientific evidence is insufficient to determine whether diabetes and cardiovascular diseases are associated with endodontic outcomes [7]. However, more recently Gupta et al. [11]. revealed a strong association between diabetes and AP in a meta-analysis study. This study evaluated the relationship between post-treatment AP and some specific systemic diseases (cardiovascular diseases, blood diseases, and diabetes mellitus). No cases of previously root-filled teeth with apical periodontitis were encountered in patients with hemophilia. According to the results of the present study, it could not be established any significant relationship between post-treatment AP and cardiovascular disease diabetes. The limitation of this research is the low number of patients with systemic disease in the study group.
Conclusion
This study showed a high prevalence of persistent AP in the Turkish population, although root canal filling was sufficient radiologically. CBCT is an important imaging method in the diagnosis of apical periodontitis, with a higher radiation dose compared to other imaging methods. Periapical conditions of root canal-filled teeth should be radiographically examined in larger populations. In addition, long-term radiographic follow-up of teeth with an adequate root canal and crown filling is recommended.
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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The effect of coronary artery bypass grafting procedure on audiovestibular system
Çiğdem Fırat Koca 1, Erdinç Koca 2
1 Department of Otolaryngology Head and Neck Surgery, Faculty of Medicine, Malatya Turgut Özal University, 2 Department of Anesthesiology and Reanimation, Malatya Training and Research Hospital, Malatya, Turkey
DOI: 10.4328/ACAM.21641 Received: 2023-02-04 Accepted: 2023-03-27 Published Online: 2023-04-03 Printed: 2023-06-01 Ann Clin Anal Med 2023;14(6):525-530
Corresponding Author: Çiğdem Fırat Koca, Department of Otolaryngology Head and Neck Surgery, Faculty of Medicine, Malatya Turgut Özal University, Malatya, Turkey. E-mail: cifirat@hotmail.com P: +90 530 223 96 24 Corresponding Author ORCID ID: https://orcid.org/0000-0001-8990-0651
This study was approved by the Clinical Research Ethics Committee of Turgut Ozal University (Date: 2021-08-03, No: 2021/40)
Aim: Coronary artery bypass grafting surgery may affect end-organ perfusion. Our aim was to examine the effect of this method on audiovestibular system.
Material and Methods: Patients who had CABG were called and invited. Pure tone audiometric test, c- and o-VEMP tests were performed for all participants.
Results: The results at 250, 500, 2000 and 4000 Hz differed for the left ears (p=0,013, p=0,045, p=0,028, p=0,045 ) and in the right ears, p13 (p = 0.040) were differentiated among the groups and the p13-n23 amplitude was lower in the bypass group (p=0,013). In the left ear results , p13-n23 amplitude (p= 0.007) and n10-p15 amplitudes (p = 0.006) differed between the groups, and the right ear n10-p15 amplitudes were lower in the bypass group (p = 0,005). Mean n10 (p=0,006) and p15 latency were high in the bypass patients (p= 0,005).
Discussion: CBAG may affect balance-connected mechanisms at varied levels and intensity.
Keywords: Coronary Artery Bypass Grafting, Vestibular Evoked Myogenic Potentials, c-VEMP, o-VEMP, Audiovestibular
Introduction
Coronary artery bypass grafting (CABG) is a surgical method that the great majority of patients experience to obtain a better quality of life despite critical risks including cardiac ischemia 3.9 %, stroke 1.3 % and even death 1.7 % [1]. It can be assumed that many factors influence the change in end-organ failure following postcardiac surgery with CABG. Systemic inflammatory reply, conversion from a dynamic flux to a static flux in the CABG course, hypoperfusion, microemboli, reperfusion and ischemia are the most significant factors. Cardiac surgical procedures provoke SIR (systemic inflammatory response). SIR is activated by various factors, including the induction of inflammatory cytokines, coagulation, complement, fibrinolysis and cytodevastating mediators emerged by white blood cells. The initiation of anesthesia and following CABG induce severe alterations at the stage of the microcirculation. Following induction, the number of perfused capillaries decreases to 70 %, and after the start of CABG, it decreases to nearly 53 %. When emboli are restricted in an organ, smaller capillary and arterial expansions are monitored in the organ [2]. It is thought that the off-pump coronary bypass grafting procedure causes less oxidative damage with no cardioplegic arrest and the continuation of normothermia [3,4]. Prior results of on-pump cardiac surgical cases demonstrate a greater level of oxidative stress in comparison to cases undergoing off-pump cardiac surgical procedures [5-8]. For this reason, we decided to analyze the effect of on-pump CABG on audiovestibuler system.
Sudden sensorineural hearing loss (SSNHL) is an infrequent pathology following cardiological surgical procedure with extracorporal cycle and has been indicated in past studies [9]. The rate of SSNHL following cardiac surgery with extracorporal circulation (CSWEC) has been declared to be 0.1 % [9-11]. Shapiro et al. reported two cases of unilateral serious SSNHL following cardiac surgical procedure with extracorporal circulation [11].
Balance association is an important task to maintain a normal life, and is achieved in the centrical nervous system based on the data released from ocular, vestibular, and as well as proprioceptive mechanisms. Vestibular-evoked myogenic potentials (VEMP) provide for the evaluation of task and entirety of vestibular routes in the brainstem and assessment and evaluation of central pathologies. Cervical VEMP (c-VEMP) can be detected via sternocleidomastoid muscle and indicates an inhibitor vestibulo-collic reflex as a reaction to an acoustic stimulant. The test represents the functionality of the ipsilaterally inferior vestibular nerve and saccule. Additionally, ocular VEMPs (o-VEMP) can be detected via the inferior oblique muscle and demonstrate the vestibulo-ocular reflex as an action on an acoustic stimulant, and the test represents the functional status of the contralateral superior vestibular nerve as well as utricle [12].
While preparing this article, we did not find any research in the literature examining the evaluation of the vestibular system after on-pump CABG. We decided to evaluate the vestibular system in patients who had undergone on-pump CABG with cervical (c-VEMP) and ocular VEMP (o-VEMP) test batteries.
Material and Methods
Study Design
The study was performed at Malatya Training and Research Hospital, Otorhinolaryngology Department between September and December 2021. Ethical approval was obtained from the Clinical Research Ethics Committee of Turgut Ozal University (ethical approval number 2021/40). In the research, our goal was to determine the vestibular functionality of cases who had previously undergone on-pump CABG with pure tone audiometry, oVEMP and cVEMP tests. Following the ethics committee approval, the patients who had on-pump CABG were identified from the information system of our hospital, they were called by phone and invited to our clinic for ENT examination. All participants underwent a complete ENT examination. We included patients younger than 60 years of age in our research to prevent the effects of aging on VEMP results, and the control group consisted of patients of the same age group. Patients with previous ear surgery, hearing loss, Meniere’s disease, chronic diseases such as diabetes mellitus that may affect the vestibular system and our test results, patients receiving vestibulo-suppressant treatment, previous COVID-19, patients with herpes simplex and herpes zoster were excluded from the study. A detailed anamnesis was taken following the ENT examination of the patients. Demographics of the participants were noted. All participants underwent the Dix-Hallpike test, pure tone audiometric evaluation, c- and o-VEMP tests. The control group was formed from patients with similar demographic characteristics who applied to the ENT outpatient clinic for other reasons and were accepted to participate in the research. Audiometric measurements were carried out via Interacoustics AC40 apparatus (Middelfart, Denmark) to determine six distinct frequencies (250 Hz, 500 Hz, 1000 Hz, 2000 Hz, 4000 Hz, and 8000 Hz) in an appropriate quiet test cabin.
Cervical VEMP test
The cervical VEMP (c-VEMP) test was carried out via Interacoustics Eclipse EP25 (Middelfart, Denmark). Tone-burst stimuli were applied to the ear via IP30 insert earphones (RadioEar, Middelfart, Denmark). Tone-burst stimuli (105 dB nHL, 500 Hz, each featured as a 2-ms rising decline and a 0-ms plateau period, stimulus density 5.1/second) were given to each ear. Electromyography (EMG) signals were expanded and the bandpass was set between 30 and 2000 Hz frequencies. c-VEMP tests were carried out between 100 microvolts (µV) root mean square (RMS) and 150 µV RMS. Interpeak latencies, peak and peak-to-peak amplitudes of the p13 and n23 waves were recorded individually for each ear. The asymmetry rate was calculated using the formula described by Murofushi et al. (Asymmetry rate: 100 (Au-Aa) / (Au + Aa) Au: p13 – n23 (the peak-to-peak amplitude of the unaffected side), Aa: p13 – n23 (the peak-to-peak amplitude of the affected side) between the left and right ear [13]. In accordance with normal data of the present study, an asymmetry rate of greater than 19 % was settled as anomalous and agreed as a sign of saccular defect on the side demonstrating a falling amplitude reply.
Ocular VEMP test
The o-VEMP test was achieved via an Interacoustics Eclipse EP25 apparatus (Middelfart, Denmark). The EMG signals were expanded and bandpass-set among 1 and 1000 Hz frequencies. The sound stimulus was applied to the contralateral part of the effective electrode with a density of 105 dB nHL. The peak latencies and peak-to-peak amplitudes of the n10 and p15 waves were recorded for each ear. The asymmetry rate was calculated adhering to the formula described by Murofushi et al. [13]. Based on our normal data, we approved asymmetry ratios of more than 28 %, as the asymmetry was presented among the two ears and has been recognized as a sign of utricular pathology on the side demonstrating a decreased amplitude reply.
Data examination was performed by utilizing the IBM SPSS version 26.0 statistical program (Chicago, IL, USA). Skewness and Kurtosis values were utilized to measure the normality of the data dispersion. Demonstrative statistical data were specified as mean, standard deviation, median, range and quartile difference (Q1-Q3) for quantitative variables. The analysis of non-normally distributed groups was carried out with the Mann-Whitney U test, and the analysis of normally-distributed groups was carried out with the Independent Sample T-test. A Two-Way Repeated ANOVA analysis was utilized to examine significance among the experimentals and controls with repetitive measurements. A p-value of <0.05 was agreed to show numerical significance [14].
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
A total of 61 participants, 31 patients and 30 controls were included in our study. The demographic data were similar for the two groups. The mean age was 48,34±5,39 for controls and 49,47±5,71 for the bypass group. In the patient group, the least time passed since bypass surgery was on the 13th postoperative month, and the longest duration was 8 years.
In audiologic assessment, while all frequencies were detected in normal ratio, a numerical significance was determined at 250 (p= 0,013), 500 (p=0,045), 2000 (p=0,028) and 4000 (p=0,045) Hz for left ears in the comparison between the groups (Table1). When both the left and right ears were evaluated, numerical significance was detected at 250 (p=0,016) and 4000 Hz (p=0,025). Mean values were higher in the bypass group for all frequencies (Table 1). When the right ears were compared, no difference was observed in any frequencies between the two groups (Table 1).
The c- and o-VEMP replies could be gained in all participants of the control group. In the bypass group, we could not obtain o-VEMP bilaterally in 4 patients and unilaterally in 4 patients from a total of 12 ears (12.9%). In the bypass group, c-VEMP responses could not be obtained bilaterally in 2 patients and unilaterally in 2 patients (6.4%). In the cVEMP test, the values of p13 latency, n13 latency, p13-n23 latency, and the p13-n23 amplitude were evaluated for both the right and left ears and analyzed between bypass and control groups. According to the outcomes of the right ear cVEMP, the latency of p13 (p = 0.040) was prominently differentiated among the two groups. The average p13 latency was 17,85±5,27 ms for the bypass group and the p13 latency was greater than the controls. Mean p13-n23 amplitude was detected as 73,77±54,43 mv in bypass group, the p13-n23 amplitude was lower in the bypass group and the differentiation was numerically significant (p=0,013) (Table 2) (Figures 1,2, 3).
In the c-VEMP outcomes for the left ear, we detected a numerical significance in p13-n23 amplitude (p= 0.007) and the average amplitude of p13-n23 declined in the bypass group (63,32 ±37,87) (Table 3).
Using the o-VEMP test, p15, n10, n10-p15 latency, and the amplitude of n10-p15 were examined. In the o-VEMP results of the left ear, we detected a numerical significance in the amplitude of n10-p15 (p = 0.006) between the groups. The mean n10-p15 amplitude value was 5,59±3,51 in the bypass group, which was lower than in controls (Table 3) (Figures 1,2, 3).
In the right ear o-VEMP, the average n10-p15 amplitude was 4,73±4,18 mv in the bypass group, which was lower than in controls, and the differentiation was numerically significant (p = 0,005). The mean n10 latency was 11,12±2,74 ms in the bypass group and greater than in controls, the difference was numerically significant (p=0,006). Similarly, the mean p15 latency was 16,28±2,85 in the bypass group, and this value was higher than in controls. The comparison showed statistical significance (p= 0,005) (Table 2) (Figures 1, 2, 3).
The cVEMP asymmetry rate of a total of 4 cases could not be calculated. The ssymmetry rate of 24 cases was found to be higher than 19.23%. None of the participants showed pathological results in the Dix-Hallpike test.
Discussion
Our results suggest that the on-pump CABG procedure may affect the audiovestibular system. While all frequencies were detected in normal ratio, a numerical significance was determined at 250 (p= 0,013), 500 (p=0,045), 2000 (p=0,028) and 4000 (p=0,045) Hz for the comparisons of left ears between groups. The average values for all frequencies were higher in the bypass group. According to the outcomes of the right ear c-VEMP, p13 (p = 0.040) was significantly differentiated between the groups. The p13 latency was higher than in the control group, and the p13-n23 amplitude was lower in the bypass group, and the differentiation was numerically significant (p=0,013). In the left ear c-VEMP outcomes, we detected a numerical significance in p13-n23 amplitude (p= 0.007) between the groups. The average amplitude of p13-n23 declined in the bypass group. In the analysis of the o-VEMP of the left ear, we detected a numerical significance in the amplitude of n10-p15 (p = 0.006) between the groups. The mean n10-p15 amplitude value was lower than in controls. On the other hand, in the right ear o-VEMP outcomes, the average n10-p15 amplitude was lower than in controls (p = 0,005). Mean n10 latency was greater in the bypass group (p=0,006). Similarly, mean p15 latency was high in the bypass patients and the comparison showed statistical significance (p= 0,005).
The otolith task is measured via VEMP test batteries as a reaction to a great intensity acoustic stimuli. Bilateral or unilateral lack of o-VEMPs is likely to demonstrate either utricular defective functions or a pathology in the superior vestibular nerve, extraocular muscles or their centrical communication [12]. We could not obtain o-VEMP responses from 12.9 % of our patients. Additionally declined p13/n23 (c-VEMP) amplitudes may indicate defective functions or pathologies. Also, the lack of c-VEMPs in nearly 6.4% of our patients and declined amplitudes are likely to indicate the presence of pathologies of the inferior vestibular nerve, saccular, or their central contacts. Walsted et al. reported that four patients developed severe left-sided SSNHL following CSWEC [9]. Although SSNHL caused by the use of gentamicin during the procedure has been reported in the literature, gentamicin was not used in any of our patients. In addition, perioperative cerebral hypoperfusion is an important agent that may play a critical role in SSNHL. The most common explanation of SSNHL following CSWEC appears to be the obstruction of the cochlear division of the internal auditory artery due to microembolisms. This may be due to fragments from calcified and/or arteriosclerotic plaques, air or fat. This mechanism is indicated in past studies demonstrating that cerebral injury due to embolism may be a complication of cardiac surgeries [9]. Although we included patients with normal hearing in this clinical study, we detected that many frequencies were higher in the bypass group in comparison with the controls. Research has indicated an increased vulnerability in males to the occurrence of higher tone injury. According to the male predominance, with an increased rate of basilar artery atherosclerosis, perfusion insufficiency and common longer pump periods appear to be the most frequent reasons for the uncommon causes of hearing impairment after cardiopulmonary bypass surgical procedure [15]. Various studies have been reported, including both irreversible and reversible hearing loss after cardiac bypass procedure. According to the prospective-controlled survey, it was indicated that mild alterations could develop in the high frequencies and researchers underlined that four cases developed an evident decrease in hearing thresholds. In their study, the control group consisted of open thoracotomy free from extra-corporeal cycle and a research group of CABG cases on extra-corporeal bypass [16-17]. Other suggested outcomes of SSNHL include occlusion of cochlear artery, intracochlear membrane ruptures, and insufficiency of the endocochlear potential. Some studies underlined the negative effects of nitrous oxide used in anesthesia induction on the middle and/or inner ear [18-19]. Due to the age-provoked alterations in the central nervous and peripheral auditory system and in the vascular mechanism may also affect the auditory dysfunction. Considering this factor, we designed a relatively young patient group who had undergone CABG procedure [20]. Vestibular deterioration was reported to be 70 % higher in participants with diabetes mellitus [21]. Li et al. reported that they could not find a significant association between cardiovascular risk factors between VEMP responses and characteristics of VEMPs [22]. Although there are publications showing that diabetes mellitus and other cardiovascular risk factors have an effect on VEMP measurements, there are publications indicating that it has no effect, and we did not include diabetic patients in our study. VEMP tests constitute a considerable part as a part of vestibulometric analysis and are utilized to detect the utricular and saccular functions. The o-VEMP measures the complete superior vestibular nerve and utricular functions and on the other hand, c-VEMP allows assessment of the integrity of the inferior vestibular nerve and as well as the saccule. The prolongation of the positive peak, the rise in latency or the lower amplitude are the markers of pathological c-VEMP and are accepted as signs of the saccular defect [23].
It may not be sufficient to evaluate the vestibular system with VEMP tests solely. We know that VEMP tests are complementary tests. However, in the conditions of our clinic, we used it because the only test battery we had was the VEMP test.
In case of changing the results of VEMP tests, we included patients who were relatively young and had no additional disease other than bypass. These features challenged us and we were able to find a few patients that fit this schedule. It would be appropriate to support the results of our study with larger patient groups in the future.
Conclusion
Consequently, it is possible to mention that the CBAG may affect balance-connected mechanisms at varied levels and intensity. We could not find a similar type of study in the literature to compare the outcomes of our study. We think that this is a feature that makes our work superior.
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. Chandrasena LG, Peiris H, Waikar HD. Biochemical changes associated with reperfusion after off-pump and on-pump coronary artery bypass graft surgery. Ann Clin Lab Sci. 2009;39(4):372-7.
4. Cavalca V, Sisillo E, Veglia F, Tremoli E, Cighetti G, Salvi L, et al. Isoprostanes and oxidative stress in off-pump and on-pump coronary bypass surgery. Ann Thorac Surg. 2006;81(2):562-7.
5. Karu I, Taal G, Zilmer K, Pruunsild C, Starkopf J, Zilmer M. Inflammatory/ oxidative stress during the first week after different types of cardiac surgery. Scand Cardiovasc J. 2010;44(2):119-24.
6. Karu I, Zilmer K, Starkopf J, Zilmer M. Changes of plasma asymmetric dimethylarginine levels after coronary artery bypass grafting. Scand Cardiovasc J. 2006;40(6):363-7.
7. Loukanov T, Arnold R, Gross J, Sebening C, Klimpel H, Eichhorn J, et al. Endothelin-1 and asymmetric dimethylarginine in children with left-to-right shunt after intracardiac repair. Clin Res Cardiol. 2008;97(6):383-8.
8. Bellinger FP, Raman AV, Reeves MA, Berry MJ. Regulation and function of selenoproteins in human disease. Biochem J. 2009;422(1):11-22.
9. Walsted A, Andreassen UK, Berthelsen PG, Olesen A. Hearing loss after cardiopulmonary bypass surgery. Eur Arch Otorhinolaryngol. 2000;257(3):124-7.
10. Plasse HM, Spencer FC, Mittleman M, Frost JO. Unilateral sudden loss of hearing. An unusual complication of cardiac operation. J Thorac Cardiovasc Surg. 1980;79(6)822-6.
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12. Yılmaz O, Mutlu BÖ, Yaman H, Bayazıt D, Demirhan H, Bayazıt YA. Assessment of balance after recovery from Covid-19 disease. Auris Nasus Larynx. 2022;49(2):291-8.
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16. Phillipps JJ, Thornton AR. Audiometric changes in patients undergoing coronary artery bypass surgery. Br J Audiol. 1996;30(1):19-25.
17. Donne AJ, Waterman P, Crawford L, Balaji HP, Nigam A. A single-blinded case controlled study on effects of cardiopulmonary circulation on hearing during coronary artery bypass grafting. Clin Otolaryngol. 2006;31(5):381-5.
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Çiğdem Fırat Koca, Erdinç Koca. The effect of coronary artery bypass grafting procedure on audiovestibular system. Ann Clin Anal Med 2023;14(6):525-530
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COVID-19 infection in kidney transplant patients: Clinical experience of Baskent University Transplantation Department
Halil İbrahim Taşcı
Department of General Surgery, Faculty of Medicine, Başkent University, Ankara, Turkey
DOI: 10.4328/ACAM.21643 Received: 2023-02-06 Accepted: 2023-03-27 Published Online: 2023-04-03 Printed: 2023-06-01 Ann Clin Anal Med 2023;14(6):531-535
Corresponding Author: Halil İbrahim Taşcı, Department of General Surgery, Faculty of Medicine, Başkent University, Ankara, Turkey. E-mail: okcu6528@gmail.com P: +90 505 481 04 45 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2269-4798
This study was approved by the Ethics Committee of Medical and Health Sciences Research Board of Baskent University (Date: 2021-06-01, No: KA21/271)
Aim: The aim of our study was to present our clinical approach to patients who underwent kidney transplantation in our clinic and were diagnosed with coronavirus disease 2019 during their follow-up, and to examine factors affecting the course of the disease and mortality.
Material and Methods: The data of patients who underwent kidney transplantation in Baskent University Faculty of Medicine between March 2020 and August 2021 and who were diagnosed with the coronavirus disease 2019 were retrospectively analyzed. The patients included in the study were divided into two groups: deceased (Group 1) and survivors (Group 2). Parameters that may have an effect on mortality were statistically analyzed.
Results: Among the admission laboratory values of 43 patients included in the study, the albumin value was statistically significantly lower, while the ferritin value was higher in Group 1 (p<0.05). Positive culture results were statistically more frequent in the mortality group (p<0.05). The length of intensive care stay and the duration of intubation were longer in the mortality group.
Discussion: The coronavirus disease 2019 may have a more severe and fatal course in kidney transplant patients due to other underlying chronic diseases and immunosuppressive agents that have to be used. There is a need for large-scale multicenter clinical studies to establish standard guidelines for the treatment and reveal other factors affecting the course of the disease and mortality.
Keywords: Kidney Transplantation, Immunosuppressive, Coronavirus Disease 2019, Mortality
Introduction
The novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory failure virus (SARS-COV-2) was first identified in Wuhan, China in December 2019 [1]. In January 2020, the World Health Organization declared COVID-19 a global public health emergency, and two months later, the coronavirus outbreak was declared a global pandemic [2]. Although the disease is known to be transmitted mainly via droplets or direct contact, it has also been reported to be transmitted indirectly through contaminated surfaces [3]. Elderly patients and those with comorbidities such as hypertension, diabetes mellitus, immune system disorders, respiratory or heart failure, chronic kidney disease, and cancer have been observed to have a more severe course [4].
The clinical symptoms, treatment, and prognosis of COVID-19 pneumonia in kidney transplantation patients are expected to differ greatly from the general population due to immunosuppressives that have to be used [5]. Considering their decreased T-cell immunity, transplant recipients are thought to be at a higher risk for bacterial and viral infections [6]. Although solid organ transplant patients infected with the respiratory syncytial virus, influenza viruses, parainfluenza virus, and adenoviruses have a poorer prognosis, such a result has not been seen in Middle East Respiratory Syndrome [7]. The available data on the course of COVID-19 in patients who had undergone solid organ transplantation and received immunosuppressive therapy are limited. The pandemic and all these uncertainties negatively affect the number of organ donations and organ transplants as well as the outpatient follow-up of patients who had previously undergone transplantation [8].
In this study, we aimed to present our clinical approach to the follow-up and treatment of patients who had previously undergone kidney transplantation in our clinic and were diagnosed with COVID-19 during their follow-up, and to examine the factors affecting the course of the disease and mortality.
Material and Methods
This study was approved by the Medical and Health Sciences Research Board of Baskent University (Project Date: 2021-06-01, No:KA21/271) and supported by Baskent University Research Fund. The data of patients who underwent kidney transplantation in Baskent University Faculty of Medicine, Department of Transplantation between March 2020 and August 2021 and who were diagnosed with COVID-19 during their follow-up and treated on an inpatient or outpatient basis were retrospectively analyzed. The study included patients with clinical findings of COVID-19 and a positive polymerase chain reaction (PCR) test result. All patients underwent posterior-anterior chest radiograph and chest computed tomography (CT). Bilateral peripheral consolidation and/or ground-glass opacity were considered lung involvement. The general approach of our transplantation discipline to altering immunosuppressive therapy was as follows:
– Not making any changes in the immunosuppressive therapy regimen of patients with a good clinical status,
– Continuing the same dose of steroids and cyclosporine, one of the calcineurin inhibitors, in all patients using these drugs,
– First reducing the dose of antimetabolite (mycophenolate) in patients with a worsening general condition or discontinuing it if the patient’s general condition does not improve,
– Reducing the drug dose in patients using tacrolimus as a calcineurin inhibitor or mTOR inhibitor (everolimus or sirolimus) if the clinical status does not improve despite the revision of the antimetabolite dose given simultaneously or completely discontinuing the drug, if necessary,
– Increasing the immunosuppressive drugs of patients with a negative follow-up PCR test result and improved clinical findings to pre-COVID-19 doses.
A total of 43 patients who met the study criteria were evaluated. The patients included in the study were divided into two groups: deceased (Group 1) and survivors (Group 2). The effects of other parameters on mortality were statistically analyzed.
Statistical analysis
The analyses of the study were performed using the SPSS V21.0 software package. The level of significance was set at p<0.05 for all analyses. The normality distribution assumption of the data was evaluated using the Kolmogorov-Smirnov test. Categorical variables were presented as frequency tables, while numerical variables were presented as descriptive measures (mean ± standard deviation or median (min-max) in nonparametric cases). One-way analysis of variance (ANOVA) was used for inter-group comparisons when parametric conditions were provided, while the Kruskal-Wallis ANOVA method was used in other cases. Of the post-hoc, Tukey, Scheffe, and Tamhane tests, the appropriate one was preferred for pairwise comparisons. The student t-test or Mann-Whitney U test was used for two-group comparisons. The chi-square analysis was used to test whether categorical variables were correlated or not, while Pearson’s or Spearman’s correlation tests were used to determine the correlation between numerical variables.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Of the 43 patients included in the study, 17 (39.5%) were female and 26 (60.5%) were male, with a mean age of 48.51±13.90 years. Of the patients, 13 (30.2%) underwent kidney transplantation due to hypertension, 10 (23.3%) due to diabetes mellitus, 6 (14%) due to cryptogenic causes, 4 (9.3%) due to hereditary causes, and 10 (23.25%) underwent kidney transplantation due to other causes. While 16 (37.2%) patients had cadaveric transplantation, 27 (62.8%) patients had living-donor transplantation (8 from parents, 6 from siblings, 12 from spouses, 1 from other donors). As immunosuppressive therapy, 25 (58.1%) patients were using tacrolimus, mycophenolate mofetil, and prednisolone, 14 (32.6%) patients were using cyclosporine, mycophenolate mofetil, and prednisolone, and 3 (7%) patients were using sirolimus, mycophenolate mofetil, and prednisolone, while 1 (2.3%) patient initially used tacrolimus, mycophenolate mofetil, and prednisolone but was switched from tacrolimus to everolimus due to the side effects (Table 1).
Twenty-three (53.5%) patients presented with cough, 18 (41.9%) patients with fever, 17 (39.5%) patients with fatigue, 11 (25.6%) patients with shortness of breath, and 9 (20.9%) patients presented with diffuse body pain complaint. The time from transplantation to COVID-19 diagnosis was calculated and found to be 62.65±48.51 months. According to clinical findings, 30 (69.76%) patients were treated on an inpatient basis, 18 (60%) of whom required intensive care (with a median length of hospital stay of 12 (range, 1-86) days and a median length of intensive care stay of 9.5 (range, 2-57) days). All patients with a requirement for intensive care required intubation, with a duration of intubation of 6 (range, 1-28) days.
Patients were divided into two groups: deceased (Group 1) and survivors (Group 2), and parameters that could affect mortality were analyzed. The mortality group had a statistically significantly higher mean age than the other group (53.88±13.35 vs. 45±13.50 (p=0.039)). The two groups were similar in terms of gender distribution (p=0.27). None of the parameters such as the presence or absence of comorbid disease (hypertension, diabetes mellitus, coronary artery disease, chronic obstructive pulmonary disease), pre-transplant hemodialysis history, right or left kidney transplantation, etiology of kidney failure, type of transplantation (living-donor or cadaveric), or donor type (parents, sibling, spouse, other) were found to have an effect on mortality (p>0.05). Although the time from transplantation to COVID-19 diagnosis was longer in Group 2 (64.80±47.93, 59.35±50.66), there was no statistically significant difference between the groups (p=0.172). The presence of a previous rejection attack had no effect on mortality during COVID-19 (p=0.41). Immunosuppressive agents used by patients before they were infected with COVID-19 were similar in both groups (p=0.72). The presenting complaints (fever, cough, fatigue, shortness of breath, diffuse body pain) were also similar in both groups (p>0.05). There was no significant difference between the groups in terms of hemoglobin, white blood cell, neutrophil, lymphocyte, neutrophil-to-lymphocyte ratio, C-reactive protein, fibrinogen, urea, creatinine, sodium, potassium, lactate dehydrogenase, D-dimer, alanine aminotransferase, aspartate aminotransferase values (p>0.05). The albumin value was significantly lower (p=0.04) but the ferritin value was significantly higher in Group 1 (p=0.029). Although the prevalence of involvement on chest CT was higher in the mortality group, there was no statistically significant difference between the groups (p=0.11). While there was growth in any of the cultures ordered for 12 (70.58%) of deceased 17 patients, only 1 (3.84%) of the survived patients had a positive culture result (p<0.001). All patients in Group 1 were admitted to the intensive care unit, but only 1 (3.84%) patient in Group 2 was admitted to the intensive care unit (p<0.001). The length of hospital stay was similar in both groups (p=0.89); however, the length of intensive care stay (p<0.001) and the duration of intubation (p <0.001) were significantly longer in Group 1. The antiviral agent preferred for the treatment and the antiaggregants/anticoagulants used were similar in both groups (p=0.24, p=0.60, respectively). The frequency of plasma use was significantly higher in Group 1 compared to Group 2 (p=0.006). Of the 13 patients who required hemodialysis during their treatment, only 2 (15.38%) survived, while 11 (84.61%) died (p<0.001). Of the 17 patients who required to use positive inotropes, 16 (94.11%) died and only 1 (5.88%) patient survived (p<0.001) (Table 2).
While the immunosuppressive agent used by the patients before COVID-19 infection did not have any effect on the length of hospital stay (p=0.31) and the length of intensive care stay (p=0.12), the duration of intubation was significantly longer in those using the combination of tacrolimus-mycophenolate mofetil and prednisolone (p=0.026). Revisions made in the immunosuppressive treatment regimen of COVID-19 patients were similar between the groups (p=0.14 for mycophenolate mofetil (unchanged/reduced/discontinued), p=0.29 for tacrolimus). No change was made in the cyclosporine dose. Revision of drug doses had no statistically significant effect on the length of hospital stay, length of intensive care, and duration of intubation (p>0.05). The changes made in the immunosuppressive dose are summarized in Table 3. The binary regression analysis showed that the presence of involvement on CT was effective in predicting the length of intensive care stay (p=0.026, R square=0.27).
As expected, the correlation analysis showed a positive correlation between the length of hospital stay, length of intensive care stay, and duration of intubation, and between the length of intensive care stay and duration of intubation (p<0.001). There was a positive correlation between mortality and age, length of intensive care stay, duration of intubation, hospital-acquired infection, positive culture, hemodialysis requirement during the disease, and positive inotropic drug requirement, and a negative correlation between mortality and albumin value (p<0.001). Twenty-six (60.46 %) patients who survived and were discharged were followed up regularly on days 15, 30, and then on a monthly basis. The median follow-up duration was calculated to be 2.5 (range, 1-8) months. The immunosuppressive therapies of patients with a negative follow-up PCR test result and improved clinical findings were increased to pre-COVID-19 doses, and their immunosuppressive drug levels were monitored based on routine practice. During the follow-ups, none of the patients had recurrent disease and all patients had normal renal functions.
Discussion
In kidney transplant patients, immune response, especially the T-cell response, is suppressed due to long-term use of immunosuppressive agents [5]. In addition to the immunosuppressive drugs used, these patients also have a high risk of COVID-19 due to their underlying chronic kidney failure and other comorbid diseases such as hypertension and diabetes mellitus [4]. Most studies have found a higher incidence of COVID-19 in kidney transplant patients compared to the normal population, with a more severe and fatal course [3,9]. Furthermore, it is believed that close follow-up of these patients will help in early diagnosis [9].
Some studies have suggested that immunosuppressed patients may not have an increased risk of COVID-19 compared to the normal population [10]. Supporting this hypothesis, the rates have not been found to be high although both a higher incidence of COVID-19 and mortality are expected in patients with post-transplant chronic immunosuppression [11]. This is interpreted as the ability of immunosuppressives to protect the patient against the dramatically increased proinflammatory cells due to COVID-19. Another hypothesis is that immunosuppressive therapy may also mitigate the viral cytopathic effect [11].
It has been found that post-transplant COVID-19 patients are mostly in their sixth decade of life, and the incidence is higher in men. Of the 43 patients included in our study, 17 (39.5%) were female and 26 (60.5%) were male, with a mean age of 48.51±13.90 years. The time from transplantation to diagnosis has usually been observed to be longer in patients diagnosed with COVID-19 [9]. In our study, the time from transplantation to COVID-19 diagnosis was calculated to be 62.65±48.51 months.
Interestingly, an improvement in radiographic findings has been observed 7-10 days after the onset of symptoms without specific antiviral therapy [12]. Although there are approaches recommending high-resolution CT to monitor the course of pneumonia, there have been centers that do not include it in their routine practice, arguing that it is not necessary [4].
A study comparing COVID-19 patients with and without kidney transplantation who were hospitalized and treated showed that the average age of kidney transplant recipients was lower (7 years) and they had more comorbid disorders [13]. Similar to the general population, the most common symptoms in kidney recipients with COVID-19 have been reported as fever, myalgia, and cough [6]. The course of the disease can be quite different. Of our patients, 23 (53.5%) had cough, 18 (41.9%) had fever, 17 (39.5%) had fatigue, 11 (25.6%) had shortness of breath, and 9 (20.9%) had diffuse body pain complaint. Of the 43 patients diagnosed with COVID-19, 30 (69.76%) required hospitalization, and 13 (30.23%) recovered with outpatient follow-up. Kidney transplant patients with COVID-19 infection have been found to have more impaired kidney functions than those who have not undergone transplantation. It is believed that this may be related to the presence of chronic renal failure in the history of kidney transplant patients as well as acute renal failure due to frequent diarrhea and elevated fever [13]. Moreover, it has been observed that kidney transplant patients with COVID-19 infection have a longer disease course with more severe symptoms due to the effect of immunosuppressive drugs used for a long time.
Other than supportive care, the management of COVID-19 patients has not yet been standardized. This also applies to other patients diagnosed with COVID-19 who had undergone solid organ transplantation. Especially during the adjustment of immunosuppressive therapy, the balance between acute rejection and infections that may be caused by bacterial and/or opportunistic pathogens should be maintained well [1]. The data on how to modify the dose of immunosuppressive drugs in transplant patients with COVID-19 is very limited. Some suggestions have been made on this subject [2, 11, 14]. There is no large-scale study investigating the efficacy of antiviral agents on solid organ transplant patients. The data obtained so far support that only remdesevir has a positive effect on the course of the disease in patients with severe COVID-19 who had undergone solid organ transplantation [15]. Although there are studies showing that the use of convalescent plasma contributes positively to the course of the disease in COVID-19 patients with solid organ transplantation, most of them are case reports [15,16]. In our study, the antiviral and immune plasma treatment option changed in parallel with the changes in the algorithms over time.
Limitations of the study
The limitations of the study are collecting the data from patient records and the absence of objective examination findings due to the retrospective nature of the study.
Conclusion
There is very limited data on how to manage immunosuppressive agents during the follow-up of these patients and on the efficacy of other treatment alternatives. Furthermore, there are many unknowns regarding other parameters that may affect the course of the disease and mortality. Although some parameters that may be associated with mortality were determined in our study, the small sample size, the lack of standard approaches to diagnosis and treatment, and the single-center design of the study prevented us from stating strong conclusion sentences. There is an urgent need for large-scale multicenter clinical studies to eliminate all these negativities, establish standard guidelines for treatment, and reveal other factors affecting mortality and the course of the disease.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Early effect of pelvic organ prolapse surgery on female sexual functions
Merve Abay 1, Levent Özgen 1, Gülten Özgen 2, Derya Sivri Aydın 3, Behiye Pınar Göksedef 3
1 Department of Obstetrics and Gynecology, Faculty of Medicine, Bursa Uludag University, 2 Department of Obstetrics and Gynecology, Faculty of Medicine, Bursa Uludag University, 3 Department of Obstetrics and Gynecology, University of Health Sciences, Bursa Yuksek Ihtisas Training and Research Hospital, Bursa, Turkey
DOI: 10.4328/ACAM.21654 Received: 2023-02-14 Accepted: 2023-04-05 Published Online: 2023-04-19 Printed: 2023-06-01 Ann Clin Anal Med 2023;14(6):536-540
Corresponding Author: Gülten Özgen, Department of Obstetrics and Gynecology, University of Health Sciences, Bursa Yüksek Ihtisas Training and Research Hospital, 16310, Yıldırım, Bursa, Turkey. E-mail: drgaslanozgen@yahoo.com.tr P: +90 224 295 54 97 Corresponding Author ORCID ID: https://orcid.org/0000-0002-7888-7583
This study was approved by the Ethics Committee of Health Science University, Haseki Training and Research Hospital (Date: 2017-05-30, No: 500)
Aim: In this study, we aimed to detect changes in sexual functions before and after surgery in women who underwent pelvic reconstruction for pelvic organ prolapse and urinary incontinence.
Material and Methods: This prospective cross-sectional study included 60 patients who underwent anterior and posterior vaginal repair due to cysto-rectocele and/or uterine prolapse. One day before and three months after the operation, FSFI scoring was performed. Patients were divided into 3 groups according to age: 30-40 years old (Group 1), 41-49 years old (Group 2) and 50-59 years old (Group 3).
Results: There was no significant difference in the total FSFI score of the patients after the operation (p = 0.072). There was a statistically significant increase in sexual desire and arousal scores (p = 0.011 and p = 0.049, respectively) but there was no statistically significant difference in the other subscale scores. There was a statistically significant difference in the sexual desire and arousal scores of Group 1 and the sexual desire score of Group 3 patients (p = 0.028, 0.046 and 0.017, respectively). There was a decrease in the total FSFI score and sexual desire, lubrication, orgasm, satisfaction subscale scores after the operation but this decrease was not statistically significant.
Discussion: There was no change in the total FSFI score in the 3rd month after pelvic organ prolapse operation, but there was a statistically significant increase in sexual desire and arousal scores. We believe that this increase may be due to the changing body image and sexual self-confidence of the patients in the postoperative period.
Keywords: Colporrhaphy Anterior, Colporrhaphy Posterior, Cystocele, FSFI, Rectocele, Sexual Function
Introduction
Sexual wellbeing, which can guide decisions in human life, can be interrupted by various factors. Sexual dysfunction is a more common problem in women than men, and its prevalence can increase by 19.7–28.7% (range 3.4–70.8%) in women with incontinence [1]. Urinary incontinence during sexual intercourse affects the sexual function of a woman by causing feelings of shame and liquidity, it can also have negative effects on the sexual life of her partner and sometimes cause him to leave the relationship [2].
Uterovaginal condition, which is characterized as herniation into or out of the vagina as a result of downward displacement of the pelvic organs, can cause inactivity and affect the patient’s sexual relations [3]. Although the mortality probability of genital organ prolapse is extremely low, it is known to have a significant negative effect on the patient’s quality of life.
In addition to physical factors, other important components of genital organ prolapse that affect sexual function include psychological aspects, genital image and sexual distress. Sociocultural factors also affect the patient’s sexuality and sexual behavior [4].
Rectocele, cystocele and uterine prolapse are conditions under the umbrella of pelvic organ prolapse (POP) [5]. Pelvic floor weakness and POP are common physical conditions that affect sexual function. Information on sexual function after surgery for POP is conflicting. However, many studies suggest that sexual function remains the same or improves in the postoperative period. Thus, there is a need for a validated questionnaire assessing sexual function after POP surgery. One such scale is the Female Sexual Function Index (FSFI) [6,7].
The aim of this study was to determine whether there were changes in women’s sexual function after undergoing pelvic floor surgery to repair POP using the FSFI questionnaire.
Material and Methods
Patients and Methods
This prospective cross-sectional study included 60 patients who underwent anterior and posterior vaginal repair due to cystorectocele and/or uterine prolapse between June 2017 and June 2018 at the gynecology clinic of the Haseki Training and Research Hospital. This study was approved by the institutional review board (Number 500. Date: 30.05.2017). Written informed consent was obtained from each patient. Patients aged 60 and over and those who were not sexually active were not included in the study. Patients’ data on the following variables were collected: age; gravida; parity; childbirth delivery type; body mass index; cigarette or alcohol use; menopausal status; hormone replacement therapy use; the presence of diabetes, hypertension or dyslipidemia; previous hysterectomy, previous vaginal operation or additional anterior or posterior vaginal repair surgical procedures.
Data collection and questionnaires
Participants were asked to fill out the FSFI questionnaire the day before the operation and three months after the operation, and pre- and post-surgery scores were determined for each patient. The patients were divided into three groups according to their age: Group 1 consisted of patients 30–40 years old, Group 2 of those 41–50 years old and Group 3 of those 51–59 years old. Calculations were done to determine if there was a relationship between patient age and FSFI scores both pre- and postoperatively.
The FSFI was developed by Rosen et al. to evaluate female sexual function [8]. A validity and reliability study of the index was conducted by Aygin and Aslan [9]. The FSFI questionnaire consists of 19 items on sexual function divided into six subsections – desire, arousal, lubrication, orgasm, satisfaction and pain. Each item is scored from 0 to 5. Thus, the highest total score possible is 95 and the lowest 4 points are obtained on the scale. Calculations were also made to determine the scoring of the subscales and the wholesale scale, and a coefficient of 0.6 was found for desire, 0.3 for arousal and lubrication, and 0.4 for orgasm, satisfaction and pain. The averages of the subsections were multiplied by the coefficients, and the highest possible score for each subsection was calculated as 36, with the lowest score being 7. Thus, preoperative and postoperative scores were calculated for each patient. Analysis was done to determine if there was a difference between the total scores and between the subscale scores before and after the operation. Many studies have reported that an FSFI score below 26.55 poses a high risk for sexual dysfunction.
Statistical analysis
Data were analyzed using the SPSS 16.0 statistics program. Numbers and percentages were given for categorical variables, and mean ± standard deviation minimum-maximum for numerical variables. Numerical variables were compared using the Student-t Test and the Mann- Whitney U test, and more than two group comparisons were made with One- Way ANOVA and the Kruskal-Wallis tests. Subgroup analyzes were performed with the Tukey test since the parametric test condition was met. Dependent group comparisons were made with Paired t-test and the Wilcoxson test. Relationships between numerical variables were examined using the Pearson and Spearman Correlation Analysis test. P <0.05 was accepted as the statistical alpha significance level.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
The mean age of the patients included in the study was 49.3 ± 8.0 years. When the patients were grouped according to age, 20% (n=12) were in Group 1, 33.3% (n=20) were in Group 2, and 46.7% (n=28) were in Group 3. Stress urinary tract incontinence (SUI) was present in 58.3% (n=35) of patients before the operation. In the study group, no additional surgical procedures other than colporrhaphy anterior and colporrhaphy posterior were performed in 20 (33%) patients, while transobturator tape (TOT) operation was added to 15 (25%) patients. In addition, while vaginal hysterectomy, sacrospinous ligament suspension (SSF) and mini sling operation were performed at the same time in 23 (38.4%) patients, abdominal hysterectomy operation was also performed in only 2 (3.3%) patients. Demographic data of the patients are shown in Table 1.
There was no significant change in the total FSFI score of the patients after the operation (p=0.072). There was a statistically significant increase in the total scores of sexual desire and arousal of the patients after the operation (p= 0.011 and p= 0.049, respectively ), while no statistically significant change was found in the other scale scores. After the operation, a statistically significant increase was found in the sexual desire and arousal scores of Group 1 patients and in the sexual desire scores of Group 3 patients (p=0.028, 0.046 and 0.017, respectively). No significant change was found in the other scale scores of Group 1 and Group 3 patients. In the postoperative period, a decrease was found in the total FSFI score and subscale scores of sexual desire, lubrication, orgasm, and satisfaction in Group 2 patients, but this decrease was not statistically significant.
It was observed that the total FSFI score and both preoperative and postoperative scores of sexual desire, arousal, lubrication and climax subscale scores decreased statistically with increasing age (preoperatively; p=0.008, 0.005, 0.007, 0.020, 0.004, postoperatively; p=0.002, 0.002, 0.001, 0.005, 0.001). It was determined that the post-operative satisfaction score decreased statistically significantly as the age of the patients increased (p=0.043). There was no statistically significant relationship between the satisfaction parameters in the preoperative period and the increase in age (p= 0.0529 ) ( Table 3).
Discussion
Pelvic floor weakness and POP are physical conditions that negatively affect sexual functions and sexual satisfaction. Information on sexual functions after POP surgery is conflicting. There are studies advocating that sexual functions improve, not change, or even worsen after surgery. While using different questionnaires, different population characteristics and different operative techniques seem to be effective in these results; age, parity, cultural differences, and history of pelvic surgery are other factors [10].
In a prospective study by Feldner et al., in which 27 patients who underwent traditional anterior colporrhaphy and 29 patients who underwent anterior vaginal repair with small bowel submucosa grafts, the FSFI scores at preoperative and postoperative 12 months were compared. A statistically significant increase was found in both groups in the postoperative period both in the total score of the FSFI scale and in the scores of desire, arousal, lubrication, orgasm, satisfaction, and pain scales [11]. In current study, a statistically significant increase was observed only in the sexual desire and arousal subscale scores in the postoperative period, while no significant change was observed in the other subscale scores. Perhaps this result can be attributed to the combination of anterior repair with other surgical procedures in this study. Colombo et al. followed up postmenopausal patients who underwent Burch due to stress urinary incontinence and cystocele and underwent anterior colporrhaphy for 8 years. They reported that dyspareunia developed in 56% of sexually active patients who underwent anterior colporrhaphy. However, it is not clear which procedure is effective in dyspareunia because simultaneous vaginal hysterectomy, posterior colporrhaphy with levator ani plication and perineorrhaphy were performed in the patient group who underwent anterior colporrhaphy [12]. Similarly, in our study, anterior colporrhaphy procedure was not performed alone, posterior colporrhaphy procedure was added in all our patients, and vaginal hysterectomy was also performed in 30% of patients; however, no significant change was observed in the dyspareunia scale in the postoperative period. We think that this may be due to the fact that we did not apply levator ani plication.
A study by Azar et al. evaluated preoperative and postoperative 3rd-month FSFI scores of patients undergoing anterior colporrhaphy and/or posterior colporrhaphy in women in the reproductive period. They stated that with the significant increase in sexual desire, arousal, lubrication, orgasm, satisfaction and total FSFI scores, postoperative dyspareunia also increased significantly [13]. The increase in dyspareunia was attributed to vaginal narrowing and levator application. In addition, the reason for the increase in the parameters of lubrication, orgasm, satisfaction and total FSFI score in this study, unlike our study, may that the mean age of the patients included in the study was 36.7 years, younger than the patients in our study. Similarly, in this study, when the preoperative and postoperative FSFI scores of the patients were compared, a statistically significant change was found in the total scores of sexual desire and arousal, but no significant change was observed in the orgasm parameter. Brandner et al. conducted a study with the postmenopausal patient group who underwent rectocele repair; although there was a statistically significant increase in the preoperative and postoperative 6th-month FSFI scores, sexual desire and satisfaction parameters of the patients, and a significant decrease in dyspareunia, there was no significant change in arousal, lubrication and orgasm parameters [14].
In the study by Roos et al., in which they performed vaginal hysterectomy, anterior repair, posterior repair, and sacrocolpopexy operations due to POP, the the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire scale showed the change in sexual functions (67%) of the perimenopausal patient group and their sexual life improved positively in the preoperative and postoperative 3rd month. The reason for this in this study is the fact that women whose body image and genital perceptions have changed do not worry about sexual activity and develop behavior of not avoiding sexual activity in the post-operative period [15]. In contrast, Helström and Nilsson found that the development of dyspareunia increased after vaginal surgery in the preoperative and postoperative 1st year in their study in which they applied the Machester technique for the descent. They stated that the reason for this is that the blood and nerve support in the vaginal wall may be damaged during surgery and thus sexual arousal and lubrication may be impaired [16]. However, in the current study, we did not find any significant change in pain and lubrication when we compared the preoperative and postoperative periods.
Sexual satisfaction can be affected by education level, cultural structure, stress, spiritual and sexual harmony between spouses. At the same time, negative anatomical changes in the genital organs such as weakness of the pelvic floor muscles and relaxation in the pelvic organs may also cause sexual dysfunction. [17,18]. Barber et al. suggested that sexual performance and sexual satisfaction would not change after colporrhaphy [19]. In the study by Hoda et al., in which they performed anterior and posterior vaginal repair using transobturator mesh for cystorectocele and SUI and evaluated the sexual functions of patients with the FSFI scale for 2 years, a statistically significant increase in sexual desire, arousal and lubrication in the postoperative period was found. Although there was a remarkable increase in orgasm and sexual satisfaction parameters, the increase in these parameters was not statistically significant [20]. Similarly, we did not find any significant difference in terms of sexual satisfaction in the postoperative period in this study.
In their study, Shahghaibi et al. reported that while increased sexual desire, sexual satisfaction and orgasm were detected in the FSFI scale applied to women with prolapse 3 months before and 6 months after the colporrhaphy operation, the frequency of intercourse and sexual arousal did not change. It has also been reported that dyspareunia due to the narrowing of the vagina as a result of colporrhaphy may also occur with increasing age and obesity [21].
In the current study, we did not detect a significant change in preoperative and postoperative pain parameters. As the age of women increases, there is a decrease in sexual desire, orgasm, arousal, lubrication and satisfaction, and there is an increase in dyspareunia. It has been shown that the decrease in estrogen causes dyspareunia, loss of desire, decrease in the number of sexual activity, decrease in genital sensitivity, and difficulty in reaching orgasm [22,23].
Conclusion
In this study, it was observed that the total FSFI score and both preoperative and postoperative scores of sexual desire, arousal, lubrication and orgasm subscale scores decreased statistically significantly as age increased. In addition, it was determined that the postoperative satisfaction score decreased significantly as the age of the patient increased. Although there are limited studies on the relationship between age and the sexual function of patients who have undergone POP-repair surgery, we found a decrease in sexual function with age in our study.
The main limitations of this study are its single-center and relatively small sample size.
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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Merve Abay, Levent Özgen, Gülten Özgen, Derya Sivri Aydın, Behiye Pınar Göksedef. Early effect of pelvic organ prolapse surgery on female sexual functions. Ann Clin Anal Med 2023;14(6):536-540
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IL-10, IL-13, IL-17 and CXCL8, CXCL10: Their relationship with the development and prognosis of type 1 and type 2 diabetes
Mina Ebrahimzadeh 1, 2, Cemil Pehlivanoğlu 1, Burçin Aydın Özgür 3, Umut Can Küçüksezer 1, Sevgin Değirmencioğlu 4, Sakin Tekin 5, Ramazan Çakmak 6, Ahmet Dirican 7, Ali Osman Gürol 1, 8
1 Department of Immunology, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, 2 Department of Immunology, Institute of Health Sciences, Istanbul University, Istanbul, 3 Department of Medical Biology and Genetics, Faculty of Medicine, Demiroglu Bilim University, Istanbul, 4 Department of Medical Biochemistry, Faculty of Medicine, Kirklareli University, Kirklareli, 5 Department of Endocrinology and Metabolism, Zonguldak Bülent Ecevit University, Zonguldak, 6 Department of Endocrinology and Metabolism, University of Istinye, Hospital of Gaziosmanpasa Medical Park, Istanbul, 7 Department of Biostatistics, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, 8 Diabetes Application and Research Center, Istanbul University, Istanbul, Turkey
DOI: 10.4328/ACAM.21655 Received: 2023-02-15 Accepted: 2023-03-27 Published Online: 2023-04-19 Printed: 2023-06-01 Ann Clin Anal Med 2023;14(6):541-545
Corresponding Author: Ali Osman Gürol, Department of Immunology, Aziz Sancar Institute of Experimental Medicine, Istanbul University, 34093, Fatih, Istanbul, Turkey. E-mail: ogurol@yahoo.com P: +90 544 794 3144 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6682-4289
This study was approved by the Clinical Research Ethics Committee of Istanbul University Faculty of Medicine (Date: 2016-08-08, No: 930)
Aim: Diabetes mellitus (DM) is a chronic high blood sugar disorder that can be classified into two groups: type 1 diabetes (T1D) and type 2 diabetes (T2D). The equilibrium between cytokines and chemokines is important for the development and prognosis of the disease. This study aimed to examine the contribution of pro-inflammatory (IL-17, CXCL8, CXCL10) and anti-inflammatory (IL-10, IL-13) factors to the development and prognosis of T1D and T2D.
Material and Methods: Cytokine and chemokine levels were evaluated in serum samples of patients with T1D and T2D, and healthy controls. Patients were divided into two groups depending on the history of the disease, as 1-5 years and 5-10 years. HbA1C levels were assessed by HPLC. Concentrations of IL-17, CXCL-8, CXCL-10 and IL-10, IL-13 were analyzed using LUMINEX.
Results: A statistically significant difference was observed in the HbA1c levels of all patients versus controls. CXCL8 was increased in patients with T1D compared with the controls. There was a significant difference in IL-13 levels between patients with T1D or T2D over five years and controls. For IL-10 and CXCL-10, there was a significant difference between T1D for more than 5 years and T1D for 5 years or less.
Discussion: Cytokines and chemokines are belonging to the immune system, but it is now known that they may also affect non-immune mechanisms. As a result, it is advantageous to take these factors almost equally into account in the diagnosis and treatment of T1D and T2D.
Keywords: Cytokines, Chemokines, Diabetes
Introduction
Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia caused by a deficit of insulin secretion and/or effect. Diabetes is divided into two primary groups as type 1 diabetes (T1D) and type 2 diabetes (T2D).
T1D is an autoimmune disease that develops depending on the selective destruction of pancreatic beta cells because of underlying genetic factors. T2D is characterized by peripheral insulin resistance, dysregulation of liver sugar production, and beta cell dysfunction. Recent studies have been carried out on the relationship between DM and insulin resistance and the immune system. B and T-cells have been reported to play a damaging and protective role in insulin resistance. Islet endocrine cells are known to produce certain cytokines that have pro-inflammatory or anti-inflammatory effects. Studies have shown that disturbance of the equilibrium between pro-and anti-inflammatory cytokines may result from the development of T1D or T2D. In both diseases, islet cells develop a complex inflammatory environment, and the microenvironment determines the fate of the islet.
Interleukin-17 (IL-17, also known as IL-17A) is a pro-inflammatory cytokine that relates the activation of T cells to the mobilization and activation of neutrophils. The activation of the IL-17 pathway in peripheral tissues and islet cells characterizes human autoimmune diabetes and promotes cell death induced by cytokines [1]. Clinical data suggests that IL-17-producing cells contribute to the underlying pathology in the early stages of the disease, and therapeutic approaches aimed at Th17-cell inhibition could be a substantial contribution to T1D treatment [2]. In the case of T2D, IL-17 has recently been shown to play a crucial role in systemic inflammation, insulin resistance, T2D and related complications [3].
Interleukin-10 (IL-10) is an anti-inflammatory cytokine, which has a suppressive effect on host defense mechanisms. It was observed that IL-10 has lower circulation rates in patients with T2D, while circulation rates are higher in patients with T1D [4]. In another study, it was found that when IL-10 shows increased genetic expression in T2D patients, metabolic control is achieved [5].
IL-13 was demonstrated to influence beta-cell survival with the protection of beta-cells from IL-1ß-triggered apoptosis [6]. The role of IL-13 in the development of insulin resistance and T2D has not been entirely clarified, while peripheral blood mononuclear cells (PBMC) in patients with T2D exhibit decreased proliferative responses [7]. One of the most important similarities between T1D and T2D is that the soluble factors released by beta cells work like chemotactic cytokines (chemokines).
CXCL8 (interleukin-8) and CXCL10 are proinflammatory chemokines. CXCL8 belongs to the chemokine family, which acts on the CXCR1 and CXCR2 receptors [8]. CXCL8 is secreted from monocytes and activates macrophage and endothelial cells [8]. CXCL8 is also involved in the migration of neutrophils to the site of inflammation and increases their phagocytic activity.
CXCL10 inhibits the formation of neovascularization and acts as an angiostatic factor [9]. CXCL10 binds to CXCL3 and regulates immune responses through the recruitment and activation of T, eosinophilic, monocyte and NK cells [9]. A recent study has demonstrated altered expressions of CCL5 and CXCL1 patients with T1D [10]. Expression of CXCL-10 is greater in isolated islets in individuals with T1D or T2D than in healthy controls [11]. In light of this background, we aimed to determine serum IL-10, IL-13, IL-17, CXCL-8 and CXCL-10 cytokine and chemokine levels to observe the development of the disease and its effects on prognosis and to obtain clues for treatment. In this context, we tried to determine serum IL-10, IL-13, IL-17, CXCL-8 and CXCL-10 levels of cytokines and chemokines to observe the progress of the disease and its effects on the prognosis and to get clues for treatment.
Material and Methods
Thirty patients with T1D or T2D without any malignancy were included in the study. The patients were referred to the study by the Diabetes Outpatient Clinic, Department of Internal Medicine, Division of Endocrinology and Metabolic Diseases, Istanbul Faculty of Medicine, Istanbul University. Thirty healthy individuals of similar age, who had not previously been diagnosed with any disorders and did not use any medications, were included in the control group.
This study was approved by the Clinical Research Ethics Committee, Faculty of Medicine, Istanbul University on 08.08.2016 with issue 930. Patients and healthy controls who agreed to take part in the study were informed about the study and signed the informed consent form.
Venous blood samples from patients and healthy controls were collected into 10 mL gel blood collection tubes. Blood samples were immediately transported by cold chain to the laboratory of Istanbul University Aziz Sancar Institute of Experimental Medicine, Department of Immunology. Serum was separated by density gradient centrifugation and stored at -80°C.
Collection of the demographic data
Patients were divided into four groups according to the etiopathogenic type of their diabetes and also according to the duration of their illness: 1. Patients suffering from T1D for more than 5 years (T1D > 5 years), 2. Patients suffering from T1D for 5 years or less (T1D ≤ 5 years), 3. Patients suffering from T2D for more than 5 years (T2D > 5 years), 4. Patients living with T2D for 5 years or less (T2D ≤ 5 years) 5. Healthy Controls.
Determination of HbA1c levels
All HbA1c measurements were performed in patients’ venous blood by High Performance Liquid Chromatography (HPLC) using the Premier Hb9210 HbA1c Analyzer (Trinity Biotech, Ireland). The normal value of HbA1c is 3-6%.
Measurement of cytokine and chemokine levels
The frozen serum samples were thawed in an incubator at 37ºC. IL-10, IL-13, IL-17, CXCL8 and CXCL10 levels were measured with the “Human Magnetic Luminex Screening Assay (LXSAHM; R&D Systems, Inc., Minneapolis, MN, USA) kit” and the steps specified in the manufacturer’s protocols were followed. The detection thresholds for these mediators are as follows: CXCL8 (1.8-1255 pg/mL), CXCL10 (1.18-690 pg/mL), IL-10 (1.6-1162 pg/mL), IL-13 (32.4-110.52 pg/mL), IL-17A (1.8-3.110 pg/mL).
Statistical evaluation
Distribution patterns in the study groups were assessed using the Kolmogorov-Smirnov test. The study groups with normal distribution were compared by “ANOVA method”. The “TUKEY HSD” test was used to perform post-hoc comparisons. “Non-parametric Kruskal-Wallis one-way ANOVA” was used to evaluate groups that did not show normal distribution, and “Dunn’s Test” was used for post hoc comparisons. P<0.05 was accepted as the significance level. Data were represented using box plots to show the median, 25th, 50th and 75th percentiles and endpoint values. SPSS 23 software was used for all statistical evaluations and graphs.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Table 1 presents the demographics of the patient group, as described in the materials and methods, demographic data collection, and healthy controls.
A statistically significant difference was observed in the HbA1c levels of all patients compared to controls (p<0.0001), while there was no statistically significant difference between the groups in the evaluation of IL-17.
In the comparison of CXCL10 serum levels, there was a significant difference between T1D for five years or less compared to healthy controls and patients with T1D for more than five years (p<0.0001). A statistically significant difference was observed between patients with T1D for five years or less and patients with T2D for more than five years (p<0.0001), between patients with T1D for five years or less and patients with T2D for five years or less (p<0.0001) (Figure 1-a).
When comparing serum CXCL8 levels, CXCL8 was found to be higher in patients with T1D than in controls (p<0.003). A significant difference close to healthy controls was found in patients with T2D for five years or less (p<0.002), while a lower level of significance was observed in patients with T2D for more than five years (p<0.009) (Figure 1-b).
A comparison of serum IL-13 concentrations revealed a statistically significant difference between patients with T1D for more than five years and healthy controls (p<0.001). There was a statistically significant difference in IL-13 levels between patients with T2D for more than five years and healthy controls (p<0.005). There was a statistically significant difference in IL-13 rates between patients with TD2 for five years or less and healthy controls (p<0.008) (Figure 1-c). When comparing serum IL-10 concentrations, they were found to be higher in patients with T1D for more than five years compared to five years or less (p<0.01). Serum concentrations of IL-10 in patients with T2D for 5 years or less were higher than those in patients with T1D for 5 years or less (p<0.017). When the IL-10 levels of patients with T1D for five years or less were compared with T2D for more than five years, a statistically significant difference was observed (p<0.026) (Figure 1-d).
Correlation evaluation showed that in patients with type 1 diabetes, a positive correlation was found between IL-13 and CXCL8 (r=0.574), between IL-13 and HbA1c (r=0.466), between CXCL8 and patient age (r=0.555), while a negative correlation was found between CXCL8 and fasting blood glucose (r= -0.458), between IL-13 and fasting blood glucose (r= -0.335), between CXCL10 and IL-10 (r= -0.918).
In patients with type 2 diabetes, a positive correlation was found between CXCL8 and patient age (r= 0.344), between CXCL10 and CXCL8 (r= 0.320), IL-13 and HbA1c (r= 0.333), CXCL8 and HbA1c (r=0.516), IL-17A and HbA1c (r=0.622), while a negative correlation was found between fasting blood glucose and HbA1c (r= -0.359), IL-13 and IL-17A (r= -0.396), IL-17A and IL-10 (r= -0.622), IL-13 and CXCL10 (r= -0.584).
Discussion
T1D and T2D have different pathogenesis in disease development, but one of the most important commonalities between T1D and T2D is that soluble factors released from beta cells function as cytokines and chemokines that can affect prognosis [11].
The balance between the pro-inflammatory (Th1 and Th17) and anti-inflammatory (Treg) subgroups is essential for maintaining homeostasis and preventing inflammatory diseases [12]. Within T2D, the adaptive immune system regulates systemic inflammation leading to insulin resistance and related complications [13]. T1D is mediated by Th1 cells that produce IFN-gamma, but, recently, Th17-secreting IL-17 cells have also played a role [14]. Activation of peripheral pathways and islets of IL-17 and its expression promotes autoimmune response and cytokine-mediated beta cell death by inducing the synthesis of other cytokines and chemokines, including CXCL8 [14].
A study has reported increased levels of CXCL8 in T1D patients, in comparison with healthy controls as well as type 1 diabetes non-affected siblings [15]. In our study, there was no statistically significant difference between the groups in the evaluation of IL-17, while CXCL8, whose production is known to be stimulated by IL-17, was found to be increased in the serum of T1D patients, compared to controls. In the comparison of T1D and T2D, a significant difference was found in patients with T2D for five years or less compared to healthy controls, and a less significant difference was found in patients with T2D for more than five years.
A recent study has reported that inhibition of the CXCL10/CXCR3 axis could enhance the β cell functionality and down-regulate the transcription of the pro-inflammatory mediators, nuclear factor κB (NF-κB) and STAT1, and therefore display an anti-inflammatory action in diabetes [16]. In concordance with this, another recent study has revealed that CXCL10 was increased in T2D patients, in comparison with healthy controls [17]. In our study, CXCL10 was observed at significantly higher levels in patients with T1D aged 5 years or less compared to other groups. Blocking CXCL10 at the time of diagnosis may be adopted as a new approach in the treatment of T1D.
In T1D and T2D, a complex inflammatory environment is developed in islet cells. In T1D, the secretion of anti-inflammatory cytokines (IL-4, IL-10, IL-13) is reduced, so their positive effects on beta cells are less [18]. Despite the low level of islet inflammation and lower levels of infiltrating immune cells in T2D compared to T1D, islet cells are still exposed to high levels of inflammatory mediators such as IL-6, TNF-alpha and IL-1beta [18]. Diminished levels of IL-10 in T2D patients were reported to be associated with insulin resistance [19].
In our study, patients with T1D for more than 5 years had higher IL-10 rates than those with T1D for 5 years or less. The IL-10 levels in the serum of patients who had T2D for less than five years were also found to be higher than the IL-10 levels of patients with T1D for five years or less. Exogenous administration of IL-13 was beneficial in the improvement of insulin sensitivity. On the other hand, IL-13 serum levels were demonstrated to be diminished in T2D patients [20]. While the presence of IL-13 in adipocytes was reported to be protective against insulin resistance [21]. Our study revealed a significant decrease in IL-13 levels in T1D and T2D patients for more than five years, in comparison with healthy subjects.
Conclusion
IL-10 rates in T1D patients remained low during the first five years and increased over longer periods. CXCL8 was higher among these patients, in comparison with patients with T2D. CXCL10 levels were also significantly higher in patients whose T1D was 5 years or less in comparison with the other groups. For IL-13, the results were in line with the literature. Although cytokines and chemokines were previously identified as immune molecules, they are now known to affect non-immune mechanisms as well. Therefore, it is beneficial to consider these factors almost equally in the diagnosis and treatment of both T1D and T2D. Future studies are required to warrant full illumination of the interrelations between diabetes pathogenesis and chemokines.
Limitations of the study
This study was designed to give an insight about the altered cytokine/chemokine levels in type1 as well as type2 diabetes patients, in comparison with that of healthy controls. This study design does not inform about the cellular sources of the cytokines/chemokines, which would be more informative. An analysis that is more detailed related with the disease durations and cytokine alterations, within the perspective of cellular sources would be more illuminative when the pathogenesis of the different diabetes types is taken into account.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: This study was funded by the Scientific Research Projects Coordination Unit of Istanbul University. Project number: TYL-2017-23598
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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2. Omidian Z, Ahmed R, Giwa A, Donner T, Rahim A, Hamad ARA. IL-17 and limits of success. Cell Immunol. 2019; 339: 33-40.
3. Abdel-Moneim A, Bakery HH, Allam G. The potential pathogenic role of IL-17/Th17 cells in both type 1 and type 2 diabetes mellitus. Biomed Pharmacother. 2018; 101: 287-92.
4. Naz S, Shafique N, Sharif S, Manzoor F , Saifi SZ, Firasat S, et al. Association of interleukin 10 (IL-10) gene with type 2 diabetes mellitus by single nucleotide polymorphism of its promotor region G/A 1082. Crit Rev Eukaryot Gene Expr. 2020; 30(4): 285-9.
5. Bare Y, Marhendra APW, Sasase T, Fatchiyah F. Differential expression of IL-10 gene and protein in target tissues of Rattus norvegicus strain Wistar model type 2 diabetes mellitus (T2DM). Acta Inform Med. 2018; 26(2): 87-92.
6. Sabine Rütti S, Howald C, Arous C, Dermitzakis E, Halban PA, Bouzakri K. IL-13 improves beta-cell survival and protects against IL-1beta-induced beta-cell death. Mol Metab. 2015; 5(2): 122-31.
7. Martínez-Reyes CP, Gómez-Arauz AY, Torres-Castro I, Manjarrez-Reyna AN, Palomera LF, Olivos-García A, et al. Serum levels of interleukin-13 increase in subjects with insulin resistance but do not correlate with markers of low-grade systemic inflammation. J Diabetes Res. 2018; 7209872.
8. Xiong X, Liao X, Qiu S, Xu H, Zhang S, Wang S, et al. CXCL8 in tumor biology and its implications for clinical translation. Front Mol Biosci. 2022; 9: 723846.
9. Xue W, Zhang J, Tong H, Xie T, Chen X, Zhou B, et al. Effects of BMPER, CXCL10, and HOXA9 on neovascularization during early-growth stage of primary high-grade glioma and their corresponding MRI biomarkers. Front Oncol. 2020; 10: 711.
10. Pan X, Kaminga AC, Kinra S, Wen SW, Liu H, Tan X et al. Chemokines in type 1 diabetes mellitus. Front Immunol. 2022; 12: 690082.
11. Collier JJ, Sparer TE, Karlstad MD, Burke SJ. Pancreatic islet inflammation: an emerging role for chemokines. J Mol Endocrinol. 2017; 59(1): R33-R46.
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14. Reinert-Hartwall L, Honkanen J, Salo HM, Nieminen JK, Luopajärvi K, Härkönen T, et al. Th1/Th17 plasticity is a marker of advanced β cell autoimmunity and impaired glucose tolerance in humans. J Immunol. 2015; 194(1): 68-75.
15. Bergamin CS, Pérez-Hurtado E, Oliveira L, Gabbay M, Piveta V, Bittencourt C, et al. Enterovirus neutralizing antibodies, monocyte toll like receptors expression and interleukin profiles are similar between non-affected and affected siblings from long-term discordant type 1 diabetes multiplex-sib families: the importance of HLA background. Front Endocrinol (Lausanne). 2020; 11: 555685.
16. Javeed N, Her TK, Brown MR, Vanderboom P, Rakshit K, Egan AM et al. Pro-inflammatory β cell small extracellular vesicles induce β cell failure through activation of the CXCL10/CXCR3 axis in diabetes. Cell Rep. 2021; 36(8): 109613.
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Download attachments: 10.4328.ACAM.21655
Mina Ebrahimzadeh, Cemil Pehlivanoğlu, Burçin Aydın Özgür, Umut Can Küçüksezer, Sevgin Değirmencioğlu, Sakin Tekin, Ramazan Çakmak, Ahmet Dirican, Ali Osman Gürol. IL-10, IL-13, IL-17 and CXCL8, CXCL10: Their relationship with the development and prognosis of type 1 and type 2 diabetes. Ann Clin Anal Med 2023;14(6):541-545
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Impact of COVID-19 pandemic on spontaneous pneumothorax
Murat Sarıçam 1, Oya Güven 2
1 Department of Thoracic Surgery, 2 Department of Emergency Medicine, Faculty of Medicine, Kırklareli University, Kırklareli, Turkey
DOI: 10.4328/ACAM.21661 Received: 2023-02-22 Accepted: 2023-03-27 Published Online: 2023-04-30 Printed: 2023-06-01 Ann Clin Anal Med 2023;14(6):546-549
Corresponding Author: Oya Güven, Department of Emergency Medicine, Faculty of Medicine, Kırklareli University, Kırklareli, Turkey. E-mail: ersinoya@yahoo.com P: +90 506 860 46 35 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6389-4561
This study was approved by the Scientific Research Ethics Committee of Kırklareli University Faculty of Medical School (Date: 2022-04-07, No: P202200011)
Aim: Deterioration of lung parenchyma due to COVID-19 infection is considered to be responsible for the development of spontaneous pneumothorax (SP). This study aimed to compare the clinical and epidemiological features of SP diagnosed in pre-pandemic and pandemic periods.
Material and Methods: Patients who developed SP before and during the pandemic were comparatively analyzed in terms of age, gender, side of SP, type of initial treatment such as observation or chest tube insertion, requirement of additional surgery and duration of hospital stay.
Results: Cases who encountered SP in the pandemic were older, required chest tubes at admission to the hospital more frequently, and stayed longer. Moreover, patients infected with COVID-19 received a higher number of subsequent surgical interventions.
Discussion: Timely interventions and careful follow-up are critical to overcome the potential complications and mortality from developing SP during the COVID-19 pandemic.
Keywords: COVID-19, Spontaneous Pneumothorax, Pandemic
Introduction
COVID-19 (SARS-CoV-2) is a zoonotic virus first identified in Wuhan City, China, in December 2019 [1]. Despite vaccine and antiviral treatment strategies, prognosis has been poor in some patients originating mostly from respiratory complications [1,2].
Recent studies have reported that pneumothorax might be present in 1% of patients who had required hospital admission, and the rate of both pneumothorax and pneumomediastinum was as high as 15% in mechanically ventilated cases [1-3].
Spontaneous pneumothorax (SP) is the accumulation of air in the pleural space due to causes exclusive of any traumatic and iatrogenic events. It has been described in some previously published case series as a complication of COVID-19-related severe acute respiratory syndrome comprising serious lung injury with an incidence of up to 1.7% in hospitalized patients [2-4].
Here, we report two series of SP, including pre-pandemic and pandemic periods. Our study aims to comparatively present the clinical and epidemiological features of the patients in both time intervals and investigate the potential differences in COVID-19 infected cases in terms of prognosis and courses of treatment.
Material and Methods
This research was approved by the Faculty of Medical Ethics Committee (P202200011-02/7.4.22) and the Ministry of Health COVID-19 study platform (2022-02-20T18_48_17).
This study was conducted to investigate the potential effects of the COVID-19 pandemic on the development and course of SP. Fifty cases diagnosed with SP were randomly selected for pre-pandemic and pandemic periods, which were confined from November 2013 to February 2016 and March 2021 to March 2022, respectively. Cases with any sign of recent chest trauma or a past history of pneumothorax were excluded from the study. Moreover, patients who developed SP during the course of non-invasive or invasive mechanical respiratory support were not included in the study. COVID-19 infection has been approved as positive through a radiological examination and/or polymerase chain reaction (PCR) swab.
The same thoracic surgeon observed all cases, performed tube thoracostomies and performed further surgeries, all for patients with air leakage lasting more than 5 days or insufficient lung expansion. Bullectomy or wedge resection combined with partial parietal pleurectomy via axillary mini-thoracotomy was performed when required. During the pandemic, the whole group of COVID-19 patients with SP was admitted to the level 1 intensive care unit, and the follow-up was assisted by anesthesiologists and infectious diseases physicians.
All patients were investigated in terms of age, gender, side of SP, type of initial treatment as observation or chest tube insertion, the requirement of additional surgery and duration of hospital stay. Comparative analysis was applied to reveal the differences regarding the potential impact of COVID-19 infection.
SPSS (IBM SPSS for Windows, ver.24) statistical package program was used for calculations. Descriptive statistics for continuous variables in the study were expressed as mean and standard deviation; categorical variables were expressed as number (n) and percentage (%). Independent Samples-T test was used to compare the averages of measurements, and the Chi-square test was employed to reveal the relationship between categorical variables. P-value <0.05 was used to indicate the statistical significance.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Mean age was 37.2 (range: 17-87) years among a total of 84 (84%) male and 16 (16%) female patients. Pneumothorax was diagnosed on the right side in 60 (60%) cases, and chest tube insertion was necessary for 84 and additional surgery for 19 patients. The mean length of in-hospital stay was 4.80 (range: 2-22) days, whereas 20 cases were diagnosed with COVID-19. Details are given in Table 1.
In comparison, the mean age was 31.1 years, and the duration of hospital stay was 3.94 days for the patients in the pre-COVID period, while these values were 43.3 years and 5.66 days for the COVID period, respectively. However, both groups did not demonstrate significant differences when examined in terms of gender, side of pneumothorax and requirement for further surgery, but cases in the COVID group underwent tube thoracostomy in larger measures. A comparison of the two periods is detailed in Table 2.
When comparing the pandemic period, cases infected and not infected with COVID-19 exhibited little diversity in demographic and clinical characteristics. Among a total of 20 COVID-positive patients, including 18 (90%) males, the mean age was 48.6 years, whereas pneumothoraxes were right-sided in 13, chest tubes were inserted in 19, additional surgeries were performed in 11 cases. Moreover, the duration of in-hospital stay was significantly longer in this group. Related data are shown in Table 3.
In summary, patients who developed SP in the pandemic demonstrated older ages, required chest tubes as the first option of initial treatment more frequently and stayed at the hospital for longer periods. Moreover, COVID-19 infected cases required a higher number of additional surgical interventions and longer hospital stays compared to disease-free individuals.
None of the patients encountered mortality or morbidity. Six of 11 COVID-19 patients who underwent additional surgery during the pandemic needed short-term home oxygen support after discharge.
Some examples of X-ray and computerized tomography (CT) images concerning SP in COVID-19 cases are given in Figure 1.
Discussion
The findings of this study clearly show that patients who developed SP during the pandemic showed distinctive clinical features such as older age or prolonged hospital stay and mainly required more challenging treatment courses to recover.
The same as the well-recognized SP, COVID-19 patients have been reported to develop clinical manifestations, including chest pain, dyspnea, and inability to breathe deeply, but also radiological findings such as a linear shadow of the visceral pleura with lack of lung markings indicating collapsed lung [5,6].
Principal causes of pneumothorax in the patients with COVID-19 who did not receive mechanical ventilation were listed as alveolar damage and rupture due to pneumonia damaging the structure of lung parenchyma with inflammatory changes and comprising cystic formations and alveolar septal thickenings [6-9].
Regarding the current literature, consisting of limited case series or studies focusing on the risk factors for the development and the prognosis of SP in intubated patients with COVID-19, we were unable to compare our findings [8, 10-13].
In comparison, patients who developed SP during the pandemic were older and more frequently required chest tube drainage due to the size of the pneumothorax and their clinical conditions. Moreover, their hospital stay was longer as a consequence of prolonged air leakage and duration of treatment. Cases with Covid-19 also underwent curative surgery more often when compared to non-COVID patients.
The development of pneumothorax has been suggested as an important prognostic marker during coronavirus infection regarding the additively arising comorbidities and complications [5, 9]. Although mortality rates have been reported to be up to 70% by some earlier published studies, including a very limited number of cases, none of our patients encountered death [8, 13, 14]. This outcome may be due to timely interventions and attentive follow-up.
The strength of this study comes from the significant number of cases included since our hospital is the largest healthcare provider, including the only thoracic surgeon in the city. Principle limitation may be noted as the retrospective and single-centered design. Moreover, strict boundaries were prescribed to present the clinical and surgical features of the patients more accurately.
Patients who develop spontaneous pneumothorax during COVID-19 infection require chest drainage and additional surgeries more frequently, resulting in prolonged hospital stays. Appropriate interventions and careful follow-up of patients are critical to prevent mortality.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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9. Pehlivanlar KM, Öksüz GB, Küçük AO, Ayçiçek O, Türkyılmaz A, Öztuna F, et al. COVID-19 Tanılı Yoğun Bakım Hastalarında Pnömotoraks ve Subkütan Amfizem Olgularının Değerlendirilmesi (Evaluation of Pneumothorax and Subcutaneous Emphysema Cases in Intensive Care Patients Diagnosed with COVID-19). J Turk Soc Intens Care. 2021; 19:95-101.
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12. Martelli G, Tiberio I. Pneumothorax and pulmonary air leaks as ventilator-induced injuries in COVID-19. Acute and Critical Care. 2021;36(1):75-7.
13. Yassin Z, Ebrahimian M, Motamedi O, Afshar H, Aloosh O, Sayyahfar S, et. al. Spontaneous pneumothorax and pneumomediastinum in patients with COVID-19: A case series from Iran. Clin Case Rep. 2022; 10(2): e05355.
14. Miro O, Llorens P, Jimenez S, Pinera P, Burillo-Putze G, Martin A, et al. Frequency, risk factors, clinical characteristics, and outcomes of spontaneous pneumothorax in patients with coronavirus disease 2019: a case-control, emergency medicine-based multicenter study. Chest. 2021; 159(3): 1241-55.
Download attachments: 10.4328.ACAM.21661
Murat Sarıçam. Oya Güven. Impact of COVID-19 pandemic on spontaneous
pneumothorax. Ann Clin Anal Med 2023;14(6):546-549
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Retrospective analysis of poisoning cases admitted to the emergency department between 2015 and 2020
Sultan Mehtap Büyüker 1, Tuğba Duvar 2, Ertuğrul Altınbilek 3
1 Department of Pharmacy Services, Üsküdar University, 2 Department of Forensic Sciences, Institute of Addiction and Forensic Sciences, Üsküdar University, 3 Department of Emergency Medicine, University of Health Sciences, Şişli Hamidiye Etfal Training and Research Hospital, İstanbul, Türkiye
DOI: 10.4328/ACAM.21665 Received: 2023-02-27 Accepted: 2023-03-27 Published Online: 2023-04-07 Printed: 2023-06-01 Ann Clin Anal Med 2023;14(6):550-555
Corresponding Author: Sultan Mehtap Büyüker, Department of Pharmacy Services, Üsküdar University, İstanbul, Türkiye. E-mail: sultanmehtap.buyuker@uskudar.edu.tr P: +90 532 324 21 53 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1344-540X
This study was approved by the Non-Interventional Research Ethics Committee of Üsküdar University (Date: 2021-08-27, No: 61351342/AĞUSTOS 2021-04)
Aim: Poisoning is defined as a clinical condition that occurs when one is exposed to an agent in an amount that can cause a toxic effect. Poisoning is a forensic case, regardless of its origin (an accident, suicide, or murder). In our study, we aimed to retrospectively analyze cases that presented to the emergency department with a diagnosis of poisoning between 2015 and 2020.
Material and Methods: Serious poisoning cases that presented to the emergency department of a densely populated training and research hospital in Istanbul and had a forensic case record were retrospectively examined in the hospital database. A total of 597 files with sufficient data and serious poisoning cases were included in the study. The data were numerically coded and analyzed on SPSS (Statistical Package for the Social Sciences) version 22 software package. The significance level was set at α=0.05. Chi-square analysis was used to examine the relationship between categorical variables.
Results: In our study, it was determined that 55.95% of the cases recorded as poisoning were female, 44.05% were male, and 4% of the women were pregnant. The highest rate of poisoning occurred in autumn (29.23%), and the least occurred in adults in the winter months (22.11%). Discussion: It was concluded that there is a need to raise the awareness of hospital personnel about keeping records of poisoning and forensic cases. It is important to keep patient records appropriately and completely.
Keywords: Poisoning, Forensic Medicine, Suicide, Toxicology
Introduction
Poisoning is a clinical condition occurring as a result of exposure to an agent in an amount that can cause a toxic effect. If poisoning, which is frequently encountered in our country and the world, is not intervened timely and appropriately, it can lead to serious consequences. Poisoning can occur due to intentional suicidal attempts, by accident (often in children), environmental or occupational exposure, the side effects of drugs, therapeutic error (wrong drug, dose, and patient, and drug-drug / drug-food interaction), drug abuse, food poisoning, animal bites, and chemical and biological warfare. Poisonings are forensic cases regardless of their origin (an accident, suicide, or murder). Forensic medicine is responsible for recording and reporting poisoning cases and carrying out procedures in case of death [1]. For the substance entering the body to be documented as a poison, it should have chemical effects, be toxic before its intake, have a high toxic effect at low doses, and be an organic or inorganic substance or a substance produced by a living thing [2]. Poisoning cases are handled in articles 86, 87, 89, 186, and 280 of the Turkish Penal Code (TPC) [3].
Poisoning is often seen as a result of home accidents. For this reason, it is not always easy to distinguish between suicide and home accidents. In cases where the origin of poisoning is a murder, answers are sought to the questions of how, who, and when via the crime scene investigation and autopsy. Forensic medicine carries out an investigation of the story of the event, the characteristics of the deceased person, the crime scene, and the outcome after death [2].
The most frequent suicides in Turkey include hanging, taking multiple drugs, sharps and piercing tools, drowning, jumping from a height, and firearms [2]. Of all cases, poisoning varies between 0.1% and 1.04% domestically and globally [(available at: https://tez.yok.gov.tr/UlusalTezMerkezi/TezGoster?key=4J_FzTwlrMCH4qBROpXPH4KPyeA42CbQptS8wrQM-xswZm-i2KqFAlF306xS_Z9C) – 5]. Acute poisonings can be caused by drugs, narcotics, alcohol, pesticides, household chemicals, carbon monoxide, food, botulism, fungi, plants, and heavy metals. According to the 2011 data of the American Association of Poison Control Centers (AAPCC), anti-epileptic drug poisonings account for 1.86% of drug poisonings [6].
According to the report of the National Poisons Information Service (NPIS), the causes of poisoning in cases who presented to the center in 2020 were suicide (43.11%), accidents (37.78%), and food poisoning (3.70%), respectively. Other causes included environmental factors (2.35%), fires (0.04%), other (adverse effects, addiction, iatrogenic, occupational, and side effects) (5.33%), and unknown (1.55%). The total number of cases was 187,528. Types of poisoning were acute (85.97%), acute on a chronic basis (13.40%), chronic (0.32%), and other (0.31%) (available at: https://hsgm.saglik.gov.tr/depo/kurumsal/yayinlarimiz/Raporlar/Uzem/uzem_raporlari_2014-2020.pdf).
Material and Methods
After obtaining the ethics committee approval of the Üsküdar University Non-Interventional Research Ethics Committee on August 27, 2021 (61351342/AĞUSTOS 2021-04), the permission of the İstanbul Governorship Provincial Health Directorate was obtained on September 3, 2021 and the study was initiated. The files that included a presentation to the emergency service with poisoning between January 1, 2015 and December 31, 2020 and a forensic case record were evaluated. A total of 597 files with enough data and serious poisoning cases were included in the study. Parameters that were obtained from the files and investigated in the study included season, age, gender, pregnancy status, poisoning agent, route of poisoning, the origin of poisoning, previous forensic case record, death/survival, communication with the poison information center, types of abused substances, and types of drugs. Cases were recorded on a Microsoft Excel spreadsheet. The data were numerically coded and analyzed on SPSS (Statistical Package for the Social Sciences) version 22 software package. The level of significance was determined as α=0.05. Chi-square analysis was used to examine the relationship between categorical variables.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
According to the distribution of poisonings by season, the majority of the cases were observed in autumn with 29.65%, and the least were observed in winter with 22.11%. The route of exposure to the poison agent was oral in 90.98% of the cases, inhalation in 7.35%, and parenteral in 1.67%.
Table 1 shows the distribution of gender, pregnancy status, season, and the origin of poisoning by age. When all cases were examined without age restriction, it was seen that the majority of cases included females with 55.95%, while the rate of poisoning was 44.05% in males. Of the poisoning cases in children (0-18 years), 51.91% were female, 48.09% were male, and no pregnancy was found. Poisoning in children occurred mostly in autumn with 30.60%, and mostly by accident with 71.04%. Of the adult poisoning cases (aged 19 and over), 57.73% were female, 42.27% were male, and 2.17% were pregnant. Poisoning cases in adults mostly occurred in autumn with 29.23% and the majority of the cases were suicide with 51.59 %.
The source of the poisonings included suicide (51.59%), accidents (30.32%), unknown (15.58%), and suspicious (2.51%). The reason for the rate of 15.58% of unknown cases was that there was not enough information in some of the files and that they were kept incomplete.
When the pregnancy status of the poisoned females was evaluated, it was seen that while there was no pregnancy in cases under the age of 18, 9 cases over the age of 18 (4%) were pregnant. Also, 4% (44.44%) of these poisoning cases were related to drugs. Of the pregnant women, one had experienced heroin poisoning, one synthetic cannabinoid poisoning, and two amphetamine poisoning.
Figure 1 shows the distribution of calls made to the poison information center (phone number: 114). The center was called in 40.2% of poisoning cases and it was not called in 19.6%. While a consultation was performed in the external center in 5.2% of the cases, there was no information about 35% of the cases (Figure 1).
The poisoning agents were drugs in 67.86% of the cases, ethyl alcohol in 8.64%, narcotics in 11.25%, CO in 4.56%, pesticides in 1.79%, corrosive substances in 2.44%, mushrooms in .32%, unknown in 0.48%, and food in 1.14% (Figure 2).
Table 2 shows the distribution of poisoning active substances according to the origin of poisoning. Accordingly, 38.71% of unknown origin of poisoning, 92.53% of suicides, 49.17% of accidents, and 40% of murders were associated with drugs.In drug poisoning cases, multiple drug intake was 38.16%, single drug intake was 60.39%, and unknown was 1.45%. In poisoning with drugs, the drug belonged to the case in 23.32%, while it did not belong to the person in 13.46%. There was no information about who owned the drug in 63.22% of the cases. The drug poisoning cases included non-steroidal anti-inflammatory drugs (NSAIDs) in 13.5%, antipsychotic in 9.1%, paracetamol in 8.9%, anxiolytics in 6.7%, cardiovascular system drugs in 6.0%, selective serotonin reuptake inhibitor (SSRI) in 5.7%, antibiotics in 5.7%, other antidepressants in 5.3%, and vitamins/minerals in 5% (Figure 3).
Table 3 shows the distribution of narcotic poisonings by age The number of narcotic poisonings in children was very low. Synthetic cannabinoids were the causes of the majority of narcotic poisonings in children (2.19%). Adults had higher rates of narcotic poisonings, with a maximum of 6.04% from narcotics of unknown origin and 4.1% from other category narcotics.
It was seen that the files were kept incomplete and the drug type was not shared by patients or their relatives. Due to the lack of information, it was revealed that the majority of cases presented to the unit with a suspicion of narcotics, which was followed by the other category. The majority of narcotics in the known cases included cannabis, which was followed by heroin (Figure 3).
Discussion
Poisoning is recognized as a public health problem. In forensic medicine, all cases of accidents, suicides, and murders are forensic cases. In all cases, poisoning cases vary between 0.1% and 1.04% domestically and globally [(available at: https://tez.yok.gov.tr/UlusalTezMerkezi/TezGoster?key=4J_FzTwlrMCH4qBROpXPH4KPyeA42CbQptS8wrQM-xswZm-i2KqFAlF306xS_Z9C), 5]. In our study, the rate in five years was 0.02%, which is quite low compared to the literature. This was thought to have been due to the examination of only serious poisoning cases obtained from the files which had a forensic case record. Only 597 of the examined files could be included in the study. Poisoning cases without a forensic case record and simple poisonings were excluded from the study.
When we look at the distribution of poisonings by months, the highest number of poisonings was observed in November. According to seasonal distribution, the highest number of cases was in autumn (29.65%), and the least in winter (22.11%). In the domestic literature, it was stated that poisoning cases increased in the spring and summer months [(available at: https://tez.yok.gov.tr/UlusalTezMerkezi/TezGoster?key=4J_FzTwlrMCH4qBROpXPH4KPyeA42CbQptS8wrQM-xswZm-i2KqFAlF306xS_Z9C), (available at: https://hdl.handle.net/11630/6768 ) -7]. The cases were found to mostly occur between 18.01 and 24.00 with 37.4%, and the least poisoning was found to occur between 06.00 and 12.00 with 13.6%.
Considering the genders, it was found in the literature that the majority of the poisoning cases were female [( available at: https://hsgm.saglik.gov.tr/depo/kurumsal/yayinlarimiz/Raporlar/Uzem/uzem_raporlari_2014-2020.pdf)-4-8]. Consistent with the literature, our research revealed that women experienced poisoning more frequently with 55.95%, while the rate of poisoning among men was 44.05%.
Of the poisoning cases in children (0-18 years), 51.91% were female, 48.09% were male, and no pregnancy was found. The majority of poisoning cases in children were in autumn (30.60%), and most of them were accidental (71.04%). The rates of childhood poisoning were consistent with the literature. For example, Berksoy et al. reported that the majority of poisoning cases were in the autumn and summer months and the rate of cases was 59.3% in females and 40.7% in males. The rate of accidental poisoning in children was 79% [9]. In our study, the majority of poisoning cases in children were in the autumn (56%) and summer (45%) months.
The origins of poisoning included suicides (51.59%), accidents (30.32%), unknown causes (15.58%), and suspicious cases (intentional) (2.51%), respectively. The reason why the rate of cases with unknown origin was 15.58% was due to the lack of enough information in the files and keeping them incomplete. The highest rate of suicidal poisoning was consistent with the literature. Some studies in the literature mostly mentioned suicidal poisonings [4-10]. According to the 2020 report of the NPIS, the origin of 43.11% of the cases were suicidal and 37.78% were accidental (available at: https://hsgm.saglik.gov.tr/depo/kurumsal/yayinlarimiz/Raporlar/Uzem/uzem_raporlari_2014-2020.pdf). This is consistent with the results of our research. In our study, 92% of drug poisonings were suicidal. In another study, 99.55% of drug poisonings were found to be suicidal [11]. The suicide rate was found to be 56.7% in another source [5]. Moreover, the suicide rate was 84.9% in the study of Ergun et al. [12].
Poisoning agents included drugs (67.86%), ethyl alcohol (8.64%), narcotics (11.25%), CO (4.56%), pesticides (1.79%), corrosive substances (2.44%), mushrooms (0.32%), unknown agents (0.48%), and food (1.14%). In another study, poisoning agents were found as drugs (80%), narcotics (2.7%), and alcohol (3.7%) [13].
Drug poisonings rank first in our country. In the study by Akköse et al., the rate of drug poisoning was 58.6% [11]. In another study, drug poisoning was 82% [4]. In our study, drug poisoning took first place with 67%. Drugs involved in poisoning were NSAII (13.5%), antipsychotics (9.1%), paracetamol (8.9%), anxiolytics (6.7%), cardiovascular system drugs (6.0%), SSRI (5.7%), antibiotics (5.7%), other antidepressants (5.3%), and vitamins/minerals (5%). Drug active ingredients vary in the literature. For example, in the study conducted by Selçuk and Çakar, the most common drugs involved in poisoning were antidepressants with 30% [14]. Kıyan et al. found analgesics as the most common drugs in suicidal poisonings with 56% [4]. In foreign literature, the most common drugs involved in poisoning were sedative and hypnotic drugs with 28.8%, analgesics with 16.6%, and psychotropic drugs with 16.4% [15]. According to the 2019 report of NPIS, drug poisoning with anti-inflammatory drugs occurred at a rate of 9.8% (available at: https://hsgm.saglik.gov.tr/depo/kurumsal/yayinlarimiz/Raporlar/Uzem/uzem_raporlari_2014-2020.pdf). Also, 38.71% of cases of unknown origin of poisoning, 92.53% of cases of suicidal origin, 49.17% of cases of accidental origin, and 40% of suspicious cases were carried out with drugs. In a study conducted in Kars province in Turkey, multiple drug intake was found to be 26.53% [16]. This rate was found as 16.4% in a study conducted abroad [5].
In a study on childhood poisoning, it was found that the cause of 43.6% of the poisonings were drugs, 28.3% were corrosive substances, 21.5% were other chemicals, and 2.78% were drug intoxication [17]. In a study conducted at Dicle University between 2015 and 2018, the cause of 59.4% of childhood poisoning were drugs, which was followed by corrosive substances with 17.4% and pesticides with 10.1% (available at: https://hdl.handle.net/11468/7128).
Conclusion
In conclusion, all poisoning cases must be reported to relevant authorities. It is necessary to raise awareness among hospital staff about this issue. Patient records must be kept properly and completely. It is thought that health workers need education, information on legal issues, and in-service training. Public awareness should be raised at the social level. Medication errors and inappropriate use of chemicals can cause accidental poisoning. Keeping these chemicals in locked places can reduce the risk of poisoning. Receiving psychotherapy and psychiatric support when necessary can reduce the risk of suicide. It is especially important for people who use antidepressants to be under regular physician control. Prevention of unconscious and uncontrolled purchase and use of medicines can help reduce the incidence of poisoning. It is also important to control the drugs or the products under the name of food supplements sold on the Internet to prevent the wrong use of medicines. Prevention of the sale of drugs without a prescription is the most important precaution to be taken.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Evaluation of antibody response to coronavac 600 u/0.5 Ml (sinovac life science, beijing, china) vaccine administration in elderly individuals
Derya Korkmaz 1, Emek Turkekul Sen 2, Petek Konya 1, Melahat Gurbuz 2, Berrin Esen 2, Nese Demırturk 1
1 Department of Infectious Disease and Clinical Microbiology, 2 Department of Microbiology, Faculty of Medicine, Afyonkarahisar Health Science University, Afyonkarahisar, Turkey
DOI: 10.4328/ACAM.21709 Received: 2023-03-31 Accepted: 2023-05-07 Published Online: 2023-05-31 Printed: 2023-06-01 Ann Clin Anal Med 2023;14(6):556-561
Corresponding Author: Derya Korkmaz, Department of Infectious Disease and Clinical Microbiology , Faculty of Medicine, Afyonkarahisar Health Science University, 03200, Afyonkarahisar, Turkey. E-mail: drderya@ymail.com P: +90 506 278 84 68 Corresponding Author ORCID ID: https://orcid.org/0000-0001-7236-2164
This study was approved by the Ethics Committee of Afyonkarahisar Health Sciences University (Date: 2021-02-05, No: 2021/99)
Aim: In this study, we aimed to evaluate the presence of anti-SARS-CoV-2 antibodies before vaccination and the antibody response after CoronaVac vaccination administered in two doses 28 days apart in elderly individuals over 60 years of age who were planned to be vaccinated against COVID-19.
Material and Methods: Antibody levels were evaluated by taking blood samples from participants aged 60 years and over who were vaccinated with inactivated COVID-19 whole virus vaccine in the vaccination outpatient clinic before the first dose of vaccine, 28 days after vaccination (before the second dose), 2 months and 4 months.
Results: Of the 81 participants, 51.9% (n=42) were female, 48.1% were male, the mean age was 67.2±4.6 years, and 48.1% (n=39) had at least one comorbidity. It was found that both seropositivity rates and antibody titres of the participants increased in the first and second months, but in the fourth month, although there was no increase in antibody titres, the mean antibody level decreased compared to the second month. Antibody seropositivity increased both in the 1st month, 2nd month and 4th month compared to the pre-vaccination period. Antibody seropositivity at 2 and 4 months was 100.0% in individuals who had all antibody measurements completed at both 2 (n=49) and 4 (n=12) months.
Discussion: Vaccination against SARS-CoV-2 with CoronaVac in individuals over 60 years of age induces an effective antibody response, but additional doses are required for the sustainability of the antibody response.
Keywords: COVID-19, Antibody, Age 60, CoronaVac, Vaccine
Introduction
The outbreak of “Coronavirus Disease 19 (COVID-19)” caused by “Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)”, which has led to millions of deaths and devastating socio-economic consequences worldwide, is still continuing its effect as a pandemic [1]. SARS-CoV-2 is a zoonotic, positive polarity RNA virus and has four important structural proteins that play a role in viral infection and replication: spike (S), envelope (E), membrane (M) and nucleocapsid (N). Coronaviruses are enveloped positive-stranded RNA viruses that enter a host cell through a fusion of the envelope lipid bilayer with the target cell membrane. This first critical step of viral infection is catalysed by the trimeric spike (S) protein, which decorates the virion surface as the main antigen and induces neutralizsing antibody responses. Therefore, the protein is an important target for the diagnosis, treatment and development of vaccines [2,3].
The CoronaVac vaccine produced by Sinovac Life Science in China contains inactivated SARS- CoV-2 virus and is adjuvanted with aluminium hydroxide [4]. Phase III trials were conducted in various parts of the world and efficacy results ranged between 50.7% (Brazil), 65.30% (Indonesia) and 83.5% (Turkey) [5]. The vaccine induces both innate and adaptive immune responses through various mechanisms, simultaneously generating a cellular response (T cells) and an antibody response (B cells) resulting in the production of antibodies directed against various SARS-CoV-2 antigens. After vaccination, the body is expected to produce specific antibodies against the SARS-CoV-2 S protein, which can neutralizse the virus and prevent it from binding to its specific receptor (Angiotensin Converting Enzyme-2, ACE 2 receptor) [6].
The SARS-CoV-2 S protein is a transmembrane fusion glycoprotein consisting of S1 and S2 subunits with a size of 180-200 kDa and a total length between 1273 and 1300 amino acids. It is the basic unit of the virus that recognizses and binds to the host cell receptor ACE-2 [7]. The S protein, the only protein responsible for entry into the host cell, is the main antigen that elicits neutralizsing antibodies. Therefore, the SARS-CoV-2 S protein appears to be the best target site in antibody detection tests [8]. Quantitative tests detecting anti-SARS-CoV-2 antibodies can help monitor individual antibody titre and the long-term course of antibody response by measuring the specific antibody response to vaccines [9].
In SARS-CoV-2 infections, neutralizsing antibodies that prevent virus entry, fusion and exit from the cell play an important role in the antibody-mediated killing of the virus. Since the antibody response against S-protein is associated with neutralizsing antibodies, the main aim is to obtain an anti-S antibody response in the immune response that develops after vaccination [10]. Epidemiological studies have reported that neutralizsing antibody titres vary greatly in convalescent serum samples and may be related to various factors (e.g. age, sex, disease severity and the number of days after infection). Therefore, it is unclear whether vaccine-induced antibody levels will persist and whether long-term memory will affect the sensitivity and pathogenesis of T cells to SARS-CoV-2 infection [11]. Studies have reported a statistically significant decrease in vaccine efficacy against symptomatic COVID-19 in the elderly in parallel with age after vaccination [12-15]. More evidence is required to determine the efficacy of the vaccine, especially in elderly individuals with a high risk of mortality due to this disease.
In this study, we aimed to evaluate the presence of anti- SARS-CoV-2 antibody before vaccination and the antibody response after the CoronaVac vaccination administered 28 days apart in elderly individuals over 60 years of age who were planned to be vaccinated against COVID-19.
Material and Methods
Participants
Participants aged 60 years and older who were vaccinated with inactivated COVID-19 whole virus vaccine in Afyonkarahisar Health Sciences University vaccine outpatient clinic were included in the study. None of the participants had a history of COVID-19 during the pandemic period and none of them had SARS-CoV-2 positivity by reverse transcriptase polymerase chain reaction (RT-PCR) method in nasopharyngeal swab samples in the pre-vaccination period. The vVaccine administration was performed intramuscularly in the left arm with two doses of CoronaVac 600 U/0.5 mL (Sinovac Life Science, Beijing, China). Blood samples were collected from the participants four times before the first dose of vaccine, on the 28th day after vaccination (before the second dose), in the 2nd month and 4th months, and antibody levels were evaluated (flow chart is given in Figure 1).
Laboratory Analyses
Venous blood samples were collected from the patients in a 10 ml Vacutainer SST tube with gel (Becton Dickinson, France). After waiting for 30 min, it was centrifuged at 4000 rpm for 10 min at +4 oC. The serum samples remaining after centrifugation were separated into Eeppendorf tubes and stored at -80 oC until the tests were performed. During the study, after quality control of the well-dissolved serum samples on the Roche cobas e 601 device (Roche Diagnostics, Germany) used in our routine laboratory, invitro quantitative detection of antibodies (Ig M and G) developed against SARS-CoV-2 spike (S) protein receptor binding domain (RBD) was performed with an immunochemical method (Roche Elecsys Anti-SARS-CoV-2 S Quant) compatible with the cobas e 601 device. The measurement range of the kit is between 0.40-250 U/ml and the manufacturer’s recommended result interpretation states that values above 0.80 U/ml should be considered positive (Available at: https://www.fda.gov/media/144037/download). The Sserum neutralizsation of the test was good and acceptable, and sera with results greater than 250 were retested at 1/10 and 1/50 dilutions and evaluated.
Ethical Approval
The study was carried out with the approval of Afyonkarahisar Health Sciences University Clinical Research Ethics Committee (Date: 05.02.2021 and Decision No: 2021/99) and the participants were informed and included with their consent
Statistical Analysis
In the study, categorical variables were presented with numbers and percentages. Confidence intervals of percentages were calculated by Wilson’s method (continuity correction). The Aage of the subjects was presented as mean and standard deviation. People with antibody levels >0.8 U/ml were considered seropositive. Antibody levels of seropositive individuals are were presented as mean, standard deviation, median and IQR. Seropositivity levels between months were determined by Cochran’s Q test in individuals with complete antibody measurements at months 2 and 4, and then differences between months were determined by post hoc Dunn’s test and the Bbonferroni correction. In addition, the seropositivity levels of individuals with complete antibody measurements at both 2 and 4 months are shown in bar graphs. The statistical significance limit for P value was accepted as 0.05. Statistics were performed with SPSS v.28.0.
Results
A total of 81 people were included in the study;. 51.9% (n=42) of the participants were female and the mean age was 67.2±4.6 years;. 48.1% (n=39) had at least one comorbidity. Of the 81 participants included in the study, 79 could be reached inat the first month, 49 in at the second month, and 12 in at the fourth month after vaccination and antibody measurements could be performed. The characteristics of the participants and antibody levels according to months are presented in Table 1 with 95% confidence intervals.
In the pre-vaccination evaluation, 34.6% of the participants were seropositive. In 23 of the 79 participants evaluated in at the first month, the antibody level was below 0.8U/ml and was considered seronegative. 39.1% (n=9) of these participants were male and 60.9% (n=14) were female. There was no statistically significant difference in terms of gender in those who failed to produce sufficient antibodies in the first month (p=0.306). Of the 23 people who were seronegative in the first month, 9 (39.1%) had any comorbidity. There was no statistically significant difference in terms of having comorbidity in seronegative people compared to seropositives (p=379).
As of the 2nd month, antibody measurements (pre-vaccination, 1st month, 2nd month) of a total of 49 individuals were completed and the findings are presented in Figure 2. Seropositivity increased statistically significantly within 2 months compared to the pre-vaccination period (n=49, Cochran Q test=40.7, df=2, p<0.001). By the 4th month, antibody measurements (pre-vaccination, 1st month, 2nd month and 4th month) of a total of 12 individuals were completed and the findings are presented in Figure 3. Seropositivity increased statistically significantly atin 4 months compared to the pre-vaccination period (n=12, Cochran Q test=16.0, df=3, p=0.001).
The differences in seropositivity between pre-vaccination, 1st month, 2nd month and 4th month are presented in Table 2. Antibody seropositivity at in the1st month, 2nd month and 4th month showed a statistically significant increase compared to the pre-vaccination period. In addition, antibody seropositivity inat the 2nd month showed a statistically significant increase compared to the seropositivity inat the 1st month. Between the 2nd and 4th months, there was no change, and the antibody seropositivity at the 2nd and 4th months was determined as 100.0% in individuals who had all antibody measurements completed in both 2 (n=49) and 4 (n=12) months.
Discussion
Serological antibody detection is an indispensable tool in the management of infectious diseases, including diagnosis, determination of protective antibody titre after vaccination and epidemiological assessment of humoral immunity. Low antibody seroprevalence against SARS-CoV-2 indicates that populations are vulnerable to a second wave of infection [16]. This study is very important because it is one of the few studies on CoronaVac administration in elderly individuals in which antibody levels were measured before vaccination, thus providing the opportunity to compare the seropositivity status before vaccination.
Although the elderly who declared that they did not have COVID-19 before vaccination and did not have PCR positivity before vaccination were included in the study, it was determined that 28 (34.6%) people were seropositive when the pre-vaccine antibody levels were examined. This may be explained by the fact that seropositive people had asymptomatic infection without the need to consult a physician before vaccination or cross-reactions that may be seen in the laboratory method. This high seropositivity rate in the patient group without evidence of infection shows the severity and prevalence of the pandemic in this period and the importance of protecting this group, which has a high risk of developing severe disease, by immunizsation [16].
In this study, antibody levels of people over the age of 60 were monitored before and for four months after the CoronaVac vaccine administration. It was found that both seropositivity rates and mean antibody levels of seropositive individuals increased in the first and second months, but in the fourth month, although there was no increase in the mean antibody levels of seropositives individuals, the mean antibody level in seropositive individuals decreased compared to the second month. Decreasing antibody levels over time suggest that reminder doses are necessary to protect this age group against the risk of severe Sars-CoV-2 infection.
It is known that neutralizsing antibodies formed after vaccination are protective against SARS-CoV-2 infection and that these antibodies prevent the virus from binding to the ACE-2 receptor of human cells by binding to the S protein [17]. CoronaVac is an inactivated SARS-CoV-2 vaccine shown to be 65.9%, 87.5%, 90.3%, and 86.3% effective in preventing COVID-19 symptoms, hospitalizsations, intensive care admissions, and COVID-19-related deaths, respectively. However, the efficacy of vaccines may be impaired by the presence of previously recognizsed diseases or pathologies. In addition, the severity of the disease may be even more pronounced in the elderly, as their immune systems are more dysfunctional than in younger people [18]. Considering the presence of increased comorbidity with age, elderly individuals show more severe symptoms of SARS-CoV-2 infection due to the development of a defective immune response. Especially hypertension, obesity, diabetes, cardiovascular diseases and malignancy cause significantly increased mortality and morbidity rates in this age group [19]. In this study, 48.1% of the patients had at least one comorbidity and hypertension, diabetes and heart failure were found most frequently, respectively. These high comorbidity rates indicate the importance of protecting people over the age of 60 against Sars-CoV-2 infection. Unfortunately, it has been observed that the mask, distance, hand hygiene and other restrictive measures implemented at the beginning of the outbreak were not effective enough in the prevention of the spread and control of the infection. This situation once again demonstrates the necessity of appropriate immunizsation with effective vaccines.
In Brazil, where CoronaVac is the most widely used vaccine, the immunogenicity of the vaccine in elderly individuals is still little known, despite the finding that the COVID-19 mortality rate decreased after vaccination in people over 70 years of age and provided protection for this age group [20]. B cells, which are responsible for responses such as the production of antibodies and secretion of cytokines, are the most important mediators of acquired immunity. Although differences in the function of B cells and plasma cells have not yet been sufficiently analyzsed in terms of COVID-19 or coronavirus infections, changes occur that are valid for any pathogen occur [21]. Although some studies have reported up to 98% seroconversion in vaccinated people, anti-spike antibody titres have been observed to be significantly lower among people aged 60 years and older [20,21]. It has been reported that aging is associated with a decline in immune function and this process, known as immune aging, generally leads to deterioration of the response to vaccines in older adults. As a matter of fact, when immune responses to inactivated vaccines such as influenza were analyzsed, it was found that elderly individuals had significantly lower protection, and vaccine efficacy in these individuals ranged between 17% and 51%, whereas this rate increased up to 90% in young individuals [20]. Our observation that post-vaccination antibody levels decrease over time in this age group is consistent with studies showing that the elderly exhibit poorer responses to the trivalent inactivated influenza vaccine [22].
In a nationwide evaluation of vaccine efficacy involving 25,639,346 Brazilians vaccinated with CoronaVac, it was found that protection against hospitalizsation, intensive care unit admission and death decreased in persons older than 79 years, and there was an increase in the rate of hospitalizsation in persons older than 80 years sixty days after the second dose of vaccination. Compared with individuals under 60 years of age vaccinated on the same calendar date, individuals over 90 years of age had higher rates of COVID-19-related hospitalizsations. When the entire post-vaccination period was considered, hospitalisation rates remained low among individuals under 60 years of age despite higher SARS-CoV-2 exposure, in contrast to the gradually increasing rates among individuals over 90 years of age [23]. These results support our belief that reminder doses are needed in older individuals.
Limitations
The major limitation of this study is the large reduction in the number of participants at month 4 months. Therefore, our analyses were interpreted by comparing the mean antibody levels of seropositive individuals. In order to make a clearer interpretation on this subject, studies with more participants and in which the number of participants did not decrease in repeated measurements are needed.
Conclusion
Our study showed that an adequate antibody response was obtained with the CoronaVac vaccine in individuals over 60 years of age, but the antibody levels obtained decreased over time. According to these results, vaccination against SARS-CoV-2 in individuals over 60 years of age with inactivated virus vaccines produces an effective antibody response, but additional doses are required for the sustainability of the antibody response.
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 Afyonkarahisar University of Health Sciences Scientific Research Projects Fund with project number 21.Tematik.002.
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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12. Ranzani OT, Hitchings MDT, Dorion M, D’Agostini TL, De Paula RC, De Paula OFP, et al. Effectiveness of the CoronaVac vaccine in older adults during a gamma variant associated epidemic of COVID-19 in Brazil: Test negative case-control study. BMJ. 2021;374:2095.
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Evaluation of Klebsiella infections in the tertiary neonatal intensive care unit
Elif Soyak Aytekin 1, Aysegul Zenciroglu 2
1 Department of Pediatric Allergy and Immunology, Etlik City Hospital, 2 Department of Neonatology, Dr. Sami Ulus Obstetrics and Gynecology and Pediatrics Training and Research Hospital, Ankara, Turkey
DOI: 10.4328/ACAM.21714 Received: 2023-04-05 Accepted: 2023-05-17 Published Online: 2023-05-29 Printed: 2023-06-01 Ann Clin Anal Med 2023;14(6):562-566
Corresponding Author: Elif Soyak Aytekin, Department of Pediatric Allergy and Immunology, Etlik City Hospital, 06560, Ankara, Turkey. E-mail: elif-soyak@hotmail.com P: +90 555 763 99 49 Corresponding Author ORCID ID: https://orcid.org/0000-0002-2329-7543
This study was approved by the Ethics Committee of Dr. Sami Ulus Obstetrics and Gynecology and Pediatrics Training and Research Hospital (Date: 2017-02-28, No: E-73799008-799)
Aim: In this study, we aimed to determine the frequency, demographic characteristics, associated risk factors, resistance patterns and factors affecting mortality and morbidity of Klebsiella infections in hospitalized neonatal patients.
Material and Methods: Neonates who were identified with culture-proven Klebsiella infection in NICU were included in the patient group, and those who were admitted to the same unit on the same day and did not suffer from Klebsiella infection were selected as a control group.
Results: One hundred nine patients and 417 patients were included in the study as patient group, and control group, respectively. Extended-spectrum β-lactamase (ESBL) producing K. pneumoniae was detected in 79% of the patients while CRKP infection was detected in 26%. Fetal distress exposure (p=0.032), prematurity (p=0.004), prior hospitalization (p=0.024), peripherally inserted central venous catheterization (p=0.018), urinary (p=0.003) and nasogastric catheterization (p=0.003), total parenteral nutrition (TPN) use (p=0.008), and long-term hospitalization (p<0.001) were found to be risk factors for Klebsiella infection. The sensitivity of colistin and meropenem were 100% and 87.9% in antibiograms. Previous antibiotic use (p=0.002) and mortality (p=0.033) were higher in patients with CRKP infection compared to the carbapenem sensitive patient group. CRKP infection developed in 21% of patients with CRKP colonization.
Discussion: Prior hospitalization, prematurity, and invasive procedures are important risk factors for Klebsiella infections in neonates. Mortality and previous antibiotic use are much higher in patients with CRKP infection than in the carbapenem sensitive group. To prevent and control Klebsiella infections, minimally invasive procedures, strict infection control protocols, and rational use of antibiotics are required. Overuse of colistin should be limited to prevent colistin-resistant Klebsiella outbreaks in NICUS in the near future.
Keywords: Carbapenems, Carbapenem-Resistant Enterobacteriaceae, Colistin, Klebsiella, Neonate, Neonatal Intensive Care Unit
Introduction
Klebsiella infections cause epidemics in neonatal intensive care units (NICU), resulting in severe morbidity and mortality and high healthcare costs [1, 2]. Infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) have increased over the past two decades [3], and mortality rates range from 33 to 50% [3]. Therefore, the rapid and global spread of Klebsiella infections raises concerns in healthcare settings. In order to prevent and control these infections and to evaluate the antibiotic beginning regimens, it is essential to reveal the clinical and epidemiological features of the infections, as well as the risk factors.
The purpose of this study was to determine the frequency, epidemiological characteristics, associated risk factors, resistance patterns, and factors affecting mortality and morbidity of infections with K. pneumoniae in hospitalized neonatal patients.
Material and Methods
Study group
This descriptive study was conducted at the Neonatal Clinic of Dr. Sami Ulus Obstetrics and Gynecology and Pediatrics Training and Research Hospital, and was approved by the local Ethics Committee of the same center in 2017, March (E-73799008-799). Patients who were hospitalized in NICU and had culture-proven Klebsiella infection were included in the study group. For each patient, 4 neonates who were hospitalized in the same service on the same day and did not suffer from Klebsiella infection were selected as a control group. The clinical and demographic data of the patients were reviewed from electronic records retrospectively. Klebsiella growth in anal swab culture was detected in 28 neonates. Among these, neonates who were not diagnosed with clinical sepsis (n=16) were considered colonized, and were excluded from the study group. Among sepsis patients, cases with a postnatal age of less than 72 hours were classified as early onset sepsis (EOS), and those ≥72 hours as late-onset neonatal sepsis (LOS). Infections such as bloodstream infection (BSI), catheter-related BSI, ventilator-associated pneumonia (VAP), urinary tract infection, peritonitis, omphalitis, meningitis, skin abscess and osteomyelitis acquired at least 48 hours after hospitalization and within 10 days of discharge were defined as healthcare-associated infections (HAI) [4, 5].
Laboratory evaluation
Blood samples of the patients were inoculated into BacT/ALERT PF Plus blood culture bottles [bioMerieux, France] and incubated in the BacT/ALERT system (bioMerieux, France) for 5 days. Upon receiving a positive signal from the device, blood culture bottles were transferred to 5% sheep blood agar, chocolate agar, and EMB (Eosin Methylene Blue) agar. Plates were incubated at 35ºC with 5% CO2. After evaluating the colony morphology and Gram staining of the growing microorganisms, manual methods or GN colorimetric identification cards of the VITEK 2 Compact automated system (bioMerieux, France) were used for species-level identification. The oxidase test, lactase fermentation test, indole test, methyl red test, motion test, citrate test, three sugar fermentation, and urease test were used as manual procedures.
Manual antibiotic susceptibility methods or GN AST cards of the VITEK 2 Compact automated system (bioMerieux, France) were used to determine the antibiotic susceptibility of the isolates. The Kirby-Bauer disc diffusion and E-test methods were used as a manual antibiotic susceptibility test, and the results were evaluated according to CLSI [72] and EUCAST [72] criteria, respectively. The Double Disc Induction Method was used to detect inducible beta-lactamase (IBL), whereas the Double Disc Synergy Test was used to detect extended-spectrum beta-lactamase (ESBL). Gradient strip test was used to re-evaluate the carbapenem-resistant isolates that were determined to be resistant using human or automated methods. Leukocyte and neutrophil values were evaluated according to Nathan and Oski’s book on Pediatric Blood Diseases. [6].
Statistical analysis
The analysis of the data was performed using the Statistical Package for the Social Sciences (SPSS) statistical package program (Version 22.0; SPSS, Inc., Chicago, IL, USA). Chi-square and Student’s T tests were used to compare parametric values. Fisher’s exact test was used if at least one expected count was less than 5. The level of statistical significance was set at p < 0.05.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
The study group consisted of 109 patients infected with Klebsiella, and the control group consisted of 417 patients. K. pneumonia was isolated from 106 (97%) patients, while K. oxytoca was isolated from 3 (3%).
Seventy patients (64%) were male, 66 (61%) were delivered by cesarean section (C/S), and 47 (43%) were preterm. Prematurity was significantly higher in the patient group (p=0.004). The mean birth weight was also significantly lower compared to the control group (2670.55 ± 87.88 gr vs. 2925.87 ± 37.55 gr, p=0.008). Fetal distress was detected in 19 (17%) patients, and was also significantly higher in the patient group (p=0.032).
Fifty patients (46%) were diagnosed with another neonatal infection before Klebsiella infection (urinary tract infection, acute gastroenteritis, pneumonia, omphalitis, sepsis, meningitis). Moreover, 16 patients (15%) were diagnosed with congenital heart diseases, 15 patients (14%) with other congenital malformations, 3 patients (3%) with metabolic diseases, 6 patients (6%) with neurological diseases, and 1 patient (1%) with hematological disease.
EOS was diagnosed in 6 patients (6%) with Klebsiella infection, while LOS was diagnosed in 103 patients (94%). Seventy-five (69%) of these infections were HAI. Of these, 43 were urinary tract infections, 19 were BSIs, 7 were catheter-related BSIs, 5 were VAPs, one was skin abscess. Seven (9%) of those with HAI were from an external center, while 68 (91%) HAIs occurred in our center. All HAIs were LOS and developed on average 31.02 ± 4.9 days after hospitalization.
At the time of the Klebsiella infection, abnormal leukocyte counts (leukopenia and/leukocytosis), thrombocytopenia, and C reactive protein (CRP) levels were significantly higher while hemoglobin levels were significantly lower than in the control group (Table 1).
CRKP infection was detected in 28 (26%) patients. Among these, 6 (21%) patients had CRKP colonization before.
Sensitivity to colistin was 100.0%, and meropenem was 87.5%, while the sensitivity to ciprofloxacin was 77.9%. Ceftazidime (32.6%), ceftriaxone (34.1%), and gentamicin (34.7%) had the lowest levels of sensitivity (Figure 1).
There were 47 patients with a prior hospitalization history, which was significantly higher than in the control group (43% vs. 32%; p=0.024). The use of peripherally inserted central venous catheters, nasogastric tubes, urine catheters and TPN feeding was significantly higher than in the control group (Table 1). Sixty-nine patients (63%) had been given antibiotics prior to Klebsiella infection. Among these, 20 patients (18%) received vancomycin, and 22 (20%) received meropenem. When antibiotic use before Klebsiella infection was compared, there was no significant difference between the patient and control groups (p=0.251). However, previous antibiotic use was higher in patients with CRKP infection than in the carbapenem sensitive group (89% vs. 52%, p=0.002) (Table 2). Five patients with CRKP infection continued to develop CRKP growths under the treatment of colistin, and three of these patients died.
The patients were hospitalized at postnatal 8.06 ± 1.53 days. The mean length of hospital stay in the patient group was significantly higher than in the control group (44.14 ± 6.25 days vs. 20.69 ± 1.66 days, p<0.001).
In the patient group, 17 (16%) patients died, and mortality was significantly higher compared to the control group (16% vs. 8%, p=0.026). Moreover, among these patients, all had HAI, three were followed up with complex congenital heart diseases, one patient with chronic renal failure, two patients with metabolic disease, two patients with undiagnosed syndromic diseases, one patient with gastroschisis, and 8 patients with prematurity.
Eight patients with CRKP infection (29%) died. Mortality in patients infected with CRKP was significantly higher than in patients infected with carbapenem-sensitive Klebsiella (29% vs 11%, p=0.033) (Table 2).
Discussion
Klebsiella is an important cause of death and morbidity leading to HAI despite new discoveries in antimicrobial therapy and advances in supportive therapy, especially in preterm and neonates with low birth weight (LBW).
In this study, 48 patients (44%) were preterm, and the rate of prematurity was significantly higher than in the control group. Due to an increase in survival rates, prolonged hospitalizations, and exposure to invasive procedures, the incidence of infections in LBW and/or preterm infants increases in the current period. It has been reported that the risk of infection in these neonates is three to ten times higher than in terms with normal birth weight [7].
In this study, among CRKP colonized patients, 6 (21%) developed CRKP infection. Wang et al. showed that 24.5% of neonates with rectal Carbapenem-resistant Enterobacteriaceae (CRE) colonization developed CRE infection [8]. Similarly, Akturk et al. reported that 24 (28.2%) of 85 patients with CRKP colonization in pediatric intensive care and NICUs developed CRKP infection [9]. K. pneumoniae is the predominant microorganism colonizing the gut in neonates with a longer stay in the NICU and in those with prolonged feeding through an enteral tube [10]. Because of the immature immune system, lower levels of mucus and gastric acid production, bacteria are able to penetrate intestinal barrier and cause sepsis. When Klebsiella infection is detected in NICUs, it is imperative to immediately include a swab culture for Klebsiella from all infants hospitalized in the unit in the general precautionary packages to detect colonization early, followed by close monitoring of colonized patients for signs of infection.
In this study, we observed LOS in 95% of the patients. HAIs developed on average 31.02±4.91 days after hospitalization. Fifty patients (46%) underwent three or more invasive operations, and peripherally inserted central venous catheterization (7%), nasogastric tube (51%), urine catheterization (23%), and TPN feeding (45%) were significantly higher in the patient group. Similarly, previous studies have reported that underlying chronic medical conditions, invasive medical devices, and frequent/prolonged hospitalizations are risk factors for CRE infections [3, 11, 12]. We conclude that invasive procedures and prolonged hospitalization increase as patients’ gestational weeks decrease, resulting in a decline in barrier functions and providing an entry for infections.
The widespread use of antibiotics in NICUs leads to the spread of multi-antibiotic-resistant bacteria [13]. In this study, Klebsiella showed the most sensitivity to colistin (100%), followed by meropenem (87.5%) and ciprofloxacin (77.9%). The sensitivity to ceftazidime (32.6%), ceftriaxone (%34.1) and gentamicin (34.7%) was the lowest. According to a previous study performed in our unit, Klebsiella strains were 97% sensitive to meropenem, 91% sensitive to ciprofloxacin, 91% to ceftriaxone, and 85% to ceftazidime [14]. In a recent study, all neonates with CRKP were reported resistant to ciprofloxacin, ceftriaxone, and ceftazidime but susceptible to colistin [15]. It is concerning that resistance to meropenem and third-generation cephalosporins has increased dramatically over time. Moreover, although colistin sensitivity was 100%, five patients with CRKP infection developed recurrent CRKP growths under colistin, and three of these patients died. We conclude that in vivo sensitivity of colistin might be low. There are also several studies that reported Colistin-resistant Klebsiella spp. in the last years in NICUs [16, 17]. Due to overuse of this antibiotic, we may face more cases of colistin resistant Klebsiella outbreaks in NICUS in the near future, and treatment options may be limited if colistin resistance develops. Therefore, it is crucial to perform susceptibility testing using phenotypic and genetic/molecular methods in order to prompt timely infection control procedures, and guide clinicians in choosing the most appropriate therapy [18].
In this study, 28 patients (26%) were infected with CRKP. Among these, six patients (29%) died, and all had HAI. In previous studies, the mortality rate of CRKP in NICU ranged from %33 to %40 [19-21]. Consistent with these reports, we showed that the carbapenem-resistant group had a higher mortality rate than the carbapenem-sensitive group. CRE infections (particularly Klebsiella) are considered to be on the rise globally and represent a public health threat [22].
The limitation of our study is that comorbidities predisposing to infection could not be evaluated due to the retrospective nature. In addition, the risk factors associated with CRKP infection could not be evaluated because the number of CRKP infections was insufficient. The advantages of our study include the sample size of 109 patients with Klebsiella infection, which is larger than in other studies, and the presence of a control group.
Conclusion
Klebsiella infections in NICUs are associated with prematurity, prolonged hospitalization, fetal distress, and invasive interventions. Moreover, hospital stay and mortality in neonates with CRKP infection are much higher than in carbapenem sensitive group. Early detection of colonization, prevention of nosocomial transmission, and early tailored diagnostic and therapeutic strategies are required for the management of Klebsiella infections.
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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Elif Soyak Aytekin, Aysegul Zenciroglu. Evaluation of klebsiella ınfections in the tertiary neonatal ıntensive care unit. Ann Clin Anal Med 2023;14(6):562-566
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Radicular Pain Outcomes for Disc Hernia Patients Undergoing Microdiscectomy: The Role of Early Preoperative Pain Duration
Mahmut Özden 1, Gülşah Öztürk 2, Melih Bozkurt 1,3
1 Department of Neurosurgery, Private Memorial Hospital, 2 Department of Neurosurgery, College of Health Sciences, Gelisim University, 3 Department of Neurosurgery, Arel University, Istanbul, Turkey
DOI: 10.4328/ACAM.21723 Received: 2023-04-12 Accepted: 2023-05-17 Published Online: 2023-05-29 Printed: 2023-06-01 Ann Clin Anal Med 2023;14(6):567-571
Corresponding Author: Melih Bozkurt, Department of Neurosurgery, Memorial Hospital, 34180, Bahcelievler, Istanbul, Turkey. E-mail: : melihbozkurt@hotmail.com P: +90 505 502 55 39 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2441-0015
This study was approved by the Ethics Committee of Memorial Bahcelievler Hospital (Date: 2022-03-28, No: 32)
Aim: This study aims to determine whether early duration of pain before microdiscectomy in patients with lumbar disc hernia and radicular pain influences postoperative pain outcomes evaluated by the Visual Analog Scale (VAS).
Material and Methods: The study included 124 patients (68 males, 56 female), who underwent lumbar microdiscectomy. The patients’ demographic features, anatomical features of disc hernia, motor paresis, and VAS values were retrospectively determined and statistically analyzed using the Number Cruncher Statistical System software.
Results: As expected, microdiscectomy significantly reduced pain intensities as assessed inthe immediate postoperative period, at the 3rd and 6th months of the postoperative period. But when patients were stratified according to the median preoperative pain duration (14 days), there was no statistically significant difference between patients with pain lasting shorter or longer than the median pain duration. Further, Spearman correlation statistics also did not reveal a significant association between preoperative duration and postoperative VAS pain scores.
Discussion: For early intervals of pain during the initial manifestation of the lumbar disc disease, patients will equally benefit from surgical treatment regardless of the pain duration. Therefore, in lumbar radicular pain, it would be appropriate to avoid being too hasty in the surgical decision in the early period and to better weigh the benefits and risks of surgery if there is no neurological deficit and unbearable pain.
Keywords: Disc Hernia, Lumbar Microdiscectomy, Radicular Pain, Visual Analog Scale
Introduction
Low back pain is the most frequent cause of disability and loss of work hours, as well as the second most common cause for seeking medical help; and lumbar disc hernias are among the most frequent causes of low back and leg pain [1-3]. Disc herniation is a localized displacement of disc material from beyond the intervertebral disc space, which is <25% of the disc circumference when determined axially [4]. Lumbar disc hernia surgery has a proven efficiency, but there is no general clinical consensus on whether it should be the first-line treatment [5-7]. In patients with lumbar radicular pain, previous studies investigated whether the preoperative duration of symptoms (mainly pain) was associated with changes in physical function and pain after lumbar disc surgery [5, 7-15]. However, there is no consensus on this issue. Additionally, in previous studies, pain durations were not stratified according to the median duration of pain, which would reflect the real-life scenarios more precisely. Moreover, many studies have included disc hernia patients involving multi-level disc disease. Further, in these studies, the surgical times after the onset of pain included very delayed periods. Here, we analyzed our cohort of patients (n=124) with a single level of disc hernia, who were surgically treated at relatively earlier periods. Also, as will be detailed below, we performed detailed and relevant statistics in a carefully selected cohort to evaluate associations between the duration of early preoperative pain with surgical outcomes both with the Mann-Whitney U test and Spearman Correlation analysis. Besides determining the pain intensities with Visual Analog Scale (VAS) scores, we also included the side and level of disc hernia and the extent of paresis in our statistical analysis. Other detailed observations in our cohort regarding the associations of other concurrent diseases seemingly unrelated to disc pathology (diabetes not accompanied with diabetic neuropathy, etc) and inflammatory factors (neutrophil/platelet and lymphocyte/platelet ratios) with pain outcomes will be discussed in another study.
Material and Methods
Study Design. Patient Population, Inclusion and Exclusion Criteria
This retrospective clinical research was designed in accordance with the ethical standards of the institutional and regional responsible committee and in accordance with the Helsinki Declaration of 1975, as revised in 2000. Ethical approval was obtained from the institutional ethics committee of Memorial Bahcelievler Hospital (approval number 32; 2022-03-28). All patients signed informed consent forms for study participation. All patients who underwent surgery were previously treated with physical therapy and/or proper medications conservatively. The pain intensities were defined with VAS (Visual Analog Scale) scores. The study included patients whose radiological features of single-level lumbar disc herniation correlated with lumbar radicular pain. All patients had radicular leg pain without spinal stenosis observed on magnetic resonance imaging. The exclusion criteria were as follows: diffuse neurological deficits (cauda equina syndrome), lumbar spine pathologies of other etiologies, including infections, previous fractures, primary spinal tumors and metastases, advanced degenerative diseases of vertebral bones, spinal column malformations, and other neurologic, osteologic, and muscular diseases associated with pain.
Clinical Assessment
Demographic factors (i.e., age, gender), preoperative pain duration, disc hernia side and levels were determined and recorded for each patient. The extent of paresis (loss of muscle strength/motor deficit) was determined with a semiquantitative scale between 0 to 5 (no paresis to complete paresis) as evaluated by physical examination. Pain intensity as determined by VAS values was recorded preoperatively, immediately after surgery, and 3 and 6 months postoperatively.
Surgical Procedure
The senior author of this study (Melih Bozkurt) performed all surgical procedures at a single institution (Memorial Bahcelievler Hospital, Istanbul, Turkey). Single-level simple lumbar microdiscectomy was performed on all patients. Microdiscectomy was performed after partial hemilaminectomy plus flavectomy and root decompression with foraminotomy under surgical microscopy.
Statistical Analysis
The statistical program NCSS (Number Cruncher Statistical System, 2007, Utah, USA) was employed for statistical analysis. Descriptive statistical methods (i.e., median, mean, standard deviation, frequency, percentage, minimum, maximum) were used to evaluate the study data. Student’s t-test and the Mann-Whitney U test were performed for comparisons between two groups of normally and non-normally distributed quantitative variables, respectively. One-way analysis of variance and the Kruskal-Wallis test were utilized for comparisons between groups of more than two normally and non-normally distributed quantitative variables, respectively. Pearson Chi-Square test and Fisher Freeman Halton test were utilized to compare qualitative data. The Friedman test was used to compare more than two repeated measurements of quantitative variables without normal distribution. Spearman correlation analysis was used to evaluate the relationships between quantitative variables. Statistical significance was set at p < 0.05.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Patients’ demographics and clinico-pathological features are summarized in Table-1. The total number of patients was 124 (68 male, 56 female). The mean duration of preoperative pain was 14 days or less in 63 patients (50.8%) and more than 14 days in the remaining 61 patients (49.2%) participating in the study. 41.9% (n=52) of the cases were on the right side and 58.1% (n=72) were on the left side. The affected levels were as follows: 1.6% (n=2) L1-2, 2.4% (n=3) L2-3, 7.3% (n=9) L3-4, 54% (n=67) L4-5, and 34.7% (n=43) L5-S1, respectively. While 39 (31.5%) had no paresis (loss of muscle strength), 7 patients (5.6%) had level 4 paresis. The mean preoperative VAS score of the patients was 9.10 ± 0.69. These values dropped to 1.53± 1.07, 1.35 ± 1.12, and 1.24 ± 1.16 in the immediate postoperative period, 3rd and 6th month of the postoperative period, respectively. Patient pain reductions at all times were statistically significant (p<0.001), indicating the expected efficacy of surgery.
The characteristics of disc hernia patients stratified according to preoperative pain duration are summarized in Table 2. Gender, age and herniation side did not exert differences according to preoperative pain duration. Statistically significant differences were found between the preoperative, immediate postoperative, postoperative 3rd-month and postoperative 6th-month VAS scores of patients with preoperative pain duration of both ≤14 and ≥15 days (P=0.001; P < 0.01 for both intervals, respectively). Postoperative VAS measurements did not differ between those with preoperative pain duration <15 and ≥15 days analyzed with the Mann-Whitney U test. Spearman’s correlation analyses between preoperative pain duration and the preoperative, immediate postoperative, 3rd-month postoperative, and 6th- month postoperative VAS scores were also not statistically significant (r = −0.112, P=0.26; r = −0.09, P=0.49; r = −0.041, P=0.653; r = 0.01, P=0.733; respectively) (data not shown in table). Table-3 summarizes the changes in VAS scores and their correlation with patient demographics and clinicopathological features. Preoperative, immediate postoperative, 3rd postoperative, and 6th postoperative month VAS measurements of the cases did not differ according to gender and level of disc hernia (P>0.05). Age, side of disc hernia, and extent of paresis had some associations with preoperative and postoperative pain, which all will be discussed in detail in another study.
Discussion
Lumbar disc hernia surgery is a treatment modality with well-established efficacy, especially in single-level sequestered discs [14, 15]. However, there is no consensus regarding its use as a first-line treatment approach compared to other major treatment options [5, 6, 13, 16, 17]. The presence of a significant motor deficit may be a valid reason for choosing surgery as the first-line treatment option [10, 11]. The contribution of preoperative symptom duration to postoperative well-being is accepted as a clinically relevant variable but there is no consensus on the length of this period [5, 17, 18, 19]. Further, recommendations for surgical timing among several earlier studies differ, ranging from 6 weeks to 12 months [5, 7, 8, 12, 13, 15, 17-19]. In our study, we aimed to analyze patients with a relatively early duration of preoperative pain and hence, we determined the median value of the preoperative pain duration of our patients as a touchstone to compare postoperative pain outcomes.
Akagi et al. retrospectively analyzed 46 lumbar disc herniation patients treated with microendoscopic discectomy [5]. They divided patients into 2 groups (23 patients each) according to their preoperative symptom duration. They selected 3 months as a threshold, since previous studies demonstrated permanent neural injury within 12 weeks of disc hernia-induced nerve compression [5, 9]. However, they did not encounter a significant effect of symptom duration on surgical outcomes as assessed with VAS pain scores. These results are compatible with our findings, including a higher number of patients. Schoenfeld and Bono reviewed 11 studies and in 9 out of 11 studies, 4 of which were prospective, longer symptom duration negatively affected postoperative recovery [13]. However, they also admitted that 5 out of 9 studies in their analysis found that surgery could be performed for 6 months or longer without affecting patient recovery [13].
Støttrup et al. conducted a prospective cohort investigation on 2144 patients who were surgically treated for lumbar disc hernia and divided the subjects into three groups based on their preoperative leg pain duration: <3 months, 3–12 months, and >12 months [15]. They revealed that patients who underwent surgery within the first 3 months of leg pain demonstrated better results 1 year postoperatively compared to others who underwent surgery at later time points [15]. The difference between our results and those of Støttrup et al. may be mainly due to our patient population with earlier duration of pain. Chen et al. retrospectively investigated the records of 521 patients who underwent full endoscopic lumbar discectomy [5]. Their median follow-up was considerably long (1685 days; range: 523-3923 days) and they found that the preoperative symptom duration longer than 1 year was associated with worse outcomes on univariate analyses. Beck et al studied the association of sciatic pain duration with the results of lumbar disc surgery in 6216 patients [8]. Patients who underwent lumbar discectomy with pain duration of less than 12 months exhibited a more prominent reduction in postoperative leg pain and were more satisfied with surgical outcomes. Sabnis and Diwan performed an analysis and review of the literature encompassing 37 years (1975-2012) and concluded that a longer duration of leg pain before surgery is associates with poorer outcomes [19]. However, they also admitted that only a broad time frame (2-12 months) could be extracted from the literature analysis due to the lack of high-quality investigations and even contrasting results of the available studies [19]. In a recent study, Mehendiretta et al analyzed 209 patients with lumbar disc hernia treated with microdiscectomy and found that preoperative symptom duration of less than 6 weeks was associated with better ODI (Oswestry Disability Index) scores [20]. There are also recent studies, which studied preoperative symptom duration with clinical outcomes in cervical disc hernia patients treated with anterior cervical discectomy and fusion [21]. In one study analyzing 34 patients with cervical disc hernia treated with cervical discectomy, shorter symptom duration was found to associate with significantly reduced postoperative pain and neck disability index scores [21]. Despite the fact that clinicopathological features and surgical treatment techniques of cervical and lumbar disc hernias certainly have differences, these studies also contribute to the knowledge of whether preoperative pain duration contributes to the postoperative well-being in disc hernia. As mentioned, our study population has relatively earlier periods of pain duration with a median of 14 days, which may explain the differences with some of the above cited studies. Nonetheless, not only the Mann- Whitney U test comparing VAS scores among patients with preoperative pain durations shorter and longer than 14 days, Spearman’s correlation analyses also did not find any statistical difference regarding the association between exact day of preoperative pain duration and postoperative pain levels. This should also be noted as 15 patients in our cohort had at least 2 months of pain duration (data not shown in tables).
Our current study has limitations. It is retrospective and the reported duration of pain is subjective since it depends on relative patient complaints. It is also possible that patients who have had surgery at a later time are inherently more tolerant to pain, causing a bias. On the other hand, there are also strengths of our study. We analyzed a homogenous patient population and selecting the median duration of preoperative pain in this cohort might have reflected more realistic results and demonstrated real-life scenarios. As said, there are previous studies evaluating the pain-associated prognostic factors in the microsurgical management of lumbar radicular pain. Nonetheless, our study selectively focuses on the role of early pain duration in a more precise manner in a highly selected patient population.
Conclusion
During early manifestation of lumbar radicular pain, postponing the time of surgery seems not to influence the pain outcomes adversely. For this reason, it can be thought that in the absence of severe neurological deficit and very intense pain, acting too hastily in directing patients with disc herniation to immediate surgery does not provide additional clinical benefit. However, additional prospective studies are needed to better determine the relationship between early preoperative pain duration and patient recovery after microdiscectomy.
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 Özden1, Gülşah Öztürk, Melih Bozkurt. Radicular Pain Outcomes for Disc Hernia Patients Undergoing Microdiscectomy: The Role of Early Preoperative Pain Duration. Ann Clin Anal Med 2023;14(6):567-571
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Investigation of the change of fluoroquinolone resistance over years in urinary Escherichia coli isolates
Sibel Doğan Kaya 1, Serap Gencer 2
1 Department of Infectious Diseases and Clinical Microbiology, University of Health Sciences, Kartal Koşuyolu Research and Training Hospital, 2 Department of Infectious Diseases and Clinical Microbiology, University of Acibadem, Istanbul, Turkey
DOI: 10.4328/ACAM.21738 Received: 2023-04-23 Accepted: 2023-05-29 Published Online: 2023-05-31 Printed: 2023-06-01 Ann Clin Anal Med 2023;14(6):572-575
Corresponding Author: Sibel Doğan Kaya, Department of Infectious Diseases and Clinical Microbiology, University of Health Sciences, Kartal Koşuyolu Research and Training Hospital, Istanbul, Turkey. E-mail: sibeldogankaya@yahoo.com P: +90 505 677 00 69 Corresponding Author ORCID ID: https://orcid.org/0000-0002-3253-7334
Aim: In the face of rapidly increasing antibiotic resistance among urinary Escherichia coli (E.coli) isolates, it is important to follow the own resistance rates off all centers. This study aimed to investigate the resistance rates of urinary E.coli isolates against fluoroquinolones, the changes in rates over the last 6 years, and correlation with resistance rates to other antibiotics in our hospital.
Material and Methods: Antibiotic susceptibilities of urinary E.coli isolates between January 2003 and December 2008 in the Clinical Microbiology Laboratory of Dr. Lütfi Kırdar Kartal Training and Research Hospital were evaluated retrospectively. The first isolate from each patient was taken into the study.
Results: Of 5543 isolates, 27% were resistant to ciprofloxacin, 26.5 % to ofloxacin, 21.4% to gentamicin, 15.4 % to amikacin and 11.9 % produced extended spectrum beta-lactamase (ESBL). The resistance rates of ciprofloxacin and ofloxacin were 22.1% and 21.6% in 2003 and 34.3% and 35.5% in 2007, respectively (for both, p<0.001). ESBL rate was 4.3% in 2003 and 19% in 2008 (p<0.001). Of the isolates resistant to ofloxacin and ciprofloxacin, 31% and 32%, respectively, produced ESBL. There were positive correlations between fluoroquinolone resistance to other antibiotics. The resistance rates of the outpatient clinics were significantly lower than the rates of the inpatient clinics (p<0.001).
Discussion: The resistance rate to quinolone group antibiotics in E.coli strains isolated in various centers in our country is up to 35%, and resistance rates were generally found to be similar among quinolones. In our study, resistance to ofloxacin was found at a rate of 26.5% and ciprofloxacin resistance at a rate of 27% for E.coli strains, and no significant difference was found between them (p<0.05). When infections caused by bacteria with and without ESBL growth are compared in terms of mortality, morbidity and health costs, excluding the patient group in which carbapenems are used as the first treatment, in infections with ESBL-producing isolates, it has been shown that mortality is higher, length of hospital stay is longer and health costs are higher. The mortality rate in infections developed by ESBL-producing bacteria, especially in intensive care patients, varies between 30-50%.
Keywords: E.coli, Fluoroquinolone, Resistance
Introduction
Urinary tract infections take first place among community or hospital-acquired infections, especially in children, women and the elderly. In many studies, Escherichia coli has been shown to be the most common isolated agent in urinary tract infections, ranging from 41% to 80% [1,2]. Similarly, in clinical studies in our country, the most common factor isolated is E.coli, and its frequency varies between 24% and 76% [3,4]. In the treatment of urinary system infections, fluoroquinolones have been the first preferred antibacterial drugs due to their effectiveness against most uropathogenic microorganisms and their pharmacokinetic properties [5]. Due to the widespread use of quinolones, an increase in the resistance rates of uropathogenic E.coli isolates has been reported.
Material and Methods
In our study, between January 2003 and December 2008, the results of the urine materials sent for culture to the Clinical Microbiology Laboratory of Dr. Lütfi Kırdar Training and Research Hospital, were evaluated retrospectively. E.coli isolated urine materials were taken into consideration, the data and colony numbers of isolates of these materials were examined. In this context, 5543 E.coli isolates were included in our study. All procedures were carried out in accordance with the ethical rules and the principles of the Declaration of Helsinki. All patients signed a free and informed consent form.
Statistics
Chi-square (x2) test and Fisher’s exact probability test were used to analyze the change in antibiotic resistance rates by years and to compare the resistance rates of patients from different groups statistically (p<0.05). Values were considered statistically significant. SSPS 11.5 statistical program was used for all analyses.
Results
Over a 6-year-period, 5543 E.coli isolates isolated as uropathogens in the microbiology laboratory of our hospital were included in the study. Of all isolates, 3503 (63.2%) were isolated from urine materials from outpatient clinics and 1510 (27.2%) from services; 1595 (28.8%) of the isolates were isolated from urine materials from pediatric outpatient clinics and services; 43.5% of the isolates showed resistance to ampicillin-sulbactam, 34.4% to cefuroxime, 35% to cefazolin, 27% to ciprofloxacin, 26.5% to ofloxacin, 24.5% to piperacillin-tazobactam, 21.4% to gentamicin, 19% to cefepime, 18% to ceftriaxone, 15.4% to amikacin, 13.5% to cefoperazone-sulbactam, 1.2% to imipenem, 1% to meropenem, 42.1% to trimethoprim-sulfamethoxazole (Figure 1).
When the distribution of resistance development of isolates against ciprofloxacin and ofloxacin was analyzed according to years, significant differences were found in the rate of resistance development. The resistance rates were determined as 22.1% and 21.6% for ofloxacin and ciprofloxacin in 2003, respectively; In 2007, it was seen that it increased to 34.3% and 35.5%, respectively. When the resistance rates between consecutive years were compared, statistically significant differences were found between the resistance rates since 2005 (p=0.030, p<0.001 and p=0.008, respectively) (Figure 2).
It was observed that 11.9% of the isolates produced extended spectrum beta-lactamases (ESBL). When the distribution of ESBL producing E.coli strains according to years is examined; the rates have increased over the years; The rate, which was determined as 4.3% in 2003, increased to 19% in 2008. Statistically significant differences were found in ESBL rates by year. There were significant differences in ESBL rates between 2005 and 2006 (10.1%) and between 2006 and 2007 (19.8%) (p=0.001, p=0.001, p<0.001, respectively).
Resistance of isolates to fluoroquinolones and ESBL production rates were investigated. It was observed that 31% of ofloxacin-resistant isolates and 32% of ciprofloxacin-resistant isolates produced ESBL. It was observed that only 4% of ofloxanin and ciprofloxacin-sensitive isolates produced ESBL. A statistically significant similarity was detected. While 9.5% of 1595 isolates isolated from urine samples from pediatric outpatient clinics and wards produced ESBL, 12.9% of 3948 isolates isolated from samples from other clinics were observed to produce ESBL. It was observed that there is a significant difference between them. Ofloxacin resistance was found in 8.9% of the pediatric patient group and 33.5% of the adult patient group. Ciprofloxacin-resistance was found in 10.2% of the pediatric patient group and 33.8% in the adult patient group (Figure 3).
The resistance rates of the isolates of urine samples from different polyclinics and services of our hospital were compared. As the most obvious difference, Cefepime-resistance was detected at a rate of 14.2% in the outpatient group and 34.8% in the inpatient group. While the rate of ESBL producing isolates in the outpatient group was 1.3%, it was 16.8% in the inpatient group.
Discussion
The resistance rate to quinolone group antibiotics in E.coli strains isolated in various centers in our country is up to 35%, and resistance rates among quinolones were generally found to be similar.
In a study by Leblecioğlu et al. in 2003, ampicillin resistance was found to be 23.9%, ceftriaxone resistance was 24.6% and quinolone resistance was 8.2% in uropathogenic E.coli isolates [6].
In our study, resistance to ofloxacin was found at a rate of 26.5% and ciprofloxacin resistance at a rate of 27% for E.coli strains, and no significant difference was found between them (p<0.05).
In a study by Zhanel et al. on outpatients, they reported ciprofloxacin resistance as 1.8%. In a study conducted by Öztürk et al. in 2008 on outpatient and service patients, they reported that ciprofloxacin resistance was 70% in hospitalized patients and 38% in outpatients [7,8]. It has been reported that resistance to norfloxacin develops in 73% of hospitalized patients and 45% of outpatients, and resistance to levofloxacin develops in 70% of hospitalized patients and 45% in outpatients.
In a study by Gonzalez et al., Ciprofloxacin resistance was found to be 24%, norfloxacin resistance was 25%, and nalidixic acid resistance was 41% in E.coli isolates. Şamlı et al. in a study they conducted in 2003 on 117 uropathogenic E.coli isolates, reported ciprofloxacin resistance as 30% and norfloxacin resistance as 58%. In our study, ciprofloxacin resistance was found to be 27% and ofloxacin resistance was found to be 27% in E. coli isolates. The rates we found are compatible with the literature. In a study by Cetin et al., ESBL was detected at a rate of 15.8% in E.coli isolates that were detected as a hospital infection. In a study by Özsoy et al. ESBL was found at a rate of 8.7% [9,10,11].
Gürdoğan et al. reported ESBL growth of 9% in hospital isolates and 7.8% in outpatient isolates, while Tünger et al. reported 13.4% growth in hospital isolates and 6.7% in non-hospital isolates. In our study, we found uropathogenic E.coli isolates producing 11.9% of ESBL in the 6 year period between 2003 and 2008 [12].
When infections caused by bacteria with and without ESBL growth are compared in terms of mortality, morbidity and health costs, excluding the patient group in which carbapenems are used as the first treatment, in infections with ESBL producing isolates, mortality has been shown to be higher, length of hospital stay longer and health costs higher. Mortality rate in infections developed by ESBL-producing bacteria, especially in intensive care patients, varies between 30-50%. It has been noted that in the case of inappropriate use of antibiotics, this rate will increase even more [13]. In particular, the close relationship between ESBL resistance and quinolone resistance makes restriction in the use of quinolones more important. Multiple resistance development is defined as the development of resistance to 3 or more different classes of antimicrobial agents.
In a study conducted to determine the resistant phenotypes of gram-negative bacteria, isolated as urinary tract infection agents, it was determined that 17.7% of E.coli isolates developed multiple resistance [14].
In a surveillance study conducted in the USA, the frequency of uropathogenic E.coli developing multiple resistance and the characteristics of infected patients were examined. 7.1% of E.coli isolates were found resistant to three or more antimicrobial drugs and were accepted as multiresistant. 97.8% of these isolates were resistant to amoxicillin, 92.8% to cotrimoxazole, 86.6% to cefazolin, 38.8% to ciprofloxacin.
Conclusion
In our study, 5543 uropathogenic E.coli isolates developed resistance to all antibiotics at certain rates. Resistance development was observed in ampicillin-sulbactam (43.5%), cefuroxime (39.4%), cefazolin (35%), ceftriaxone (18%), from aminoglycosides, 21.4% to gentamicin and 15.4% to amikacin.
In the face of increasing antibiotic resistance, especially in preventing the development of resistance against fluoroquinolones seen in uropathogenic E.coli isolates, preventing unnecessary and inappropriate antibiotic use, monitoring of regional antibiotic sensitivities and planning empirical treatments in the light of these data are essential and have vital importance.
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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Sibel Doğan Kaya, Serap Gencer. Investigation of the change of fluoroquinolone resistance over years in urinary Escherichia coli isolates. Ann Clin Anal Med 2023;14(6):572-575
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