Evaluation of Autonomic Nervous System Status with Sympathetic Skin Response in Patients Undergoing Laparoscopic Sleeve Gastrectomy for Morbid Obesity

Evaluation of Autonomic Nervous System Status with Sympathetic Skin Response in Patients Undergoing Laparoscopic Sleeve Gastrectomy for Morbid Obesity | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Evaluation of Autonomic Nervous System Status with Sympathetic Skin Response in Patients Undergoing Laparoscopic Sleeve Gastrectomy for Morbid Obesity Hasan Elkan, Dilek Ağırcan, Baran Yüksekyayla, Hamza Erdoğdu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4560191/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction and Purpose: Obesity is the most common metabolic disease of our time. Bariatric surgery is now accepted as the definitive treatment for morbidly obese patients. The most commonly performed bariatric surgery method is “Laparoscopic Sleeve Gastrectomy (LSG)”. Patients often report various complaints related to the autonomic nervous system after obesity surgery. Sympathetic Skin Response (SSR) is a simple and non-invasive test used for the early diagnosis of dysautonomia in peripheral neuropathy, demonstrating the function of postganglionic unmyelinated sympathetic sudomotor fibers by using changes in skin resistance. This study aims to evaluate the autonomic nervous system status in patients undergoing LSG for morbid obesity using Sympathetic Skin Response (SSR). Method: The study was conducted prospectively with 40 volunteer patients who applied to Harran University Hospital General Surgery Department, had a BMI over 40, and underwent obesity surgery. Patients were neurologically evaluated in the preoperative period. The patients deemed suitable in the evaluation had their SSR recorded with tests conducted by the Neurology Department. The same group of patients had their sympathetic skin responses evaluated and recorded 6 months postoperatively, and statistical analyses were conducted. Findings: The decrease in BMI and SSR latency values before surgery compared to after surgery (p<0.001; p<0.001, respectively) and the increase in SSR amplitude values were found to be statistically significant (p<0.001). Discussion and Conclusion: Our study detected a significant increase in sympathetic skin response post-surgery. Hormonal changes such as the improvement of insulin resistance and the decrease in leptin levels, as well as the stressful nature of the surgical process, might lead to an increase in sympathetic nervous system activity. We believe that performing the low-cost and simple SSR test in patients undergoing obesity surgery could be important for the follow-up of potential neuropathies in the future. Bariatric surgery SSR obesity Introduction Weight loss after obesity surgery can be a life-changing milestone for many people. However, this surgical intervention can also have some unexpected consequences. Particularly, its effects on the autonomic nervous system require significant attention (An, Wang, & Mokadem, 2021 ). Patients often report various complaints related to the autonomic nervous system after obesity surgery, such as irregular heartbeats, sweating disorders, gastrointestinal problems, circulation issues, and even psychological symptoms like anxiety and depression. This situation can affect the quality of life post-surgery and is an important issue for patients (Alyahya, Alnujaidi, & Alnujaidi Sr, 2022 ; Sutanto, Wungu, Susilo, & Sutanto, 2021 ). In addition to surgical complications related to the operation, clinical conditions due to nutritional deficiencies are frequently encountered in the long term. Daily maintenance therapies of vitamins, minerals, and trace elements absorbed from the bypassed area after surgery need to be provided to these patients. Peripheral neuropathy is the most common neurological complication after gastric surgery, with rates ranging from 5–16% in studies (2,3). This can be due to deficiencies in B12, thiamine, and copper (Gasmi et al., 2022 ; Stoll et al., 2021 ). This study aims to evaluate the autonomic nervous system status in patients undergoing laparoscopic sleeve gastrectomy for morbid obesity using Sympathetic Skin Response (SSR). SSR is a simple and non-invasive test used for the early diagnosis of dysautonomia in peripheral neuropathy, demonstrating the function of postganglionic unmyelinated sympathetic sudomotor fibers by using changes in skin resistance. Autonomic nervous system functions can be evaluated with non-invasive electrophysiological tests like SSR and R-R interval variation (RRIV) (Jin, Liu, Liu, Zhao, & Sun, 2023 ; Lin et al., 2021 ). Material and Method The study was conducted prospectively. Forty patients aged 18–65 years with isolated morbid obesity (BMI over 40) and without any comorbidities were selected. Patients were neurologically evaluated in the preoperative period. Those with normal nerve conduction studies and deemed suitable in other evaluations had their SSR recorded with tests conducted by the Neurology Department. Additional diseases that could cause autonomic nervous system pathology were excluded from the study by conducting tests such as hemogram, HbA1c, C-peptide, LDL, HDL, triglyceride, insulin, and EKG before surgery. The same group of patients had their sympathetic skin responses evaluated and recorded 6 months postoperatively. Electrophysiological studies were conducted on all patients at the Harran University Faculty of Medicine Research and Application Hospital Neurology Department Electrophysiology Laboratory using a "Dantec Keypoint (Japan) V5-11" EMG device. Sympathetic skin response recordings were taken in the morning, ensuring the room temperature was between 22–24°C, with normal lighting and ventilation. The patient was positioned supine on the EMG bed, with skin temperature above 32°C, avoiding any external stimuli that could affect the recording. Patients were advised not to consume substances like cigarettes, tea, or coffee or exercise within 1 hour before the procedure. All participants were informed to keep their eyes open during the test, avoid deep breathing, talking, coughing, moving, laughing, and keep their hands relaxed. SSR was recorded with active electrodes placed on the palm and reference electrodes on the back of the hand. The device settings were adjusted to a filter range of 0.5 Hz-1 kHz, sensitivity of 500 µV, and sweep duration of 0.2 seconds. Stimulation was applied irregularly five times with at least 3-minute intervals to avoid habituation, with the highest amplitude evaluation considered. SSR latency was defined as the time from the stimulus artifact's onset to the first deflection's onset (usually negative), and amplitude was defined as the distance between the peak points of the negative and positive deflections. Findings The study was conducted with 32 patients, 9 (28.1%) male and 23 (71.9%) female, with an average age of 48.4 ± 22 years. The preoperative and postoperative values of BMI, SSR Latency, and SSR Amplitude were examined. It was found that the preoperative and postoperative BMI, SSR Latency, and SSR Amplitude values and age averages were similar in male and female patients (p > 0.05) (Table 1 ). Table 1 Comparison of BMI and SSR Values of Patients According to Gender Male (n = 9) Female (n = 23) Total (n = 32) Mean ± Sd (Med) Mean ± Sd (Med) Mean ± Sd (Med) Pre BMI 45.3 ± 4.9 (44) 46.6 ± 6.7 (45) 46.6 ± 6.7 (45) Post BMI 32.3 ± 3.7 (32) 32.7 ± 4.9 (34) 32.6 ± 4.5 (34) Pre SSR Latency 1741.1 ± 224.9 (1688) 1791.4 ± 206.3 (1753) 1777.3 ± 209.3 (1750) Post SSR Latency 1340.9 ± 137.9 (1244) 1392.3 ± 122.0 (1391) 1377.8 ± 126.6 (1337.5) Pre SSR Amplitude 1.72 ± 0.4 (1.73) 1.85 ± 0.8 (1.74) 1.81 ± 0.7 (1.74) Post SSR Amplitude 2.65 ± 0.6 (2.39) 2.78 ± 0.8 (2.80) 2.75 ± 0.8 (2.65) Age 49.2 ± 2.6 (48) 48.1 ± 2.1 (47) 48.4 ± 2.2 (48) * p < 0.05, Mann Whitney U The decrease in preoperative BMI and SSR latency values compared to postoperative values (p < 0.001; p < 0.001, respectively) and the increase in SSR amplitude values were found to be statistically significant (p < 0.001) (Table 2 ). Table 2 Comparison of BMI, Latency, and SSR Amplitude Values Before and After the Operation Pre-Operation Post- Operation p BMI (kg/m²) median (IQR) 44.5 (9) 34.0 (5) < 0.001** SSR Latency (unit) mean ± SD 1777.3 ± 209.2 1377.8 ± 126.6 < 0.001** SSR Amplitude (unit) mean ± SD 1.81 ± 0.7 2.75 ± 0.8 < 0.001** **p < 0.01, Wilxocon sign-rank, Paired sample testing A statistically significant (p = 0.50) weak negative correlation was found between ΔSSR latency and ΔSSR amplitude (p < 0.05) (Table 3 ). Table 3 Relationship between ΔSSR Latency Value and ΔBMI Unstandardized coefficients Standardized coefficients p β SE Still 25,168 5,406 < 0.001** ΔBMI -0.113 0.179 -0.114 0.533 **p < 0.01, linear regression </tr Statistical Analysis SPSS (Statistical Package for the Social Sciences) 25.0 package program was used for statistical analysis of the data. Categorical measurements were summarized as numbers and percentages, and continuous measurements as mean and standard deviation (where necessary, median and minimum-maximum IQR). The Kolmogorov-Smirnov test was used to determine whether the parameters showed normal distribution. The Mann-Whitney U test was used for parameters not showing normal distribution. Paired sample t-tests were used to examine differences between pre and post values showing normal distribution, and Wilcoxon sign-rank tests for those not showing normal distribution. Spearman’s rho correlation and linear regression tests were used to determine the relationship between continuous measurement parameters. The level of statistical significance was set at 0.05 for all tests. Discussion Obesity is the most common metabolic disease of our time, with a steadily increasing incidence worldwide. It is accepted that obesity shortens human life and reduces quality of life due to numerous accompanying comorbidities. Various methods, such as diet, exercise, and medical treatment, have been tried for obesity treatment for many years. However, bariatric surgery is now accepted as the definitive treatment for morbidly obese patients, with Laparoscopic Sleeve Gastrectomy (LSG) being the most commonly performed method. Patients with significant reductions in BMI after LSG show improvements in many comorbidities (Jiang et al., 2023 ; Vitiello, Abu-Abeid, Dayan, Berardi, & Musella, 2023 ). In addition to surgical complications related to the operation, clinical conditions due to nutritional deficiencies are frequently encountered in the long term. Daily maintenance therapies of vitamins, minerals, and trace elements absorbed from the bypassed area after surgery need to be provided to these patients. Peripheral neuropathy is the most common neurological complication after gastric surgery (Machado, Nienov, & Schmid, 2021 ). Particularly, autonomic dysfunctions and polyneuropathy starting from thiamine deficiency after obesity surgery occur between 6 weeks and 6 months. Initial symptoms in thiamine deficiency include tingling and numbness in the feet, followed by foot weakness, and later autonomic dysfunctions such as neurogenic bladder and constipation (Sethi et al., 2024 ). Studies have shown that neuropathies due to various nutritional deficiencies can start as late as 6 months, hence patients were evaluated 6 months post-surgery. In studies on obesity and the sympathetic nervous system, and polyneuropathy, Electromyoneurography (EMNG) is generally applied; however, while EMNG reflects pathologies in large myelinated fibers, it is not possible to evaluate small diameter fibers (Tavee & Zhou, 2009 ). Today, intraepidermal nerve fiber density (IENFD) with skin biopsy is used for the evaluation of small diameter fibers. Since IENFD is an invasive procedure, it has application difficulties (Thomas et al., 2023 ). Therefore, we applied the SSR test, which demonstrates sudomotor sympathetic functions, for the evaluation of small diameter fibers in our patients. SSR is used for diagnostic purposes in many diseases, one of which is peripheral autonomic neuropathies. SSR, which measures peripheral autonomic nerve activity, was described by Tarchanoff in 1890 (Bari, Rammoo, Aldosky, Jaqsi, & Martinsen, 2023 ). Due to the increase in secretion in the sweat glands after stimuli (noise, temperature change, electrical stimulation, deep breathing, etc.) that activate the sympathetic system, changes in skin conductance occur. By placing electrodes in appropriate areas, these changes can be recorded and evaluated, providing information about sympathetic system function (Jin, Liu, Liu, Zhao, Zhao, et al., 2023). In peripheral neuropathies, SSR may not be obtainable or may show abnormalities such as low amplitude and prolonged latency (Momose et al., 2020 ). At the time this study was conducted, there was no study in the literature evaluating sympathetic skin response in obesity using SSR. However, there were many studies examining the sympathetic nervous system conditions in obesity. Increased body fat ratio has been associated with sympathetic overactivity, especially at rest, and some studies have reported more than a 50% increase in resting muscle sympathetic nerve activity (MSNA) in obese individuals (Alvarez, Beske, Ballard, & Davy, 2002 ; Grassi et al., 2004 ; Sivenius, Niskanen, Laakso, & Uusitupa, 2003 ). Some studies have associated high levels of MSNA with subclinical organ damage in the heart, blood vessels, and kidneys in young individuals without hypertension but with obesity (Lambert et al., 2010 ). To date, various hypotheses have been proposed to explain the etiology of metabolic syndrome, and sympathetic overactivity appears to play a fundamental role in all of them (Straznicky, Eikelis, Lambert, & Esler, 2008 ). A study conducted in 2011 achieved a 9% weight loss in obese individuals following a hypocaloric diet, and during active weight loss, MSNA and whole-body norepinephrine levels dramatically decreased. However, during the weight maintenance period following weight loss, while MSNA levels returned to their previous state, norepinephrine secretion was maintained (Straznicky et al., 2011 ). This shows that sympathetic nervous system adaptation under conditions of negative and stable energy balance is quite complex and variable. Casellini et al. (Casellini et al., 2016 ) reported an improvement in sudomotor function in type 2 diabetes patients following bariatric surgery. Another recent study reported that bariatric surgery caused an increase in small nerve fiber regeneration but did not result in changes in quantitative sensory tests or autonomic functions (Azmi et al., 2021 ). Considering the current studies, changes in SSR after obesity surgery might differ depending on the type of surgical intervention, the patient's initial sympathetic nerve activity, and the degree of weight loss post-surgery. Generally, a decrease in SSR after obesity surgery could be expected due to reasons such as reduced hormone secretion and decreased insulin resistance. Obesity is a condition that increases inflammation, theoretically increasing sympathetic nerve activity. However, in our study, we observed an increase in sympathetic skin response similar to the study by Casellini et al. (Azmi et al., 2021 ), with increases in both amplitude levels and decreases in latency times compared to pre-surgery. These findings were statistically highly significant. When examining our findings, we detected an increase in sympathetic sudomotor activities post-LSG. Performing the low-cost and simple SSR test in patients undergoing obesity surgery could be important for the follow-up of potential neuropathies in the future. Contrary to the general opinion in the literature, we think there might be reasons for the increase in sympathetic nerve activity with weight loss. In our clinic, special attention is given to ensuring adequate nutrition in the postoperative period through collaborative efforts with dietetics and internal medicine departments, particularly for preventing nutritional conditions that cause polyneuropathy. Hormonal changes, such as the improvement of insulin resistance and the decrease in leptin levels, might lead to an increase in sympathetic nervous system activity. Additionally, the surgical process itself is stressful, which could also enhance the sympathetic response. Conclusion In our study, we detected a significant increase in the sympathetic skin response in patients after surgery. While there are no studies in the literature examining this topic using SSR, the differences in results compared to similar studies might be explained by the fact that those studies measured sympathetic nerve activity in skeletal muscle rather than in the skin. Although our study group is superior to many studies due to the absence of comorbidities and medication use, more comprehensive studies using different techniques together are needed to obtain clearer data on this subject. Declarations Ethics Approval: The study was approved by the Ethics Committee of the Medical Faculty of the Harran University and was performed in accordance with the Helsinki Declaration (Approval date and number: 22.03.2022/31). Funding: The authors received no financial support for the research and/or authorship of this article. Author Contribution All authors contributed to the study’s conception and design. Material preparation, data collection, and analysis were performed. The first draft of the manuscript was written by [HE]. All authors read and approved the final manuscript. The first author [HE] had the idea for the article, and all authors reviewed the manuscript and data analysis and who drafted and/or critically revised the work. References Alvarez, G. E., Beske, S. D., Ballard, T. P., & Davy, K. P. (2002). Sympathetic neural activation in visceral obesity. Circulation, 106 (20), 2533-2536. Alyahya, R. A., Alnujaidi, M. A., & Alnujaidi Sr, M. (2022). Prevalence and outcomes of depression after bariatric surgery: a systematic review and meta-analysis. Cureus, 14 (6). An, Z., Wang, H., & Mokadem, M. (2021). Role of the autonomic nervous system in mechanism of energy and glucose regulation post bariatric surgery. Frontiers in neuroscience, 15 , 770690. Azmi, S., Ferdousi, M., Liu, Y., Adam, S., Iqbal, Z., Dhage, S., . . . Soran, H. (2021). Bariatric surgery leads to an improvement in small nerve fibre damage in subjects with obesity. International Journal of Obesity, 45 (3), 631-638. doi:10.1038/s41366-020-00727-9 Bari, D. S., Rammoo, M. N. S., Aldosky, H. Y., Jaqsi, M. K., & Martinsen, Ø. G. (2023). The five basic human senses evoke electrodermal activity. Sensors, 23 (19), 8181. Casellini, C. M., Parson, H. K., Hodges, K., Edwards, J. F., Lieb, D. C., Wohlgemuth, S. D., & Vinik, A. I. (2016). Bariatric surgery restores cardiac and sudomotor autonomic C-fiber dysfunction towards normal in obese subjects with type 2 diabetes. PLoS One, 11 (5), e0154211. Gasmi, A., Bjørklund, G., Mujawdiya, P. K., Semenova, Y., Peana, M., Dosa, A., . . . Costea, D. O. (2022). Micronutrients deficiences in patients after bariatric surgery. European journal of nutrition, 61 (1), 55-67. Grassi, G., Dell'Oro, R., Facchini, A., Trevano, F. Q., Bolla, G. B., & Mancia, G. (2004). Effect of central and peripheral body fat distribution on sympathetic and baroreflex function in obese normotensives. Journal of hypertension, 22 (12), 2363-2369. Jiang, Z., Zhang, Z., Feng, T., Cheng, Y., Zhang, G., Zhong, M., & Hu, S. (2023). Trocar number and placement for laparoscopic sleeve gastrectomy and comparison of single-incision and conventional laparoscopic sleeve gastrectomy: a systematic review and meta-analysis. International Journal of Surgery, 109 (6), 1783-1795. Jin, M., Liu, J., Liu, K., Zhao, L., Zhao, Z., & Sun, S. (2023). Sympathetic skin response (SSR) in pediatric Guillain–Barré syndrome. Frontiers in Neurology, 14 , 1177394. Jin, M., Liu, J., Liu, K., Zhao, Z., & Sun, S. (2023). Evaluation of sympathetic skin response for early diagnosis and follow-up of diabetic peripheral neuropathy in children. BMC pediatrics, 23 (1), 483. Lambert, E., Sari, C. I., Dawood, T., Nguyen, J., McGrane, M., Eikelis, N., . . . Head, G. (2010). Sympathetic nervous system activity is associated with obesity-induced subclinical organ damage in young adults. Hypertension, 56 (3), 351-358. Lin, X., Chen, C., Liu, Y., Peng, Y., Chen, Z., Huang, H., & Xu, L. (2021). Peripheral nerve conduction and sympathetic skin response are reliable methods to detect diabetic cardiac autonomic neuropathy. Frontiers in Endocrinology, 12 , 709114. Machado, F. D., Nienov, O. H., & Schmid, H. (2021). Prevalence of peripheral polyneuropathy before and after Roux-en-Y gastric bypass and sleeve gastrectomy. Obesity Surgery, 31 , 4427-4435. Momose, H., Morimitsu, N., Ikeda, E., Kanai, S., Sakaguchi, M., & Ohhashi, T. (2020). Eyes closing and drowsiness in human subjects decrease baseline galvanic skin response and active palmar sweating: relationship between galvanic skin and palmar perspiration responses. Frontiers in Physiology, 11 , 558047. Sethi, I., Lam, K., Sanicola, C., Lee, E., Tuppo, C., Spaniolas, K., & Pryor, A. D. (2024). Efficacy of Bowel Regimen in Decreasing Postoperative Constipation in Bariatric Surgery Patients. Obesity Surgery , 1-6. Sivenius, K., Niskanen, L., Laakso, M., & Uusitupa, M. (2003). A Deletion in the α2B‐Adrenergic Receptor Gene and Autonomic Nervous Function in Central Obesity. Obesity research, 11 (8), 962-970. Stoll, A., Ferreira, D., da Silva, E., Papes, K., MianoSelbach, M., & de Souza, M. (2021). Peripheral Neuropathies after Bariatric Surgery: A Current Review. Int J Neurol Neurother, 8 , 107. Straznicky, N. E., Eikelis, N., Lambert, E. A., & Esler, M. D. (2008). Mediators of sympathetic activation in metabolic syndrome obesity. Current hypertension reports, 10 (6), 440-447. Straznicky, N. E., Grima, M. T., Eikelis, N., Nestel, P. J., Dawood, T., Schlaich, M. P., . . . Sari, C. I. (2011). The effects of weight loss versus weight loss maintenance on sympathetic nervous system activity and metabolic syndrome components. The Journal of Clinical Endocrinology & Metabolism, 96 (3), E503-E508. Sutanto, A., Wungu, C. D. K., Susilo, H., & Sutanto, H. (2021). Reduction of major adverse cardiovascular events (MACE) after bariatric surgery in patients with obesity and cardiovascular diseases: a systematic review and meta-analysis. Nutrients, 13 (10), 3568. Tavee, J., & Zhou, L. (2009). Small fiber neuropathy: a burning problem. Cleve Clin J Med, 76 (5), 297-305. Thomas, S., Enders, J., Kaiser, A., Rovenstine, L., Heslop, L., Hauser, W., . . . Wright, D. (2023). Abnormal intraepidermal nerve fiber density in disease: A scoping review. Frontiers in Neurology, 14 , 1161077. Vitiello, A., Abu-Abeid, A., Dayan, D., Berardi, G., & Musella, M. (2023). Long-term results of laparoscopic sleeve gastrectomy: a review of studies reporting 10+ years outcomes. Obesity Surgery, 33 (11), 3565-3570. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4560191","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":327282438,"identity":"7d89e6db-1232-4bac-ba36-c6617515a2d6","order_by":0,"name":"Hasan Elkan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4klEQVRIie3RMQrCMBiG4U8qdgl0k0guERBEsNirpBQylVrwAp10EbtWvIxQ0CUeQFx0cRPq5uBgVHRwiLo55J0SyMOfEMBm+9Mc8C7gZr8RCpCFXoqvCTSh4kvisdWBpSnt563jsjqd/QTNcmEkrWncYQWn0WyeRLNCyCGYNM/iijQY0YRv47ZDRBlmLOZGEij3cCfBRj3JoDJPIejcSJ9T8ppiFKCKtHv6LYKqJKoVUoYjJs0X8ybufpte/MAbr0tUvh/mLNqZxwB1/SkIM5DHtvHpvM65vTbAk9hsNpvtvSsfqDyz6+6yeQAAAABJRU5ErkJggg==","orcid":"","institution":"Harran University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Hasan","middleName":"","lastName":"Elkan","suffix":""},{"id":327282439,"identity":"2cb57ecb-db53-46c7-884c-75f4559af5c3","order_by":1,"name":"Dilek Ağırcan","email":"","orcid":"","institution":"Harran University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Dilek","middleName":"","lastName":"Ağırcan","suffix":""},{"id":327282440,"identity":"c7eb6922-1f50-405d-a75d-1b62bf483fa4","order_by":2,"name":"Baran Yüksekyayla","email":"","orcid":"","institution":"Harran University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Baran","middleName":"","lastName":"Yüksekyayla","suffix":""},{"id":327282441,"identity":"35f9c10b-7c5e-4c7c-b236-53c10400f3c5","order_by":3,"name":"Hamza Erdoğdu","email":"","orcid":"","institution":"Harran University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hamza","middleName":"","lastName":"Erdoğdu","suffix":""}],"badges":[],"createdAt":"2024-06-10 22:08:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4560191/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4560191/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":63710396,"identity":"3be513a9-b9bf-4e32-bd51-2fa04807a719","added_by":"auto","created_at":"2024-09-01 01:16:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":362069,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4560191/v1/9372feed-a6f7-43a5-a0cb-e845f202d457.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Evaluation of Autonomic Nervous System Status with Sympathetic Skin Response in Patients Undergoing Laparoscopic Sleeve Gastrectomy for Morbid Obesity","fulltext":[{"header":"Introduction","content":"\u003cp\u003eWeight loss after obesity surgery can be a life-changing milestone for many people. However, this surgical intervention can also have some unexpected consequences. Particularly, its effects on the autonomic nervous system require significant attention (An, Wang, \u0026amp; Mokadem, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). Patients often report various complaints related to the autonomic nervous system after obesity surgery, such as irregular heartbeats, sweating disorders, gastrointestinal problems, circulation issues, and even psychological symptoms like anxiety and depression. This situation can affect the quality of life post-surgery and is an important issue for patients (Alyahya, Alnujaidi, \u0026amp; Alnujaidi Sr, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Sutanto, Wungu, Susilo, \u0026amp; Sutanto, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn addition to surgical complications related to the operation, clinical conditions due to nutritional deficiencies are frequently encountered in the long term. Daily maintenance therapies of vitamins, minerals, and trace elements absorbed from the bypassed area after surgery need to be provided to these patients. Peripheral neuropathy is the most common neurological complication after gastric surgery, with rates ranging from 5–16% in studies (2,3). This can be due to deficiencies in B12, thiamine, and copper (Gasmi et al., \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Stoll et al., \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThis study aims to evaluate the autonomic nervous system status in patients undergoing laparoscopic sleeve gastrectomy for morbid obesity using Sympathetic Skin Response (SSR). SSR is a simple and non-invasive test used for the early diagnosis of dysautonomia in peripheral neuropathy, demonstrating the function of postganglionic unmyelinated sympathetic sudomotor fibers by using changes in skin resistance. Autonomic nervous system functions can be evaluated with non-invasive electrophysiological tests like SSR and R-R interval variation (RRIV) (Jin, Liu, Liu, Zhao, \u0026amp; Sun, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Lin et al., \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e\u003c/p\u003e \u003cp\u003e\u003c/p\u003e \u003cp\u003e\u003c/p\u003e"},{"header":"Material and Method","content":"\u003cp\u003eThe study was conducted prospectively. Forty patients aged 18–65 years with isolated morbid obesity (BMI over 40) and without any comorbidities were selected. Patients were neurologically evaluated in the preoperative period. Those with normal nerve conduction studies and deemed suitable in other evaluations had their SSR recorded with tests conducted by the Neurology Department. Additional diseases that could cause autonomic nervous system pathology were excluded from the study by conducting tests such as hemogram, HbA1c, C-peptide, LDL, HDL, triglyceride, insulin, and EKG before surgery. The same group of patients had their sympathetic skin responses evaluated and recorded 6 months postoperatively.\u003c/p\u003e\u003cp\u003eElectrophysiological studies were conducted on all patients at the Harran University Faculty of Medicine Research and Application Hospital Neurology Department Electrophysiology Laboratory using a \"Dantec Keypoint (Japan) V5-11\" EMG device. Sympathetic skin response recordings were taken in the morning, ensuring the room temperature was between 22–24°C, with normal lighting and ventilation. The patient was positioned supine on the EMG bed, with skin temperature above 32°C, avoiding any external stimuli that could affect the recording. Patients were advised not to consume substances like cigarettes, tea, or coffee or exercise within 1 hour before the procedure. All participants were informed to keep their eyes open during the test, avoid deep breathing, talking, coughing, moving, laughing, and keep their hands relaxed.\u003c/p\u003e\u003cp\u003eSSR was recorded with active electrodes placed on the palm and reference electrodes on the back of the hand. The device settings were adjusted to a filter range of 0.5 Hz-1 kHz, sensitivity of 500 µV, and sweep duration of 0.2 seconds. Stimulation was applied irregularly five times with at least 3-minute intervals to avoid habituation, with the highest amplitude evaluation considered. SSR latency was defined as the time from the stimulus artifact's onset to the first deflection's onset (usually negative), and amplitude was defined as the distance between the peak points of the negative and positive deflections.\u003c/p\u003e"},{"header":"Findings","content":"\u003cp\u003eThe study was conducted with 32 patients, 9 (28.1%) male and 23 (71.9%) female, with an average age of 48.4 ± 22 years. The preoperative and postoperative values of BMI, SSR Latency, and SSR Amplitude were examined. It was found that the preoperative and postoperative BMI, SSR Latency, and SSR Amplitude values and age averages were similar in male and female patients (p \u0026gt; 0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e \u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"±\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"±\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"±\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of BMI and SSR Values of Patients According to Gender\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003cp\u003e(n = 9)\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003cp\u003e(n = 23)\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003e(n = 32)\u003c/p\u003e \u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean ± Sd (Med)\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMean ± Sd (Med)\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMean ± Sd (Med)\u003c/p\u003e \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre BMI\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\"±\" colname=\"c2\"\u003e \u003cp\u003e45.3 ± 4.9 (44)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\"±\" colname=\"c3\"\u003e \u003cp\u003e46.6 ± 6.7 (45)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\"±\" colname=\"c4\"\u003e \u003cp\u003e46.6 ± 6.7 (45)\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost BMI\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\"±\" colname=\"c2\"\u003e \u003cp\u003e32.3 ± 3.7 (32)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\"±\" colname=\"c3\"\u003e \u003cp\u003e32.7 ± 4.9 (34)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\"±\" colname=\"c4\"\u003e \u003cp\u003e32.6 ± 4.5 (34)\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre SSR Latency\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\"±\" colname=\"c2\"\u003e \u003cp\u003e1741.1 ± 224.9 (1688)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\"±\" colname=\"c3\"\u003e \u003cp\u003e1791.4 ± 206.3 (1753)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\"±\" colname=\"c4\"\u003e \u003cp\u003e1777.3 ± 209.3 (1750)\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost SSR Latency\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\"±\" colname=\"c2\"\u003e \u003cp\u003e1340.9 ± 137.9 (1244)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\"±\" colname=\"c3\"\u003e \u003cp\u003e1392.3 ± 122.0 (1391)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\"±\" colname=\"c4\"\u003e \u003cp\u003e1377.8 ± 126.6 (1337.5)\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre SSR Amplitude\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\"±\" colname=\"c2\"\u003e \u003cp\u003e1.72 ± 0.4 (1.73)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\"±\" colname=\"c3\"\u003e \u003cp\u003e1.85 ± 0.8 (1.74)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\"±\" colname=\"c4\"\u003e \u003cp\u003e1.81 ± 0.7 (1.74)\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost SSR Amplitude\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\"±\" colname=\"c2\"\u003e \u003cp\u003e2.65 ± 0.6 (2.39)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\"±\" colname=\"c3\"\u003e \u003cp\u003e2.78 ± 0.8 (2.80)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\"±\" colname=\"c4\"\u003e \u003cp\u003e2.75 ± 0.8 (2.65)\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\"±\" colname=\"c2\"\u003e \u003cp\u003e49.2 ± 2.6 (48)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\"±\" colname=\"c3\"\u003e \u003cp\u003e48.1 ± 2.1 (47)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\"±\" colname=\"c4\"\u003e \u003cp\u003e48.4 ± 2.2 (48)\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003e* p \u0026lt; 0.05, Mann Whitney U\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe decrease in preoperative BMI and SSR latency values compared to postoperative values (p \u0026lt; 0.001; p \u0026lt; 0.001, respectively) and the increase in SSR amplitude values were found to be statistically significant (p \u0026lt; 0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e \u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of BMI, Latency, and SSR Amplitude Values Before and After the Operation\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePre-Operation\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePost- Operation\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m²) median (IQR)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e44.5 (9)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e34.0 (5)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt; 0.001**\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSSR Latency (unit) mean ± SD\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1777.3 ± 209.2\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1377.8 ± 126.6\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt; 0.001**\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSSR Amplitude (unit) mean ± SD\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.81 ± 0.7\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.75 ± 0.8\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt; 0.001**\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003e**p \u0026lt; 0.01, Wilxocon sign-rank, Paired sample testing\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eA statistically significant (p = 0.50) weak negative correlation was found between ΔSSR latency and ΔSSR amplitude (p \u0026lt; 0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e \u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRelationship between ΔSSR Latency Value and ΔBMI\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUnstandardized coefficients\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eStandardized coefficients\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eβ\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSE\u003c/p\u003e \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStill\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25,168\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5,406\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt; 0.001**\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eΔBMI\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.113\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.179\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.114\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.533\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cem\u003e**p \u0026lt; 0.01, linear regression\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e \u003cstrong\u003eStatistical Analysis\u003c/strong\u003e \u003c/p\u003e\u003cp\u003eSPSS (Statistical Package for the Social Sciences) 25.0 package program was used for statistical analysis of the data. Categorical measurements were summarized as numbers and percentages, and continuous measurements as mean and standard deviation (where necessary, median and minimum-maximum IQR). The Kolmogorov-Smirnov test was used to determine whether the parameters showed normal distribution. The Mann-Whitney U test was used for parameters not showing normal distribution. Paired sample t-tests were used to examine differences between pre and post values showing normal distribution, and Wilcoxon sign-rank tests for those not showing normal distribution. Spearman’s rho correlation and linear regression tests were used to determine the relationship between continuous measurement parameters. The level of statistical significance was set at 0.05 for all tests.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eObesity is the most common metabolic disease of our time, with a steadily increasing incidence worldwide. It is accepted that obesity shortens human life and reduces quality of life due to numerous accompanying comorbidities. Various methods, such as diet, exercise, and medical treatment, have been tried for obesity treatment for many years. However, bariatric surgery is now accepted as the definitive treatment for morbidly obese patients, with Laparoscopic Sleeve Gastrectomy (LSG) being the most commonly performed method. Patients with significant reductions in BMI after LSG show improvements in many comorbidities (Jiang et al., \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Vitiello, Abu-Abeid, Dayan, Berardi, \u0026amp; Musella, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2023\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn addition to surgical complications related to the operation, clinical conditions due to nutritional deficiencies are frequently encountered in the long term. Daily maintenance therapies of vitamins, minerals, and trace elements absorbed from the bypassed area after surgery need to be provided to these patients. Peripheral neuropathy is the most common neurological complication after gastric surgery (Machado, Nienov, \u0026amp; Schmid, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). Particularly, autonomic dysfunctions and polyneuropathy starting from thiamine deficiency after obesity surgery occur between 6 weeks and 6 months. Initial symptoms in thiamine deficiency include tingling and numbness in the feet, followed by foot weakness, and later autonomic dysfunctions such as neurogenic bladder and constipation (Sethi et al., \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). Studies have shown that neuropathies due to various nutritional deficiencies can start as late as 6 months, hence patients were evaluated 6 months post-surgery.\u003c/p\u003e \u003cp\u003eIn studies on obesity and the sympathetic nervous system, and polyneuropathy, Electromyoneurography (EMNG) is generally applied; however, while EMNG reflects pathologies in large myelinated fibers, it is not possible to evaluate small diameter fibers (Tavee \u0026amp; Zhou, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2009\u003c/span\u003e). Today, intraepidermal nerve fiber density (IENFD) with skin biopsy is used for the evaluation of small diameter fibers. Since IENFD is an invasive procedure, it has application difficulties (Thomas et al., \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Therefore, we applied the SSR test, which demonstrates sudomotor sympathetic functions, for the evaluation of small diameter fibers in our patients.\u003c/p\u003e \u003cp\u003eSSR is used for diagnostic purposes in many diseases, one of which is peripheral autonomic neuropathies. SSR, which measures peripheral autonomic nerve activity, was described by Tarchanoff in 1890 (Bari, Rammoo, Aldosky, Jaqsi, \u0026amp; Martinsen, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Due to the increase in secretion in the sweat glands after stimuli (noise, temperature change, electrical stimulation, deep breathing, etc.) that activate the sympathetic system, changes in skin conductance occur. By placing electrodes in appropriate areas, these changes can be recorded and evaluated, providing information about sympathetic system function (Jin, Liu, Liu, Zhao, Zhao, et al., 2023). In peripheral neuropathies, SSR may not be obtainable or may show abnormalities such as low amplitude and prolonged latency (Momose et al., \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2020\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAt the time this study was conducted, there was no study in the literature evaluating sympathetic skin response in obesity using SSR. However, there were many studies examining the sympathetic nervous system conditions in obesity. Increased body fat ratio has been associated with sympathetic overactivity, especially at rest, and some studies have reported more than a 50% increase in resting muscle sympathetic nerve activity (MSNA) in obese individuals (Alvarez, Beske, Ballard, \u0026amp; Davy, \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2002\u003c/span\u003e; Grassi et al., \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2004\u003c/span\u003e; Sivenius, Niskanen, Laakso, \u0026amp; Uusitupa, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2003\u003c/span\u003e). Some studies have associated high levels of MSNA with subclinical organ damage in the heart, blood vessels, and kidneys in young individuals without hypertension but with obesity (Lambert et al., \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2010\u003c/span\u003e). To date, various hypotheses have been proposed to explain the etiology of metabolic syndrome, and sympathetic overactivity appears to play a fundamental role in all of them (Straznicky, Eikelis, Lambert, \u0026amp; Esler, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2008\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eA study conducted in 2011 achieved a 9% weight loss in obese individuals following a hypocaloric diet, and during active weight loss, MSNA and whole-body norepinephrine levels dramatically decreased. However, during the weight maintenance period following weight loss, while MSNA levels returned to their previous state, norepinephrine secretion was maintained (Straznicky et al., \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2011\u003c/span\u003e). This shows that sympathetic nervous system adaptation under conditions of negative and stable energy balance is quite complex and variable.\u003c/p\u003e \u003cp\u003eCasellini et al. (Casellini et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2016\u003c/span\u003e) reported an improvement in sudomotor function in type 2 diabetes patients following bariatric surgery. Another recent study reported that bariatric surgery caused an increase in small nerve fiber regeneration but did not result in changes in quantitative sensory tests or autonomic functions (Azmi et al., \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eConsidering the current studies, changes in SSR after obesity surgery might differ depending on the type of surgical intervention, the patient's initial sympathetic nerve activity, and the degree of weight loss post-surgery. Generally, a decrease in SSR after obesity surgery could be expected due to reasons such as reduced hormone secretion and decreased insulin resistance. Obesity is a condition that increases inflammation, theoretically increasing sympathetic nerve activity. However, in our study, we observed an increase in sympathetic skin response similar to the study by Casellini et al. (Azmi et al., \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2021\u003c/span\u003e), with increases in both amplitude levels and decreases in latency times compared to pre-surgery. These findings were statistically highly significant.\u003c/p\u003e \u003cp\u003eWhen examining our findings, we detected an increase in sympathetic sudomotor activities post-LSG. Performing the low-cost and simple SSR test in patients undergoing obesity surgery could be important for the follow-up of potential neuropathies in the future. Contrary to the general opinion in the literature, we think there might be reasons for the increase in sympathetic nerve activity with weight loss. In our clinic, special attention is given to ensuring adequate nutrition in the postoperative period through collaborative efforts with dietetics and internal medicine departments, particularly for preventing nutritional conditions that cause polyneuropathy. Hormonal changes, such as the improvement of insulin resistance and the decrease in leptin levels, might lead to an increase in sympathetic nervous system activity. Additionally, the surgical process itself is stressful, which could also enhance the sympathetic response.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn our study, we detected a significant increase in the sympathetic skin response in patients after surgery. While there are no studies in the literature examining this topic using SSR, the differences in results compared to similar studies might be explained by the fact that those studies measured sympathetic nerve activity in skeletal muscle rather than in the skin. Although our study group is superior to many studies due to the absence of comorbidities and medication use, more comprehensive studies using different techniques together are needed to obtain clearer data on this subject.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003cstrong\u003eEthics Approval:\u003c/strong\u003e \u003cp\u003e The study was approved by the Ethics Committee of the Medical Faculty of the Harran University and was performed in accordance with the Helsinki Declaration (Approval date and number: 22.03.2022/31).\u003c/p\u003e\n\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eThe authors received no financial support for the research and/or authorship of this article.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors contributed to the study\u0026rsquo;s conception and design. Material preparation, data collection, and analysis were performed. The first draft of the manuscript was written by [HE]. All authors read and approved the final manuscript. The first author [HE] had the idea for the article, and all authors reviewed the manuscript and data analysis and who drafted and/or critically revised the work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAlvarez, G. E., Beske, S. D., Ballard, T. P., \u0026amp; Davy, K. P. (2002). Sympathetic neural activation in visceral obesity. \u003cem\u003eCirculation, 106\u003c/em\u003e(20), 2533-2536. \u003c/li\u003e\n\u003cli\u003eAlyahya, R. A., Alnujaidi, M. A., \u0026amp; Alnujaidi Sr, M. (2022). Prevalence and outcomes of depression after bariatric surgery: a systematic review and meta-analysis. \u003cem\u003eCureus, 14\u003c/em\u003e(6). \u003c/li\u003e\n\u003cli\u003eAn, Z., Wang, H., \u0026amp; Mokadem, M. (2021). Role of the autonomic nervous system in mechanism of energy and glucose regulation post bariatric surgery. \u003cem\u003eFrontiers in neuroscience, 15\u003c/em\u003e, 770690. \u003c/li\u003e\n\u003cli\u003eAzmi, S., Ferdousi, M., Liu, Y., Adam, S., Iqbal, Z., Dhage, S., . . . Soran, H. (2021). Bariatric surgery leads to an improvement in small nerve fibre damage in subjects with obesity. \u003cem\u003eInternational Journal of Obesity, 45\u003c/em\u003e(3), 631-638. doi:10.1038/s41366-020-00727-9\u003c/li\u003e\n\u003cli\u003eBari, D. S., Rammoo, M. N. S., Aldosky, H. Y., Jaqsi, M. K., \u0026amp; Martinsen, \u0026Oslash;. G. (2023). The five basic human senses evoke electrodermal activity. \u003cem\u003eSensors, 23\u003c/em\u003e(19), 8181. \u003c/li\u003e\n\u003cli\u003eCasellini, C. M., Parson, H. K., Hodges, K., Edwards, J. F., Lieb, D. C., Wohlgemuth, S. D., \u0026amp; Vinik, A. I. (2016). Bariatric surgery restores cardiac and sudomotor autonomic C-fiber dysfunction towards normal in obese subjects with type 2 diabetes. \u003cem\u003ePLoS One, 11\u003c/em\u003e(5), e0154211. \u003c/li\u003e\n\u003cli\u003eGasmi, A., Bj\u0026oslash;rklund, G., Mujawdiya, P. K., Semenova, Y., Peana, M., Dosa, A., . . . Costea, D. O. (2022). Micronutrients deficiences in patients after bariatric surgery. \u003cem\u003eEuropean journal of nutrition, 61\u003c/em\u003e(1), 55-67. \u003c/li\u003e\n\u003cli\u003eGrassi, G., Dell\u0026apos;Oro, R., Facchini, A., Trevano, F. Q., Bolla, G. B., \u0026amp; Mancia, G. (2004). Effect of central and peripheral body fat distribution on sympathetic and baroreflex function in obese normotensives. \u003cem\u003eJournal of hypertension, 22\u003c/em\u003e(12), 2363-2369. \u003c/li\u003e\n\u003cli\u003eJiang, Z., Zhang, Z., Feng, T., Cheng, Y., Zhang, G., Zhong, M., \u0026amp; Hu, S. (2023). Trocar number and placement for laparoscopic sleeve gastrectomy and comparison of single-incision and conventional laparoscopic sleeve gastrectomy: a systematic review and meta-analysis. \u003cem\u003eInternational Journal of Surgery, 109\u003c/em\u003e(6), 1783-1795. \u003c/li\u003e\n\u003cli\u003eJin, M., Liu, J., Liu, K., Zhao, L., Zhao, Z., \u0026amp; Sun, S. (2023). Sympathetic skin response (SSR) in pediatric Guillain\u0026ndash;Barr\u0026eacute; syndrome. \u003cem\u003eFrontiers in Neurology, 14\u003c/em\u003e, 1177394. \u003c/li\u003e\n\u003cli\u003eJin, M., Liu, J., Liu, K., Zhao, Z., \u0026amp; Sun, S. (2023). Evaluation of sympathetic skin response for early diagnosis and follow-up of diabetic peripheral neuropathy in children. \u003cem\u003eBMC pediatrics, 23\u003c/em\u003e(1), 483. \u003c/li\u003e\n\u003cli\u003eLambert, E., Sari, C. I., Dawood, T., Nguyen, J., McGrane, M., Eikelis, N., . . . Head, G. (2010). Sympathetic nervous system activity is associated with obesity-induced subclinical organ damage in young adults. \u003cem\u003eHypertension, 56\u003c/em\u003e(3), 351-358. \u003c/li\u003e\n\u003cli\u003eLin, X., Chen, C., Liu, Y., Peng, Y., Chen, Z., Huang, H., \u0026amp; Xu, L. (2021). Peripheral nerve conduction and sympathetic skin response are reliable methods to detect diabetic cardiac autonomic neuropathy. \u003cem\u003eFrontiers in Endocrinology, 12\u003c/em\u003e, 709114. \u003c/li\u003e\n\u003cli\u003eMachado, F. D., Nienov, O. H., \u0026amp; Schmid, H. (2021). Prevalence of peripheral polyneuropathy before and after Roux-en-Y gastric bypass and sleeve gastrectomy. \u003cem\u003eObesity Surgery, 31\u003c/em\u003e, 4427-4435. \u003c/li\u003e\n\u003cli\u003eMomose, H., Morimitsu, N., Ikeda, E., Kanai, S., Sakaguchi, M., \u0026amp; Ohhashi, T. (2020). Eyes closing and drowsiness in human subjects decrease baseline galvanic skin response and active palmar sweating: relationship between galvanic skin and palmar perspiration responses. \u003cem\u003eFrontiers in Physiology, 11\u003c/em\u003e, 558047. \u003c/li\u003e\n\u003cli\u003eSethi, I., Lam, K., Sanicola, C., Lee, E., Tuppo, C., Spaniolas, K., \u0026amp; Pryor, A. D. (2024). Efficacy of Bowel Regimen in Decreasing Postoperative Constipation in Bariatric Surgery Patients. \u003cem\u003eObesity Surgery\u003c/em\u003e, 1-6. \u003c/li\u003e\n\u003cli\u003eSivenius, K., Niskanen, L., Laakso, M., \u0026amp; Uusitupa, M. (2003). A Deletion in the \u0026alpha;2B‐Adrenergic Receptor Gene and Autonomic Nervous Function in Central Obesity. \u003cem\u003eObesity research, 11\u003c/em\u003e(8), 962-970. \u003c/li\u003e\n\u003cli\u003eStoll, A., Ferreira, D., da Silva, E., Papes, K., MianoSelbach, M., \u0026amp; de Souza, M. (2021). Peripheral Neuropathies after Bariatric Surgery: A Current Review. \u003cem\u003eInt J Neurol Neurother, 8\u003c/em\u003e, 107. \u003c/li\u003e\n\u003cli\u003eStraznicky, N. E., Eikelis, N., Lambert, E. A., \u0026amp; Esler, M. D. (2008). Mediators of sympathetic activation in metabolic syndrome obesity. \u003cem\u003eCurrent hypertension reports, 10\u003c/em\u003e(6), 440-447. \u003c/li\u003e\n\u003cli\u003eStraznicky, N. E., Grima, M. T., Eikelis, N., Nestel, P. J., Dawood, T., Schlaich, M. P., . . . Sari, C. I. (2011). The effects of weight loss versus weight loss maintenance on sympathetic nervous system activity and metabolic syndrome components. \u003cem\u003eThe Journal of Clinical Endocrinology \u0026amp; Metabolism, 96\u003c/em\u003e(3), E503-E508. \u003c/li\u003e\n\u003cli\u003eSutanto, A., Wungu, C. D. K., Susilo, H., \u0026amp; Sutanto, H. (2021). Reduction of major adverse cardiovascular events (MACE) after bariatric surgery in patients with obesity and cardiovascular diseases: a systematic review and meta-analysis. \u003cem\u003eNutrients, 13\u003c/em\u003e(10), 3568. \u003c/li\u003e\n\u003cli\u003eTavee, J., \u0026amp; Zhou, L. (2009). Small fiber neuropathy: a burning problem. \u003cem\u003eCleve Clin J Med, 76\u003c/em\u003e(5), 297-305. \u003c/li\u003e\n\u003cli\u003eThomas, S., Enders, J., Kaiser, A., Rovenstine, L., Heslop, L., Hauser, W., . . . Wright, D. (2023). Abnormal intraepidermal nerve fiber density in disease: A scoping review. \u003cem\u003eFrontiers in Neurology, 14\u003c/em\u003e, 1161077. \u003c/li\u003e\n\u003cli\u003eVitiello, A., Abu-Abeid, A., Dayan, D., Berardi, G., \u0026amp; Musella, M. (2023). Long-term results of laparoscopic sleeve gastrectomy: a review of studies reporting 10+ years outcomes. \u003cem\u003eObesity Surgery, 33\u003c/em\u003e(11), 3565-3570. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Bariatric surgery, SSR, obesity","lastPublishedDoi":"10.21203/rs.3.rs-4560191/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4560191/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction and Purpose:\u003c/strong\u003e Obesity is the most common metabolic disease of our time. Bariatric surgery is now accepted as the definitive treatment for morbidly obese patients. The most commonly performed bariatric surgery method is “Laparoscopic Sleeve Gastrectomy (LSG)”. Patients often report various complaints related to the autonomic nervous system after obesity surgery. Sympathetic Skin Response (SSR) is a simple and non-invasive test used for the early diagnosis of dysautonomia in peripheral neuropathy, demonstrating the function of postganglionic unmyelinated sympathetic sudomotor fibers by using changes in skin resistance. This study aims to evaluate the autonomic nervous system status in patients undergoing LSG for morbid obesity using Sympathetic Skin Response (SSR).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethod:\u003c/strong\u003e The study was conducted prospectively with 40 volunteer patients who applied to Harran University Hospital General Surgery Department, had a BMI over 40, and underwent obesity surgery. Patients were neurologically evaluated in the preoperative period. The patients deemed suitable in the evaluation had their SSR recorded with tests conducted by the Neurology Department. The same group of patients had their sympathetic skin responses evaluated and recorded 6 months postoperatively, and statistical analyses were conducted.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFindings:\u003c/strong\u003e The decrease in BMI and SSR latency values before surgery compared to after surgery (p\u0026lt;0.001; p\u0026lt;0.001, respectively) and the increase in SSR amplitude values were found to be statistically significant (p\u0026lt;0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion and Conclusion:\u003c/strong\u003e Our study detected a significant increase in sympathetic skin response post-surgery. Hormonal changes such as the improvement of insulin resistance and the decrease in leptin levels, as well as the stressful nature of the surgical process, might lead to an increase in sympathetic nervous system activity. We believe that performing the low-cost and simple SSR test in patients undergoing obesity surgery could be important for the follow-up of potential neuropathies in the future.\u003c/p\u003e","manuscriptTitle":"Evaluation of Autonomic Nervous System Status with Sympathetic Skin Response in Patients Undergoing Laparoscopic Sleeve Gastrectomy for Morbid Obesity","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-19 13:53:28","doi":"10.21203/rs.3.rs-4560191/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"dc3d3669-b2f2-4787-bc7a-5a89ddf27870","owner":[],"postedDate":"July 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-09-01T01:08:28+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-19 13:53:28","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4560191","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4560191","identity":"rs-4560191","version":["v1"]},"buildId":"GqpaHPwrfC8PjnIFayRh5","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}