Posterior lumbar interbody fusion for degenerative spondylolisthesis; slippage reduction can be a risk factor for adjacent segment disease.

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Abstract Several risk factors for adjacent segment disease (ASD) after posterior lumbar interbody fusion (PLIF) have been reported. However, the reducing the slipped vertebra has not been investigated as a risk factor for ASD. The objective of this study is to identify the risk factors for ASD following single-segment PLIF in patients with L4 spondylolisthesis, with a particular focus on the reduction of vertebral body slippage. Fifty-two patients who underwent PLIF at the L4-L5 level for L4 degenerative spondylolisthesis were investigated. Patients were divided into two groups: the ASD group and the non-ASD group. The ASD group consisted of 12 of the 52 patients (23.1%). %Slip before surgery and at follow-up, Δ%Slip (Δ%Slip = %Slip before surgery - %Slip at follow-up), L4-L5 interbody height, and L4-L5 lordosis angle were evaluated. Stepwise multivariate regression analysis revealed Δ%Slip to be a risk factor for ASD (odds ratio: 1.22, 95% confidence interval: 1.04–1.43, p = 0.015). In the receiver operating characteristic analysis, the cutoff value for Δ%Slip was 7.3% (sensitivity: 75.0%, specificity: 67.5%, area under the curve = 0.725). Our findings suggest that the reduction of L4 slippage may contribute to the development of ASD in patients with L4 spondylolisthesis.
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Posterior lumbar interbody fusion for degenerative spondylolisthesis; slippage reduction can be a risk factor for adjacent segment disease. | 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 Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Posterior lumbar interbody fusion for degenerative spondylolisthesis; slippage reduction can be a risk factor for adjacent segment disease. Sosuke Saito, Kazuyoshi Nakanishi, Hirokatsu Sawada, Koji Matsumoto, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4923331/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 Several risk factors for adjacent segment disease (ASD) after posterior lumbar interbody fusion (PLIF) have been reported. However, the reducing the slipped vertebra has not been investigated as a risk factor for ASD. The objective of this study is to identify the risk factors for ASD following single-segment PLIF in patients with L4 spondylolisthesis, with a particular focus on the reduction of vertebral body slippage. Fifty-two patients who underwent PLIF at the L4-L5 level for L4 degenerative spondylolisthesis were investigated. Patients were divided into two groups: the ASD group and the non-ASD group. The ASD group consisted of 12 of the 52 patients (23.1%). %Slip before surgery and at follow-up, Δ%Slip (Δ%Slip = %Slip before surgery - %Slip at follow-up), L4-L5 interbody height, and L4-L5 lordosis angle were evaluated. Stepwise multivariate regression analysis revealed Δ%Slip to be a risk factor for ASD (odds ratio: 1.22, 95% confidence interval: 1.04–1.43, p = 0.015). In the receiver operating characteristic analysis, the cutoff value for Δ%Slip was 7.3% (sensitivity: 75.0%, specificity: 67.5%, area under the curve = 0.725). Our findings suggest that the reduction of L4 slippage may contribute to the development of ASD in patients with L4 spondylolisthesis. Health sciences/Medical research Health sciences/Risk factors lumbar spine degenerative spondylolisthesis posterior intervertebral fusion adjacent segment disease % slip Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Lumbar degenerative spondylolisthesis is a spinal disease that causes low back pain and leg pain, and many treatment results have been reported to date [ 1 – 3 ]. Previous studies investigating the causes of degenerative spondylolisthesis have identified older age, gender, body mass index (BMI), and sagittal facet orientation as a potential risk factors [ 4 – 8 ]. More recently, several authors have highlighted the relationship between degenerative spondylolisthesis and spino-pelvic parameters. These studies demonstrated that a high pelvic incidence (PI) might be a predisposing factor for the development of degenerative spondylolisthesis [ 9 – 13 ]. Fusion surgery for degenerative spondylolisthesis with instability has been performed, but spinal fusion has been associated with adjacent segment disease (ASD) as a potential long-term complication. Two types of ASD have been identified: radiographic ASD, which features no symptoms but is diagnosed by imaging, and symptomatic ASD, which actually features neurological symptoms such as pain and numbness. According to a systematic review by Xia et al., the incidence of radiographic ASD was reported to be approximately 16-27.6% about 2 years after surgery and 21.8–45.4% from 2 to 5 years after surgery, showing an increasing trend during the postoperative course. The incidence of symptomatic ASD was reported to be approximately 4.8–8.1% about 2 years after surgery, and 8.2–16% from 2 to 5 years after surgery [ 14 ]. ASD is the leading cause of spinal re-operation. Risk factors for ASD have been identified in various studies, including age, gender, obesity, excessive distraction of lumbar disc space, number of segments fused, sagittal malalignment, pre-existing degeneration of discs and facet joints, facet tropism and laminectomy of the adjacent segment [ 15 – 20 ]. However, slip reduction has not been investigated as a risk factor for ASD. Previous studies have reported that there is no correlation between slip reduction and postoperative results, and it is uncertain whether slip reduction is necessary [ 21 ]. When undergoing corrective surgery for vertebral slippage via fixation in patients with lumbar degenerative spondylolisthesis attributed to a high PI, a forward-slipping force is expected to persist on the reduced vertebra even after fixation, as the PI remains unchanged post-surgery. Therefore, we hypothesized that reduction of vertebral slippage can be one of the causes of ASD. The objective of this study is to investigate the association between reduction surgery for slippage vertebra and postoperative adjacent segment disorders in the patients with lumbar degenerative spondylolisthesis. Materials and methods L4-L5 Posterior lumbar interbody fusion (PLIF) was performed for 82 patients with L4 degenerative spondylolisthesis at our institution between 2011 and 2019. 30 patients who suffered from any of the following conditions, were excluded: degenerative scoliosis (defined as a lateral spinal curvature with a Cobb angle of 10 degrees or more), sacralization or lumbalization, ankylosing or fusion, severe osteoarthritis in the lower limbs, history of spine surgery. Then, 52 patients (14 men and 38 women) with complete medical records including radiographs and at least three years follow-up after surgery were included in this retrospective study. The mean age at surgery was 65 years (range 37–84 years), and the average follow-up period was 62 months (range 36–138 months, Table 1). The study was carried out in accordance with the Declaration of Helsinki, and the study protocol was approved by the Institutional Review Board of Nihon University School of Medicine, and all subjects provided written informed consent after receiving a full explanation of the treatment. As radiographic parameters, pelvic incidence (PI), lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), thoracic kyphosis (TK), and sagittal vertical axis (SVA) were measured before surgery using standing radiography. Computed tomography (CT) images were used to measure the facet angle (Fig. 1) and the facet tropism, and to evaluate a presence or absence of a vacuum phenomenon in adjacent L3-L4 and L5-S1 disc levels before surgery [ 22 , 23 ]. The presence (Fig. 2A) or absence of a facet joint edema (Fig. 2B) in adjacent facet joints was established before surgery using T2 weighted magnetic resonance images (MRI). The trunk muscle mass before surgery was measured the cross-sectional area of the psoas major (PM), the erector spinae (ES), and the multifidus (MF) muscles in an axial MRI at the L4-L5 disc level, based on previous reports (Fig. 3) [ 24 ]. %Slip was calculated on CT (%Slip = b/a, Fig. 4A). The L4-L5 interbody height, (Fig. 4B) and the L4-L5 lordosis angle (Fig. 4C) were also measured on CT before surgery and at follow-up. Δ%Slip, ΔL4-L5 interbody height, and Δ L4-L5lordosis angle were calculated using following formulae (Δ%Slip = Δ%Slip at follow-up - %Slip before surgery, ΔL4-L5 interbody height = interbody height at follow-up - interbody height before surgery, ΔL4-L5 lordosis angle = L4-L5 lordosis angle at follow-up - L4-L5 lordosis angle before surgery. Comparative evaluation was performed between preoperative and postoperative data, and the ASD and non-ASD groups. ASD was identified using radiographic images taken before surgery and at follow-up, irrespective of the presence or absence of concomitant clinical symptoms. ASD comprised the development of either anterolisthesis or retrolisthesis more than 3mm, a decrease in adjacent disc height of more than 3mm, or an intervertebral angle smaller than − 5° during flexion [ 25 , 26 ]. In cases where ASD was identified, past radiographic images were used to determine the onset of ASD. Statistical analysis was performed using the Mann-Whitney U test and the Fischer exact test. Multivariate logistic regression was performed stepwise using variables showing statistical significance in the univariate analysis. A p value of less than 0.05 was considered statistically significant. Statistical analysis was performed using EZR software version1.33. Results ASD was found in 12 of the 52 cases (ASD group, 23.1%) at follow-up (Table 1). ASD was found on the cranial side in 10 cases, on the caudal side in 3 cases, and bilaterally in 1 case. ASD was identified as a disc height decrease of more than 3mm in 9 cases, a development of anterolisthesis of more than 3mm in 3 cases, and a combination of decreased disc height and anterolisthesis development in 1 case. ASD was found in 4 cases within 3 years after surgery, and in 8 cases at four years or more after surgery. Table 1 shows patient demographic data and radiographic parameters before surgery. No significant differences were found in age gender, BMI, and follow up period between the ASD group and the non-ASD group (Table 1). In the radiographic parameters, the SS in the ASD group was significantly smaller than that in the non-ASD group (p = 0.020). Table 2 shows the adjacent level findings and the trunk muscle parameters before surgery. There were no significant differences in the adjacent level findings before surgery in the adjacent level findings between the ASD group and the non-ASD group. As the trunk muscle parameters, a significant difference was found between the ASD group and the non-ASD group in the PM (p = 0.040), and the MF (p < 0.001). Table 3 shows the %Slip, L4-L5 interbody height, and L4-L5 lordosis angle before and at follow-up. The %Slip in the ASD group was 21.3 ± 5.3 (15.7–31.3), which was significantly larger than 16.4 ± 7.4 (3.3–35.9) in the non-ASD group (p = 0.02). Moreover, the Δ%Slip in the ASD groups was 9.7 ± 5.6 (2.3–20.4), and was significantly large than 5.5 ± 3.9 (0-13.5) in the Non-ASD group (p = 0.030, Table 4). There were no significant differences in the ΔL4L-5 interbody height and the ΔL4-L5 lordosis angle. Between both groups. In the stepwise multivariate analysis evaluating the parameters exhibiting significant difference among the univariate analysis (SS, PM, MF, %Slip, and Δ%Slip,), Δ%Slip was found to be a risk factor for ASD (odds ratio: 1.22, 95% CI: 1.04–1.43, p = 0.015, Table 5). The receiver operating characteristic (ROC) curve for Δ%Slip had an area under the curve (AUC) of 0.725. The cutoff value for Δ%Slip of 7.3% demonstrated a sensitivity of 75.0% and a specificity of 67.5% (Fig. 5). Discussion The key result of this retroactive study was that Δ%Slip was found to be a risk factor for ASD. There have been no studies reporting slip reduction as a risk factor for ASD to date, and the present study is the first to reveal such a correlation. Much research has been done to determine the risk factors for adjacent segment disease. Among the suggested risk factors are patient background parameters such as age, gender, obesity, facet tropism, laminar inclination, pre-existing disc degeneration, and facet degeneration [ 16 , 27 – 28 ]. Aota et al. reported the age of patients was the most significant risk factor for ASD. 27 Lee et al. reported in their study of 1069 patients following lumbar fusion that pre-existing degeneration of the facet joints may be a main risk factor [ 29 ]. Okuda et al. also reported that facet tropism was a risk factor for ASD [ 25 ]. In the present study, none of these parameters were identified as risk factors. Surgery-related parameters such as the number of segments fused, excessive distraction of lumbar disc space, laminectomy of the adjacent segment, floating fusion, and low postoperative lordotic angle have been reported as potential risk factors for ASD [ 30 , 31 ]. Kaito et al. investigated 97 cases of L4-L5 PLIF. The L4-L5 disc space distraction by cage insertion was 3.1mm in the non-ASD group, 4.4mm in the radiographic ASD group, and 6.2mm in the group with symptomatic ASD. The authors concluded that excessive distraction of the disc space is a significant and potentially avoidable risk factor for ASD [ 20 ]. In our study, ΔL4-L5 interbody height distraction before and after surgery was 1.9mm in the ASD group and 1.6mm in the non-ASD group, which was significantly smaller than the disc distraction reported by Kaito et al. It is possible that in the study by Kaito et al., ASD was not caused by interbody height distraction but rather due to slip reduction. While their study does not mention the procedure, it is likely that ligament taxis was performed in the cases of excessive interbody height distraction in order to correct the slip. In a biomechanical analysis using human cadaveric lumbar spine, Cunningham et al. measured cranial and caudal disc pressure in fused L3/4, and reported a 45% increase in cranial disc pressure due to fixation. The authors surmised that adjacent intradiscal pressure would increase further with distraction of the disc space, and concluded that it is necessary to maintain interbody height before and after surgery to avoid the risk of ASD [ 31 ]. In recent years, it has been reported that lumbar degenerative spondylolisthesis is associated with spino-pelvic parameters, and among such reports, there are some that identify high PI as a risk factor [ 9 – 11 ]. Nakamae et al. investigated the spino-pelvic alignment in 104 patients with low back pain and reported predictors for L4 anterior slip, identifying the cut-off value for PI as 51.3° with a sensitivity of 87.5% and a specificity of 76.5%. In the present study, the average value for PI was 55.5° (ASD group: 53.1°, non-ASD group: 56.3°) which exceeded the cut off value reported by Nakamae et al [ 32 ]. In cases in which PI is assumed to be the cause of slippage, the PI does not change, even when the slippage is corrected by surgery. It would seem that the L4 vertebral body is always subject to the force of slippage, even after fixation. PI has subsequently been generally acknowledged to be a predictor of the amount of LL required to assume a balanced sagittal posture. It has been suggested that correction of spino-pelvic parameters reduces the incidence of ASD [ 33 , 34 ]. In cases of lumbar degenerative spondylolisthesis, it would be beneficial to investigate LL acquired due to high PI. However, evaluating local lordosis in a single PLIF can be difficult in practice, as it proved to be in the present study, which found the L4-L5 lordosis angle to be 16.7 ± 4.8° preoperatively and 17.8 ± 5.2° postoperatively. In recent years, it has been reported that trunk muscle mass is a factor that affects spinal sagittal alignment [ 35 ]. Our study evaluated trunk muscle mass as a potential risk factor for ASD. Trunk muscle mass can be measured using the DEXA method and the BIA method. However, our study used a method in which the cross-sectional area of PM, ES, and MF muscles is measured using horizontal MRI images at the L4-L5 level [ 24 ]. The results of this study indicate that preoperative trunk muscle mass may have an effect on ASD occurring within three years. Rehabilitation interventions may play a more important role in the future. ASD may result from a combination of various factors. Our findings indicate that the reduction of L4 slippage may also contribute to the development of ASD in patients with L4 spondylolisthesis. Further research is needed in order to obtain a clearer understanding of the causes of ASD. Figure legends: Figure 1. The presence (A) or absence (B) of facet joint edema in the adjacent facet joints was established using preoperative magnetic resonance imaging (MRI). Figure 2. The facet angle and facet tropism in the adjacent facet joints was established using preoperative computed tomography (CT). Facet angle=(α་β) / 2 Facet tropism=α-β or β-α Figure 3A %slip = b / a×100 (%) Figure 3B L4/5 interbody height was measured as shown in the figure. Figure 3C. L4/5 lordosis angle was measured as shown in the figure. Figure 4. Trunk mass muscles (PM, ES, MF) were measured using magnetic resonance imaging (MRI) cross-sectional area at the L4/5 level. PM, psoas major; ES, erector spinae; MF, multifidus Figure 5. The Receiver Operatorating Characteristic (ROC) curve was calculated at Δ%slip (Δ%slip = preoperative % slip - postoperative % slip) Declarations Author Contribution S.S. and K.N. wrote the main manuscript text, H.S., K.M., M.O., H.U., and K.S. performed the surgery, S.S., T.F., and Y.M. measured the parameters. All authors reviewed the manuscript. The study was carried out in accordance with the Declaration of Helsinki, and the study protocol was approved by the Institutional Review Board of Nihon University School of Medicine, and all subjects provided written informed consent after receiving a full explanation of the treatment. Data Availability All data generated or analyzed during this study are included in this published article. References Fritzell P, Hagg O, Wessberg P, et al. 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Medicine","correspondingAuthor":false,"prefix":"","firstName":"Tomohiro","middleName":"","lastName":"Furuya","suffix":""},{"id":345982321,"identity":"0dff288f-3204-46dc-b4ac-7618abfd6ed5","order_by":9,"name":"Yuya Miyanaga","email":"","orcid":"","institution":"Nihon University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yuya","middleName":"","lastName":"Miyanaga","suffix":""}],"badges":[],"createdAt":"2024-08-16 07:48:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4923331/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4923331/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":66707396,"identity":"37ddfced-e77d-45b6-badd-aa853383ed48","added_by":"auto","created_at":"2024-10-15 17:02:51","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":205602,"visible":true,"origin":"","legend":"\u003cp\u003eThe presence (A) or absence (B) of facet joint edema in the adjacent facet joints was established using preoperative magnetic resonance imaging (MRI).\u003c/p\u003e","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4923331/v1/1260f952a507fee76f36348c.jpg"},{"id":66707395,"identity":"73590efb-a3ac-4bbb-885e-d60dce3b6385","added_by":"auto","created_at":"2024-10-15 17:02:51","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":445018,"visible":true,"origin":"","legend":"\u003cp\u003eThe facet angle and facet tropism in the adjacent facet joints was established using preoperative computed tomography (CT).\u003c/p\u003e\n\u003cp\u003eFacet angle=(α+β) / 2\u003c/p\u003e\n\u003cp\u003eFacet tropism=α-β or β-α\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4923331/v1/63d680fcb74c0dc41322d267.png"},{"id":66708531,"identity":"dcf4eea7-e7f4-4830-ba31-791a538a5a3b","added_by":"auto","created_at":"2024-10-15 17:18:51","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":390135,"visible":true,"origin":"","legend":"\u003cp\u003eA %slip =b / a×100 (%)\u003c/p\u003e\n\u003cp\u003eB L4/5 interbody height was measured as shown in the figure.\u003c/p\u003e\n\u003cp\u003eC. L4/5 lordosis angle was measured as shown in the figure.\u003c/p\u003e","description":"","filename":"Fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4923331/v1/8d6dc086c79f4fc859ded365.jpg"},{"id":66707400,"identity":"8661172c-f634-474a-be85-1a7245221524","added_by":"auto","created_at":"2024-10-15 17:02:51","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":687730,"visible":true,"origin":"","legend":"\u003cp\u003eTrunk mass muscles (PM, ES, MF) were measured using magnetic resonance imaging (MRI) cross-sectional area at the L4/5 level.\u003c/p\u003e\n\u003cp\u003ePM, psoas major; ES, erector spinae; MF, multifidus\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-4923331/v1/c016f9b42f437ebaf1c72f8f.png"},{"id":66708532,"identity":"cd885355-6741-41a6-934a-f6477af41245","added_by":"auto","created_at":"2024-10-15 17:18:51","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":308651,"visible":true,"origin":"","legend":"\u003cp\u003eThe Receiver Operatorating Characteristic (ROC) curve was calculated at Δ%slip\u003c/p\u003e\n\u003cp\u003e(Δ%slip = preoperative % slip - postoperative % slip)\u003c/p\u003e","description":"","filename":"Fig5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4923331/v1/f2109bf736be008ea199ea16.jpg"},{"id":66709450,"identity":"eeff1662-f392-4654-a44c-6c876668eb44","added_by":"auto","created_at":"2024-10-15 17:34:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2566591,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4923331/v1/54a2bb04-37f4-46d0-a74c-79f232a74546.pdf"},{"id":66708099,"identity":"aff847bd-bf4d-4909-a9cf-2bc78e7a2dd2","added_by":"auto","created_at":"2024-10-15 17:10:51","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":23100,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-4923331/v1/1431f592de0b6ad0a74c3133.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Posterior lumbar interbody fusion for degenerative spondylolisthesis; slippage reduction can be a risk factor for adjacent segment disease.","fulltext":[{"header":"Introduction","content":"\u003cp\u003eLumbar degenerative spondylolisthesis is a spinal disease that causes low back pain and leg pain, and many treatment results have been reported to date [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Previous studies investigating the causes of degenerative spondylolisthesis have identified older age, gender, body mass index (BMI), and sagittal facet orientation as a potential risk factors [\u003cspan additionalcitationids=\"CR5 CR6 CR7\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. More recently, several authors have highlighted the relationship between degenerative spondylolisthesis and spino-pelvic parameters. These studies demonstrated that a high pelvic incidence (PI) might be a predisposing factor for the development of degenerative spondylolisthesis [\u003cspan additionalcitationids=\"CR10 CR11 CR12\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFusion surgery for degenerative spondylolisthesis with instability has been performed, but spinal fusion has been associated with adjacent segment disease (ASD) as a potential long-term complication. Two types of ASD have been identified: radiographic ASD, which features no symptoms but is diagnosed by imaging, and symptomatic ASD, which actually features neurological symptoms such as pain and numbness. According to a systematic review by Xia et al., the incidence of radiographic ASD was reported to be approximately 16-27.6% about 2 years after surgery and 21.8\u0026ndash;45.4% from 2 to 5 years after surgery, showing an increasing trend during the postoperative course. The incidence of symptomatic ASD was reported to be approximately 4.8\u0026ndash;8.1% about 2 years after surgery, and 8.2\u0026ndash;16% from 2 to 5 years after surgery [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eASD is the leading cause of spinal re-operation. Risk factors for ASD have been identified in various studies, including age, gender, obesity, excessive distraction of lumbar disc space, number of segments fused, sagittal malalignment, pre-existing degeneration of discs and facet joints, facet tropism and laminectomy of the adjacent segment [\u003cspan additionalcitationids=\"CR16 CR17 CR18 CR19\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. However, slip reduction has not been investigated as a risk factor for ASD. Previous studies have reported that there is no correlation between slip reduction and postoperative results, and it is uncertain whether slip reduction is necessary [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhen undergoing corrective surgery for vertebral slippage via fixation in patients with lumbar degenerative spondylolisthesis attributed to a high PI, a forward-slipping force is expected to persist on the reduced vertebra even after fixation, as the PI remains unchanged post-surgery. Therefore, we hypothesized that reduction of vertebral slippage can be one of the causes of ASD. The objective of this study is to investigate the association between reduction surgery for slippage vertebra and postoperative adjacent segment disorders in the patients with lumbar degenerative spondylolisthesis.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003eL4-L5 Posterior lumbar interbody fusion (PLIF) was performed for 82 patients with L4 degenerative spondylolisthesis at our institution between 2011 and 2019. 30 patients who suffered from any of the following conditions, were excluded: degenerative scoliosis (defined as a lateral spinal curvature with a Cobb angle of 10 degrees or more), sacralization or lumbalization, ankylosing or fusion, severe osteoarthritis in the lower limbs, history of spine surgery. Then, 52 patients (14 men and 38 women) with complete medical records including radiographs and at least three years follow-up after surgery were included in this retrospective study. The mean age at surgery was 65 years (range 37\u0026ndash;84 years), and the average follow-up period was 62 months (range 36\u0026ndash;138 months, Table\u0026nbsp;1). The study was carried out in accordance with the Declaration of Helsinki, and the study protocol was approved by the Institutional Review Board of Nihon University School of Medicine, and all subjects provided written informed consent after receiving a full explanation of the treatment.\u003c/p\u003e \u003cp\u003eAs radiographic parameters, pelvic incidence (PI), lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), thoracic kyphosis (TK), and sagittal vertical axis (SVA) were measured before surgery using standing radiography. Computed tomography (CT) images were used to measure the facet angle (Fig.\u0026nbsp;1) and the facet tropism, and to evaluate a presence or absence of a vacuum phenomenon in adjacent L3-L4 and L5-S1 disc levels before surgery [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. The presence (Fig.\u0026nbsp;2A) or absence of a facet joint edema (Fig.\u0026nbsp;2B) in adjacent facet joints was established before surgery using T2 weighted magnetic resonance images (MRI). The trunk muscle mass before surgery was measured the cross-sectional area of the psoas major (PM), the erector spinae (ES), and the multifidus (MF) muscles in an axial MRI at the L4-L5 disc level, based on previous reports (Fig.\u0026nbsp;3) [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e%Slip was calculated on CT (%Slip\u0026thinsp;=\u0026thinsp;b/a, Fig.\u0026nbsp;4A). The L4-L5 interbody height, (Fig.\u0026nbsp;4B) and the L4-L5 lordosis angle (Fig.\u0026nbsp;4C) were also measured on CT before surgery and at follow-up. Δ%Slip, ΔL4-L5 interbody height, and Δ L4-L5lordosis angle were calculated using following formulae (Δ%Slip\u0026thinsp;=\u0026thinsp;Δ%Slip at follow-up - %Slip before surgery, ΔL4-L5 interbody height\u0026thinsp;=\u0026thinsp;interbody height at follow-up - interbody height before surgery, ΔL4-L5 lordosis angle\u0026thinsp;=\u0026thinsp;L4-L5 lordosis angle at follow-up - L4-L5 lordosis angle before surgery.\u003c/p\u003e \u003cp\u003eComparative evaluation was performed between preoperative and postoperative data, and the ASD and non-ASD groups. ASD was identified using radiographic images taken before surgery and at follow-up, irrespective of the presence or absence of concomitant clinical symptoms. ASD comprised the development of either anterolisthesis or retrolisthesis more than 3mm, a decrease in adjacent disc height of more than 3mm, or an intervertebral angle smaller than \u0026minus;\u0026thinsp;5\u0026deg; during flexion [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. In cases where ASD was identified, past radiographic images were used to determine the onset of ASD.\u003c/p\u003e \u003cp\u003eStatistical analysis was performed using the Mann-Whitney U test and the Fischer exact test. Multivariate logistic regression was performed stepwise using variables showing statistical significance in the univariate analysis. A p value of less than 0.05 was considered statistically significant. Statistical analysis was performed using EZR software version1.33.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eASD was found in 12 of the 52 cases (ASD group, 23.1%) at follow-up (Table\u0026nbsp;1). ASD was found on the cranial side in 10 cases, on the caudal side in 3 cases, and bilaterally in 1 case. ASD was identified as a disc height decrease of more than 3mm in 9 cases, a development of anterolisthesis of more than 3mm in 3 cases, and a combination of decreased disc height and anterolisthesis development in 1 case. ASD was found in 4 cases within 3 years after surgery, and in 8 cases at four years or more after surgery.\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;1 shows patient demographic data and radiographic parameters before surgery. No significant differences were found in age gender, BMI, and follow up period between the ASD group and the non-ASD group (Table\u0026nbsp;1). In the radiographic parameters, the SS in the ASD group was significantly smaller than that in the non-ASD group (p\u0026thinsp;=\u0026thinsp;0.020).\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;2 shows the adjacent level findings and the trunk muscle parameters before surgery. There were no significant differences in the adjacent level findings before surgery in the adjacent level findings between the ASD group and the non-ASD group. As the trunk muscle parameters, a significant difference was found between the ASD group and the non-ASD group in the PM (p\u0026thinsp;=\u0026thinsp;0.040), and the MF (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;3 shows the %Slip, L4-L5 interbody height, and L4-L5 lordosis angle before and at follow-up. The %Slip in the ASD group was 21.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3 (15.7\u0026ndash;31.3), which was significantly larger than 16.4\u0026thinsp;\u0026plusmn;\u0026thinsp;7.4 (3.3\u0026ndash;35.9) in the non-ASD group (p\u0026thinsp;=\u0026thinsp;0.02). Moreover, the Δ%Slip in the ASD groups was 9.7\u0026thinsp;\u0026plusmn;\u0026thinsp;5.6 (2.3\u0026ndash;20.4), and was significantly large than 5.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9 (0-13.5) in the Non-ASD group (p\u0026thinsp;=\u0026thinsp;0.030, Table\u0026nbsp;4). There were no significant differences in the ΔL4L-5 interbody height and the ΔL4-L5 lordosis angle. Between both groups.\u003c/p\u003e \u003cp\u003eIn the stepwise multivariate analysis evaluating the parameters exhibiting significant difference among the univariate analysis (SS, PM, MF, %Slip, and Δ%Slip,), Δ%Slip was found to be a risk factor for ASD (odds ratio: 1.22, 95% CI: 1.04\u0026ndash;1.43, p\u0026thinsp;=\u0026thinsp;0.015, Table\u0026nbsp;5). The receiver operating characteristic (ROC) curve for Δ%Slip had an area under the curve (AUC) of 0.725. The cutoff value for Δ%Slip of 7.3% demonstrated a sensitivity of 75.0% and a specificity of 67.5% (Fig.\u0026nbsp;5).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe key result of this retroactive study was that Δ%Slip was found to be a risk factor for ASD.\u003c/p\u003e \u003cp\u003eThere have been no studies reporting slip reduction as a risk factor for ASD to date, and the present study is the first to reveal such a correlation. Much research has been done to determine the risk factors for adjacent segment disease. Among the suggested risk factors are patient background parameters such as age, gender, obesity, facet tropism, laminar inclination, pre-existing disc degeneration, and facet degeneration [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Aota et al. reported the age of patients was the most significant risk factor for ASD.\u003csup\u003e27\u003c/sup\u003e Lee et al. reported in their study of 1069 patients following lumbar fusion that pre-existing degeneration of the facet joints may be a main risk factor [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Okuda et al. also reported that facet tropism was a risk factor for ASD [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In the present study, none of these parameters were identified as risk factors.\u003c/p\u003e \u003cp\u003eSurgery-related parameters such as the number of segments fused, excessive distraction of lumbar disc space, laminectomy of the adjacent segment, floating fusion, and low postoperative lordotic angle have been reported as potential risk factors for ASD [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Kaito et al. investigated 97 cases of L4-L5 PLIF. The L4-L5 disc space distraction by cage insertion was 3.1mm in the non-ASD group, 4.4mm in the radiographic ASD group, and 6.2mm in the group with symptomatic ASD. The authors concluded that excessive distraction of the disc space is a significant and potentially avoidable risk factor for ASD [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. In our study, ΔL4-L5 interbody height distraction before and after surgery was 1.9mm in the ASD group and 1.6mm in the non-ASD group, which was significantly smaller than the disc distraction reported by Kaito et al. It is possible that in the study by Kaito et al., ASD was not caused by interbody height distraction but rather due to slip reduction. While their study does not mention the procedure, it is likely that ligament taxis was performed in the cases of excessive interbody height distraction in order to correct the slip.\u003c/p\u003e \u003cp\u003eIn a biomechanical analysis using human cadaveric lumbar spine, Cunningham et al. measured cranial and caudal disc pressure in fused L3/4, and reported a 45% increase in cranial disc pressure due to fixation. The authors surmised that adjacent intradiscal pressure would increase further with distraction of the disc space, and concluded that it is necessary to maintain interbody height before and after surgery to avoid the risk of ASD [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn recent years, it has been reported that lumbar degenerative spondylolisthesis is associated with spino-pelvic parameters, and among such reports, there are some that identify high PI as a risk factor [\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Nakamae et al. investigated the spino-pelvic alignment in 104 patients with low back pain and reported predictors for L4 anterior slip, identifying the cut-off value for PI as 51.3\u0026deg; with a sensitivity of 87.5% and a specificity of 76.5%. In the present study, the average value for PI was 55.5\u0026deg; (ASD group: 53.1\u0026deg;, non-ASD group: 56.3\u0026deg;) which exceeded the cut off value reported by Nakamae et al [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. In cases in which PI is assumed to be the cause of slippage, the PI does not change, even when the slippage is corrected by surgery. It would seem that the L4 vertebral body is always subject to the force of slippage, even after fixation. PI has subsequently been generally acknowledged to be a predictor of the amount of LL required to assume a balanced sagittal posture.\u003c/p\u003e \u003cp\u003eIt has been suggested that correction of spino-pelvic parameters reduces the incidence of ASD [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. In cases of lumbar degenerative spondylolisthesis, it would be beneficial to investigate LL acquired due to high PI. However, evaluating local lordosis in a single PLIF can be difficult in practice, as it proved to be in the present study, which found the L4-L5 lordosis angle to be 16.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8\u0026deg; preoperatively and 17.8\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2\u0026deg; postoperatively.\u003c/p\u003e \u003cp\u003eIn recent years, it has been reported that trunk muscle mass is a factor that affects spinal sagittal alignment [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Our study evaluated trunk muscle mass as a potential risk factor for ASD. Trunk muscle mass can be measured using the DEXA method and the BIA method. However, our study used a method in which the cross-sectional area of PM, ES, and MF muscles is measured using horizontal MRI images at the L4-L5 level [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The results of this study indicate that preoperative trunk muscle mass may have an effect on ASD occurring within three years. Rehabilitation interventions may play a more important role in the future.\u003c/p\u003e \u003cp\u003eASD may result from a combination of various factors. Our findings indicate that the reduction of L4 slippage may also contribute to the development of ASD in patients with L4 spondylolisthesis. Further research is needed in order to obtain a clearer understanding of the causes of ASD.\u003c/p\u003e \u003cp\u003eFigure legends:\u003c/p\u003e \u003cp\u003eFigure 1. The presence (A) or absence (B) of facet joint edema in the adjacent facet joints was established using preoperative magnetic resonance imaging (MRI).\u003c/p\u003e \u003cp\u003eFigure 2. The facet angle and facet tropism in the adjacent facet joints was established using preoperative computed tomography (CT).\u003c/p\u003e \u003cp\u003eFacet angle=(α་β) / 2\u003c/p\u003e \u003cp\u003eFacet tropism=α-β or β-α\u003c/p\u003e \u003cp\u003eFigure 3A\u003c/p\u003e \u003cp\u003e%slip\u0026thinsp;=\u0026thinsp;b / a\u0026times;100 (%)\u003c/p\u003e \u003cp\u003eFigure 3B\u003c/p\u003e \u003cp\u003eL4/5 interbody height was measured as shown in the figure.\u003c/p\u003e \u003cp\u003eFigure 3C.\u003c/p\u003e \u003cp\u003eL4/5 lordosis angle was measured as shown in the figure.\u003c/p\u003e \u003cp\u003eFigure 4. Trunk mass muscles (PM, ES, MF) were measured using magnetic resonance imaging (MRI) cross-sectional area at the L4/5 level.\u003c/p\u003e \u003cp\u003ePM, psoas major; ES, erector spinae; MF, multifidus\u003c/p\u003e \u003cp\u003eFigure 5. The Receiver Operatorating Characteristic (ROC) curve was calculated at Δ%slip\u003c/p\u003e \u003cp\u003e(Δ%slip\u0026thinsp;=\u0026thinsp;preoperative % slip - postoperative % slip)\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eS.S. and K.N. wrote the main manuscript text, H.S., K.M., M.O., H.U., and K.S. performed the surgery, S.S., T.F., and Y.M. measured the parameters. All authors reviewed the manuscript. The study was carried out in accordance with the Declaration of Helsinki, and the study protocol was approved by the Institutional Review Board of Nihon University School of Medicine, and all subjects provided written informed consent after receiving a full explanation of the treatment.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eAll data generated or analyzed during this study are included in this published article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFritzell P, Hagg O, Wessberg P, et al. (2001) 2001 Volvo Award Winner in Clinical Studies: Lumbar fusion versus nonsurgical treatment for chronic low back pain: a multicenter randomized controlled trial from the Swedish Lumbar Spine Study Group. Spine (Phila Pa 1976) 26:2521\u0026ndash;32; discussion 32\u0026thinsp;\u0026ndash;\u0026thinsp;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeyo RA, Gray DT, Kreuter W, et al. 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Spine (Phila Pa 1976) 35:887\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXia XP, Chen HL, Cheng HB. (2013) Prevalence of adjacent segment degeneration after spine surgery: a systematic review and meta-analysis. Spine (Phila Pa 1976) 38:597\u0026ndash;608.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLawrence BD, Hilibrand AS, Brodt ED, et al. (2012) Predicting the risk of adjacent segment pathology in the cervical spine: a systematic review. Spine (Phila Pa 1976) 37:S52-64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePark P, Garton HJ, Gala VC, et al. (2004) Adjacent segment disease after lumbar or lumbosacral fusion: review of the literature. Spine (Phila Pa 1976) 29:1938\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRadcliff KE, Kepler CK, Jakoi A, et al. (2013) Adjacent segment disease in the lumbar spine following different treatment interventions. 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Eur Spine J 31:1431\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\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":"lumbar spine, degenerative spondylolisthesis, posterior intervertebral fusion, adjacent segment disease, % slip","lastPublishedDoi":"10.21203/rs.3.rs-4923331/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4923331/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eSeveral risk factors for adjacent segment disease (ASD) after posterior lumbar interbody fusion (PLIF) have been reported. However, the reducing the slipped vertebra has not been investigated as a risk factor for ASD. The objective of this study is to identify the risk factors for ASD following single-segment PLIF in patients with L4 spondylolisthesis, with a particular focus on the reduction of vertebral body slippage. Fifty-two patients who underwent PLIF at the L4-L5 level for L4 degenerative spondylolisthesis were investigated. Patients were divided into two groups: the ASD group and the non-ASD group. The ASD group consisted of 12 of the 52 patients (23.1%). %Slip before surgery and at follow-up, Δ%Slip (Δ%Slip = %Slip before surgery - %Slip at follow-up), L4-L5 interbody height, and L4-L5 lordosis angle were evaluated. Stepwise multivariate regression analysis revealed Δ%Slip to be a risk factor for ASD (odds ratio: 1.22, 95% confidence interval: 1.04\u0026ndash;1.43, p\u0026thinsp;=\u0026thinsp;0.015). In the receiver operating characteristic analysis, the cutoff value for Δ%Slip was 7.3% (sensitivity: 75.0%, specificity: 67.5%, area under the curve\u0026thinsp;=\u0026thinsp;0.725). Our findings suggest that the reduction of L4 slippage may contribute to the development of ASD in patients with L4 spondylolisthesis.\u003c/p\u003e","manuscriptTitle":"Posterior lumbar interbody fusion for degenerative spondylolisthesis; slippage reduction can be a risk factor for adjacent segment disease.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-15 17:02:46","doi":"10.21203/rs.3.rs-4923331/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":"8e6ee4ef-772a-438e-b092-5127e1074d19","owner":[],"postedDate":"October 15th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":36682615,"name":"Health sciences/Medical research"},{"id":36682616,"name":"Health sciences/Risk factors"}],"tags":[],"updatedAt":"2025-01-08T05:53:40+00:00","versionOfRecord":[],"versionCreatedAt":"2024-10-15 17:02:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4923331","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4923331","identity":"rs-4923331","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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