Comparative outcomes of obese and non-obese patients with lumbar disc herniation receiving full endoscopic transforaminal discectomy: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to assess the impact of full endoscopic transforaminal discectomy (FETD) on clinical outcomes and complications in both obese and non-obese patients presenting with lumbar disc herniation (LDH). METHODS: A systematic search of relevant literature was conducted across various primary databases until November 18, 2023. Operative time and hospitalization were evaluated. Clinical outcomes included preoperative and postoperative assessments of the Oswestry Disability Index (ODI) and visual analogue scale (VAS) scores, conducted to delineate improvements at 3 months postoperatively and during the final follow-up, respectively. Complications were also documented. RESULTS: Four retrospective studies meeting inclusion criteria provided a collective cohort of 258 patients. Obese patients undergoing FETD experienced significantly longer operative times compared to non-obese counterparts (P = 0.0003). Conversely, no statistically significant differences (P > 0.05) were observed in hospitalization duration, improvement of VAS for back and leg pain scores at 3 months postoperatively and final follow-up, improvement of ODI at 3 months postoperatively and final follow-up. Furthermore, the overall rate of postoperative complications was higher in the obese group (P = 0.02). The obese group demonstrated a total incidence of complications of 17.17%, notably higher than the lower rate of 9.43% observed in the non-obese group. CONCLUSION: The utilization of FETD for managing LDH in individuals with obesity is associated with prolonged operative times and a higher total complication rate compared to their non-obese counterparts. Nevertheless, it remains a safe and effective surgical intervention for treating herniated lumbar discs in the context of obesity.

Research relating to three-dimensional (3D) printing in spine surgery: a bibliometric analysis.

PURPOSE: Although numerous publications on three-dimensional printing (3DP) in spine surgery have been published, bibliometric analysis studies are scarce. Thus, this study aimed to present a bibliometric analysis of the status, hot spots, and frontiers of 3DP in spine surgery and associated research disciplines. METHODS: All publications relating to the utilization of 3DP in spine surgery from 1999 to May 9, 2022, were retrieved from the Web of Science. The bibliometric analysis was performed using CiteSpace software, and information on the country, institution, author, journal, and keywords for each publication was collected. RESULTS: A total of 270 articles were identified. From 2016 onward, a significant increase in publications on spinal surgery was observed. China was the most productive and influential country (98 publications) and H-index (22), followed by the USA and Australia. The most productive institution was Capital Medical University (9 publications). P. S. D'urso (8 publications, 46 citations) and R. J. Mobbs (8 publications, 39 citations) were the most prolific authors. European Spine Journal contributed the highest number of publications. The eight main clusters were: "rapid prototyping" #0, "3D printed" #1, "spine fusion" #2, "scoliosis" #3, "spine surgery" #4, "patient-specific" #5, "nervous system" #6, and "neuronavigation" #7. The strongest keyword bursts in 3DP in spine surgery were "fixation," "drill template," "instrumentation," "fusion," "complication," and "atlantoaxial instability." CONCLUSION: This analysis provides information on research trends and frontiers in the application of 3DP in spine surgery, as well as research and collaboration partners, institutions, and countries.

Comparison of full-endoscopic and tubular-based microscopic decompression in patients with lumbar spinal stenosis: a randomized controlled trial.

PURPOSE: We aimed to demonstrate non-inferiority in terms of functional outcomes in patients with lumbar spinal stenosis who underwent full-endoscopic decompression compared with tubular-based microscopic decompression. METHODS: This prospective, randomized controlled, non-inferiority trial included 60 patients with single-level lumbar spinal stenosis who required decompression surgery. The patients were randomly assigned in a 1:1 ratio to the full-endoscopic group (FE group) or the tubular-based microscopic group (TM group). Based on intention-to-treat analysis, the primary outcome was the Oswestry Disability Index score at 24 months postoperative. The secondary outcomes included the visual analog scale (VAS) score for back and leg pain, European Quality of Life-5 Dimensions (EQ-5D) score, walking time, and patient satisfaction rate according to the modified MacNab criteria. Surgery-related outcomes were also analyzed. RESULTS: Of the total patients, 92% (n = 55) completed a 24-month follow-up. The primary outcomes were comparable between the two groups (p = 0.748). However, the FE group showed a statistically significant improvement in the mean VAS score for back pain at day 1 and at 6, 12, and 24 months after surgery (p < 0.05). No significant difference was observed in the VAS score for leg pain, EQ-5D score, or walking time (p > 0.05). Regarding the modified MacNab criteria, 86.7% of patients in the FE group and 83.3% in the TM group had excellent or good results at 24 months after surgery (p = 0.261). Despite the similar results in surgery-related outcomes, including operative time, radiation exposure, revision rate, and complication rate, between the two groups (p > 0.05), less blood loss and shorter length of hospital stay were observed in the FE group (p ≤ 0.001 and 0.011, respectively). CONCLUSION: This study suggests that full-endoscopic decompression is an alternative treatment for patients with lumbar spinal stenosis because it provides non-inferior clinical efficacy and safety compared with tubular-based microscopic surgery. In addition, it offers advantages in terms of less invasive surgery. Trial registration number (TRN): TCTR20191217001.

An Effectiveness Evaluation of Nucleo-Annuloplasty for Lumbar Discogenic Lesions Using Disc-FX: A Scoping Review.

Background and Objectives: Degenerative disk disease is a widespread chronic condition that causes diskogenic pain. Diskogenic pain can be treated with various therapy methods. Disc-FX is a revolutionary, minimally invasive, percutaneous nucleo-annuloplasty method that combines manual diskectomy with nuclear and annular remodeling using radiofrequency ablation to relieve diskogenic pain. In this study, the technical features, clinical outcomes, and complications of Disc-FX are summarized. Materials and Methods: A comprehensive literature review was performed. By exploring several databases, we collected studies on Disc-FX for treating diskogenic pain. The outcomes included perioperative data, clinical results, and complications. Results: In the 15 studies included, data from 570 patients were collected. L4-L5 was the most frequently operated level, and most cases underwent single-level procedures. The follow-up period for these patients ranged from 2 months to 24 months. One study reported a procedure time between 35 and 60 min, whereas the remaining studies reported a procedure time of less than 30 min. The mean visual analog scale score decreased from 7.22 preoperatively to 1.81 at the final follow-up. The mean numerical rating scale score decreased from 6.98 preoperatively to 3.9 at the final follow-up. The mean Japanese Orthopaedic Association score improved from 16.26 preoperatively to 25.88 in the final follow-up. The mean Oswestry Disability Index score decreased from 35.37 preoperatively to 14.66 at the final follow-up. The mean satisfaction rate (based on the Macnab criteria) was 87.6% (range, 78.4-95.2%). The total incidence of postoperative transient pain was 8.77% (50/570) after nucleo-annuloplasty using Disc-FX, and recurrence was 1.58% (9/570). Conclusions: According to our comprehensive evaluation, using percutaneous nucleo-annuloplasty for treating lumbar diskogenic diseases provided considerable pain alleviation and improved functional outcomes with fewer complications. Disc-FX is a safe and effective procedure that is a good treatment option for patients with diskogenic pain.

Letter to the editor regarding "Full­endoscopic (bi­portal or uni­portal) versus microscopic lumbar decompression laminectomy in patients with spinal stenosis: systematic review and meta­analysis".

A recent article entitled "Full­endoscopic (bi­portal or uni­portal) versus microscopic lumbar decompression laminectomy in patients with spinal stenosis: systematic review and meta­analysis" written by Pairuchvej et al. (Eur J Orthop Surg Traumatol 30(4):595-611, 2019) published in "European Journal of Orthopaedic Surgery & Traumatology" has aroused our great interest. The authors concluded that compared with minimally invasive decompression surgery, full endoscopic spinal surgery had better pain relief (back pain and leg pain) in the treatment of lumbar spinal stenosis and had a lower complication rate, but no statistical difference in oswestry disability index score and operative time between both groups. Comparing to minimally invasive spinal surgery, bi-portal endoscopic spinal surgery had better back pain relief in the early stage, while uni-portal full endoscopic spinal surgery had better pain relief in the leg and a lower rate of complications.

A pilot study of endoscope-assisted MITLIF with fluoroscopy-guided technique: intraoperative objective and subjective evaluation of disc space preparation.

BACKGROUND: Adequate discectomy and endplate preparation are extremely crucial steps for spinal interbody fusion. Minimally invasive transforaminal lumbar interbody fusion MITLIF technique is safe and effective. However, concerns exist regarding sufficient disc space preparation from unilateral access. The purpose of this study, was to demonstrate our preliminary experience in objective and subjective evaluation of disc space preparation intraoperatively during endoscope-assisted MITLIF with fluoroscopy-guided, describing some of its possible advantages, and analyzing its safety and feasibility. METHODS: From March 2018 to July 2019, three patients with degenerative spinal stenosis with radiculopathy and instability underwent endoscope-assisted MITLIF with fluoroscopy-guided. Patients' demographic data, clinical parameters, subsidence, and fusion were collected. RESULTS: Patients were successfully treated by endoscope-assisted MITLIF with fluoroscopy-guided at single-level or two-level. Symptoms improved postoperatively in all patients, and no complications occurred during follow-up. No cage subsidence was observed. At 6-month postoperatively, there was bony fusion observed on computed tomography in two patients. CONCLUSION: Endoscope-assisted MITLIF with fluoroscopy-guided is a safe and feasible technique to improve visualization during discectomy and endplate preparation objectively and subjectively, possibly increasing fusion rate and early time to fusion.

Bibliometric analysis and visualization of research trends on oblique lumbar interbody fusion surgery.

PURPOSE: To determine trends and hot subjects in the field of oblique lumbar interbody fusion (OLIF) research during the last decade using bibliometric analysis and visualization tools, in order to assist researchers in exploring new directions for future research in that field. METHODS: Articles published from January 1, 2012, to August 15, 2021, were screened in the Web of Science database. The data were analyzed with CiteSpace software, which generated visualization knowledge maps. All literature was assessed for the following parameters: the number of total publications, distribution, h-index, institutions, journals, authors, co-occurrence state, and research hotspots. RESULTS: A total of 173 articles were identified. The country with the largest number of articles was China (41.04%), followed by South Korea (20.81%), the USA (15.61%), Japan (9.83%), and Thailand (2.89%). South Korea and the USA had the highest h-index (9), followed by China (8), Japan (7), and Thailand (2). Catholic University of Korea was the organization that produced the most literature. World Neurosurgery published the most papers about OLIF (12.50%), but articles in Spine were most frequently cited (151). Kim JS was the most productive author, whereas Silvestre C was the most cited author. The main research hotspots are anatomy, discectomy, approach, injure, and diseases. CONCLUSIONS: The number of publications in the field of OLIF has increased considerably in recent years. The USA, China, South Korea, and Japan have made substantial contributions to this field. Anatomy, complications, decompression surgery, and application in various degenerative lumbar diseases have been the research hotspots in recent years.

Postoperative Pain Management after Full Endoscopic Lumbar Discectomy: An Observational Study.

Background: Surgical incision pain, rebound pain, and recurrence can manifest themselves in different forms of postoperative pain after full endoscopic lumbar discectomy (FELD). This study aims to evaluate various postoperative pains after FELD and summarize their characteristics. Methods: Data about the demographic characteristics of patients, pain intensity, and functional assessment results were collected from January 2016 to September 2019. Clinical outcomes including Oswestry Disability Index (ODI) and visual analog scale (VAS) scores, were obtained. Results: A total of 206 patients were enrolled. ODI and VAS of the patients significantly decreased after FELD at 12-month follow-up. A total of 193 (93.7%) patients had mild surgical incision pain after FELD and generally a VAS < 4, and it mostly resolved on its own within 3 days. A total of 12 (5.8%) patients experienced rebound pain, which was typically characterized by pain (mainly leg pain with or without back pain), generally occurring within 2 weeks after FELD and lasting < 3 weeks. The pain levels of rebound pain were equal to or less than those of preoperative pain, and generally scored a VAS of < 6. The recurrence rate was 4.4%. Recurrence often occurs within three months after surgery, with the pain level of the recurrence being greater than or equal to the preoperative pain. Conclusions: Different types of postoperative pain have their own unique characteristics and durations, and treatment options are also distinct. Conservative treatment and analgesia may be indicated for rebound pain and surgical incision pain, but recurrence usually requires surgical treatment.

Is Biportal Endoscopic Spine Surgery More Advantageous Than Uniportal for the Treatment of Lumbar Degenerative Disease? A Meta-Analysis.

Background and Objectives: To estimate the clinical outcomes of uniportal and biportal full-endoscopic spine surgery for the treatment of lumbar degenerative disease (LDD), and to provide the latest evidence for clinical selection. Materials and Methods: Relevant literatures published in PubMed, Web of Science, Embase, CNKI, and WanFang Database before 21 November 2021 were searched systematically. Two researchers independently screened the studies, extracted data, and evaluated the risk of bias of the included studies. The systematic review and meta-analysis were performed using the Review Manager software (version 5.4; The Cochrane Collaboration). Results: A total of seven studies were included in this meta-analysis, including 198 patients in a uniportal endoscopy group and 185 patients in a biportal endoscopy group. The results of this meta-analysis demonstrated that the biportal endoscopy group experienced less intraoperative estimated blood loss (WMD = -2.54, 95%CI [-4.48, -0.60], p = 0.01), while the uniportal endoscopy group displayed significantly better recovery results in Visual Analog Scale (VAS) assessments of the back within 3 days of surgery (WMD = 0.69, 95%CI [0.02, 1.37], p = 0.04). However, no significant differences in operation time, length of hospital stay, complication rates, Oswestry Disability Index (ODI) (within 3 months), ODI (last follow-up), VAS for back (within 3 months), VAS for back (last follow-up), and VAS for leg (within 3 days, within 3 months, last follow-up) were identified between the two groups. Conclusions: According to our meta-analysis, patients who underwent the uniportal endoscopic procedure had more significant early postoperative back pain relief than those who underwent the biportal endoscopic procedure. Nevertheless, both surgical techniques are safe and effective.

The correlation of intraoperative distraction of intervertebral disc with the postoperative canal and foramen expansion following oblique lumbar interbody fusion.

PURPOSE: To examine the correlation of intraoperative distraction of intervertebral disc with the postoperative central canal and foramen expansion by oblique lumbar interbody fusion (OLIF) with indirect decompression. METHODS: Patients who underwent OLIF between October 2013 and April 2017 were included. Clinical outcomes included back and leg pain evaluated by visual analog scale (VAS) and Oswestry Disability Index (ODI). Intraoperative radiographic parameters of height ratio [(HR) = disc height/intervertebral body height)] and cage location were evaluated on intraoperative fluoroscopic images. Disc height (DH), foraminal height (FH), cross-sectional area of spinal canal (CSAC), and CSA of the foramen (CSAF) were measured. RESULTS: A total of 47 patients involving 62 levels were enrolled in this study. Mean follow-up was 43.8 ± 12.0 months. These patients reported an improvement of 61.7% in VAS back, 68.1% in VAS leg, and 46% in ODI (all p < 0.01). Radiographic parameters including HR, DH, FH, CSAC, and CSAF were also significantly increased by 32.6%, 48.2%, 21.4%, 44.0%, and 40.1% (left-side CSAF) or 45.4% (right-side CSAF), respectively (p < 0.05). HR increment was correlated with CSA (canal and foramen) increment. Slightly higher improvements of HR, DH, FH, CSAC, and CSAF (both sides) were noted when cage was located at middle rather than anterior (p > 0.05). CONCLUSIONS: The ligamentotaxis effect of OLIF is capable of supporting indirect decompression of central canal and neural foramina and clinical improvement. HR is a reliable intraoperative assessment method. In addition, intraoperative HR increment was correlated with postoperative neural elements expansion.

Decreasing thickness and remodeling of ligamentum flavum after oblique lumbar interbody fusion.

PURPOSE: Ligamentum flavum is one of the structures that could compress the spinal canal. Few studies have reported atrophy of ligamentum flavum after spinal fusion. The purpose of this study was to demonstrate the reduction of ligamentum flavum size after oblique lumbar interbody fusion (OLIF) using magnetic resonance imaging (MRI). METHOD: Seventeen patients who underwent OLIF without direct decompression were included. The MRI was obtained at the preoperative period, immediate postoperative period, and the follow-up period. Disc height (DH) was measured in plain radiograph. MRI measurements were spinal canal cross-sectional area (SCSA), ligamentum flavum thickness (LFT), ligamentum flavum area (LFA), and foraminal area (FA). RESULTS: Mean age of the patients was 68.5 ± 10.8. Mean times between postoperative MRI and follow-up MRI were 20.2 ± 11.9 months. Mean disc height increased from 7.6 ± 1.6 to 11.6 ± 1.7 mm at an immediate postoperative period but decreased to 10.1 ± 1.6 mm during follow-up (p < 0.001). SCSA increased from 96.9 ± 54.9 to 136.0 ± 72.7 mm2 and 171.4 ± 76.10 mm2 during follow-up (p < 0.001). LFT decreased from 3.9 ± 1.2 to 3.2 ± 0.8 mm (17.9%) and further decreased to 2.9 ± 0.7 mm during follow-up (9.4%) (p < 0.001). LFA decreased from 97.4 ± 36.9 to 86.1 ± 36.9 mm2 (11.6%) and further decreased to 77.2 ± 32.5 mm2 during follow-up (10.3%) (p = 0.001). FA increased from 69.2 ± 26.6 to 96.1 ± 23.0 mm2 and increased to 112.9 ± 23.0 mm2 during follow-up (p < 0.001). CONCLUSION: OLIF could decompress the spinal canal and foraminal canal indirectly. Despite the diminishing disc height during the follow-up period, the spinal canal was further increased in size from the remodeling of the ligamentum flavum.

Correction to: Decreasing thickness and remodeling of ligamentum flavum after oblique lumbar interbody fusion.

In the article "Decreasing Thickness and Remodeling of Ligamentum Flavum After Oblique Lumbar Interbody Fusion", Figure 2 captions contained mistakes as descriptions for the Figure sections were not assigned correctly.

Worldwide research productivity in the field of full-endoscopic spine surgery: a bibliometric study.

PURPOSE: To investigate the quantity and quality of articles in the field of full-endoscopic spine surgery (FESS) from different countries and assess characteristics of worldwide research productivity. METHODS: Articles published from 1997 to July 23, 2018, were screened using the Web of Science database. All studies were assessed for the following parameters: the number of total publications, h-index, contribution of countries, authors, journals, and institutions. RESULTS: A total of 408 articles were identified between 1997 and 2018. Between 1997 and 2017, the number of published articles tended to increase by 41 times. The largest number of articles was from China (30.15%), followed by South Korea (28.68%), the USA (13.97%), Germany (9.31%), and Japan (4.90%). The highest h-index was found for articles from South Korea (23), followed by the USA (18), Germany (16), China (11), and Japan (7). The highest number of articles was published in World Neurosurgery (12.50%), followed by Pain Physician (10.29%), Spine (6.62%), European Spine Journal (4.66%), and Journal of Neurosurgery: Spine (4.17%). Wooridul Spine Hospital published the largest number of articles (10.29%), followed by Tongji University (5.88%), University of Witten/Herdecke (5.39%), Brown University (5.15%), and Third Military Medical University (3.43%). CONCLUSIONS: The number of articles published in the field of FESS has increased rapidly in the past 20 years. In terms of quantity, China is the most contributive country based on the number of publications. High-quality papers as measured by h-index and the large quantity is from South Korea (second only to China). These slides can be retrieved under Electronic Supplementary Material.

Comparative analysis of the intervertebral disc signal and annulus changes between immediate and 1-year postoperative MRI after transforaminal endoscopic lumbar discectomy and annuloplasty.

PURPOSE: Postoperative magnetic resonance imaging (MRI) after microdiscectomy for lumbar disc herniation frequently shows spinal canal compression by the remaining annulus, which gradually decreases over time. Transforaminal endoscopic lumbar discectomy (TELD) can remove the herniation with minimal trauma to surrounding soft tissue. We aim to identify this remodeling of annulus fibrosus and the change of disc signal after TELD. METHODS: We reviewed patients who underwent TELD. Clinical data obtained were Oswestry disability index (ODI) and visual analog scale (VAS) for back and leg pain. Residual mass signal and disc protrusion size were measured in postoperative MRI. RESULTS: Thirty-one patients were reviewed. The mean age was 38.3 ± 14.4 years (range 18 to 76 years). ODI was 18.2% at the first follow-up and 12.7% at the last follow-up (p = 0.009). VAS for back and leg pain were 2.0 and 1.0 without significant change during follow-up. Disc protrusion size was reduced by 67.7% at the 1-year follow-up (p < 0.001). The residual mass signals at postoperative day 1 were high in 12 cases, intermediate in 18 cases, and low in1 case. The signal intensity was correlated with the percentage of disc protrusion reduction (p = 0.048). The percentage of disc protrusion reduction correlated with the last follow-up ODI (p = 0.018). CONCLUSION: One year after TELD, annulus remodeling was observed with an average of 67.7% of size reduction. The high signal intensity of residual mass at day 1 correlated with disc protrusion reduction at follow-up MRI. The percentage of disc protrusion reduction associated with the ODI at the final follow-up.

Dimensions of the spinous process and interspinous space: a morphometric study.

PURPOSE: To measure the morphological dimensions of the spinous process (SP) and interspinous space, and provide a basis for the development of interspinous devices for the Korean or East Asian populations. METHODS: We retrospectively analyzed the anatomical parameters of 120 patients. The parameters included height, length, and width of SP, interspinous distance (supine, standing, and dynamic), cortical thickness of SP, and spino-laminar (S-L) angle. Correlations between measurements, age, and gender were investigated. RESULTS: The largest height, length, and cortical thickness and S-L angle were noted at L3. The largest width was observed at S1. The interspinous distance decreased significantly from L2-3 to L5-S1 and was significantly larger in the supine than in standing posture for L5-S1. Cortical thickness was gradually tapered from the anterior to the posterior position. The S-L angle at L2 and L3 was similar and significantly decreased from L3 to S1. An increased trend in width with aging and a decreased trend in distance (supine) were noted. A significant increase in height, length, and distance in males compared with females was also observed. CONCLUSIONS: The interspinous space is wider at the anterior, and the cortex is thicker anteriorly. Accordingly, it appears that the optimized implant position lies in the interspinous space anteriorly. The varying interspinous space with different postures and gradually narrowing with age suggest the need for caution when sizing the device. Gender differences also need to be considered when designing implantable devices.

Impact of Postoperative Bracing Following Spinal Fusion for Degenerative Lumbar Conditions: An Updated Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: There is a lack of consensus on the use of postoperative bracing for lumbar degenerative conditions. Spine surgeons typically determine whether to apply postoperative braces based primarily on clinical experience rather than robust, evidence-based medical data. Thus, the present study sought to assess the impact of postoperative bracing on clinical outcomes, complications, and fusion rates following lumbar fusion surgery in patients with degenerative spinal conditions. METHODS: Only randomized controlled studies published between January 1990 and 20 October 2023 were included in this meta-analysis. The primary outcome measures consisted of pre- and postoperative assessments of the Oswestry Disability Index (ODI) and visual analog scale (VAS) scores. Improvements in VAS and ODI scores were analyzed in the early postoperative period (1 month after operation) and at final follow-up, respectively. The analysis also encompassed fusion rates and complications. RESULTS: Five studies with 362 patients were included in the present meta-analysis. In the early postoperative period, the brace group showed a relatively better improvement in ODI scores compared with the no-brace group (19.47 vs 18.18), although this difference was not statistically significant (P = 0.34). Similarly, during the late postoperative period, the brace group demonstrated a slightly greater improvement in VAS scores in comparison to the no-brace group (4.05 vs 3.84), but this difference did not reach statistical significance (P = 0.30). The complication rate was relatively lower in the brace group compared with the no-brace group (14.9% vs 17.4%), although there was no statistical difference between the 2 groups (P = 0.83). Importantly, there were no substantial differences in fusion rates between patients with or without braces. CONCLUSION: The present meta-analysis revealed that the implementation of a brace following lumbar fusion surgery did not yield substantial differences in terms of postoperative pain relief, functional recovery, complication rates, or fusion rates when compared with cases where no brace was employed. CLINICAL RELEVANCE: This meta-analysis provides valuable insights into the clinical impact of postoperative bracing following lumbar fusion surgery for degenerative spinal conditions.

Discovering potential mechanisms of intervertebral disc disease using systematic Mendelian randomization of human circulating immunocytomics.

BACKGROUND: Although intervertebral disc degeneration (IVDD) is a critical factor in many spine-related diseases and has an extremely high prevalence in the aging population, the potential pathogenesis remains to be clarified entirely. Immune cells have been found to perform an essential function during the onset and progression of IVDD in recent years. Therefore, we explored the association between immune cell characteristics and IVDD through Mendelian randomization (MR) analysis and further delved into the mediating role of potential metabolites. METHODS: Based on the MR analysis, the association of 731 immune cell phenotypes and 1400 metabolites on IVDD were assessed. Single nucleotide polymorphisms (SNPs) were closely associated the expression levels of immune cell characteristics and the concentrations of metabolites and have been used as instrumental variables (IVs) for deducing them as risk factors or protective factors for IVDD. In addition, mediation analyses have been performed to identify potential metabolite mediators between immune cell characteristics and IVDD. RESULTS: MR analysis identified 27 immune cell phenotypes and 79 metabolites significantly associated with IVDD. In addition, mediation analysis was performed by selecting the immune cell phenotype that most significantly increased the risk of IVDD - CD86 on monocytes. A total of four metabolite-mediated mediation relationships were revealed (3b-hydroxy-5-cholenoic acid, X-22509, N-acetyl-L-glutamine, and N2-acetyl, N6, N6-dimethyllysine). CONCLUSION: The findings of this analysis identified underlying association between immune cell phenotypes, metabolite, and IVDD that may serve as predictive and prognostic clinical biomarkers and benefit IVDD pathogenesis research.