Surgically treated degenerative disk disease in twins.

PURPOSE: Previous studies have suggested that genetic factors are important in the development of degenerative disk disease (DDD). However, the concordance rates for the phenotypes requiring surgery are unknown. The purpose of this study was to determine the concordance rates for DDD requiring surgery by studying monozygotic (MZ) and dizygotic (DZ) twin pairs. METHODS: Patients, aged between 18 and 85 years, operated for DDD between 1996 and 2022 were identified in the national Swedish spine register (Swespine) and matched with the Swedish twin registry (STR) to identify MZ and DZ twins. Pairwise and probandwise concordance rates were calculated. RESULTS: We identified 11,207 patients, 53% women, operated for DDD. By matching the Swespine patients with the STR, we identified 121 twin pairs (37 MZ and 84 DZ) where one or both twins were surgically treated for DDD. The total twin incidence for operated DDD was 1.1%. For DDD requiring surgery, we found no concordant MZ pair and no concordant DZ pair where both twins were operated for DDD. When we evaluated pairs where at least one twin was operated for DDD, we found two concordant MZ pairs (the co-twins were operated for spinal stenosis) and two  concordant DZ pairs (one co-twin operated for spinal stenosis and one (co-twin operated for disk herniation). CONCLUSIONS: Our findings suggest that genetic factors are probably not a major etiologic component in most cases of DDD requiring surgery. The findings of this study can be used for counseling patients about the risk for requiring DDD surgery.

Treatment of the two-level degenerative cervical disk diseases based on algorithmic anterior approach: a multicenter prospective study.

To analyze the effectiveness of an algorithmic anterior approach to the surgical treatment of patients with two-level cervical degenerative disk disease based on the preoperative clinical and imaging parameters. The study included 244 patients with two-level cervical degenerative disk disease. Three groups of patients were evaluated at 3 neurosurgical centers between 2016-2019. The prospective group (Group I, n = 126) consisted of patients who were treated using an algorithm to decide whether they should be treated with a two-level Total Disk replacement (TDR), Anterior Cervical Discectomy and Fusion (ACDF) and hybrid technique. The control group (Group II, n = 118) consisted of patients who underwent two-level anterior decompression with TDR, ACDF and hybrid stabilization between 2005-2015. Visual Analogue Scale (VAS) neck pain, VAS upper limbs pain, Neck Disability Index (NDI), SF-36, Macnab and Nurick scales were collected. Perioperative complications were identified. At 2 years of follow up Group I had significantly better clinical outcomes based on VAS neck pain score (p = 0.02), VAS upper limbs pain (p = 0.04), NDI score (p = 0.02), SF-36 score (p = 0.01), satisfaction with surgery on the Macnab scale (p < 0.001) and outcome of surgery based on Nurick scale (p < 0.001). Complication rate was lower in Group I, 6.3% compared to 24.6% in Group II, p = 0.0001. The algorithmic anterior approach to the surgical treatment of patients with two-level cervical degenerative disk disease resulted in significant improvement of functional outcomes and a decrease in complications at a minimum 2 years of follow-up.

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.

Lumbar interbody fusion using oblique (OLIF) and lateral (LLIF) approaches for degenerative spine disorders: a meta-analysis of the comparative studies.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: Historically, posterior approaches to the lumbar spine have allowed surgeons to manage degenerative conditions affecting the lumbar spine. However, spinal muscles injury, post-surgical vertebral instability, cerebrospinal fluid (CSF) leakage, and failed back surgery syndrome (FBSS) represent severe complications that may occur after these surgeries. Lumbar interbody fusion using anterior (ALIF), oblique (OLIF), or lateral (LLIF) approaches may represent valuable surgical alternatives, in case fusion is indicated on single or multiple levels. METHODS: The present study is a systematic review, conducted according to the PRISMA statement, of comparative studies on OLIF, and LLIF for degenerative spine disorders, and a meta-analysis of their clinical-radiological outcomes and complications. RESULTS: After screening 1472 papers on PubMed, Scopus, and Cochrane Library, only 3 papers were included in the present study. 318 patients were included for data meta-analysis, 128 in OLIF group, and 190 in LLIF group. There were no significative differences in terms of surgical (intraoperative blood loss and surgical duration) and clinical (VAS-back, VAS-leg, and ODI scores) outcomes, or fusion rates at last follow-up (> 2 years). Significantly higher rates of abdominal complications, system failure, and vascular injuries were recorded in the OLIF group. Conversely, postoperative neurological symptoms and psoas weakness were significatively more common in LLIF group. CONCLUSIONS: The meta-analysis suggests that OLIF and LLIF are both effective for lumbar degenerative disorders, although each of them presents specific complications and this should represent a relevant element in the surgical planning.

One-level open vs. minimally invasive transforaminal lumbar interbody fusion: a systematic review and advanced meta-analytic assessment of prospective studies with at least two years follow-up.

PURPOSE: To determine whether the open or the minimally invasive transforaminal lumbar interbody fusion (O-TLIF, MI-TLIF) is the favored treatment, we provide first meta-analyses using prospective studies with at least two years follow-up only and present the clinical relevance of statistical results for the first time. METHODS: After a systematic review of six databases, we conducted 10 meta-analyses of randomized controlled trials (RCTs) and 10 meta-analyses of eligible prospective studies (EPSs) to compare fusion rate, patient-reported outcome measures (back pain (B-VAS), leg pain, Oswestry Disability Index (ODI)), for the first time safety outcome measures as operative and postoperative complications per case, and the perioperative outcome measures estimated blood loss (EBL), operation time and length of hospital stay (LOS). The clinical relevance was assessed by overall effect sizes (OESs) of statistically significant meta-analytic results. RESULTS: In our meta-analyses of RCTs, MI-TLIF is statistically significantly superior in ODI, EBL and LOS, with clinically meaningful OESs only in EBL and LOS. In meta-analyses of EPSs, MI-TLIF is statistically significantly superior in B-VAS, postoperative complications per case, EBL and LOS, all with clinically meaningful OESs except for B-VAS. The meta-analyses of remaining outcome measures present statistically nonsignificant results. In a descriptive analysis of complications, postoperative wound infections predominate in O-TLIF and hardware malposition in MI-TLIF. CONCLUSION: After at least two years, O-TLIF and MI-TLIF can be considered equally efficacious, which simplifies surgeons' decision between both treatments, however, with the safety outcome measure postoperative complications per case and the perioperative outcome measures EBL and LOS in favor of MI-TLIF. LEVEL OF EVIDENCE I: Well conducted meta-analyses, systematic reviews, or RCTs with a low risk of bias.

Cost-effectiveness of anterior surgical decompression surgery for cervical degenerative disk disease: a systematic review of economic evaluations.

PURPOSE: No clear consensus exists on which anterior surgical technique is most cost-effective for treating cervical degenerative disk disease (CDDD). One of the most common treatment options is anterior cervical discectomy with fusion (ACDF). Anterior cervical discectomy with arthroplasty (ACDA) was developed in an effort to reduce the incidence of clinical adjacent segment pathology and associated additional surgeries by preserving motion. This systematic review aims to evaluate the evidence regarding the cost-effectiveness of anterior surgical decompression techniques used to treat radiculopathy and/or myelopathy caused by CDDD. METHODS: The search was conducted in PubMed, EMBASE, Web of Science, CINAHL, EconLit, NHS-EED and the Cochrane Library. Studies were included if healthcare costs and utility or effectivity measurements were mentioned. RESULTS: A total of 23 studies were included out of the 1327 identified studies. In 9 of the 13 studies directly comparing ACDA and ACDF, ACDA was the most cost-effective technique, with an incremental cost effectiveness ratio ranging from $2.900/QALY to $98.475/QALY. There was great heterogeneity between the costs of due to different in- and exclusion criteria of costs and charges, cost perspective, baseline characteristics, and calculation methods. The methodological quality of the included studies was moderate. CONCLUSION: The majority of studies report ACDA to be a more cost-effective technique in comparison with ACDF. The lack of uniform literature impedes any solid conclusions to be drawn. There is a need for high-quality cost-effectiveness research and uniformity in the conduct, design and reporting of economic evaluations concerning the treatment of CDDD. TRIAL REGISTRATION: PROSPERO Registration: CRD42020207553 (04.10.2020).

Incidence and risk factors of spinal cord stimulation for persistent or recurrent pain after lumbar spine surgery: a population-based study.

PURPOSE: This study aims to elucidate the incidence of and independent risk factors for spinal cord stimulator implantations for patients who underwent lumbar spine surgery. METHODS: The PERFormance, Effectiveness, and Cost of Treatment (PERFECT) episodes database, which was established for selected diseases and procedures in Finland, includes all patients who underwent lumbar spine surgery for degenerative spine conditions or spinal cord stimulation (SCS) in Finland from 1986 to 2018. The data on age, sex, hospital diagnoses, surgical procedures, and causes of death were imported from the Finnish national registers into the PERFECT database. RESULTS: Between 1986 and 2018, 157,824 patients had their first lumbar spine procedure and for 1769 (1.1%) of them, a subsequent SCS procedure was observed during the follow-up. The cumulative incidence of SCS for persistent or recurrent pain after lumbar disk herniation, spinal stenosis, degenerative disk disease, and spondylolysis and spondylolisthesis surgery at 15 years was 1.2%, 1.0%, 2.7%, and 2.6% respectively. At 15 years, the cumulative incidence of SCS for persistent or recurrent pain after lumbar spine surgery after five or more lumbar spinal operations was 11.9%. CONCLUSION: Repeated surgery was the most prominent significant risk factor for SCS for persistent or recurrent pain after lumbar spine surgery. The risk of SCS for persistent or recurrent pain after lumbar spine surgery increases significantly along with the number of lumbar spine procedures. When considering repeated lumbar spine surgery, careful evaluation of treatment options should take place to ensure good patient outcomes.

Preoperative lordosis in L4/5 predicts segmental lordosis correction achievable by transforaminal lumbar interbody fusion.

PURPOSE: The mean potential of lordosis restoration by transforaminal lumbar interbody fusion (TLIF) is supposed to be low in general. In contrast, clinical experience shows a wide range of segmental lordosis correction. In this study, the predictability of lordosis correction should be investigated. METHODS: Prospectively collected register data were analyzed retrospectively. One hundred twenty-one consecutive patients (2014-2016) operated with single-level TLIF L4/5 (10°-lordotic cage). Segmental lordosis (L4/5) and overall lordosis (L1-S1) were measured on lumbar X-rays: preoperatively (pre), after 3-5 days (post), at least 24 months postoperatively (2yFU). Outcome and satisfaction of patients were assessed. Parameters were statistically compared by students t-tests (a = 0.05). In addition, predictors of correction were analyzed. RESULTS: Age was 60.7 years, rate of 2yFU 41.3% (n = 50). Lordosis correction L4/5 was statistically significant with (post-pre) 4.9 ± 5.7° (p < 0.01), but not significant for L1-S1 (post-pre) 1.6 ± 8.0° (p = 0.3). A strong-moderate correlation of lordosis L4/5 (pre) and lordosis correction L4/5 (post-pre) was shown (r = - 0.6, p < 0,01). In a rising range of preoperative lordosis L4/5 from 15-30° the likelihood of lordosis loss increased. In 2yFU correction, L4/5 was significant with (post-pre) 5.4 ± 5.4° (p < 0.01), no significant long-term change (2yFU-postop) - 1.5 ± 4.9° (p = 0.2). No correlation (r = - 0.1) of correction and ODI. VAS-B improved by means of 2.9, VAS-L by 2.5, ODI by 19.1% (pre vs. 2yFU), each statistically significant (p < 0.01). CONCLUSION: Significant segmental relordosation can be performed by TLIF L4/5. The potential of correction strongly correlates with preoperative lordosis. Therefore, TLIF technique should be considered carefully in cases with a preoperative segmental lordosis of more than 15° and additional need of lordosation.

Is there any use? Validity of 4D rasterstereography compared to EOS 3D X-ray imaging in patients with degenerative disk disease.

INTRODUCTION: Previous studies of 4D rasterstereography show a high intra- and interday reliability. However, only few studies validate rasterstereography to conventional X-ray imaging. We utilized EOS X-ray imaging system (EOS Imaging, Paris, France) for accurate 3D spinal modeling and compared the results to parameters obtained by 4D rasterstereography. The aim of the present study was to validate 4D rasterstereography in patients with degenerative disk disease (DDD). MATERIALS AND METHOD: Thirty-four individuals with DDD (female = 22 and male = 12) were included. EOS X-ray images were analyzed to determine spinal [lumbar lordosis (LL) and thoracic kyphosis (TK)] and pelvic parameters [pelvic obliquity (PO) and pelvic axial rotation (PR)]. Patients received 4D rasterstereographic measurements on the same day as EOS imaging. Parameters obtained by rasterstereography were compared to those obtained by EOS X-ray imaging. We used Bland and Altman's test as well as Pearson test to validate rasterstereography. Additionally, we calculated interrater reliability of EOS X-ray analysis using the intraclass correlation coefficient (ICC). RESULTS: Our data showed only weak correlation between 4D rasterstereography and EOS X-ray imaging for spinal parameters (LL and TK). Pelvic parameters (PO and PR) showed no correlation. Interrater correlation reliability for EOS analysis was excellent (ICC > 0.8). CONCLUSION: Our data suggest that rasterstereographic systems are no reliable substitute for X-ray-based imaging systems in patients with degenerative disk disease. EOS imaging was shown to provide reliable and accurate spinal modeling. Based on our results, rasterstereographic imaging should be used with caution for evaluating spinal and pelvic parameters in patients with DDD. These slides can be retrieved under Electronic Supplementary Material.

Motion analysis of dynamic cervical implant stabilization versus anterior discectomy and fusion: a retrospective analysis of 70 cases.

PURPOSE: Retrospective kinematic analysis of treated level, adjacent levels, and overall cervical spine after single-level dynamic cervical implant (DCI) stabilization versus anterior cervical discectomy and fusion (ACDF). METHODS: Between June 2009 and March 2013, 70 consecutive patients with a symptomatic single-level cervical degenerative disk disease (DDD) were enrolled in this study and divided into DCI (n = 35) group and ACDF (n = 35) group. All cases were followed up for more than 5 years. The study compared perioperative parameters; clinical outcomes; and radiological parameters. Kinematic analysis included range of motion (ROM) of treated level and adjacent level, overall ROM (C2-C7), and changes in adjacent disk spaces. RESULTS: There were no significant differences between the DCI group and ACDF group in terms of improvement in the SF-36, VAS, NDI, and JOA scores. DCI stabilization resulted in better ROM of C2-C7 and the treated level than ACDF did. The ROM of treated level decreased significantly at 24 months after surgery and last follow-up in the DCI group, and the C2-C7 ROM showed different degrees of reduction after the 24 months after surgery. Radiological evidence of adjacent segment degeneration (ASD) at last follow-up was observed in 4/22 patients (18.2%) in the DCI group and 5/23 patients (21.7%) in the ACDF group which was not a significant difference between groups (p > 0.05). CONCLUSIONS: DCI stabilization for the treatment of cervical DDD cannot preserve the normal kinematics of the cervical spine for a long time, especially the treated level. DCI stabilization cannot decrease the risk of ASD compared with ACDF. These slides can be retrieved under Electronic Supplementary Material.

A prospective randomized multicenter phase I/II clinical trial to evaluate safety and efficacy of NOVOCART disk plus autologous disk chondrocyte transplantation in the treatment of nucleotomized and degenerative lumbar disks to avoid secondary disease: safety results of Phase I-a short report.

NOVOCART® Disk plus, an autologous cell compound for autologous disk chondrocyte transplantation, was developed to reduce the degenerative sequel after lumbar disk surgery or to prophylactically avoid degeneration in adjacent disks, if present. The NDisc trial is an ongoing multi-center, randomized study with a sequential phase I study within the combined phase I/II trial with close monitoring of tolerability and safety. Twenty-four adult patients were randomized and treated with the investigational medicinal product NDisc plus or the carrier material only. Rates of adverse events in Phase I of this trial were comparable with those expected in the early time course after elective disk surgery. There was one reherniation 7 months after transplantation, which corresponds to an expected reherniation rate. Immunological markers like CRP and IL-6 were not significantly elevated and there were no imaging abnormalities. No indications of harmful material extrusion or immunological consequences due to the investigational medicinal product NDplus were observed. Therefore, the study appears to be safe and feasible. Safety analyses of Phase I of this trial indicate a relatively low risk considering the benefits that patients with debilitating degenerative disk disease may gain.

New Axially Expandable Oblique Cage Designed for Anterior to Psoas (ATP) Approach: Indications-Surgical Technique and Clinical-Radiological Outcomes in Patients with Symptomatic Degenerative Disc Disease.

Background: Standard oblique cages cannot cover endplates side-to-side, which is an important biomechanical factor for reducing the risk of cage subsidence and for restoring correct segmental lordosis. The aim of this study is to evaluate the radiological and clinical results of a new oblique lumbar interbody fusion (OLIF) axially expandable cage. Methods: This is a prospective observational case-control study. From March 2018 to June 2020, 28 consecutive patients with lumbar degenerative disease underwent an ATP approach, with the insertion of a new axially expandable cage, which was used as a stand-alone procedure or followed by posterior percutaneous pedicle fixation. Results: Twenty-eight patients in both groups met the inclusion criteria. The mean follow-up time was 31.2 months (range of 13-37). The clinical results were not significantly different, although in the control group, two major intraoperative complications were recorded, and slight improvements in ODI and SF-36 scores were observed in the study group. The radiological results showed a less frequent incidence of subsidence and a higher rate of fusion in the study group compared to controls. Conclusions: The axially expandable oblique cage for lumbar inter body fusion, specifically designed for the ATP approach, represents an innovation and a technical improvement. The insertion and the axial expansion technique are safe and easy. The large footprint could obtain solid and effective arthrodesis, potentially reducing the risk of subsidence.

Platelet-Rich Plasma for Degenerative Spine Disease: A Brief Overview.

Background: The emergence of novel minimally invasive techniques has opened new horizons for the management of degenerative diseases of the spine. Platelet-rich plasma (PRP) has gained considerable attention through its applications in various pathologies. In the present review, an overview of the science behind the application of PRP is provided, ultimately focusing on the clinical trials that may render it a useful tool in the hands of spine surgeons in the future. Methods: A review of the available literature is conducted, focusing on its existing clinical and experimental applications with a particular interest in the degenerative diseases of the spine. Results: In terms of the degenerative diseases of the spine, initial studies suggest that it is a safe and effective method that could change the practice of spinal cord medicine in the years to come. The available studies demonstrate that besides being minimally invasive, causing less discomfort than that of surgery, it provides longer lasting improvement than standard pharmaceutical interventions. Conclusions: PRP is an emerging and promising biodrug for the treatment of patients with spinal pain. PRP has demonstrated some promising qualities; however, careful consideration of its indications of use and strict protocols of application need to be established before widespread clinical induction.

Novel Biomarkers of Health and Degeneration in Human Intervertebral Discs: In-depth Proteomic Analysis of Collagen Framework of Fetal, Healthy, Scoliotic, Degenerate, and Herniated Discs.

STUDY DESIGN: Profiling proteins expressed in the nucleus pulposus (NP) of intervertebral discs (IVDs) in five different biological states. PURPOSE: To evaluate the molecular complexity of the collagen (COL) framework and its role in the health and disease of human IVDs. OVERVIEW OF LITERATURE: Changes in COL composition have been linked to degenerative disk disease (DDD). Despite the fact that humans have 28 different types of COLs, most of the literature focuses solely on COL-1 and COL-2. This study used high-end proteomic technology to examine the entire COL composition of the human IVD across fetal (developmental-FD), normal (healthy-ND), scoliotic (early degeneration-SD), herniated (degenerate-DH), and degenerated (DD) disk phenotypes. METHODS: Forty NP tissues were snap-frozen in liquid nitrogen (-196°C) immediately before being subjected to proteomic and bioinformatic analyses from five different disk phenotypes (eight each). RESULTS: Tandem mass spectrometric analysis revealed a total of 1,050 proteins in FDs, 1,809 in ND, 1,487 in SD, 1,859 in DH, and 1,538 in the DD group. Of 28 major collagens reported in the human body, this study identified 24 different collagens with 34 subtypes in NP. Fibril-forming collagens (COL-1, 2, and 11A1) and fibril-associated collagens with interrupted triple helices (COL-9A1, 12A1, and 14A1) were abundantly expressed in FDs, representing their role in the development of NP. Multiplexin (COL-15), a hybrid proteoglycan-collagen molecule, was discovered only in FDs. Degeneration was associated with COL2A1 downregulation and COL-10A1 upregulation. CONCLUSIONS: COL10 was discovered to be a new biomarker for disk degeneration. Besides COL-1 and 2, other important COLs (6, 9, 11, 12, 14, 15) with anabolic potential and abundant expression in the fetal phenotype could be investigated for tissue engineering and novel DDD therapy.

Arthrodesis versus dynamic neutralization: A short/mid- and long-term retrospective evaluation in degenerative disk disease treatment.

Study Design: This was a retrospective comparative study. Objectives: The aim of this study was to perform a clinical and radiological retrospective evaluation of the most used techniques for the lumbar degenerative disk disease (DDD) treatment: arthrodesis versus dynamic neutralization (DN)-Dynesys dynamic stabilization system. Methods: The study included 58 consecutive patients affected by lumbar DDD, 28 treated with rigid stabilization and 30 with DN at our department between 2003 and 2013. The clinical evaluation was performed through the Visual Analog Scale (VAS) and the Oswestry Disability Index (ODI). The radiographic evaluation was performed through standard and dynamic X-ray projections and magnetic resonance imaging. Results: Both techniques determined a clinical improvement in the postoperative period compared to the preoperative one. There were no significant differences between the postoperative VAS of the two techniques. The DN group postoperative ODI percentage showed a significant improvement (P = 0.026) compared to the arthrodesis group. During the follow-up, no clinically significant differences were highlighted between the two techniques. At a long term follow up period, radiographic results showed, in both groups, a L3-L4 disk mean height reduction and an increase of segmental and lumbar lordosis without significant differences between the two techniques. During an average of 96-month follow-up period, 5 (18%) patients developed an adjacent segment disease in the arthrodesis group and 6 (20%) patients developed this syndrome in the DN group. Conclusions: We are confident in recommending arthrodesis and DN as effective techniques for lumbar DDD treatment. Both techniques are potentially burdened, with similar frequency, by the development of long-term adjacent segment disease.

Strong association of lumbar disk herniation with diabetes mellitus: a 12-year nationwide retrospective cohort study.

Background: Despite reports on the association between diabetes mellitus (DM) and lumbar disk herniation (LDH), large-scale, nationwide studies exploring this relationship are lacking. We aimed to examine the profiles of DM in individuals with LDH and explore the potential mechanisms underlying the development of these disorders. Methods: This retrospective, population-based study was conducted between 2008 and 2019 using data from the National Health Insurance (NHI) research database in Taiwan. The primary outcome was the date of initial LDH diagnosis, death, withdrawal from the NHI program, or end of the study period. Results: In total, 2,662,930 individuals with and 16,922,546 individuals without DM were included in this study; 719,068 matched pairs were established following propensity score matching (1:1 ratio) for sex, age, comorbidities, smoking, alcohol consumption, antihyperglycemic medications, and index year. The adjusted risk for developing LDH was 2.33-fold (95% confidence interval: 2.29-2.37; P<0.001), age-stratified analysis revealed a significantly greater risk of LDH in every age group, and both males and females were approximately twice as likely to develop LDH in the DM compared with non-DM cohort. Individuals with DM and comorbidities had a significantly higher risk of developing LDH than those without, and the serial models yielded consistent results. Treatment with metformin, sulfonylureas, meglitinides, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, or alpha-glucosidase inhibitors was associated with a more than 4-fold increased risk of LDH in the DM cohort. DM was strongly associated with the long-term development of LDH; over the 12-year follow-up period, the cumulative risk of LDH was significantly higher in patients with than without DM (log-rank P<0.001). Conclusion: DM is associated with an increased risk of LDH, and advanced DM may indicate a higher risk of LDH.

Mechanobiology of MicroRNAs in Intervertebral Disk Degeneration.

Intervertebral disk degeneration (IDD) is an intricate pathological process contributing to one of the major causes of low back pain. The degradation of the extracellular matrix (ECM), inflammation, and apoptosis have all been investigated as critical factors involved in the pathology of degenerative disk disease. Additionally, the presence of aberrant microRNAs (miRNAs), conserved molecules that regulate the amount protein post-transcriptionally, may play a crucial role in the pathogenesis of IDD. Research regarding the dysfunction of miRNAs in IDD has been well researched over the past five years. Here, we provide a critical overview of the current knowledge of miRNAs, emphasizing the processes involved in the degenerative disk pathology.

Synergetic enrichment of aggrecan in nucleus pulposus cells by scAAV6-shRNA-mediated knockdown of aggrecanase-1 and aggrecanase-2.

Degenerative disk disease (DDD) that aggravates structural deterioration of intervertebral disks (IVDs) can be accompanied by painful inflammation and immunopathological progressions. Current surgical or pharmacological therapies cannot repair the structure and function of IVDs. Nucleus pulposus (NP) cells are crucial for the preservation or restoration of IVDs by balancing the anabolic and catabolic factors affecting the extracellular matrix. Imbalanced anabolic and catabolic factors cause increased degradation of aggrecan. Aggrecanases A Disintegrin And Metalloproteinase with ThromboSpondin motifs (ADAMTS)4 and ADAMTS5 are the main degrading enzymes of aggrecan. Previously, we characterized adeno-associated virus (AAV6) as the most suitable serotype with marked NP cellular tropism and demonstrated that ADAMTS4 could be silenced by self-complementary adeno-associated virus grade 6 small helix ribonucleic acid (scAAV6-shRNA) in NP cells of degeneration grade III, which resulted in enrichment of aggrecan. Nonetheless, neither scAAV6-shRNA-mediated inhibition of ADAMTS5 nor joint inhibitions of ADAMTS4 and ADAMTS5 have been investigated, although both enzymes are regulated by analogous proinflammatory cytokines and have the same cleavage sites in aggrecan. Therefore, we attempted scAAV6-shRNA-mediated inhibitions of both enzymes in NP cells of degeneration grade IV to increase efficacies in treatments of DDD. The degeneration grade of IVDs in patients was determined by magnetic resonance imaging (MRI) before surgical operations. After isolation and culturing of NP cells, cells were transduced with scAAV6-shRNAs targeting ADAMTS4 or ADAMTS5. Transduced cells were analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR), fluorescence microscopy, flow cytometry-assisted cell sorting (FACS), MTT assay (3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay), immunoblotting, and enzyme-linked immunosorbent assay (ELISA). Joint transduction of NP cells exhibited high transduction efficacies (98.1%), high transduction units (TU) (1381 TU/Cell), and no effect on cell viability or proliferation. Above all joint treatments resulted in effective knockdown of ADAMTS4 (92.8%) and ADAMTS5 (93.4%) along with additive enrichment of aggrecan (113.9%). Treatment effects were significant for more than 56 days after transduction (P < 0.001). In conclusion, scAAV6-shRNA-mediated combined molecular therapy could be very valuable for more effective, durable, and less immunogenic treatment approaches in DDD.

Safety and Effectiveness of the Flexible Cervical Implant: Preliminary Short-Term Clinical Results.

OBJECTIVE: We sought to determine the safety and effectiveness of the Flexible Cervical Implant in 1- or 2-level cervical segments. METHODS: Retrospective data collection was carried out on consecutive patients who underwent the implantation of the Flexible Cervical Implant in a local private health institution. Demographics, clinical pictures, magnetic resonance images, x-ray images, technical considerations, and postoperative clinical results were reviewed. RESULTS: Twelve patients were treated with 15 implants. The mean age was 57.5 years (range 28-81), and 6 patients were males. The most common level was C5/C6 (7 cases). Radicular pain was the main symptom in all patients. Short-term postoperative clinical outcomes showed improvement in the visual analog scale (VAS) and the Neck Disability Index (NDI). The median VAS score for radicular pain improved from 6 to 2 (P < 0.001), whereas the median NDI showed a significant improvement from 25 to 5 (P < 0.001). No implant-related complications were reported. The mean follow-up was 7.3 months. CONCLUSIONS: The newly developed Flexible Cervical Implant was safe and effective in terms of morbidity and improvement in clinical outcomes. This new cervical artificial disk is promising, and further long-term clinical and radiologic follow-up is needed to determine its benefits.

Preoperative Magnetic Resonance Imaging Abnormalities Predictive of Lumbar Herniation Recurrence After Surgical Repair.

OBJECTIVE: There are currently no standard criteria for evaluating the risk of recurrent disk herniation after surgical repair. This study investigated the predictive values of 5 presurgical imaging parameters: paraspinal muscle quality, annular tear size, Modic changes, modified Phirrmann disk degeneration grade, and presence of sacralization or fusion. METHODS: Between 2015 and 2018, 188 patients (89 female, 99 male, median age 50) receiving first corrective surgery for lumbar disk herniation were enrolled. Microdiskectomy was performed in 161 of these patients, and endoscopic translaminar diskectomy approach was performed in 27 patients. Clinical status was evaluated before surgery and 4, 12, and 24 months post surgery using a visual analog scale, Oswestry Disability Index, and Short Form 36. RESULTS: Recurrent disk herniation was observed in 21 of 188 patients. Seventeen of the recurrent disk herniations were seen in those who underwent microdiskectomy and 4 in those who underwent endoscopic translaminar diskectomy. There were significant differences in visual analog scale, Oswestry Disability Index, and Short Form 36 scores at 4, 12, and 24 months between patients with recurrence and the 167 no-recurrence patients. The median annular tear length was significantly greater in patients with recurrence than without recurrence. In addition, there were significant differences in recurrence rate according to Modic change type distribution, sacralization or fusion presence, Pfirmann disk; degeneration grade distribution, dichotomized annular tear size, dichotomized Modic change; and type and simplified 3-tier muscle degeneration classification distribution. CONCLUSIONS: Patients with poor clinical scores and recurrence exhibited additional radiologic abnormalities before surgery, such as poor paraspinal muscle quality, longer annular tears, higher Modic change type, higher modified Phirrmann disk degeneration grade, and sacralization or fusion. This risk evaluation protocol may prove valuable for patient selection, surgical planning, and choice of postoperative recovery regimen.