Practice Variation Research in Degenerative Lumbar Disc Surgery: A Literature Review on Design Characteristics and Outcomes

Study Design Literature review. Objective To describe whether practice variation studies on surgery in patients with lumbar degenerative disc disease used adequate study methodology to identify unwarranted variation, and to inform quality improvement in clinical practice. Secondary aim was to describe whether variation changed over time. Methods Literature databases were searched up to May 4th, 2021. To define whether study design was appropriate to identify unwarranted variation, we extracted data on level of aggregation, study population, and case-mix correction. To define whether studies were appropriate to achieve quality improvement, data were extracted on outcomes, explanatory variables, description of scientific basis, and given recommendations. Spearman’s rho was used to determine the association between the Extreme Quotient (EQ) and year of publication. Results We identified 34 articles published between 1990 and 2020. Twenty-six articles (76%) defined the diagnosis. Prior surgery cases were excluded or adjusted for in 5 articles (15%). Twenty-three articles (68%) adjusted for case-mix. Variation in outcomes was analyzed in 7 articles (21%). Fourteen articles (41%) identified explanatory variables. Twenty-six articles (76%) described the evidence on effectiveness. Recommendations for clinical practice were given in 9 articles (26%). Extreme Quotients ranged between 1-fold and 15-fold variation and did not show a significant change over time (rho= −.33, P= .09). Conclusions Practice variation research on surgery in patients with degenerative disc disease showed important limitations to identify unwarranted variation and to achieve quality improvement by public reporting. Despite the availability of new evidence, we could not observe a significant decrease in variation over time.

Degenerative disc disease in young adults: cytokine profile and angiogenic factors

Back pain (BP), associated with the degenerative disc disease (DDD), poses a heavy social and economic burden due to early disability and indications to surgery, emerging in young adults. Pathophysiological basis of premature intervertebral disc (IVD) degeneration is being actively studied. The study was aimed to define the profiles of inflammatory cytokines in DDD, as well as their relationship to the structural spine diseases. The molecular genetic analysis of the mRNA gene abundance in patients with BP and herniated IVD after discectomy and healthy individuals was performed by the quantitative polymerase chain reaction method. High expression of TNFα, IL17 was revealed in the IVD tissues of the affected patients (p < 0.01); the levels of TNFα and IL1β correlated with the DDD severity (r = 0.301 and 0.37; p < 0.05). Elevated expression of IL1β, IL6 was found in peripheral white blood cells (p < 0.01); the levels of IL6 negatively correlated with Modic type 1 and 2 changes (r = –0.31; p < 0.05), and the levels of IL17 positively correlated with the IVD herniation in combination with erosions of the adjacent vertebral body endplates and Modic changes (r = 0.401; p < 0.05). The expression of VEGF-А in the IVD tissues and white blood cells negatively correlated with the DDD grades (r = –0.85; p < 0.001), indicating reduced vascularization in the terminal phase of the disease. The findings on DDD demonstrate the contribution of the local low-immune inflammation, coupled with the intense disc vascularization at the earlier stages, and associated with the reactive inflammation in vertebral bodies. The results are prerequisites for developing the anti-inflammatory and reparative therapy based on the DDD grade and the presence of Modic changes in young adults with BP.

Disc Degeneration in Direct Injury or Instability Models Share Common Metabolic Pathways

Introduction: Disc degeneration is the central component involved in numerous common spinal pathologies. Degenerative disc disease affects millions of people every year, yet the mechanisms driving degeneration remain poorly understood. Previous work to date has shown that high levels of intracellular lactate seem to be involved in driving this pathology once thought to be purely mechanical. Here, we present a series of studies utilizing mouse models of mechanical injuring or loading of the intervertebral disc (IVD), with a goal of better defining the role of lactate and lactate transport in degenerative disc disease. Methodology: Four models of disc degeneration were studied: (i) lumbar disc poke, (ii) tail disc poke, (iii) spinal instability, and (iv) sham. Female mice (C57BL/6J, n = 30) were randomly assigned to one group. In group 1, a retroperitoneal approach exposed the IVD of the lumbar spine, and a 27G needle was used to injure the disc. In group 2, the needle was inserted in the tail IVD. In group 3, lumbar instability was induced by resection of bilateral facet joints and supraspinous/interspinous ligaments. In group 4, a sham was used for each. The mice were euthanized at two, four, and eight weeks. IVD was evaluated by histological and immunofluorescence analysis. RNA extraction from disc tissue was analyzed with QPCR. Result: Sham mice did not have significant disc degeneration. In groups 1 and 2, the degenerative process at two, four, and eight weeks was characterized by loss of nucleus pulposus (NP) cells and the gradual increase in matrix components in NP. The distinction between NP and annulus fibroids (AF) or endplate cartilage is lost. There was increased expression of collagen X and MMP13 in the NP, and MCT4 was decreased, while MCT3 was increased. In group 3, disorder of the AF was evident in the first two weeks post surgery, the collapsed disc space and the NP area gradually lessened. The proteoglycan detected in the inner layer of AF and the periphery of NP decreased after eight weeks. There was increase in type X collagen and MMP13 in the inner AF and NP. Conclusion: Our results demonstrate a common molecular pathway whereby discs degenerate after direct injury or becoming unstable. In our model, there was a rapid degeneration of the IVD in mice who exhibit up- and downregulation of several important markers. Importantly, MCT4 was downregulated, while MCT3 was upregulated. While MCT4 was associated with lactate exportation, and its loss resulted in elevated intracellular lactate and disc degradation, MCT3 is rarely expressed and may be acting as a rescue lactate transporter.