Postoperative recovery patterns following discectomy surgery in patients with lumbar radiculopathy.

This retrospective study of prospectively collected data aimed to identify unique pain and disability trajectories in patients following lumbar discectomy surgery. Patients of this study population presented chiefly with lumbar radiculopathy and underwent discectomy surgery from thirteen sites enrolled in the CSORN registry. Outcome variables of interest included numeric rating scales for leg/back pain and modified Oswestry disability index scores at baseline, 3, 12, and 24 months post-operatively. Latent class growth analysis was used to identify distinct courses in each outcome. Data from 524 patients revealed three unique trajectories for leg pain (excellent = 18.4%, good = 55.4%, poor = 26.3%), disability (excellent = 59.7%, fair = 35.6%, poor = 4.7%) and back pain (excellent = 13.0%, good = 56.4%, poor = 30.6%). Construct validity was supported by statistically significant differences in the proportions of patients attaining the criteria for minimal important change (MIC; 30%) or clinical success in disability (50% or Oswestry score ≤ 22) (p < 0.001). The variable proportions of patients belonging to poor outcome trajectories shows a disconnect between improved disability and persistence of pain. It will be beneficial to incorporate this information into the realm of patient expectation setting in concert with future findings of potential factors predictive of subgroup membership.

Paralogues of Mmp11 and Timp4 Interact during the Development of the Myotendinous Junction in the Zebrafish Embryo.

The extracellular matrix (ECM) of the myotendinous junction (MTJ) undergoes dramatic physical and biochemical remodeling during the first 48 h of development in zebrafish, transforming from a rectangular fibronectin-dominated somite boundary to a chevron-shaped laminin-dominated MTJ. Matrix metalloproteinase 11 (Mmp11, a.k.a. Stromelysin-3) is both necessary and sufficient for the removal of fibronectin at the MTJ, but whether this protease acts directly on fibronectin and how its activity is regulated remain unknown. Using immunofluorescence, we show that both paralogues of Mmp11 accumulate at the MTJ during this time period, but with Mmp11a present early and later replaced by Mmp11b. Moreover, Mmp11a also accumulates intracellularly, associated with the Z-discs of sarcomeres within skeletal muscle cells. Using the epitope-mediated MMP activation (EMMA) assay, we show that despite having a weaker paired basic amino acid motif in its propeptide than Mmp11b, Mmp11a is activated by furin, but may also be activated by other mechanisms intracellularly. One or both paralogues of tissue inhibitors of metalloproteinase-4 (Timp4) are also present at the MTJ throughout this process, and yeast two-hybrid assays reveal distinct and specific interactions between various domains of these proteins. We propose a model in which Mmp11a activity is modulated (but not inhibited) by Timp4 during early MTJ remodeling, followed by a phase in which Mmp11b activity is both inhibited and spatially constrained by Timp4 in order to maintain the structural integrity of the mature MTJ.