Role of Inflammatory Mediators, Growth Factors, and Osteodystrophy in Recurrent Lumbar Disk Herniation

Introduction. Reintervention in patients with spinal disk herniation is shown to significantly decrease likelihood of favorable outcomes in the postoperative period. Thus, it is important to individually assess risk factors for and likelihood of spinal disk herniation recurrence for each patient, and choose a suitable surgical option. Objective: to evaluate changes in the levels of immunoregulatory mediators in the blood serum and extracted spinal disc tissue of allegedly healthy individuals and patients with lumbar disk herniation relapses. Materials and methods. We examined 60 patients. The control group included 19 patients with traumatic spinal cord injuries at the lumbar level. The main group included 41 patients with spinal disk herniation. Twenty-two individuals had primary herniation while 11 patients presented with single clinical and neurological relapses at the pre-operated lumbar level and 8 patients presented with recurrent relapses. Solid-phase enzyme immunoassay detected proinflammatory cytokines (interleukin-6, tumor necrosis factor-), chemokines (interleukin-8, monocyte chemoattractant protein-1), growth factors (vascular endothelial growth factor, transforming growth factor-1), and osteodestruction markers (osteoprogesterin, matrix metalloproteinase-8) in the blood serum and the extracted spinal disc tissue. Results. We found that spinal disk destruction and chronic inflammation developed with both locally and generally elevating levels of proinflammatory cytokines/chemokines, growth factors, and matrix metalloproteinase 8. Conclusion. The results emphasize the significance of local changes in the studied parameters to choose and plan personalized surgical treatment in patients with spinal disk herniation

Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial

Background: Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial. Methods: NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy. Findings: Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk of recurrent ischaemic stroke between rivaroxaban and aspirin (hazard ratio [HR] 0·54; 95% CI 0·22–1·36), and the risk was similar for those without known PFO (1·06; 0·84–1·33; pinteraction=0·18). The risks of major bleeding with rivaroxaban versus aspirin were similar in patients with PFO detected (HR 2·05; 95% CI 0·51–8·18) and in those without PFO detected (HR 2·82; 95% CI 1·69–4·70; pinteraction=0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24–0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity. Interpretation: Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted. Funding: Bayer and Janssen