Virginia Spine Research Institute

Abstract Background. Our previous studies reveal that impaired draining function of the synovial lymphatic vessel (LV) contributes to the pathogenesis of inflammatory arthritis, but the cellular and molecular mechanisms involved are not fully understood.Objective. To investigate the involvement of lymphatic muscle cells (LMCs) in mediating impaired LV function in inflammatory arthritis. Methods. TNF transgenic (TNF-Tg) arthritic mice were used. Structure and function of the LVs that drained the hind limbs were examined by whole-mount immunofluorescence staining, electron microscopy, and near-infrared lymphatic imaging. Primary LMCs were treated with TNF, and the changes in proliferation, apoptosis, and functional gene expression were assessed. The roles of the herbal drug, Panax Notoginseng Saponins (PNS), in arthritis and LVs were studied.Results. TNF-Tg mice developed ankle arthritis with age, which was associated with abnormalities of LVs: 1) dilated capillary LVs with few branch points; 2) mature LVs with reduced LMC coverage and draining function; 3) degenerative and apoptotic appearance of LMCs. TNF caused LMC apoptosis, reduced expression of muscle functional genes, and promoted the production of nitric oxide (NO) by lymphatic endothelial cells (LECs). PNS attenuated arthritis, restored LMC coverage and draining function of mature LVs, inhibited TNF-mediated NO expression, and reduced LMC apoptosis. Conclusion. The impaired draining function of LVs in TNF-Tg mice involves LMC apoptosis. TNF promotes LMC death directly and indirectly via NO production by LECs. PNS attenuates arthritis, improves LVs, and prevents TNF-induced LMC apoptosis by inhibiting NO production of LECs. LMCs contribute to the dysfunction of synovial LVs in inflammatory arthritis.

Background and ObjectivesOsteoarthritis (OA) of the knee affects the aging population and has an associated influence on the health care system. Rigorous studies evaluating radiofrequency ablation for OA-related knee pain are lacking. This study compared long-term clinical safety and effectiveness of cooled radiofrequency ablation (CRFA) with intra-articular steroid (IAS) injection in managing OA-related knee pain.MethodsThis is a prospective, multicenter, randomized trial with 151 subjects with chronic (≥6 months) knee pain that was unresponsive to conservative modalities. Knee pain (Numeric Rating Scale [NRS]), Oxford Knee Score, overall treatment effect (Global Perceived Effect), analgesic drug use, and adverse events were compared between CRFA and IAS cohorts at 1, 3, and 6 months after intervention.ResultsThere were no differences in demographics between study groups. At 6 months, the CRFA group had more favorable outcomes in NRS: pain reduction 50% or greater: 74.1% versus 16.2%, P < 0.0001 (25.9% and 83.8% of these study cohorts, respectively, were nonresponders). Mean NRS score reduction was 4.9 ± 2.4 versus 1.3 ± 2.2, P < 0.0001; mean Oxford Knee Score was 35.7 ± 8.8 vs 22.4 ± 8.5, P < 0.0001; mean improved Global Perceived Effect was 91.4% vs 23.9%, P < 0.0001; and mean change in nonopioid medication use was CRFA > IAS (P = 0.02). There were no procedure-related serious adverse events.ConclusionsThis study demonstrates that CRFA is an effective long-term therapeutic option for managing pain and improving physical function and quality of life for patients with painful knee OA when compared with IAS injection.Clinical Trial Registration: ClinicalTrials.gov (NCT02343003).

To determine if a history of severe episodic low back pain (LBP) correlates with positive discography. A retrospective chart review identified patients undergoing discography from January 2012 through February 2016. The review determined if the patient's LBP began or continued with severe disabling episodes (lasting a minimum of two days). A gradual onset or initiating event with continuous symptoms was considered a nonepisodic history. Patients were excluded for unclear record, workers' compensation, litigation, prior lumbar surgery, radiologic instability, or indeterminate discography. Seventy-eight patients underwent discography. Thirty-nine patients were included, 31 of which had positive discograms. Eight had negative discograms. Nineteen patients had a history of episodic LBP, and 20 had no history of episodic LBP. Of those 19 with a history of episodic LBP, 18 had positive discography and one had negative discography. Of those with no history of episodic LBP, 13 had positive discography and seven had negative discography. Using the historical finding of severe episodic LBP as a test for discogenic source of LBP, the sensitivity is 58% (95% confidence interval [CI] = 41-75%) and the specificity is 88% (95% CI = 65-100%). The likelihood ratio is 4.7 (95% CI = 0.72-30). The positive predictive value (PPV) is 95% (95% CI = 72-100%). The PPV is based upon a prevalence of 79% (discogram positive) in our sample of patients considering fusion surgery. The diagnostic confidence odds are 18.2, with a diagnostic confidence of 95%. A positive history of severe episodic LBP may be a strong indicator for a discogenic etiology.

We would like to conclude by stating that the measured angle approach is the safest and most reliable approach in determining the appropriate obliquity for the CLO view during cervical epidural access.An angle of 50 may be substituted for the measured angle with minor loss of accuracy.For subsequent epidural access, the angle at which the needle tip aligns with the VILL (to be determined precontrast) may be used while remaining cognizant of the dangers of overobliquity [3].Additionally, the access of epidural space would need to be done at the same exact location as index access.Because of the anatomical discord that this approach creates, only a very large case series may inspire some confidence in using this approach.A desire for accuracy should not compromise safety.In this regard, not exceeding the anatomical obliquity is the only safe approach.

Contralateral oblique (CLO) angle view has been a useful addition to standard views in fluoroscopically guided interlaminar epidural injections. Determination of the appropriate CLO angle is paramount in the usefulness of this technique. Using MRI laminar angle measurements as a pre-procedural guide for the intra-procedural fluoroscopic CLO angle has been proposed. The purpose of this study was to help determine if using axial MRI laminar measurements prior to a cervical or thoracic epidural steroid injection would be useful in predicting the appropriate fluoroscopic CLO angle. A retrospective review was performed for patients who underwent cervical or thoracic interlaminar injections. In the performance of interlaminar injections, the authors had routinely determined the true fluoroscopic contra-lateral oblique angle after epidural access was confirmed, for use during any potential future injections. The fluoroscopic CLO angle measurements were obtained from a chart review and compared blindly to each patient's MRI axial laminar angle measurements. 34 injections were included. Inter-rater reliability comparing the two authors' MRI angle measurements was considered fair, ICC = 0.395. Accuracy was only 57% comparing MRI laminar angle measurements to within five degrees of the true fluoroscopic CLO angle as determined during the injection procedure. Accuracy by ICC showed only fair agreement, 0.47 and 0.22, for the two authors. The findings of this study indicate fair inter-rater reliability in manual measurements of laminar angle on axial MRI images. MRI laminar angle measurements do not appear to be highly accurate in determining the appropriate fluoroscopic CLO angle.