Genicular Artery Embolization, Radiofrequency Ablation, and Corticosteroid Therapy for Knee Osteoarthritis: A Cost-Effectiveness Analysis Using Randomized Clinical Trial Data.

Background: Many patients with symptomatic knee osteoarthritis (KOA) are refractory to traditional nonsurgical treatments such as intraarticular corticosteroid (CS) injection but are not yet eligible for or decline surgery. Genicular artery embolization (GAE) and radiofrequency ablation (RFA) are emerging adjunctive or alternative minimally invasive treatments. Objective: To perform a cost-effectiveness analysis (CEA) comparing CS, GAE, and RFA, for treatment of symptomatic KOA using a Markov model based on a de novo network meta-analysis (NMA) of randomized control trials. Methods: CEA was conducted to compare GAE and RFA to CS using a Markov cohort state-transition model from a U.S. Medicare payer's perspective over a 4-year time horizon. The model incorporated each treatment's success and attrition rates, costs, and utility benefit. Utility benefit values were derived at short-term (0.5-3 months) and long-term (6-12 months) posttreatment follow-up from NMA of published RCTs using an outcome of improved knee pain and/or function. Analyses were conducted at a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY). Sensitivity analyses were performed, including when simulating various cost setting scenarios (i.e., office vs hospital outpatient treatment). Results: RFA demonstrated larger treatment effect than GAE, more pronounced at short-term [standardized mean difference (SMD), -1.6688, 95% CI [-2.7806; -0.5571], p=.003] than long-term (SMD -0.3822, 95% CI [-1.9743; 1.2100], p=.64) follow-up. Across cost setting scenarios, incremental cost-effectiveness ratios relative to CS were $561-1563/QALY for GAE versus $76-429/QALY for RFA (not counting scenarios in which RFA was dominated by CS). GAE demonstrated higher cost-effectiveness probability compared to RFA (41.6-54.8% vs. 18.4-29.2%, respectively). GAE was more cost-effective than RFA when the GAE clinical success rate and post-GAE utility value exceeded 32.1-51.0% and 0.562-0.617, respectively, and when the GAE quarterly attrition rate was less than 8.8-17.4%. RFA was more cost-effective when baseline pre-treatment utility values exceeded 0.695-0.713. Neither GAE costs nor RFA costs were sensitive parameters. Conclusion: Across scenarios, GAE was consistently the most likely cost-effective treatment option compared to RFA and CS, although clinical success rates, attrition rates, and utility values impact its cost-effectiveness. Clinical Impact: GAE is likely to be more cost-effective than RFA or CS for treatment of symptomatic KOA.

Geniculate Artery Embolization: Role in Knee Hemarthrosis and Osteoarthritis.

Roughly 37% of Americans 60 years of age and older experience chronic pain due to osteoarthritis (OA) of the knee. After conservative treatment (pharmacologic, physical therapy, and joint injections) fails, patients often require total knee arthroplasty to alleviate pain and regain knee function. Given the high economic burden of surgery paired with its invasive nature, many patients with this degenerative joint disease seek alternative treatment. Moreover, many patients with severe knee OA who also have comorbidities that preclude surgery-most often morbid obesity-are left without options. Geniculate artery embolization (GAE) is a minimally invasive intra-arterial intervention that was originally developed for the treatment of knee hemarthrosis that has recently been adapted for symptomatic knee OA. Through selective embolization of geniculate branches corresponding to the site of knee pain, GAE inhibits the neovascularity that contributes to the catabolic and inflammatory drive of OA. Preliminary trials over the past decade have demonstrated promising clinical results, including decreased pain and improved function and quality of life after treatment. Given such success, GAE provides another minimally invasive treatment option for knee OA to patients who feel reluctant to undergo or are ineligible for surgery. The authors review the radiographic manifestations and current standard of treatment of OA and hemarthrosis of the knee. Procedural technique, embolic selection, and clinical evidence for GAE in the treatment of OA and hemarthrosis of the knee are also explored. The online slide presentation from the RSNA Annual Meeting is available for this article. ©RSNA, 2021.

Preparation Methods and Clinical Outcomes of Platelet-Rich Plasma for Intra-articular Hip Disorders: A Systematic Review and Meta-analysis of Randomized Clinical Trials.

BACKGROUND: Despite its increasing use in the management of musculoskeletal conditions, questions remain regarding the preparation methods of platelet-rich plasma (PRP) and its clinical applications for intra-articular hip disorders, including femoroacetabular impingement syndrome (FAIS), labral pathology, and osteoarthritis (OA). PURPOSE: To systematically review and assess the preparation methods and clinical outcomes from randomized clinical trials (RCTs) on the use of PRP for intra-articular hip disorders. STUDY DESIGN: Systematic review; Level of evidence, 2. METHODS: A systematic review in accordance with the 2009 PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines was performed in September 2019. The Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, PubMed, Ovid Medline, and Embase were queried for studies regarding the use of PRP to treat intra-articular hip disorders. Qualifying articles were English-language RCTs describing the use of PRP for intra-articular hip disorders, either as standalone treatment or surgical augmentation. Two authors independently assessed article eligibility. Data pertaining to patient characteristics, indication for treatment, PRP preparation method, follow-up period, and clinical outcomes were extracted. Study results were qualitatively reported and quantitatively compared using meta-analysis when appropriate. RESULTS: Seven RCTs met inclusion criteria. Four studies described the use of PRP for hip OA and 3 utilized PRP at arthroscopy for FAIS and labral tears. Outcomes after PRP for OA demonstrated improvement in validated patient-reported outcome measures for up to 1 year; however, pooled effect sizes found no statistically significant difference between PRP and hyaluronic acid (HA) regarding pain visual analog scale scores at short-term (≤2 months; P = .27), midterm (4-6 months; P = .85), or long-term (1 year; P = .42) follow-up. When injected at arthroscopy, 1 study reported improved outcomes, 1 reported no difference in outcomes, and 1 reported worse outcomes compared with controls. The meta-analysis demonstrated no statistically significant difference on the modified Harris Hip Score (mHHS) between PRP and control cohorts at a minimum 1-year follow-up. There were considerable deficiencies and heterogeneity in the reporting of PRP preparation methods for both indications. CONCLUSION: Treatment of OA with PRP demonstrated reductions in pain and improved patient-reported outcomes for up to 1 year. However, there was no statistically significant difference between PRP and HA in pain reduction. Likewise, for FAIS and labral surgery there was no statistically significant difference in mHHS outcomes between patients treated with PRP and controls. Given the limited number of studies and variability in PRP preparations, additional high-quality randomized trials are warranted.

The Electrophysiological Determinants of Corticospinal Motor Neuron Vulnerability in ALS.

The brain is complex and heterogeneous. Even though numerous independent studies indicate cortical hyperexcitability as a potential contributor to amyotrophic lateral sclerosis (ALS) pathology, the mechanisms that are responsible for upper motor neuron (UMN) vulnerability remain elusive. To reveal the electrophysiological determinants of corticospinal motor neuron (CSMN, a.k.a UMN in mice) vulnerability, we investigated the motor cortex of hSOD1G93A mice at P30 (postnatal day 30), a presymptomatic time point. Glutamate uncaging by laser scanning photostimulation (LSPS) revealed altered dynamics especially within the inhibitory circuitry and more specifically in L2/3 of the motor cortex, whereas the excitatory microcircuits were unchanged. Observed microcircuitry changes were specific to CSMN in the motor column. Electrophysiological evaluation of the intrinsic properties in response to the microcircuit changes, as well as the exon microarray expression profiles of CSMN isolated from hSOD1G93A and healthy mice at P30, revealed the presence of a very dynamic set of events, ultimately directed to establish, maintain and retain the balance at this early stage. Also, the expression profile of key voltage-gated potassium and sodium channel subunits as well as of the inhibitory GABA receptor subunits and modulatory proteins began to suggest the challenges CSMN face at this early age. Since neurodegeneration is initiated when neurons can no longer maintain balance, the complex cellular events that occur at this critical time point help reveal how CSMN try to cope with the challenges of disease manifestation. This information is critically important for the proper modulation of UMNs and for developing effective treatment strategies.

Absence of UCHL 1 function leads to selective motor neuropathy.

OBJECTIVE: The aim of this study was to investigate the role of ubiquitin C-terminal hydrolase-L1 (UCHL1) for motor neuron circuitry and especially in spinal motor neuron (SMN) health, function, and connectivity. METHODS: Since mutations in UCHL1 gene leads to motor dysfunction in patients, we investigated the role of UCHL1 on SMN survival, axon health, and connectivity with the muscle, by employing molecular and cellular marker expression analysis and electrophysiological recordings, in healthy wild-type and Uchl1 (nm3419) (UCHL1-/-) mice, which lack all UCHL1 function. RESULTS: There is pure motor neuropathy with selective degeneration of the motor, but not sensory axons in the absence of UCHL1 function. Neuromuscular junctions (NMJ) are impaired in muscle groups that are innervated by slow-twitch or fast-twitch SMN. However, unlike corticospinal motor neurons, SMN cell bodies remain intact with no signs of elevated endoplasmic reticulum (ER) stress. INTERPRETATION: Presence of NMJ defects and progressive retrograde axonal degeneration in the absence of major SMN soma loss suggest that defining pathology as a function of neuron number is misleading and that upper and lower motor neurons utilize UCHL1 function in different cellular events. In line with findings in patients with mutations in UCHL1 gene, our results suggest a unique role of UCHL1, especially for motor neuron circuitry. SMN require UCHL1 to maintain NMJ and motor axon health, and that observed motor dysfunction in the absence of UCHL1 is not due to SMN loss, but mostly due to disintegrated circuitry.