The Safety and Effectiveness of Orthobiologic Injections for Discogenic Chronic Low Back Pain: A Multicenter Prospective, Crossover, Randomized Controlled Trial with 12 Months Follow-up.

BACKGROUND: Chronic low back pain is one of the most common causes of disability, affecting more than 600 million people worldwide with major social and economic costs. Current treatment options include conservative, surgical, and minimally invasive interventional treatment approaches. Novel therapeutic treatment options continue to develop, targeting the biological cascades involved in the degenerative processes to prevent invasive spinal surgical procedures. Both intradiscal platelet-rich plasma (PRP) and bone marrow concentrate (BMC) applications have been introduced as promising regenerative treatment procedures. OBJECTIVES: The primary objective of this study is to assess the safety and effectiveness of an orthobiologic intradiscal injection, PRP or BMC, when compared to control patients. The secondary objectives are to measure: patient satisfaction and incidence of hospitalization, emergency room visit and spine surgery at predetermined follow-up intervals. STUDY DESIGN: A multicenter, prospective, crossover, randomized, controlled trial. SETTING: Comprehensive Spine and Sports Center and participating centers. METHODS: Forty patients were randomized into saline trigger point injection, intradiscal PRP, or BMC. Follow-up was 1, 3, 6, and 12 months posttreatment. Placebo patients were randomized to PRP and BMC injection if < 50% decrease in numeric rating scale (NRS) scores in 3 months, while PRP and BMC patients to the other active group if < 50% decrease in NRS scores in 6 months. RESULTS: Both PRP and BMC demonstrated statistically significant improvement in pain and function. All the placebo patients reported < 50% pain relief and crossed to the active arm. None of the patients had any adverse effects, hospitalization, or surgery up to 12 months posttreatment. LIMITATIONS: The limitations of our study were the small number of patients and open-label nature of the study. CONCLUSION: This is the only human lumbar disc study that evaluates both PRP and BMC in the same study and compares it to placebo. PRP and BMC were found to be superior to placebo in improving pain and function; however, larger randomized clinical trials are needed to answer further questions on the comparative effectiveness of various biologics as well as to identify outcome differences specific to disc pathology.

Comprehensive, evidence-based, consensus guidelines for prescription of opioids for chronic non-cancer pain from the American Society of Interventional Pain Physicians (ASIPP)

Opioid prescribing in the United States is decreasing, however, the opioid epidemic is continuing at an uncontrollable rate. Available data show a significant number of opioid deaths, primarily associated with illicit fentanyl use. It is interesting to also note that the data show no clear correlation between opioid prescribing (either number of prescriptions or morphine milligram equivalent [MME] per capita), opioid hospitalizations, and deaths. Furthermore, the data suggest that the 2016 guidelines from the Centers for Disease Control and Prevention (CDC) have resulted in notable problems including increased hospitalizations and mental health disorders due to the lack of appropriate opioid prescribing as well as inaptly rapid tapering or weaning processes. Consequently, when examined in light of other policies and complications caused by COVID-19, a fourth wave of the opioid epidemic has been emerging. In light of this, we herein seek to provide guidance for the prescription of opioids for the management of chronic non-cancer pain. These clinical practice guidelines are based upon a systematic review of both clinical and epidemiological evidence and have been developed by a panel of multidisciplinary experts assessing the quality of the evidence and the strength of recommendations and offer a clear explanation of logical relationships between various care options and health outcomes. The methods utilized included the development of objectives and key questions for the various facets of opioid prescribing practice. Also utilized were employment of trustworthy standards, and appropriate disclosures of conflicts of interest(s). The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed. The recommendations were developed after the appropriate review of text and questions by a panel of multidisciplinary subject matter experts, who tabulated comments, incorporated changes, and developed focal responses to questions posed

Comprehensive, Evidence-Based, Consensus Guidelines for Prescription of Opioids for Chronic Non-Cancer Pain from the American Society of Interventional Pain Physicians (ASIPP).

BACKGROUND: Opioid prescribing in the United States is decreasing, however, the opioid epidemic is continuing at an uncontrollable rate. Available data show a significant number of opioid deaths, primarily associated with illicit fentanyl use. It is interesting to also note that the data show no clear correlation between opioid prescribing (either number of prescriptions or morphine milligram equivalent [MME] per capita), opioid hospitalizations, and deaths. Furthermore, the data suggest that the 2016 guidelines from the Centers for Disease Control and Prevention (CDC) have resulted in notable problems including increased hospitalizations and mental health disorders due to the lack of appropriate opioid prescribing as well as inaptly rapid tapering or weaning processes. Consequently, when examined in light of other policies and complications caused by COVID-19, a fourth wave of the opioid epidemic has been emerging. OBJECTIVES: In light of this, we herein seek to provide guidance for the prescription of opioids for the management of chronic non-cancer pain. These clinical practice guidelines are based upon a systematic review of both clinical and epidemiological evidence and have been developed by a panel of multidisciplinary experts assessing the quality of the evidence and the strength of recommendations and offer a clear explanation of logical relationships between various care options and health outcomes. METHODS: The methods utilized included the development of objectives and key questions for the various facets of opioid prescribing practice. Also utilized were employment of trustworthy standards, and appropriate disclosures of conflicts of interest(s). The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed. The recommendations were developed after the appropriate review of text and questions by a panel of multidisciplinary subject matter experts, who tabulated comments, incorporated changes, and developed focal responses to questions posed. The multidisciplinary panel finalized 20 guideline recommendations for prescription of opioids for chronic non-cancer pain. Summary of the results showed over 90% agreement for the final 20 recommendations with strong consensus. The consensus guidelines included 4 sections specific to opioid therapy with 1) ten recommendations particular to initial steps of opioid therapy; 2) five recommendations for assessment of effectiveness of opioid therapy; 3) three recommendations regarding monitoring adherence and side effects; and 4) two general, final phase recommendations. LIMITATIONS: There is a continued paucity of literature of long-term opioid therapy addressing chronic non-cancer pain. Further, significant biases exist in the preparation of guidelines, which has led to highly variable rules and regulations across various states. CONCLUSION: These guidelines were developed based upon a comprehensive review of the literature, consensus among expert panelists, and in alignment with patient preferences, and shared decision-making so as to improve the long-term pain relief and function in patients with chronic non-cancer pain. Consequently, it was concluded - and herein recommended - that chronic opioid therapy should be provided in low doses with appropriate adherence monitoring and understanding of adverse events only to those patients with a proven medical necessity, and who exhibit stable improvement in both pain relief and activities of daily function, either independently or in conjunction with other modalities of treatments.

Biologics in Interventional Spinal Procedure: The Past, the Present, and the Vision.

BACKGROUND: Orthobiologics have shown promise in repair, restoration and regeneration of damaged and degenerated spine, joint and musculoskeletal tissues. The role of MSCs is to reduce inflammation, gliosis, and oxidative stress, while encouraging angiogenesis, neuronal proliferation, cell survival, and differentiation. While autologous MSCs have homologous advantages, they present with challenges related to donor predisposition, harvesting skills, and processing times. In this regard, allogenic MSCs show promise, but face ethical challenges, contamination, and survival risks. Ongoing efforts to overcome challenges and enhance performance include bioprinting, tissue engineering, artificial intelligence, nanotechnology, and microenvironmental alteration, among many others. Genetically programmed MSCs are being explored and tissue regeneration is now considered a real possibility. In this article, we discuss some of the leading-edge technologies in the process of being developed and perfected for widespread clinical application. OBJECTIVES: The aim of this narrative review is both to update on orthobiologics, especially MSCs and provide a vision for their future potential in interventional spine medicine. STUDY DESIGN: Narrative review. METHODS: The PubMed database of the National Institute of Medicine and Google Scholar were searched for keywords "mesenchymal stem cell," "mesenchymal stem cell + regenerative medicine," and "mesenchymal stem cell + spine." The bibliographies of these articles and authoritative Web sites were also consulted. RESULTS: There are hundreds of ongoing clinical trials exploring the role of MSCs in regenerative medicine for treating a wide range of diverse conditions, including spine conditions, neurodegenerative disorders, and cardiovascular disease. LIMITATIONS: This visionary narrative review has several limitations. It is a narrative, rather than a systematic review. Many of the ideas and treatments presented here are not perfected and are still in development. CONCLUSIONS: The role of MSCs in regenerative medicine is still emerging, but their promise for spinal cord injury and other disorders of the spine is clear. Using allogenic or autologous MSCs can help stimulate healing and neural regeneration remains a tantalizing possibility.

A Multidisciplinary Rehabilitation Approach to Chronic Pain Patients in the Post-COVID-19 Era.

BACKGROUND: The global health care system has been shaken by the unprecedented pandemic. Chronic pain management has suffered through the pandemic due to lack of access and challenges in care delivery only to be faced by a new set of chronic pain conditions resulting from prolonged and persistent COVID-19 symptoms referred to as "long COVID syndrome." OBJECTIVES: Long COVID is emerging as a complex and debilitating condition that occurs in a subpopulation of patients following acute COVID-19 infection. Our goals were to explore how to best treat and manage long COVID syndrome based on current experience. METHODS: This is a perspective rather than a systematic review. It is based on the limited available literature and current clinical experience. RESULTS: Although a few pharmacological agents have been proposed to mitigate symptoms, none have emerged to provide meaningful, long-term pain relief. Long COVID is associated with numerous and diverse symptoms. Risk factors for developing long COVID subsequent to acute COVID-19 remain unknown. Due to the multidimensional impact of long COVID chronic pain, a structured interdisciplinary rehabilitation model has been proposed to relieve pain, restore function, and maximize quality of life. LIMITATIONS: This is a perspective with an editorial point of view rather than a systematic literature study. Long COVID syndrome is a new condition, with which no clinicians have extensive experience. This is not a systematic review so there is no Preferred Reporting Items for Systematic reviews and Meta-Analyses diagram. This is not a clinical study so there was no need for institutional review board approvals. CONCLUSIONS: Treatment goals for the postviral syndrome of long COVID are multifaceted. In addition to pain control, patients may have functional deficits, cognitive issues, mental health issues, and reduced quality of life. Thus, a structured interdisciplinary rehabilitation model seems most appropriate to manage long COVID. KEY WORDS: Chronic pain, long COVID, pandemic, COVID-19, brain fog, fatigue, pain program, functional restoration, back pain, joint pain.

Systematic Review of Platelet-Rich Plasma for Low Back Pain.

BACKGROUND: Low back pain (LBP) has a high economic burden and is strongly related to the degenerative process of the spine, especially in the intervertebral disc and of the facet joints. Numerous treatment modalities have been proposed for the management of LBP, and the use of platelet-rich plasma (PRP) has emerged as an innovative therapeutic option for degenerative disease of the spine. The present study aims to evaluate the efficacy of PRP injections in managing low back pain. METHODS: We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, a registered at PROSPERO Systematic Reviews Platform, under number CRD42021268491. The PubMed, Web of Science, and Scopus databases were searched to identify relevant articles, along with hand searching to identify gray literature articles, with no language restrictions. Randomized clinical trials (RCTs), nonrandomized trials (NRTs), and case series (CSs) with more than 10 patients were considered eligible. The quality assessment and the risk of bias of the randomized clinical trials were evaluated using the RoB II tool. An evaluation of the description of the preparation methods was performed using an adapted version of the MIBO checklist. RESULTS: An electronic database search resulted in 2324 articles, and after the exclusion of noneligible articles, 13 RCTs and 27 NRTs or CSs were analyzed. Of the 13 RCTs, 11 found favorable results in comparison to the control group in pain and disability, one showed no superiority to the control group, and one was discontinued because of the lack of therapeutic effect at eight-week evaluation. Description of the PRP preparation techniques were found in almost all papers. The overall risk of bias was considered high in 2 papers and low in 11. An adapted MIBO checklist showed a 72.7% compliance rate in the selected areas. CONCLUSIONS: In this systematic review, we analyzed articles from English, Spanish and Russian language, from large databases and grey literature. PRP was in general an effective and safe treatment for degenerative LPB. Positive results were found in almost studies, a small number of adverse events were related, the risk of bias of the RCTs was low. Based on the evaluation of the included studies, we graded as level II the quality of the evidence supporting the use of PRP in LBP. Large-scale, multicenter RCTs are still needed to confirm these findings.

A Systematic Review and Meta-analysis of the Effectiveness of Radiofrequency Neurotomy in Managing Chronic Neck Pain.

BACKGROUND: Extensive research into potential sources of neck pain and referred pain into the upper extremities and head has shown that the cervical facet joints can be a potential pain source confirmed by precision, diagnostic blocks. STUDY DESIGN: Systematic review and meta-analysis utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, quality assessment of the included studies, conventional and single-arm meta-analysis, and best evidence synthesis. OBJECTIVE: The objective of this systematic review and meta-analysis is to evaluate the effectiveness of radiofrequency neurotomy as a therapeutic cervical facet joint intervention in managing chronic neck pain. METHODS: Available literature was included. Methodologic quality assessment of studies was performed from 1996 to September 2021. The level of evidence of effectiveness was determined. RESULTS: Based on the qualitative and quantitative analysis with single-arm meta-analysis and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system of appraisal, with inclusion of one randomized controlled trial (RCT) of 12 patients in the treatment group and eight positive observational studies with inclusion of 589 patients showing positive outcomes with moderate to high clinical applicability, the evidence is level II in managing neck pain with cervical radiofrequency neurotomy. The evidence for managing cervicogenic headache was level III to IV with qualitative analysis and single-arm meta-analysis and GRADE system of appraisal, with the inclusion of 15 patients in the treatment group in a positive RCT and 134 patients in observational studies. An overwhelming majority of the studies produced multiple lesions. LIMITATIONS: There was a paucity of literature and heterogeneity among the available studies. CONCLUSION: This systematic review and meta-analysis shows level II evidence with radiofrequency neurotomy on a long-term basis in managing chronic neck pain with level III to IV evidence in managing cervicogenic headaches.

A Systematic Review and Meta-analysis of the Effectiveness of Radiofrequency Neurotomy in Managing Chronic Neck Pain.

Background: Extensive research into potential sources of neck pain and referred pain into the upper extremities and head has shown that the cervical facet joints can be a potential pain source confirmed by precision, diagnostic blocks. Study Design: Systematic review and meta-analysis utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, quality assessment of the included studies, conventional and single-arm meta-analysis, and best evidence synthesis. Objective: The objective of this systematic review and meta-analysis is to evaluate the effectiveness of radiofrequency neurotomy as a therapeutic cervical facet joint intervention in managing chronic neck pain. Methods: Available literature was included. Methodologic quality assessment of studies was performed from 1996 to September 2021. The level of evidence of effectiveness was determined. Results: Based on the qualitative and quantitative analysis with single-arm meta-analysis and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system of appraisal, with inclusion of one randomized controlled trial (RCT) of 12 patients in the treatment group and eight positive observational studies with inclusion of 589 patients showing positive outcomes with moderate to high clinical applicability, the evidence is level II in managing neck pain with cervical radiofrequency neurotomy. The evidence for managing cervicogenic headache was level III to IV with qualitative analysis and single-arm meta-analysis and GRADE system of appraisal, with the inclusion of 15 patients in the treatment group in a positive RCT and 134 patients in observational studies. An overwhelming majority of the studies produced multiple lesions. Limitations: There was a paucity of literature and heterogeneity among the available studies. Conclusion: This systematic review and meta-analysis shows level II evidence with radiofrequency neurotomy on a long-term basis in managing chronic neck pain with level III to IV evidence in managing cervicogenic headaches. Supplementary Information: The online version contains supplementary material available at 10.1007/s40122-022-00455-0.

Comparative Systematic Review and Meta-Analysis of Cochrane Review of Epidural Injections for Lumbar Radiculopathy or Sciatica.

BACKGROUND: Epidural injections are among the most commonly performed procedures for managing low back and lower extremity pain. Pinto et al and Chou et al previously performed systematic reviews and meta-analyses, which, along with a recent update from Oliveira et al showing the lack of effectiveness of epidural steroid injections in managing lumbar disc herniation, spinal stenosis, and radiculopathy. In contrast to these papers, multiple other systematic reviews and meta-analyses have supported the effectiveness and use of epidural injections utilizing fluoroscopically guided techniques. A major flaw in the review can be related to attributing active-controlled trials to placebo-controlled trials. The assumption that local anesthetics do not provide sustained benefit, despite extensive evidence that local anesthetics provide long-term relief, similar to a combination of local anesthetic with steroids is flawed. STUDY DESIGN: The Cochrane Review of randomized controlled trials (RCTs) of epidural injections in managing chronic low back and lower extremity pain with sciatica or lumbar radiculopathy were reanalyzed using systematic methodology and meta-analysis. OBJECTIVES: To re-evaluate Cochrane data on RCTs of epidural injections in managing chronic low back and lower extremity pain with sciatica or lumbar radiculopathy utilizing qualitative and quantitative techniques with dual-arm and single-arm analysis. METHODS: In this systematic review, we have used the same RCTs from the Cochrane Review of a minimum of 20% change in pain scale or significant pain relief of >= 50%. The outcome measures were pain relief and functional status improvement. Significant improvement was defined as 50% or greater pain relief and functional status improvement. Our review was performed utilizing the Cochrane Review methodologic quality assessment and the Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB). Evidence was summarized utilizing the principles of best evidence synthesis and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system. Clinical relevance of the pragmatic nature of each study was assessed. RESULTS: In evaluating the RCTs in the Cochrane Review, 10 trials were performed with fluoroscopic guidance. Utilizing conventional dual-arm and single-arm meta-analysis, the evidence is vastly different from the interpretation of the data within the Cochrane Review. The overall combined evidence is Level I, or strong evidence, at one and 3 months, and Level II, or moderate evidence, at 6 and 12 months. LIMITATIONS: The limitation of this study is that only data contained in the Cochrane Review were analyzed. CONCLUSION: A comparative systematic review and meta-analysis of the Cochrane Review of randomized controlled trials (RCTs) of epidural injections in managing chronic low back and lower extremity pain with sciatica or lumbar radiculopathy yielded different results. This review, based on the evidence derived from placebo-controlled trials and active-controlled trials showed Level I, or strong evidence, at one and 3 months and Level II at 6 and 12 months. This review once again emphasizes the importance of the allocation of studies to placebo-control and active-control groups, utilizing standards of practice with inclusion of only the studies performed under fluoroscopic guidance.

Regenerative Medicine: Pharmacological Considerations and Clinical Role in Pain Management.

PURPOSE OF REVIEW: Low back pain affects at least 80% of individuals at some point in their lifetime and is the fifth most common reason for physician visits in the USA. Treatment of an acute episode of LBP generally includes rest, activity modification, physical therapy, NSAIDs, and patient education. RECENT FINDINGS: A small percentage of patients will develop chronic pain lasting > 6 months duration. Platelet-rich plasma (PRP) is one of the main pillars of regenerative medicine, as its release of bioactive proteins supports the aim of RM of restoring the anatomical function in degenerative conditions. Mesenchymal stem cells (MSCs) are multipotent stem cells, multipotent progenitor cells, or marrow stromal cells found in various body tissues, including bone marrow, lung, and adipose tissue. Evidence from well-designed case-control or cohort studies for the use of PRP and MSCs in lumbar facet joint, lumbar epidural, and sacroiliac joint injections is currently described as level IV evidence. PRP and MSCs are used autogenously to help facilitate the healing process, and their injection has been studied in the long-term management of discogenic low back pain. PRP has been compared to steroid injections in the sacroiliac joint for chronic low back pain, with favorable results. MSCs have also been shown to be useful in intervertebral disc regeneration and treatment of chronic low back pain associated with degenerative disc disease. Currently, the price for these treatments is extremely high, and thus the standard of care continues to be steroid injections and other treatments. This could change, however, with more robust data and research on the safety and long-term efficacy of biologics compared to other interventional management.

Epidural Interventions in the Management of Chronic Spinal Pain: American Society of Interventional Pain Physicians (ASIPP) Comprehensive Evidence-Based Guidelines.

BACKGROUND: Chronic spinal pain is the most prevalent chronic disease with employment of multiple modes of interventional techniques including epidural interventions. Multiple randomized controlled trials (RCTs), observational studies, systematic reviews, and guidelines have been published. The recent review of the utilization patterns and expenditures show that there has been a decline in utilization of epidural injections with decrease in inflation adjusted costs from 2009 to 2018. The American Society of Interventional Pain Physicians (ASIPP) published guidelines for interventional techniques in 2013, and guidelines for facet joint interventions in 2020. Consequently, these guidelines have been prepared to update previously existing guidelines. OBJECTIVE: To provide evidence-based guidance in performing therapeutic epidural procedures, including caudal, interlaminar in lumbar, cervical, and thoracic spinal regions, transforaminal in lumbar spine, and percutaneous adhesiolysis in the lumbar spine. METHODS: The methodology utilized included the development of objective and key questions with utilization of trustworthy standards. The literature pertaining to all aspects of epidural interventions was viewed with best evidence synthesis of available literature and  recommendations were provided. RESULTS: In preparation of the guidelines, extensive literature review was performed. In addition to review of multiple manuscripts in reference to utilization, expenditures, anatomical and pathophysiological considerations, pharmacological and harmful effects of drugs and procedures, for evidence synthesis we have included 47 systematic reviews and 43 RCTs covering all epidural interventions to meet the objectives.The evidence recommendations are as follows: Disc herniation: Based on relevant, high-quality fluoroscopically guided epidural injections, with or without steroids, and results of previous systematic reviews, the evidence is Level I for caudal epidural injections, lumbar interlaminar epidural injections, lumbar transforaminal epidural injections, and cervical interlaminar epidural injections with strong recommendation for long-term effectiveness.The evidence for percutaneous adhesiolysis in managing disc herniation based on one high-quality, placebo-controlled RCT is Level II with moderate to strong recommendation for long-term improvement in patients nonresponsive to conservative management and fluoroscopically guided epidural injections. For thoracic disc herniation, based on one relevant, high-quality RCT of thoracic epidural with fluoroscopic guidance, with or without steroids, the evidence is Level II with moderate to strong recommendation for long-term effectiveness.Spinal stenosis: The evidence based on one high-quality RCT in each category the evidence is Level III to II for fluoroscopically guided caudal epidural injections with moderate to strong recommendation and Level II for fluoroscopically guided lumbar and cervical interlaminar epidural injections with moderate to strong recommendation for long-term effectiveness.The evidence for lumbar transforaminal epidural injections is Level IV to III with moderate recommendation with fluoroscopically guided lumbar transforaminal epidural injections for long-term improvement. The evidence for percutaneous adhesiolysis in lumbar stenosis based on relevant, moderate to high quality RCTs, observational studies, and systematic reviews is Level II with moderate to strong recommendation for long-term improvement after failure of conservative management and fluoroscopically guided epidural injections. Axial discogenic pain: The evidence for axial discogenic pain without facet joint pain or sacroiliac joint pain in the lumbar and cervical spine with fluoroscopically guided caudal, lumbar and cervical interlaminar epidural injections, based on one relevant high quality RCT in each category is Level II with moderate to strong recommendation for long-term improvement, with or without steroids. Post-surgery syndrome: The evidence for lumbar and cervical post-surgery syndrome based on one relevant, high-quality RCT with fluoroscopic guidance for caudal and cervical interlaminar epidural injections, with or without steroids, is Level II with moderate to strong recommendation for long-term improvement. For percutaneous adhesiolysis, based on multiple moderate to high-quality RCTs and systematic reviews, the evidence is Level I with strong recommendation for long-term improvement after failure of conservative management and fluoroscopically guided epidural injections. LIMITATIONS: The limitations of these guidelines include a continued paucity of high-quality studies for some techniques and various conditions including spinal stenosis, post-surgery syndrome, and discogenic pain. CONCLUSIONS: These epidural intervention guidelines including percutaneous adhesiolysis were prepared with a comprehensive review of the literature with methodologic quality assessment and determination of level of evidence with strength of recommendations.

Nebulization of glutathione and N-Acetylcysteine as an adjuvant therapy for COVID-19 onset.

Ever since its emergence, the highly transmissible and debilitating coronavirus disease spread at an incredibly fast rate, causing global devastation in a matter of months. SARS-CoV-2, the novel coronavirus responsible for COVID-19, infects hosts after binding to ACE2 receptors present on cells from many structures pertaining to the respiratory, cardiac, hematological, neurological, renal and gastrointestinal systems. COVID-19, however, appears to trigger a severe cytokine storm syndrome in pulmonary structures, resulting in oxidative stress, exacerbated inflammation and alveolar injury. Due to the recent nature of this disease no treatments have shown complete efficacy and safety. More recently, however, researchers have begun to direct some attention towards GSH and NAC. These natural antioxidants play an essential role in several biological processes in the body, especially the maintenance of the redox equilibrium. In fact, many diseases appear to be strongly related to severe oxidative stress and deficiency of endogenous GSH. The high ratios of ROS over GSH, in particular, appear to reflect severity of symptoms and prolonged hospitalization of COVID-19 patients. This imbalance interferes with the body's ability to detoxify the cellular microenvironment, fold proteins, replenish antioxidant levels, maintain healthy immune responses and even modulate apoptotic events. Oral administration of GSH and NAC is convenient and safe, but they are susceptible to degradation in the digestive tract. Considering this drawback, nebulization of GSH and NAC as an adjuvant therapy may therefore be a viable alternative for the management of the early stages of COVID-19.

Comprehensive Evidence-Based Guidelines for Facet Joint Interventions in the Management of Chronic Spinal Pain: American Society of Interventional Pain Physicians (ASIPP) Guidelines Facet Joint Interventions 2020 Guidelines.

BACKGROUND: Chronic axial spinal pain is one of the major causes of significant disability and health care costs, with facet joints as one of the proven causes of pain. OBJECTIVE: To provide evidence-based guidance in performing diagnostic and therapeutic facet joint interventions. METHODS: The methodology utilized included the development of objectives and key questions with utilization of trustworthy standards. The literature pertaining to all aspects of facet joint interventions, was reviewed, with a best evidence synthesis of available literature and utilizing grading for recommendations.Summary of Evidence and Recommendations:Non-interventional diagnosis: • The level of evidence is II in selecting patients for facet joint nerve blocks at least 3 months after onset and failure of conservative management, with strong strength of recommendation for physical examination and clinical assessment. • The level of evidence is IV for accurate diagnosis of facet joint pain with physical examination based on symptoms and signs, with weak strength of recommendation. Imaging: • The level of evidence is I with strong strength of recommendation, for mandatory fluoroscopic or computed tomography (CT) guidance for all facet joint interventions. • The level of evidence is III with weak strength of recommendation for single photon emission computed tomography (SPECT) . • The level of evidence is V with weak strength of recommendation for scintography, magnetic resonance imaging (MRI), and computed tomography (CT) .Interventional Diagnosis:Lumbar Spine: • The level of evidence is I to II with moderate to strong strength of recommendation for lumbar diagnostic facet joint nerve blocks. • Ten relevant diagnostic accuracy studies with 4 of 10 studies utilizing controlled comparative local anesthetics with concordant pain relief criterion standard of ≥80% were included. • The prevalence rates ranged from 27% to 40% with false-positive rates of 27% to 47%, with ≥80% pain relief.Cervical Spine: • The level of evidence is II with moderate strength of recommendation. • Ten relevant diagnostic accuracy studies, 9 of the 10 studies with either controlled comparative local anesthetic blocks or placebo controls with concordant pain relief with a criterion standard of ≥80% were included. • The prevalence and false-positive rates ranged from 29% to 60% and of 27% to 63%, with high variability. Thoracic Spine: • The level of evidence is II with moderate strength of recommendation. • Three relevant diagnostic accuracy studies, with controlled comparative local anesthetic blocks, with concordant pain relief, with a criterion standard of ≥80% were included. • The prevalence varied from 34% to 48%, whereas false-positive rates varied from 42% to 58%.Therapeutic Facet Joint Interventions: Lumbar Spine: • The level of evidence is II with moderate strength of recommendation for lumbar radiofrequency ablation with inclusion of 11 relevant randomized controlled trials (RCTs) with 2 negative studies and 4 studies with long-term improvement. • The level of evidence is II with moderate strength of recommendation for therapeutic lumbar facet joint nerve blocks with inclusion of 3 relevant randomized controlled trials, with long-term improvement. • The level of evidence is IV with weak strength of recommendation for lumbar facet joint intraarticular injections with inclusion of 9 relevant randomized controlled trials, with majority of them showing lack of effectiveness without the use of local anesthetic. Cervical Spine: • The level of evidence is II with moderate strength of recommendation for cervical radiofrequency ablation with inclusion of one randomized controlled trial with positive results and 2 observational studies with long-term improvement. • The level of evidence is II with moderate strength of recommendation for therapeutic cervical facet joint nerve blocks with inclusion of one relevant randomized controlled trial and 3 observational studies, with long-term improvement. • The level of evidence is V with weak strength of recommendation for cervical intraarticular facet joint injections with inclusion of 3 relevant randomized controlled trials, with 2 observational studies, the majority showing lack of effectiveness, whereas one study with 6-month follow-up, showed lack of long-term improvement. Thoracic Spine: • The level of evidence is III with weak to moderate strength of recommendation with emerging evidence for thoracic radiofrequency ablation with inclusion of one relevant randomized controlled trial and 3 observational studies. • The level of evidence is II with moderate strength of recommendation for thoracic therapeutic facet joint nerve blocks with inclusion of 2 randomized controlled trials and one observational study with long-term improvement. • The level of evidence is III with weak to moderate strength of recommendation for thoracic intraarticular facet joint injections with inclusion of one randomized controlled trial with 6 month follow-up, with emerging evidence. Antithrombotic Therapy: • Facet joint interventions are considered as moderate to low risk procedures; consequently, antithrombotic therapy may be continued based on overall general status. Sedation: • The level of evidence is II with moderate strength of recommendation to avoid opioid analgesics during the diagnosis with interventional techniques. • The level of evidence is II with moderate strength of recommendation that moderate sedation may be utilized for patient comfort and to control anxiety for therapeutic facet joint interventions. LIMITATIONS: The limitations of these guidelines include a paucity of high-quality studies in the majority of aspects of diagnosis and therapy. CONCLUSIONS: These facet joint intervention guidelines were prepared with a comprehensive review of the literature with methodologic quality assessment with determination of level of evidence and strength of recommendations. KEY WORDS: Chronic spinal pain, interventional techniques, diagnostic blocks, therapeutic interventions, facet joint nerve blocks, intraarticular injections, radiofrequency neurolysis.

Comprehensive evidence-based guidelines for facet joint interventions in the management of Chronic Spinal Pain: American Society of Interventional Pain Physicians (ASIPP) guidelines

Chronic axial spinal pain is one of the major causes of significant disability and health care costs, with facet joints as one of the proven causes of pain. To provide evidence-based guidance in performing diagnostic and therapeutic facet joint interventions. The methodology utilized included the development of objectives and key questions with utilization of trustworthy standards. The literature pertaining to all aspects of facet joint interventions, was reviewed, with a best evidence synthesis of available literature and utilizing grading for recommendations.

Bone Marrow Concentrate (BMC) Therapy in Musculoskeletal Disorders: Evidence-Based Policy Position Statement of American Society of Interventional Pain Physicians (ASIPP).

BACKGROUND: The use of bone marrow concentrate (BMC) for treatment of musculoskeletal disorders has become increasingly popular over the last several years, as technology has improved along with the need for better solutions for these pathologies. The use of cellular tissue raises a number of issues regarding the US Food and Drug Administration's (FDA) regulation in classifying these treatments as a drug versus just autologous tissue transplantation. In the case of BMC in musculoskeletal and spine care, this determination will likely hinge on whether BMC is homologous to the musculoskeletal system and spine. OBJECTIVES: The aim of this review is to describe the current regulatory guidelines set in place by the FDA, specifically the terminology around "minimal manipulation" and "homologous use" within Regulation 21 CFR Part 1271, and specifically how this applies to the use of BMC in interventional musculoskeletal medicine. METHODS: The methodology utilized here is similar to the methodology utilized in preparation of multiple guidelines employing the experience of a panel of experts from various medical specialties and subspecialties from differing regions of the world. The collaborators who developed these position statements have submitted their appropriate disclosures of conflicts of interest. Trustworthy standards were employed in the creation of these position statements. The literature pertaining to BMC, its effectiveness, adverse consequences, FDA regulations, criteria for meeting the standards of minimal manipulation, and homologous use were comprehensively reviewed using a best evidence synthesis of the available and relevant literature. RESULTS/Summary of Evidence: In conjunction with evidence-based medicine principles, the following position statements were developed: Statement 1: Based on a review of the literature in discussing the preparation of BMC using accepted methodologies, there is strong evidence of minimal manipulation in its preparation, and moderate evidence for homologous utility for various musculoskeletal and spinal conditions qualifies for the same surgical exemption. Statement 2: Assessment of clinical effectiveness based on extensive literature shows emerging evidence for multiple musculoskeletal and spinal conditions. • The evidence is highest for knee osteoarthritis with level II evidence based on relevant systematic reviews, randomized controlled trials and nonrandomized studies. There is level III evidence for knee cartilage conditions. • Based on the relevant systematic reviews, randomized trials, and nonrandomized studies, the evidence for disc injections is level III. • Based on the available literature without appropriate systematic reviews or randomized controlled trials, the evidence for all other conditions is level IV or limited for BMC injections. Statement 3: Based on an extensive review of the literature, there is strong evidence for the safety of BMC when performed by trained physicians with the appropriate precautions under image guidance utilizing a sterile technique. Statement 4: Musculoskeletal disorders and spinal disorders with related disability for economic and human toll, despite advancements with a wide array of treatment modalities. Statement 5: The 21st Century Cures Act was enacted in December 2016 with provisions to accelerate the development and translation of promising new therapies into clinical evaluation and use. Statement 6: Development of cell-based therapies is rapidly proliferating in a number of disease areas, including musculoskeletal disorders and spine. With mixed results, these therapies are greatly outpacing the evidence. The reckless publicity with unsubstantiated claims of beneficial outcomes having putative potential, and has led the FDA Federal Trade Commission (FTC) to issue multiple warnings. Thus the US FDA is considering the appropriateness of using various therapies, including BMC, for homologous use. Statement 7: Since the 1980's and the description of mesenchymal stem cells by Caplan et al, (now called medicinal signaling cells), the use of BMC in musculoskeletal and spinal disorders has been increasing in the management of pain and promoting tissue healing. Statement 8: The Public Health Service Act (PHSA) of the FDA requires minimal manipulation under same surgical procedure exemption. Homologous use of BMC in musculoskeletal and spinal disorders is provided by preclinical and clinical evidence. Statement 9: If the FDA does not accept BMC as homologous, then it will require an Investigational New Drug (IND) classification with FDA (351) cellular drug approval for use. Statement 10: This literature review and these position statements establish compliance with the FDA's intent and corroborates its present description of BMC as homologous with same surgical exemption, and exempt from IND, for use of BMC for treatment of musculoskeletal tissues, such as cartilage, bones, ligaments, muscles, tendons, and spinal discs. CONCLUSIONS: Based on the review of all available and pertinent literature, multiple position statements have been developed showing that BMC in musculoskeletal disorders meets the criteria of minimal manipulation and homologous use. KEY WORDS: Cell-based therapies, bone marrow concentrate, mesenchymal stem cells, medicinal signaling cells, Food and Drug Administration, human cells, tissues, and cellular tissue-based products, Public Health Service Act (PHSA), minimal manipulation, homologous use, same surgical procedure exemption.

Responsible, Safe, and Effective Use of Biologics in the Management of Low Back Pain: American Society of Interventional Pain Physicians (ASIPP) Guidelines.

BACKGROUND: Regenerative medicine is a medical subspecialty that seeks to recruit and enhance the body's own inherent healing armamentarium in the treatment of patient pathology. This therapy's intention is to assist in the repair, and to potentially replace or restore damaged tissue through the use of autologous or allogenic biologics. This field is rising like a Phoenix from the ashes of underperforming conventional therapy midst the hopes and high expectations of patients and medical personnel alike. But, because this is a relatively new area of medicine that has yet to substantiate its outcomes, care must be taken in its public presentation and promises as well as in its use. OBJECTIVE: To provide guidance for the responsible, safe, and effective use of biologic therapy in the lumbar spine. To present a template on which to build standardized therapies using biologics. To ground potential administrators of biologics in the knowledge of the current outcome statistics and to stimulate those interested in providing biologic therapy to participate in high quality research that will ultimately promote and further advance this area of medicine. METHODS: The methodology used has included the development of objectives and key questions. A panel of experts from various medical specialties and subspecialties as well as differing regions collaborated in the formation of these guidelines and submitted (if any) their appropriate disclosures of conflicts of interest. Trustworthy standards were employed in the creation of these guidelines. The literature pertaining to regenerative medicine, its effectiveness, and adverse consequences was thoroughly reviewed using a best evidence synthesis of the available literature. The grading for recommendation was provided as described by the Agency for Healthcare Research and Quality (AHRQ). SUMMARY OF EVIDENCE: Lumbar Disc Injections: Based on the available evidence regarding the use of platelet-rich plasma (PRP), including one high-quality randomized controlled trial (RCT), multiple moderate-quality observational studies, a single-arm meta-analysis and evidence from a systematic review, the qualitative evidence has been assessed as Level III (on a scale of Level I through V) using a qualitative modified approach to the grading of evidence based on best-evidence synthesis. Based on the available evidence regarding the use of medicinal signaling/ mesenchymal stem cell (MSCs) with a high-quality RCT, multiple moderate-quality observational studies, a single-arm meta-analysis, and 2 systematic reviews, the qualitative evidence has been assessed as Level III (on a scale of Level I through V) using a qualitative modified approach to the grading of evidence based on best evidence synthesis. Lumbar Epidural Injections Based on one high-quality RCT, multiple relevant moderate-quality observational studies and a single-arm meta-analysis, the qualitative evidence has been assessed as Level IV (on a scale of Level I through V) using a qualitative modified approach to the grading of evidence based on best evidence synthesis. Lumbar Facet Joint Injections Based on one high-quality RCT and 2 moderate-quality observational studies, the qualitative evidence for facet joint injections with PRP has been assessed as Level IV (on a scale of Level I through V) using a qualitative modified approach to the grading of evidence based on best evidence synthesis. Sacroiliac Joint Injection Based on one high-quality RCT, one moderate-quality observational study, and one low-quality case report, the qualitative evidence has been assessed as Level IV (on a scale of Level I through V) using a qualitative modified approach to the grading of evidence based on best evidence synthesis. CONCLUSION: Based on the evidence synthesis summarized above, there is Level III evidence for intradiscal injections of PRP and MSCs, whereas the evidence is considered Level IV for lumbar facet joint, lumbar epidural, and sacroiliac joint injections of PRP, (on a scale of Level I through V) using a qualitative modified approach to the grading of evidence based on best evidence synthesis.Regenerative therapy should be provided to patients following diagnostic evidence of a need for biologic therapy, following a thorough discussion of the patient's needs and expectations, after properly educating the patient on the use and administration of biologics and in full light of the patient's medical history. Regenerative therapy may be provided independently or in conjunction with other modalities of treatment including a structured exercise program, physical therapy, behavioral therapy, and along with the appropriate conventional medical therapy as necessary. Appropriate precautions should be taken into consideration and followed prior to performing biologic therapy. Multiple guidelines from the Food and Drug Administration (FDA), potential limitations in the use of biologic therapy and the appropriate requirements for compliance with the FDA have been detailed in these guidelines. KEY WORDS: Regenerative medicine, platelet-rich plasma, medicinal signaling cells, mesenchymal stem cells, stromal vascular fraction, bone marrow concentrate, chronic low back pain, discogenic pain, facet joint pain, Food and Drug Administration, minimal manipulation, evidence synthesis.

Platelet Rich Plasma in Musculoskeletal Pathology: A Necessary Rescue or a Lost Cause?

BACKGROUND: Platelet rich plasma (PRP) has been used for decades to facilitate surgical tissue repair; therefore, the current trend of percutaneously injecting PRP to theoretically enhance tissue regeneration and repair is a logical progression. Applications include treatment of osteoarthritis, tendinopathy, chondropathy, acute and chronic soft tissue injuries, muscle or ligament tear, as well as enhancement of healing after bone or tissue reconstruction. However, there is limited evidence to support the use of PRP in the abovementioned conditions. Variations in the preparation of PRP and its application in various conditions influence its effect on various orthopedic conditions. OBJECTIVE: To provide a basic overview of the current use of PRP in treating musculoskeletal conditions. METHODS: Studies relevant to PRP were extracted from the PubMed and Medline database within the dates ranging from 1990 through 2015. These studies included in vitro as well as in-vivo animal experiments and careful analysis of the study population, type of intervention, and outcomes was made. RESULTS: PRP has been noted to be a beneficial solution for tissue healing based on limited current literature. However a variety of factors such as method of preparation, composition, medical condition of the patient, anatomic location of the lesion, and tissue type can alter outcome. CONCLUSION: The effectiveness and potential adverse effects of this treatment require high quality studies prior to widespread clinical application.Key words: Growth factors, platelet rich plasma, regeneration, regenerative healing, tissue repair, stem cells, mesenchymal stem cells, tissue engineering.

Responsible, Safe, and Effective Prescription of Opioids for Chronic Non-Cancer Pain: American Society of Interventional Pain Physicians (ASIPP) Guidelines.

BACKGROUND: Opioid use, abuse, and adverse consequences, including death, have escalated at an alarming rate since the 1990s. In an attempt to control opioid abuse, numerous regulations and guidelines for responsible opioid prescribing have been developed by various organizations. However, the US opioid epidemic is continuing and drug dose deaths tripled during 1999 to 2015. Recent data show a continuing increase in deaths due to natural and semisynthetic opioids, a decline in methadone deaths, and an explosive increase in the rates of deaths involving other opioids, specifically heroin and illicit synthetic fentanyl. Contrary to scientific evidence of efficacy and negative recommendations, a significant proportion of physicians and patients (92%) believe that opioids reduce pain and a smaller proportion (57%) report better quality of life. In preparation of the current guidelines, we have focused on the means to reduce the abuse and diversion of opioids without jeopardizing access for those patients suffering from non-cancer pain who have an appropriate medical indication for opioid use. OBJECTIVES: To provide guidance for the prescription of opioids for the management of chronic non-cancer pain, to develop a consistent philosophy among the many diverse groups with an interest in opioid use as to how appropriately prescribe opioids, to improve the treatment of chronic non-cancer pain and to reduce the likelihood of drug abuse and diversion. These guidelines are intended to provide a systematic and standardized approach to this complex and difficult arena of practice, while recognizing that every clinical situation is unique. METHODS: The methodology utilized included the development of objectives and key questions. The methodology also utilized trustworthy standards, appropriate disclosures of conflicts of interest, as well as a panel of experts from various specialties and groups. The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed, with a best evidence synthesis of the available literature, and utilized grading for recommendation as described by the Agency for Healthcare Research and Quality (AHRQ).Summary of Recommendations:i. Initial Steps of Opioid Therapy 1. Comprehensive assessment and documentation. (Evidence: Level I; Strength of Recommendation: Strong) 2. Screening for opioid abuse to identify opioid abusers. (Evidence: Level II-III; Strength of Recommendation: Moderate) 3. Utilization of prescription drug monitoring programs (PDMPs). (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 4. Utilization of urine drug testing (UDT). (Evidence: Level II; Strength of Recommendation: Moderate) 5. Establish appropriate physical diagnosis and psychological diagnosis if available. (Evidence: Level I; Strength of Recommendation: Strong) 6. Consider appropriate imaging, physical diagnosis, and psychological status to collaborate with subjective complaints. (Evidence: Level III; Strength of Recommendation: Moderate) 7. Establish medical necessity based on average moderate to severe (≥ 4 on a scale of 0 - 10) pain and/or disability. (Evidence: Level II; Strength of Recommendation: Moderate) 8. Stratify patients based on risk. (Evidence: Level I-II; Strength of Recommendation: Moderate) 9. Establish treatment goals of opioid therapy with regard to pain relief and improvement in function. (Evidence: Level I-II; Strength of Recommendation: Moderate) 10. Obtain a robust opioid agreement, which is followed by all parties. (Evidence: Level III; Strength of Recommendation: Moderate)ii. Assessment of Effectiveness of Long-Term Opioid Therapy 11. Initiate opioid therapy with low dose, short-acting drugs, with appropriate monitoring. (Evidence: Level II; Strength of Recommendation: Moderate) 12. Consider up to 40 morphine milligram equivalent (MME) as low dose, 41 to 90 MME as a moderate dose, and greater than 91 MME as high dose. (Evidence: Level II; Strength of Recommendation: Moderate) 13. Avoid long-acting opioids for the initiation of opioid therapy. (Evidence: Level I; Strength of Recommendation: Strong) 14. Recommend methadone only for use after failure of other opioid therapy and only by clinicians with specific training in its risks and uses, within FDA recommended doses. (Evidence: Level I; Strength of Recommendation: Strong) 15. Understand and educate the patients of the effectiveness and adverse consequences. (Evidence: Level I; Strength of Recommendation: Strong) 16. Similar effectiveness for long-acting and short-acting opioids with increased adverse consequences of long-acting opioids. (Evidence: Level I-II; Strength of recommendation: Moderate to strong) 17. Periodically assess pain relief and/or functional status improvement of ≥ 30% without adverse consequences. (Evidence: Level II; Strength of recommendation: Moderate) 18. Recommend long-acting or high dose opioids only in specific circumstances with severe intractable pain. (Evidence: Level I; Strength of Recommendation: Strong)iii. Monitoring for Adherence and Side Effects 19. Monitor for adherence, abuse, and noncompliance by UDT and PDMPs. (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 20. Monitor patients on methadone with an electrocardiogram periodically. (Evidence: Level I; Strength of Recommendation: Strong). 21. Monitor for side effects including constipation and manage them appropriately, including discontinuation of opioids when indicated. (Evidence: Level I; Strength of Recommendation: Strong)iv. Final Phase 22. May continue with monitoring with continued medical necessity, with appropriate outcomes. (Evidence: Level I-II; Strength of Recommendation: Moderate) 23. Discontinue opioid therapy for lack of response, adverse consequences, and abuse with rehabilitation. (Evidence: Level III; Strength of Recommendation: Moderate) CONCLUSIONS: These guidelines were developed based on comprehensive review of the literature, consensus among the panelists, in consonance with patient preferences, shared decision-making, and practice patterns with limited evidence, based on randomized controlled trials (RCTs) to improve pain and function in chronic non-cancer pain on a long-term basis. Consequently, chronic opioid therapy should be provided only to patients with proven medical necessity and stability with improvement in pain and function, independently or in conjunction with other modalities of treatments in low doses with appropriate adherence monitoring and understanding of adverse events.Key words: Chronic pain, persistent pain, non-cancer pain, controlled substances, substance abuse, prescription drug abuse, dependency, opioids, prescription monitoring, drug testing, adherence monitoring, diversionDisclaimer: The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."

A case of pulsed radiofrequency lesioning for occipital neuralgia.

OBJECTIVE: This report describes a case where pulsed radiofrequency lesioning (RFL) of the greater occipital nerve (GON) offered a valuable and safe treatment for the management of greater occipital neuralgia. The case is considered in relation to a review of the medical literature on greater occipital neuralgia and RFL interventions. CASE REPORT: A 62-year-old man with a 43-year history of left suboccipital pain underwent pulsed RFL of the left GON (20-millisecond bursts at intervals of 0.5 second for 4 minutes at 42 degrees C) after failing to achieve substantial analgesia with naproxen, a transcutaneous electrical nerve stimulator (TENS) unit and a greater occipital nerve blockade (GONB) utilizing local anesthetic and steroid. After obtaining 4 months of 70% pain relief, pulsed RFL was repeated and resulted in an additional 5 months of 70% pain relief. CONCLUSIONS: Pulsed RFL of the GON is an alternative to continuous RFL with the proposed advantage of mitigating pain, as in continuous RFL, but without the potential risk of causing deafferentation pain. While placebo and other nonspecific analgesic effects cannot be ruled out, the apparent safety profile and potential efficacy of pulsed RFL suggests it may be a compelling option to consider before irreversible neuroablative therapies are applied.

An injection from the past: fluoroscopic evidence of remote injections of radiopaque substances.

OBJECTIVE: Although uncommon, residual effects from contrast agents used more than 2 decades ago are possible. This case report is to alert clinicians to the implications of residual oil-based ionic contrast agents in the intrathecal space. CASE REPORT: A 70-year-old female with evidence of degenerative disc disease underwent a series of lumbar epidural steroid injections. Fluoroscopy during the procedure revealed diffuse residual intrathecal iophendylate (Pantopaque) dye. We were able to demonstrate unrestricted epidural spread of 1 mL iohexol (Omnipaque 180) alongside the preexisting dye. CONCLUSIONS: The goal of this case report is to highlight the potential of residual myelographic dye to complicate interventional procedures. Such residual dye can increase the level of difficulty in performing interventional pain treatments and perhaps the rate of complications associated with epidural injections, such as dural puncture. The presence of large amounts of residual oil-based intrathecal dye can lead to erroneous interpretations of the dye patterns as intraspinal lipoma or hemorrhage. As a consequence, the patient can be submitted to unnecessary diagnostic and therapeutic interventions. In addition, concerns of worsening oil-based dye-induced arachnoiditis with the use of epidural steroid injections can complicate the treatment of patients with back pain.