A Systematic Guideline by the ASPN Workgroup on the Evidence, Education, and Treatment Algorithm for Painful Diabetic Neuropathy: SWEET.

Introduction: Painful diabetic neuropathy (PDN) is a leading cause of pain and disability globally with a lack of consensus on the appropriate treatment of those suffering from this condition. Recent advancements in both pharmacotherapy and interventional approaches have broadened the treatment options for PDN. There exists a need for a comprehensive guideline for the safe and effective treatment of patients suffering from PDN. Objective: The SWEET Guideline was developed to provide clinicians with the most comprehensive guideline for the safe and appropriate treatment of patients suffering from PDN. Methods: The American Society of Pain and Neuroscience (ASPN) identified an educational need for a comprehensive clinical guideline to provide evidence-based recommendations for PDN. A multidisciplinary group of international experts developed the SWEET guideline. The world literature in English was searched using Medline, EMBASE, Cochrane CENTRAL, BioMed Central, Web of Science, Google Scholar, PubMed, Current Contents Connect, Meeting Abstracts, and Scopus to identify and compile the evidence for diabetic neuropathy pain treatments (per section as listed in the manuscript) for the treatment of pain. Manuscripts from 2000-present were included in the search process. Results: After a comprehensive review and analysis of the available evidence, the ASPN SWEET guideline was able to rate the literature and provide therapy grades for most available treatments for PDN utilizing the United States Preventive Services Task Force criteria. Conclusion: The ASPN SWEET Guideline represents the most comprehensive review of the available treatments for PDN and their appropriate and safe utilization.

Pacific Spine and Pain Society (PSPS) Evidence Review of Surgical Treatments for Lumbar Degenerative Spinal Disease: A Narrative Review.

INTRODUCTION: Interventional treatment options for the lumbar degenerative spine have undergone a significant amount of innovation over the last decade. As new technologies emerge, along with the surgical specialty expansion, there is no manuscript that utilizes a review of surgical treatments with evidence rankings from multiple specialties, namely, the interventional pain and spine communities. Through the Pacific Spine and Pain Society (PSPS), the purpose of this manuscript is to provide a balanced evidence review of available surgical treatments. METHODS: The PSPS Research Committee created a working group that performed a comprehensive literature search on available surgical technologies for the treatment of the degenerative spine, utilizing the ranking assessment based on USPSTF (United States Preventative Services Taskforce) and NASS (North American Spine Society) criteria. RESULTS: The surgical treatments were separated based on disease process, including treatments for degenerative disc disease, spondylolisthesis, and spinal stenosis. CONCLUSIONS: There is emerging and significant evidence to support multiple approaches to treat the symptomatic lumbar degenerative spine. As new technologies become available, training, education, credentialing, and peer review are essential for optimizing patient safety and successful outcomes.

Safety and Efficacy of Intravenous ExoFlo in the Treatment of Complex Regional Pain Syndrome.

BACKGROUND: Complex regional pain syndrome (CRPS) is an extremely painful disorder driven primarily by inflammation. OBJECTIVES: We hypothesized that the immunomodulatory biologic, ExoFloTM, composed of bone marrow mesenchymal stem cell-derived extracellular vesicles, could be safely administered to CRPS patients and alleviate symptoms. STUDY DESIGN: Ten patients received 2 intravenous (IV) infusions, each containing 15 mL ExoFlo, on day one and day 4. A series of tests were performed at baseline (day 0, prior to infusion), week one, and months one, 3, and 6 after the second infusion. SETTING: All patients were treated in one of 2 outpatient pain management clinics in Orange County, CA. METHODS: Testing for clinical improvement included: visual analog scale of pain, brief pain inventory, 36-item short-form questionnaire, range of motion analysis, and jamar dynamometer testing. RESULTS: No serious adverse events related to ExoFlo treatment occurred. Statistically significant improvements in pain and motion assessments occurred across the patient pool. LIMITATIONS: This study was limited by its patient number enrolled (10), it lacked a control arm, and one patient who dropped out of the study. CONCLUSIONS: IV delivery of ExoFlo appears safe in patients with CRPS. In addition, ExoFlo exhibited efficacy in addressing CRPS symptoms. Given the lack of effective and safe treatments available to CRPS patients, these results suggest that further studies are warranted to explore and validate this potential treatment for CRPS.

Pain Education and Knowledge (PEAK) Consensus Guidelines for Neuromodulation: A Proposal for Standardization in Fellowship and Training Programs.

The need to be competent in neuromodulation is and should be a prerequisite prior to completing a fellowship in interventional pain medicine. Unfortunately, many programs lack acceptable candidates for these advanced therapies, and fellows may not receive adequate exposure to neuromodulation procedures. The American Society of Pain and Neuroscience (ASPN) desires to create a consensus of experts to set a minimum standard of competence for neurostimulation procedures, including spinal cord stimulation (SCS), dorsal root ganglion stimulation (DRG-S), and peripheral nerve stimulation (PNS). The executive board of ASPN accepted nominations for colleagues with excellence in the subject matter of neuromodulation and physician education. This diverse group used peer-reviewed literature and, based on grading of evidence and expert opinion, developed critical consensus guides for training that all accredited fellowship programs should adopt. For each consensus point, transparency and recusal were used to eliminate bias, and an author was nominated for evidence grading oversight and bias control. Pain Education and Knowledge (PEAK) Consensus Guidelines for Neuromodulation sets a standard for neuromodulation training in pain fellowship training programs. The consensus panel has determined several recommendations to improve care in the United States for patients undergoing neuromodulation. As neuromodulation training in the United States has evolved dramatically, these therapies have become ubiquitous in pain medicine. Unfortunately, fellowship programs and the Accreditation Council for Graduate Medical Education (ACGME) pain program requirements have not progressed training to match the demands of modern advancements. PEAK sets a new standard for fellowship training and presents thirteen practice areas vital for physician competence in neuromodulation.

Best Practices for Dorsal Root Ganglion Stimulation for Chronic Pain: Guidelines from the American Society of Pain and Neuroscience.

With continued innovations in neuromodulation comes the need for evolving reviews of best practices. Dorsal root ganglion stimulation (DRG-S) has significantly improved the treatment of complex regional pain syndrome (CRPS), and it has broad applicability across a wide range of other conditions. Through funding and organizational leadership by the American Society for Pain and Neuroscience (ASPN), this best practices consensus document has been developed for the selection, implantation, and use of DRG stimulation for the treatment of chronic pain syndromes. This document is composed of a comprehensive narrative literature review that has been performed regarding the role of the DRG in chronic pain and the clinical evidence for DRG-S as a treatment for multiple pain etiologies. Best practice recommendations encompass safety management, implantation techniques, and mitigation of the potential complications reported in the literature. Looking to the future of neuromodulation, DRG-S holds promise as a robust intervention for otherwise intractable pain.

Physical Therapy Considerations and Recommendations for Patients Following Spinal Cord Stimulator Implant Surgery.

OBJECTIVES: Spinal cord stimulation (SCS) is an established therapy option in interventional pain medicine. Recent advances in technology have allowed for greater compliance with treatment and improved efficacy in pain control. This article was proposed to fill the gap in the literature addressing this specific patient population and to facilitate further research. Even though there is a lack of consensus among societies and experts on exact parameters of physical therapy (PT) considerations and postoperative limitations in patients with SCS, we propose rehabilitative care for this population should be standardized. As the number of patients with SCS implants grow, it is vital to understand how to appropriately approach patients with implantable devices when additional treatments such as PT are prescribed. MATERIALS AND METHODS: A literature search was performed on the use of PT following SCS implantation. Presently, there is no literature to date which addresses the use of PT in this patient population. The lack of data is the largest hurdle in the creation of formal SCS therapy guidelines. The authors therefore proposed recommendations for rehabilitation based upon a detailed understanding of SCS hardware alongside well-studied physiotherapy concepts. RESULTS: Considerations when initiating PT in the SCS patient population should include: 1) biomechanics and quality of SCS output; 2) therapeutic exercise and spinal manipulation in association with risk for lead migration and fracture; 3) the application of therapeutic modalities and risk for injury to the patient and/or damage to the SCS componentry; and 4) integration of a biopsychosocial, person-centered approach. CONCLUSIONS: PT treatment protocol in patients with a recently implanted SCS device should be person-centered addressing individual needs, values, and goals. Further research is needed to fully appreciate the impact of an interprofessional approach to management of SCS patients, particularly following stimulator implantation.

The American Society of Pain and Neuroscience (ASPN) Evidence-Based Clinical Guideline of Interventional Treatments for Low Back Pain.

Introduction: Painful lumbar spinal disorders represent a leading cause of disability in the US and worldwide. Interventional treatments for lumbar disorders are an effective treatment for the pain and disability from low back pain. Although many established and emerging interventional procedures are currently available, there exists a need for a defined guideline for their appropriateness, effectiveness, and safety. Objective: The ASPN Back Guideline was developed to provide clinicians the most comprehensive review of interventional treatments for lower back disorders. Clinicians should utilize the ASPN Back Guideline to evaluate the quality of the literature, safety, and efficacy of interventional treatments for lower back disorders. Methods: The American Society of Pain and Neuroscience (ASPN) identified an educational need for a comprehensive clinical guideline to provide evidence-based recommendations. Experts from the fields of Anesthesiology, Physiatry, Neurology, Neurosurgery, Radiology, and Pain Psychology developed the ASPN Back Guideline. The world literature in English was searched using Medline, EMBASE, Cochrane CENTRAL, BioMed Central, Web of Science, Google Scholar, PubMed, Current Contents Connect, Scopus, and meeting abstracts to identify and compile the evidence (per section) for back-related pain. Search words were selected based upon the section represented. Identified peer-reviewed literature was critiqued using United States Preventive Services Task Force (USPSTF) criteria and consensus points are presented. Results: After a comprehensive review and analysis of the available evidence, the ASPN Back Guideline group was able to rate the literature and provide therapy grades to each of the most commonly available interventional treatments for low back pain. Conclusion: The ASPN Back Guideline represents the first comprehensive analysis and grading of the existing and emerging interventional treatments available for low back pain. This will be a living document which will be periodically updated to the current standard of care based on the available evidence within peer-reviewed literature.

Far-Contralateral Oblique (FCO) Sacroiliac Joint Injection: Description of a Novel Technique.

Sacroiliac (SI) joint arthropathy is the primary pain generator in approximately 15-25% of patients with axial low back pain and traditionally diagnosed with >50% pain reduction following an intra-articular injection localized to the inferior 1/3 of the SI joint. The conventional technique for accessing the SI joint encompasses a posterior approach with fluoroscopic guidance at 10-20° contralateral oblique angulation, and minor adjustments to this approach have been implemented with varying degrees of success. The authors present a novel technique for SI joint injection, infiltrating the middle third of the joint through an alternative far-contralateral oblique (FCO) approach, angulation between 20-40°. This approach theoretically endows easier access to the SI joint and at the very least provides another option for interventionalists in the diagnosis and treatment of sacroiliac joint pain. It can also be utilized to determine if a patient is a candidate for posterior percutaneous SI joint fusion. The authors sought to document this approach to ensure that it was both reproducible and safe, while recognizing the need for future studies.

Review of Interventional Treatments for Cluneal Neuropathy.

BACKGROUND: The most common presentation of cluneal neuropathy is ipsilateral low back and gluteal pain. Cluneal neuralgia has been described historically in surgical contexts, with much of the description and treatment related to entrapment and decompression, respectively. Treatment options for addressing axial low back pain have evolved with advancements in the field of interventional pain medicine, though clinical results remain inconsistent. Recent attention has turned toward peripheral nerve stimulation. Nonsurgical interventions targeting the superior and medial cluneal nerve branches have been performed in cases of low back and buttock pain, but there is no known review of the resulting evidence to support these practices. OBJECTIVES: In this manuscript we provide a robust exploration and analysis of the available literature regarding treatment options for cluneal neuropathy. We provide clinical manifestations and recommendations for future study direction. STUDY DESIGN: Narrative review. METHODS: This was a systematic, evidence-based narrative, performed after extensive review of the literature to identify all manuscripts associated with interventional treatment of the superior and medial cluneal nerves. RESULTS: Eleven manuscripts fulfilled inclusion criteria. Interventional treatment of the superior and middle cluneal nerves includes blockade with corticosteroid, alcohol neurolysis, peripheral nerve stimulation, radiofrequency neurotomy, and surgical decompression. LIMITATIONS: The supportive evidence for interventions in cluneal neuropathy is largely lacking due to small, uncontrolled, observational studies with multiple confounding factors. There is no standardized definition of cluneal neuropathy. CONCLUSION: Limited studies promote beneficial effects from interventions intended to target cluneal neuropathy. Despite increased emphasis and treatment options for this condition, there is little consensus on the diagnostic criteria, endpoints, and measures of therapeutics, or procedural techniques for blocks, radiofrequency, and neuromodulation. It is imperative to delineate pathology associated with the cluneal nerves and perform rigorous analysis of associated treatment options.

Social Media and Professional Conduct (SMART): Best Practice Guidelines from the American Society of Pain and Neuroscience (ASPN).

Social media has revolutionized internet communication and become ubiquitous in modern life. Though it originated as a medium for friendship, social media has evolved into an ideal venue for professional networking, scientific exchange, and brand building. As such, it is a powerful tool with which interventional pain physicians should become familiar. However, given the permanence and visibility of online posts, it is prudent for interventional pain physicians to utilize social media in a manner that is consistent with the ethical and professionalism standards to which they are held by their patients, employers, peers, and state medical boards. While there are extensive publications of professional codes of conduct by medical societies, there is a paucity of literature regarding social media best practices guidelines. Further, to date there have been no social media best practices recommendations specific to interventional pain medicine physicians. While not exhaustive, the aim of this document is to provide recommendations to pain physicians on how to maintain an effective professional and ethical online presence. Specifically, we provide guidance on online persona and professional image, patient-physician interactions online, patient privacy, industry relations, patient education, and brand building.

Best Practices for Postoperative Management of Posterior Sacroiliac Joint Fusion.

Sacroiliac joint (SIJ) pain is a common cause of low back pain. Traditionally, treatment for SIJ joint pain and dysfunction has consisted of physical therapy, medication management, SIJ injections, and SIJ ablations. Improved recognition of the SIJ as an etiology for back pain has led to advances in treatment options. Radiofrequency of the lateral sacral branches has been shown to be effective, though evidence is fraught with inconsistent patient selection, study design and procedural technique. It also does not directly address the mechanical dysfunction of the SIJ. In order to create a more enduring approach SIJ fusion has become an attractive option to reduce pain and to improve function. This method of SI joint treatment requires guidance in the perioperative phase of care from both the physicians and advanced practice providers (APP). In order to improve care and outcomes of those undergoing posterior SI joint fusion the American Society of Pain and Neuroscience appointed an expert panel of physicians and advanced practice providers to create a best practice for the post operative care of this approach. As with any best practice, the panel considered current peer reviewed literature and clinical expertise to create guidance today. This is intended to be a living document with modifications as additional evidence comes to light in data publication. The goals of this paper are to focus on (1) wound care, (2) medication use, (3) physical activity and (4) therapeutic exercises.

Successful Diagnosis of Sacroiliac Joint Dysfunction.

BACKGROUND: Sacroiliac joint (SIJ) pain is one of the most common causes of low back pain, accounting for 15 to 30% of all cases. Although SIJ dysfunction accounts for a large portion of chronic low back pain prevalence, it is often overlooked or under diagnosed and subsequently under treated. The purpose of this review was to establish a best practices model to effectively diagnose SIJ pain through detailed history, physical exam, review of imaging, and diagnostic block. METHODS: A literature search was performed on the diagnosis of sacroiliac joint pain and sacroiliac joint dysfunction. The authors proposed diagnostic recommendations based upon the available literature and a detailed understanding of diagnosing SIJ pain. RESULTS: The practitioner must focus on the history, location of pain, observed gait pattern, and perform key points of the physical exam including sacroiliac provocative maneuvers. If the patient exhibits at least three provocative maneuvers then the SIJ may be considered as a possible source of pain. Additionally, a thorough review of the imaging should be performed to rule out other etiologies of low back pain. In the absence of any pathognomonic tests or examination findings, diagnostic SIJ blocks have evolved as the diagnostic standard. CONCLUSION: The diagnosis of SIJ pain is a multifaceted process that involves a careful assessment including differentiating other pain generators in the region. This involves careful history taking, appropriate physical examination including provocative maneuvers and diagnostic injections. Once the diagnosis is confirmed, long-term solutions may be considered, including recent advances in sacral lateral branch denervation and sacroiliac joint fusion.

Latest Evidence-Based Application for Radiofrequency Neurotomy (LEARN): Best Practice Guidelines from the American Society of Pain and Neuroscience (ASPN).

Radiofrequency neurotomy (RFN), also known as radiofrequency ablation (RFA), is a common interventional procedure used to treat pain from an innervated structure. RFN has historically been used to treat chronic facet-joint mediated pain. The use of RFN has more recently expanded beyond facet-joint mediated pain to peripherally innervated targets. In addition, there has also been the emergence of different radiofrequency modalities, including pulsed and cooled RFN. The use of RFN has been particularly important where conservative and/or surgical measures have failed to provide pain relief. With the emergence of this therapeutic option and its novel applications, the American Society of Pain and Neuroscience (ASPN) identified the need for formal evidence-based guidance. The authors formed a multidisciplinary work group tasked to examine the latest evidence-based medicine for the various applications of RFN, including cervical, thoracic, lumbar spine; posterior sacroiliac joint pain; hip and knee joints; and occipital neuralgia. Best practice guidelines, evidence and consensus grading were provided for each anatomical target.

Review of Current Evidence for Minimally Invasive Posterior Sacroiliac Joint Fusion.

The sacroiliac joint (SIJ) is a large, irregularly shaped, serpentine joint structure bordered anteriorly and posteriorly by the sacroiliac ligaments. With increased recognition of the SIJ as a pain source, treatments have been historically nonsurgical in nature. Common treatments include bracing, medications, activity modification, manual therapy, chiropractic manipulation, physical therapy, and intra-articular SIJ injections. Surgical stabilization and/or fusion of the SIJ may be considered when a patient has persistent moderate to severe pain, functional impairment, and failed conservative management. Surgical stabilization and fusion has traditionally been by way of the transiliac approach. More recent SIJ fusion systems have proposed not only a posterior approach but one that stabilizes the joint space by placing an allograft within the SIJ. Anatomically, a posterior approach is able to avoid neurovascular structures that otherwise are encountered with the transiliac approach and may be performed percutaneously. Preliminary evidence reports consistent pain reduction with minimal complications. This paper is purposed to detail the present evidence of minimally invasive posterior SIJ fusion, as well as highlight the need for further research moving forward.

In vitro activity of a G-quadruplex-stabilizing small molecule that synergizes with Navitoclax to induce cytotoxicity in acute myeloid leukemia cells.

BACKGROUND: Acute Myeloid Leukemia (AML) is a malignancy of myeloid precursor cells that arise from genomic alterations in the expression of key growth regulatory genes causing cells to assume an undifferentiated state and continue to proliferate. Recent efforts have focused on developing therapies that target specific protein products of aberrantly expressed genes. However, many of the identified proteins are difficult to target and thought to be "undrugable" because of structural challenges, protein overexpression, or mutations that confer resistance to therapy. A novel technology that circumvents some of these issues is the use of small molecules that stabilize secondary DNA structures present in the promoters of many potential oncogenes and modulate their transcription. METHODS: This study characterizes the in vitro activity of the G-quadruplex-stabilizing small molecule GQC-05 in AML cells. The effect of GQC-05 on three AML cell lines was analyzed using viability and apoptosis assays. GQC-05 has been shown to down-regulate MYC through G-quadruplex stabilization in Burkitt's lymphoma cell lines. MYC expression was evaluated through qPCR and immunoblotting in the three AML cell lines following the treatment of GQC-05. In order to identify other therapeutic agents that potentiate the activity of GQC-05, combination drug screening was performed. The drug combinations were validated using in vitro cytotoxicity assays and compared to other commonly used chemotherapeutic agents. RESULTS: GQC-05 treatment of KG-1a, CMK and TF-1 cells decreased cell viability and resulted in increased DNA damage and apoptosis. Additionally, treatment of KG-1a, CMK and TF-1 with GQC-05 resulted in decreased expression of MYC mRNA and protein, with a more pronounced effect in KG-1a cells. Combination drug screening identified the Bcl-2/Bcl-XL inhibitor Navitoclax as a compound that potentiated GQC-05 activity. Co-treatment with GQC-05 and Navitoclax showed a synergistic decrease in cell viability of AML cells as determined by Chou-Talalay analysis, and induced more DNA damage, apoptosis, and rapid cytotoxicity. The cytotoxicity induced by GQC-05 and Navitoclax was more potent than that of Navitoclax combined with either cytarabine or doxorubicin. CONCLUSION: These results suggest that the G-quadruplex stabilizing small molecule GQC-05 induces down regulated MYC expression and DNA damage in AML cells. Treatment with both GQC-05 with a Bcl-2/Bcl-XL inhibitor Navitoclax results in increased cytotoxic activity, which is more pronounced than Navitoclax or GQC-05 alone, and more significant than Navitoclax in combination with cytarabine and doxorubicin that are currently being used clinically.

Periprocedural Myocardial Infarction in Contemporary Practice.

"Periprocedural myocardial infarction (MI) occurs infrequently in the current era of percutaneous coronary interventions (PCI) and is associated with an increased risk of mortality and morbidity. Periprocedural MI can occur due to acute side branch occlusion, distal embolization, slow flow or no reflow phenomenon, abrupt vessel closure, and nonidentifiable mechanical processes. Therapeutic strategies to reduce the risk of periprocedural MI include dual antiplatelet therapy, intravenous cangrelor in the periprocedural setting, intravenous glycoprotein IIb/IIIa inhibitor in high-risk patients, anticoagulation with unfractionated heparin, low-molecular-weight heparin or bivalirudin, and embolic protection devices during saphenous vein graft interventions."