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Ryan S D’Souza,1 Yeng F Her,1 Nasir Hussain,2 Jay Karri,3 Michael E Schatman,4 Aaron K Calodney,5 Christopher Lam,6 Thomas Buchheit,7 Brennan J Boettcher,8 George C Chang Chien,9 Scott G Pritzlaff,10 Christopher Centeno,11 Shane A Shapiro,12 Johana Klasova,1 Jay S Grider,13 Ryan Hubbard,14 Eliana Ege,15 Shelby Johnson,8 Max H Epstein,16 Eva Kubrova,8 Mohamed Ehab Ramadan,17 Alexandra Michelle Moreira,18 Swarnima Vardhan,19 Yashar Eshraghi,20 Saba Javed,21 Newaj M Abdullah,22 Paul J Christo,17 Sudhir Diwan,23 Leslie C Hassett,24 Dawood Sayed,6 Timothy R Deer25 1Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA; 2Department of Anesthesiology, The Ohio State Wexner Medical Center, Columbus, OH, USA; 3Departments of Orthopedic Surgery and Anesthesiology, University of Maryland School of Medicine, Baltimore, MD, USA; 4Department of Anesthesiology, Perioperative Care, & Pain Medicine, NYU Grossman School of Medicine, New York, NY, USA; 5Precision Spine Care, Tyler, TX, USA; 6Department of Anesthesiology and Pain Medicine, The University of Kansas Medical Center, Kansas City, KS, USA; 7Department of Anesthesiology, Duke University, Durham, NC, USA; 8Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USA; 9Department of Regenerative Medicine, GCC Institute, Torrance, CA, USA; 10Department of Anesthesiology and Pain Medicine, University of California, Davis, Sacramento, CA, USA; 11Centeno-Schultz Clinic, Broomfield, CO, USA; 12Department of Orthopedic Surgery, Mayo Clinic, Jacksonville, FL, USA; 13Department of Anesthesiology, University of Kentucky College of Medicine, Lexington, KY, USA; 14Department of Sports Medicine, Anderson Orthopedic Clinic, Arlington, VA, USA; 15Department of Physical Medicine & Rehabilitation, Baylor College of Medicine, Houston, TX, USA; 16Department of Physical Medicine & Rehabilitation, Harvard Medical School, Boston, MA, USA; 17Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Hospital, Baltimore, MD, USA; 18Department of Physical Medicine & Rehabilitation, University of Miami/Jackson Memorial Hospital, Miami, FL, USA; 19Department of Internal Medicine, Yale New Haven Health – Bridgeport Hospital, Bridgeport, CT, USA; 20Department of Anesthesiology & Critical Care Medicine, Ochsner Health System, New Orleans, LA, USA; 21Department of Pain Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA; 22Department of Anesthesiology, University of Utah, Salt Lake City, UT, USA; 23Department of Pain Medicine, Advanced Spine on Park Avenue, New York City, NY, USA; 24Mayo Clinic Libraries, Mayo Clinic, Rochester, MN, USA; 25Department of Anesthesiology and Pain Medicine, West Virginia University School of Medicine, Charleston, WV, USACorrespondence: Ryan S D’Souza, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA, Tel +1-(507)-284-9696, Fax +1-(507)-266-7732, Email dsouza.ryan@mayo.eduPurpose: Injectable biologics have not only been described and developed to treat dermal wounds, cardiovascular disease, and cancer, but have also been reported to treat chronic pain conditions. Despite emerging evidence supporting regenerative medicine therapy for pain, many aspects remain controversial.Methods: The American Society of Pain and Neuroscience (ASPN) identified the educational need for an evidence-based guideline on regenerative medicine therapy for chronic pain. The executive board nominated experts spanning multiple specialties including anesthesiology, physical medicine and rehabilitation, and sports medicine based on expertise, publications, research, and clinical practice. A steering committee selected preliminary questions, which were reviewed and refined. Evidence was appraised using the United States Preventive Services Task Force (USPSTF) criteria for evidence level and degree of recommendation. Using a modified Delphi approach, consensus points were distributed to all collaborators and each collaborator voted on each point. If collaborators provided a decision of “disagree” or “abstain”, they were invited to provide a rationale in a non-blinded fashion to the committee chair, who incorporated the respective comments and distributed revised versions to the committee until consensus was achieved.Results: Sixteen questions were selected for guideline development. Questions that were addressed included type of injectable biologics and mechanism, evidence in treating chronic pain indications (eg, tendinopathy, muscular pathology, osteoarthritis, intervertebral disc disease, neuropathic pain), role in surgical augmentation, dosing, comparative efficacy between injectable biologics, peri-procedural practices to optimize therapeutic response and quality of injectate, federal regulations, and complications with mitigating strategies.Conclusion: In well-selected individuals with certain chronic pain indications, use of injectable biologics may provide superior analgesia, functionality, and/or quality of life compared to conventional medical management or placebo. Future high-quality randomized clinical trials are warranted with implementation of minimum reporting standards, standardization of preparation protocols, investigation of dose–response associations, and comparative analysis between different injectable biologics.Keywords: regenerative medicine, injectable biologics, platelet-rich plasma, mesenchymal stem cell, bone marrow aspirate concentrate, pain medicine

Introduction: Artificial intelligence (AI), particularly large-language models like Chat Generative Pre-Trained Transformer (ChatGPT), has demonstrated potential in streamlining research methodologies. Systematic reviews and meta-analyses, often considered the pinnacle of evidence-based medicine, are inherently time-intensive and demand meticulous planning, rigorous data extraction, thorough analysis, and careful synthesis. Despite promising applications of AI, its utility in conducting systematic reviews with meta-analysis remains unclear. This study evaluated ChatGPT's accuracy in conducting key tasks of a systematic review with meta-analysis., Methods: This validation study used data from a published meta-analysis on emotional functioning after spinal cord stimulation. ChatGPT-4o performed title/abstract screening, full-text study selection, and data pooling for this systematic review with meta-analysis. Comparisons were made against human-executed steps, which were considered the gold standard. Outcomes of interest included accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for screening and full-text review tasks. We also assessed for discrepancies in pooled effect estimates and forest plot generation., Results: For title and abstract screening, ChatGPT achieved an accuracy of 70.4%, sensitivity of 54.9%, and specificity of 80.1%. In the full-text screening phase, accuracy was 68.4%, sensitivity 75.6%, and specificity 66.8%. ChatGPT successfully pooled data for five forest plots, achieving 100% accuracy in calculating pooled mean differences, 95% CIs, and heterogeneity estimates ( I 2 score and tau-squared values) for most outcomes, with minor discrepancies in tau-squared values (range 0.01-0.05). Forest plots showed no significant discrepancies., Conclusion: ChatGPT demonstrates modest to moderate accuracy in screening and study selection tasks, but performs well in data pooling and meta-analytic calculations. These findings underscore the potential of AI to augment systematic review methodologies, while also emphasizing the need for human oversight to ensure accuracy and integrity in research workflows., Competing Interests: Competing interests: RSD'S received investigator-initiated research grant funding from Nevro Corp and Saol Therapeutics paid to his institution. Other authors declare no conflicts of interest., (© American Society of Regional Anesthesia & Pain Medicine 2025. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ Group.)

Background: Complex regional pain syndrome (CRPS) is a debilitating and painful condition accompanied by sensory, autonomic, trophic, and/or motor abnormalities. Although CRPS is rare in the general population, the prevalence among individuals at higher risk, particularly posttraumatic and postsurgical patients, remains unknown. This study aims to provide a benchmark that quantifies CRPS prevalence in high-risk groups, and offers insights on potential predictors of developing CRPS., Methods: We conducted a systematic review and meta-analysis to identify studies reporting prevalence of CRPS after an inciting event (eg, fracture, surgery), specifically 12-month and 24-month prevalence (primary outcomes), as well as 3-month and 6-month prevalence (secondary outcomes). Estimates from individual studies were transformed using double-arcsine transformation, and the resulting estimates with 95% confidence interval (CI) were pooled in a meta-analysis using a random-effects model., Results: We included 214 articles with data from 2491,378 participants worldwide (35 countries), of which 16,873 had CRPS. The pooled 12-month and 24-month global prevalence was 3.04% (95% CI, 2.64-3.48) and 6.46% (95% CI, 5.46-7.53), respectively. Subgroup analysis and meta-regression were performed to understand the impact of population-dependent (mechanism of injury, type of CRPS), contextual-dependent (socioeconomic status), and methodological-dependent (study design, publication year) factors. The 12-month prevalence was higher in countries with a high human development index (HDI) compared to those with a medium or very high HDI, was higher in participants with a traumatic inciting injury only versus those with surgical injury only or traumatic/surgical injury, and was higher in prospective versus retrospective studies. Meta-regression analysis showed that publication year was a significant moderator, with more recent articles reporting lower 12-month prevalence., Conclusions: This study provides a benchmark of the global prevalence of CRPS, which anesthesiologists and pain specialists can use to prioritize early diagnosis and identify those at the highest risk for CRPS., Competing Interests: Conflicts of Interest, Funding: Please see DISCLOSURES at the end of this article., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Anesthesia Research Society.)

Competing Interests: Competing interests: RSD is an Associate Editor of Regional Anesthesia and Pain Medicine. RSD receives investigator-initiated research grant funding paid to his institution from Nevro Corp and Saol Therapeutics.

Introduction: Epidural steroid injections and epidural blood patches commonly involve the injection of a small amount of radiocontrast media under fluoroscopy to properly identify the target tissue or anatomic space and prevent off-target or intravascular delivery of therapeutic or diagnostic drugs. Iodinated low osmolar non-ionic contrast media is the standard preparation used as it is considered safe and cost-effective, but gadolinium-based preparations have been used as an alternative for patients with an 'iodine'-related or radiocontrast media allergy label to prevent hypersensitivity reactions. The risk of neurotoxic events when gadolinium is inadvertently injected into the intrathecal space has been reported in recent years, raising concerns when gadolinium-based contrast media is used in lieu of iodinated low osmolar non-ionic contrast media., Methods: A retrospective review was conducted of patients who received gadolinium-based contrast media for procedures with risk of inadvertent intrathecal access from January 1, 2019 to May 1, 2022. Information on patient demographics, allergy label information, and procedure description was documented for all patients who received g adolinium-based contrast media for axial spine procedures (including epidural steroid injections, epidural blood patch procedures, and selective nerve root blocks), and all side effects reported within 1 month of the procedure were recorded. Saved fluoroscopy images of all procedures for which there was concern for possible gadolinium-based contrast media-related side effect were reviewed for evidence of inadvertent intrathecal gadolinium-based contrast media administration. Descriptive statistical analysis was performed using REDCap and IBM SPSS Statistics V.28., Results: We identified 508 patients who received gadolinium-based contrast media during a fluoroscopically guided axial spine procedure. These patients underwent 697 epidural procedures and 23 patients were identified as experiencing an adverse event that could be consistent with possible, probable, or clear signs of exposure to intrathecal gadolinium. Our calculated adverse event rate was 3.3%. Ten patients required additional medical evaluation or treatment., Discussion: Almost all patients in our cohort had an allergy label on their chart that guided the provider to switch to gadolinium-based contrast media, but most were incomplete, ill-defined, or related to allergy to iodine but not iodinated contrast media. Such practice is not recommended based on current guidelines. The current study raises concern regarding the use of gadolinium-based contrast media in axial spine procedures, with the risk of potential severe adverse events, without evidence-based need for avoiding iodinated contrast media., Competing Interests: Competing interests: AH-C received a travel stipend from ASRA to present the poster describing this research at the 2022 Annual Meeting. DAP is the President of ASRA Pain Medicine and has received consulting fees from Avanos, Boston Scientific, Nevro, SI Bone and Medtronic. Pain Diagnostics and Interventional Care has received research support from Avanos, Boston Scientific, Medtronic, Abbott, Nevro and Stimgenics. CH has received funding from Nevro in support of research, unrelated to this work, paid to her institution., (© American Society of Regional Anesthesia & Pain Medicine 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Randomized clinical trials (RCTs) are considered the gold standard for evaluating the efficacy of healthcare interventions. However, conflicts of interest (COIs) can compromise the scientific integrity in these trials. This study characterized COIs in RCTs on spinal cord stimulation for chronic pain, focusing on the prevalence, disclosure, and monetary value of COIs., Methods: This cross-sectional study analyzed RCTs published from January 1, 2013 to July 27, 2023. Primary outcomes included the presence, disclosure, and monetary value of COIs, while secondary outcomes assessed the presence of direct/indirect COIs, sponsor access to data, and associations between COIs and select variables, including journal impact factor, publication year, and study outcomes., Results: Of 38 RCTs, 30 (78.9%) reported COIs. On average, 35.6% of authors per RCT had at least one COI, with a mean of 0.7 COIs per author. The mean annual monetary value of COIs was US$41,157.83 per author per RCT. 29 RCTs (76.3%) had undisclosed COIs, with an average of 24.2% of authors per RCT having undisclosed COIs. Sponsor access to data was reported in 67.6% of RCTs. No associations were observed between the mean percentage of authors with COIs and the monetary value of COIs and select dependent variables (impact factor, publication year, and study outcomes)., Conclusions: A substantial majority of RCTs reported COIs with many authors having undisclosed conflicts, highlighting the need for stringent COI disclosure guidelines to maintain research integrity. Expanding COI registry systems globally and increasing non-industry funding are crucial steps toward enhancing transparency and reducing biases in medical research., Competing Interests: Competing interests: RSD received investigator-initiated grant funding from Nevro and Saol Therapeutics paid to his institution., (© American Society of Regional Anesthesia & Pain Medicine 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The efficacy of spinal cord stimulation (SCS) in chronic pain studies is traditionally assessed by pain scores, which do not reflect the multidimensional nature of pain perception. Despite the evidence of SCS's influence on emotional functioning comprehensive assessments of its effect remain lacking., Objective: To assess changes in emotional and psychosocial functioning in patients who underwent SCS implantation for chronic pain., Evidence Review: Ovid MEDLINE, EMBASE, PsychINFO, Cochrane CENTRAL and Scopus databases were searched for original peer-reviewed publications reporting emotional functioning after SCS. The primary outcomes were a pooled mean difference (MD) in anxiety, depression, global functioning, mental well-being and pain catastrophizing at 12 months. The Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) was used to determine the quality of evidence., Findings: Thirty-two studies were included in the primary analysis. Statistically significant improvements were observed in anxiety (MD -2.16; 95% CI -2.84 to -1.49; p<0.001), depression (MD -4.66; 95% CI -6.26 to -3.06; p<0.001), global functioning (MD 20.30; 95% CI 14.69 to 25.90; p<0.001), mental well-being (MD 4.95; 95% CI 3.60 to 6.31; p<0.001), and pain catastrophizing (MD -12.09; 95% CI -14.94 to -9.23; p<0.001). Subgroup analyses revealed differences in Global Assessment of Functioning and mental well-being based on study design and in depression based on waveform paradigm., Conclusion: The results highlight the statistically and clinically significant improvements in emotional and psychosocial outcomes in patients with chronic pain undergoing SCS therapy. However, these results need to be interpreted with caution due to the very low certainty of evidence per the GRADE criteria., Prospero Registration: CRD42023446326., Competing Interests: Competing interests: RDS received investigator-initiated grant funding pain to his institution from Nevro Corp and Saol Therapeutics., (© American Society of Regional Anesthesia & Pain Medicine 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Persistent chest pain (PCP) following acute COVID-19 infection is a commonly reported symptom with an unclear etiology, making its management challenging. This scoping review aims to address the knowledge gap surrounding the characteristics of PCP following COVID-19, its causes, and potential treatments. This is a scoping review of 64 studies, including observational (prospective, retrospective, cross-sectional, case series, and case-control) and one quasi-experimental study, from databases including Embase, PubMed/MEDLINE, Cochrane CENTRAL, Google Scholar, Cochrane Database of Systematic Reviews, and Scopus. Studies on patients with PCP following mild, moderate, and severe COVID-19 infection were included. Studies with patients of any age, with chest pain that persisted following acute COVID-19 disease, irrespective of etiology or duration were included. A total of 35 studies reported PCP symptoms following COVID-19 (0.24%-76.6%) at an average follow-up of 3 months or longer, 12 studies at 1-3 months and 17 studies at less than 1-month follow-up or not specified. PCP was common following mild-severe COVID-19 infection, and etiology was mostly not reported. Fourteen studies proposed potential etiologies including endothelial dysfunction, cardiac ischemia, vasospasm, myocarditis, cardiac arrhythmia, pneumonia, pulmonary embolism, postural tachycardia syndrome, or noted cardiac MRI (cMRI) changes. Evaluation methods included common cardiopulmonary tests, as well as less common tests such as flow-mediated dilatation, cMRI, single-photon emission computed tomography myocardial perfusion imaging, and cardiopulmonary exercise testing. Only one study reported a specific treatment (sulodexide). PCP is a prevalent symptom following COVID-19 infection, with various proposed etiologies. Further research is needed to establish a better understanding of the causes and to develop targeted treatments for PCP following COVID-19., (© 2023 American Academy of Physical Medicine and Rehabilitation.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of infections to date and has led to a worldwide pandemic. Most patients had a complete recovery from the acute infection, however, a large number of the affected individuals experienced symptoms that persisted more than 3 months after diagnosis. These symptoms most commonly include fatigue, memory difficulties, brain fog, dyspnea, cough, and other less common ones such as headache, chest pain, paresthesias, mood changes, muscle pain, and weakness, skin rashes, and cardiac, endocrine, renal and hepatic manifestations. The treatment of this syndrome remains challenging. A multidisciplinary approach to address combinations of symptoms affecting multiple organ systems has been widely adopted. This narrative review aims to bridge the gap surrounding the broad treatment approaches by providing an overview of multidisciplinary management strategies for the most common long COVID conditions., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Prusinski et al.)

Background: Facet joint cysts (FJCs) are a cause of radiculopathy, back pain, cauda equina syndrome, and/or claudication. They mostly affect the lumbar spine in the elderly, prevailing in women, and are connected to spinal degeneration and instability. We aimed to evaluate the safety and efficacy of open surgical decompression and cyst excision without a subsequent fusion., Methods: We evaluated neurologic symptoms and potential signs of spinal instability on preoperative versus postoperative radiological examination. We performed a histological assessment of the extirpated cysts. Statistical analysis was then performed., Results: Of a total of 66 patients, 44 were included in the present study. The average age was 61.2 years. Female patients prevailed (61.4%). The mean follow-up was 5.3 years. The segment most frequently affected by a FJC was L4-L5 (65.9%). Cyst resection led to significant relief from neurologic symptoms for most patients. Thus, 95.5% of our patients reported their postoperative outcome as excellent. Preoperatively, 43.2% and 47.4% of patients had had radiographic signs of instability on magnetic resonance imaging and signs of spondylolisthesis on dynamic radiographs in the operated segment, respectively, with 54.5% manifesting signs of spondylolisthesis in the same segment on a postoperative dynamic radiograph. Despite spondylolisthesis progression, no patient required reoperation. Histologically, pseudocysts without synovium were more frequent than were synovial cysts., Conclusions: Simple FJC extirpation is a safe and effective method for resolving radicular symptoms, with excellent long-term outcomes. It does not lead to the development of clinically significant spondylolisthesis in the operated segment; thus, no supplementary fusion with instrumented stabilization is required., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Tinnitus is an intrusive and chronic illness affecting a significant portion of the population, decreasing affected individuals' quality of life and socioeconomic functioning. Transcranial Direct Current Stimulation (tDCS) is a non-invasive neuromodulatory method utilizing weak electrical currents to elicit short and long-term central nervous system changes. Several studies have proven its effect on tinnitus. We aimed to broaden the knowledge and provide data on the effect and its retention., Methods: In the randomized, double-blinded, sham-controlled trial, 39 patients (active n = 19, sham n = 20) underwent bifrontal tDCS (anode over right dorsolateral prefrontal cortex (DLPFC), cathode left DLPFC, current of 1.5 mA, 20 min, 6 sessions in 2 weeks). Tinnitus Functional Index (TFI), Iowa Tinnitus Handicap Questionnaire (ITHQ), Beck Anxiety Inventory (BAI), Zung Self-Rating Depression Scale (SDS), and WHO-Quality of Life-BREF were employed in 4 evaluation points, including the follow-ups of 6 weeks and 6 months., Results: We reached a delayed, significant long-term improvement ( p < 0.05) in auditory difficulties associated with tinnitus and noticed it even after 6 months compared to placebo. We also reached a short-term, negative effect in the psychological domain of WHO-Quality of Life-BREF ( p < 0.05). Not all subdomains of TFI and ITHQ reached statistical significance during the data analysis, even though specific positive trends were noticed., Conclusion: We proved partial, positive, long-term effects of tDCS on tinnitus and short-term, negative, transient effect on a specific aspect of the general quality of life. We expanded upon the results of previous trials and provided data concerning the longevity and the precise effect of multiple sessions, bifrontal DLPFC tDCS. Our sample size ( n = 39) was limited, which might have contributed to the lesser statistical power of the analyzed items., Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT05437185]., Competing Interests: Author JA was employed by Krajska zdravotni a.s. – Most Hospital, Most, Czechia since January 2022. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mares, Albrecht, Buday, Podgorna, Le, Magyarova, Poshor, Halik, Buna, Capek, Kostylkova, Klasova, Fabian and Anders.)

The relationship between tDCS (transcranial direct current stimulation) and its influence on glycemia has been the aim of limited research efforts. Usually, the focus has been set on lowering the blood sugar level or interference with insulin resistance, but also the treatment of diabetic polyneuropathy and pain management. In this case report, we outline the development of hyperglycemia and the following onset of type I diabetes during a series of tDCS in a 24-year old Caucasian female patient treated with our research protocol (10 sessions; 2 mA; 30 min; the anode over F3; the cathode over Fp2) for anorexia nervosa., (Copyright © 2020 Mares, Ceresnakova, Albrecht, Buday, Klasova, Horackova, Raboch, Papezova and Anders.)

The genome of Mycoplasma gallisepticum A5969 contains a truncated pseudogene for 16S rRNA in addition to a single unsplit rRNA-operon and a second discontinuous set of rRNA genes. Other M. gallisepticum strains tested do not possess the truncated gene. This gene is almost identical to full-size isolated 16S rRNA gene starting from at least 500 nucleotides upstream of the coding sequence and ending at the 977th nucleotide within the structural part of 16S rRNA.