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Ana P Pereira,1,&ast; Dora Janela,1,&ast; Anabela C Areias,1 Maria Molinos,1 Xin Tong,2 Virgílio Bento,1 Vijay Yanamadala,1,3,4 Steven P Cohen,5,6 Fernando Dias Correia,1,7 Fabíola Costa1 1Sword Health, Inc, Draper, Utah, USA; 2Department of Psychology, University of Virginia, Charlottesville, VA, USA; 3Department of Surgery, Quinnipiac University Frank H. Netter School of Medicine, Hamden, Connecticut, USA; 4Department of Neurosurgery, Hartford Healthcare Medical Group, Westport, Connecticut, USA; 5Northwestern Feinberg School of Medicine, Chicago, Illinois, USA; 6Walter Reed National Military Medical Center, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA; 7Neurology Department, Centro Hospitalar E Universitário Do Porto, Porto, Portugal&ast;These authors contributed equally to this workCorrespondence: Fabíola Costa, Sword Health Inc, 13937 Sprague Lane Ste 100, Draper, UT, 84020, USA, Tel +1 385-308-8034, Fax +1 801-206-3433, Email f.costa@swordhealth.comBackground: Obesity is a known risk factor and aggravator of musculoskeletal (MSK) conditions. The rising prevalence of obesity calls for scalable solutions to address MSK conditions in this population, given their complex clinical profile and barriers to accessing care.Purpose: To evaluate the engagement and clinical outcomes of a fully remote digital care program in patients with MSK conditions, focusing on those with and without comorbid obesity.Patients and Methods: A post-hoc analysis of a prospective, longitudinal, single-arm observational home-based study conducted between August, 2023, and August, 2024. Adults suffering from chronic MSK pain were categorized according to their body mass index (BMI) into non-obesity, obesity and severe obesity. Outcomes included completion rates, engagement, satisfaction, pain (minimal clinically important change: 30%), impairment in daily activities, and patient global impression of change (PGIC). Depending on the clinical outcomes, latent basis growth analysis and logistic regression were used.Results: Completion rates were high across all groups (77.5– 85.6%), although slightly lower in the obesity groups. Fairly similar engagement was observed with both exercise sessions and the educational content (1.9– 2.2 exercise sessions per week; 8.10– 9.31 educational content videos watched). Obesity groups interacted more with the physical therapists than the non-obesity group (severe obesity: 24.6 (SD 10.1); obesity: 23.2 (SD 10.46) vs non-obesity: 22.4 (SD 9.8), P < 0.001). Despite higher baseline risk and clinical impairment in the obesity groups, all groups showed significant pain reductions, with pain responder rates ranging from 56.6 to 63.6%, slightly lower in the severe obesity group. Improvements in daily activities were significant across groups, alongside a positive PGIC (50.4– 53.6%). Satisfaction was very high (> 9/10) in all BMI groups.Conclusion: Despite worse baseline clinical presentations, obesity groups achieved high completion rates, engagement, and significant clinical improvements comparable to the non-obesity group, highlighting the potential of a digital program for this population.Plain Language Summary: Obesity is a common risk factor for musculoskeletal conditions. With obesity rates rising, it is important to find scalable ways to help people with musculoskeletal conditions who are also dealing with obesity, especially since these patients often face challenges in accessing care. Digital telerehabilitation has emerged as an alternative to improve care access, while promoting similar results to in-person care, but its suitability to manage patients with both musculoskeletal and obesity conditions remains underexplored. This study evaluated the suitability of a fully remote digital care program for patients with musculoskeletal conditions, both with and without obesity. We analyzed data from a study of patients with chronic pain, grouping them by body mass index (BMI) into non-obesity, obesity, and severe obesity. Completion rates were high for all BMI groups (77.5– 85.6%), though slightly lower for people with obesity. Despite patients with obesity starting the program with more severe pain and limitations, all groups showed significant reductions in pain. Improvements in daily activities were seen across all groups, and over half of the participants reported positive changes in their condition. Satisfaction with the program was very high in all groups (over 9 out of 10). In conclusion, the remote digital care program was effective for patients with musculoskeletal conditions, including those with obesity, helping them achieve high participation and significant clinical improvements. This study highlights the potential of digital care to effectively manage musculoskeletal conditions among patients with obesity.Keywords: body mass index, physical therapy, telerehabilitation, ehealth, pain

Fabíola Costa,1 Dora Janela,1 Maria Molinos,1 Robert G Moulder,2 Jorge Lains,3,4 Virgílio Bento,1 Justin Scheer,5 Vijay Yanamadala,1,6,7 Fernando Dias Correia,1,8 Steven P Cohen9,10 1SWORD Health, Inc, Clinical Research, Draper, UT, USA; 2Institute for Cognitive Science, University of Colorado Boulder, Boulder, CO, USA; 3Rovisco Pais Medical and Rehabilitation Centre, Tocha, Portugal; 4Faculty of Medicine, Coimbra University, Coimbra, Portugal; 5Department of Neurological Surgery, University of California, San Francisco, CA, USA; 6Department of Surgery, Quinnipiac University Frank H. Netter School of Medicine, Hamden, CT, USA; 7Department of Neurosurgery, Hartford Healthcare Medical Group, Westport, CT, USA; 8Neurology Department, Centro Hospitalar e Universitário do Porto, Porto, Portugal; 9Departments of Anesthesiology & Critical Care Medicine, Physical Medicine and Rehabilitation, Neurology, and Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA; 10Departments of Anesthesiology and Physical Medicine and Rehabilitation and Anesthesiology, Uniformed Services University of the Health Sciences, Bethesda, MD, USACorrespondence: Fernando Dias Correia, 65 E Wadsworth Park Dr Ste 230, Draper, UT, 84020, USA, Tel +1 385-308-8034, Fax +1 801-206-3433, Email fcorreia@swordhealth.comBackground: Low back pain (LBP) has a lifetime prevalence of 70– 80%. Access to timely and personalized, evidence-based care is key to prevent chronic progression. Digital solutions may ease accessibility to treatment while reducing healthcare-related costs.Purpose: We aim to report the results of a fully remote digital care program (DCP) for acute LBP.Patients and Methods: This was an interventional, single-arm, cohort study of patients with acute LBP who received a DCP. Primary outcome was the mean change in disability (Oswestry Disability Index – ODI) after 12 weeks. Secondary outcomes included change in pain (NPRS), analgesic consumption, surgery likelihood, depression (PHQ-9), anxiety (GAD-7), fear-avoidance beliefs (FABQ-PA), work productivity (WPAI) and engagement.Results: A total of 406 patients were enrolled in the program and of those, 332 (81.8%) completed the intervention. A significant disability reduction of 55.1% (14.93, 95% CI 13.95; 15.91) was observed, corresponding to a 76.1% responder rate (30% cut-off). Disability reduction was accompanied by significant improvements in pain (61.0%), depression (55.4%), anxiety (59.5%), productivity (65.6%), fear-avoidance beliefs (46.3%), intent to pursue surgery (59.1%), and analgesic consumption (from 35.7% at baseline to 10.8% at program end). DCP-related patient satisfaction score was 8.7/10.0 (SD 1.4).Conclusion: This study demonstrated the utility of a multimodal DCP for patients with acute LBP. Very high adherence rates and patient satisfaction were observed, alongside significant reductions in all assessed outcomes, consistent with the growing body of evidence supporting the management of acute LBP with DCPs.Keywords: physical therapy, telerehabilitation, digital therapy, eHealth, musculoskeletal conditions

Background: Intra-articular corticosteroid (IACS) injection and peri-articular corticosteroid injection are commonly used to treat musculoskeletal conditions. Results vary by musculoskeletal region, but most studies report short-term benefit with mixed results on long-term relief. Publications showed adverse events from single corticosteroid injections. Recommended effective doses were lower than those currently used by clinicians., Methods: Development of the practice guideline for joint injections was approved by the Board of Directors of the American Society of Regional Anesthesia and Pain Medicine and the participating societies. A Corticosteroid Safety Work Group coordinated the development of three guidelines: peripheral nerve blocks and trigger points; joints; and neuraxial, facet, and sacroiliac joint injections. The topics included safety of the technique in relation to landmark-guided, ultrasound-guided, or radiology-aided injections; effect of the addition of the corticosteroid on the efficacy of the injectate; and adverse events related to the injection. Experts on the topics were assigned to extensively review the literature and initially develop consensus statements and recommendations. A modified version of the US Preventive Services Task Force grading of evidence and strength of recommendation was followed. A modified Delphi process was adhered to in arriving at a consensus., Results: This guideline focuses on the safety and efficacy of corticosteroid joint injections for managing joint chronic pain in adults. The joints that were addressed included the shoulder, elbow, hand, wrist, hip, knee, and small joints of the hands and feet. All the statements and recommendations were approved by all participants and the Board of Directors of the participating societies after four rounds of discussion. There is little evidence to guide the selection of one corticosteroid over another. Ultrasound guidance increases the accuracy of injections and reduces procedural pain. A dose of 20 mg triamcinolone is as effective as 40 mg for both shoulder IACS and subacromial subdeltoid bursa corticosteroid injections. The commonly used dose for hip IACS is 40 mg triamcinolone or methylprednisolone. Triamcinolone 40 mg is as effective as 80 mg for knee IACS. Overall, IACS injections result in short-term pain relief from a few weeks to a few months. The adverse events include an increase in blood glucose, adrenal suppression, detrimental effect on cartilage lining the joint, reduction of bone mineral density, and postoperative joint infection., Conclusions: In this practice guideline, we provided specific recommendations on the role of corticosteroids in joint, bursa, and peritendon injections for musculoskeletal pain., Competing Interests: Competing interests: HTB: NIH NIAMS P30AR072579; DAP: consulting: Avanos, Boston Scientific, Medtronic, Nevro, and SI Bone; Research support: Avanos, Boston Scientific, Medtronic, Nevro; AN: speaker: Averitas Pharmaceuticals; Research: Saol Therapeutics; DS: Advisory Board, funded research: Scilex; speaker: AbbVie; MSE: funded research: SPR Therapeutics; consultant: Avanos, Abbott; MM: consultant: Juris Medicus; AA-E: consultant: Curonix; AC: research funding: NIH RM1NS128956; consultant: Swing Therapeutics, Scilex Pharmaceuticals; TLD: research support: Biohaven, NIH; consultant: Guidepoint Global; speaker honorarium: Remedy Health Media; CP: consulting: Mainstay Medical; royalties, UpToDate; SS: consultant: SPR Therapeutics, Allergan; AS: NIH R34AR080279; SPC: consulting (past 2 years): Avanos, Scilex, SPR, SWORD, Releviate (ended), Clearing (ended), Persica (inactive); research funds paid to institution: Scilex, Avanos; JAH: grants: Neiman Health Policy Institute (no number associated with this foundation grant); consulting (last 12 months): Medtronic, Relievant, Persica; DMC Chair: Balt, Rapid Medical, Arsenal; BS: consultant: State Farm, Carelon; TM: consultant, Interventional AnalgesiX; SN: consultant, Shiratonics; AW: investigator-initiated grant, Goodblends; TH: Acella: Advisory Board, speaker: Acella; CH: research grant: Nevro. The remaining authors declare no competing interests., (© American Society of Regional Anesthesia & Pain Medicine 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Introduction: This exploratory study investigates the potential of perineuromal hydrodissection as an adjunct to opioid therapy for postamputation pain, specifically focusing on residual limb and phantom limb pain (PLP). Given the correlations between acute pain and the development of chronic pain, the primary aims were to estimate the effect size of early hydrodissection of scar tissue around residual limb neuroma(s) and to identify the best time frame for treatment., Methods: Seventy-four patients with war-related limb amputations and painful neuromas were included in this observational analysis. Thirty-eight Ukrainian patients with war-related limb amputation and a painful neuroma(s) who underwent hydrodissection and opioid therapy within 6 months of amputation were compared with 36 patients who received opioids alone. Co-primary outcome measures were median reduction from baseline in average residual limb and PLP at 12 weeks. The composite positive outcome was designated as a ≥2-point decrease or 30% reduction in average residual limb and PLP, satisfaction with treatment, and not requiring an increase in analgesics., Results: Hydrodissection as an add-on to opioids resulted in a greater reduction in average residual limb pain at 12 weeks (-2.00±1.00 vs -1.00±1.00; p<0.001) and earlier time periods, but PLP only through 4 weeks. At 12 weeks, Hospital Anxiety and Depression Scale anxiety (10.00±2.00 vs 11.00±1.00; p<0.001) but not depression score was lower in the hydrodissection group. Opioid use in the hydrodissection group significantly declined from 41.32±9.63 to 33.42±8.78 morphine equivalents per day (p=0.001) over the study, but not in the opioid-only group (p=0.20). Differences in 12-week satisfaction rates were not significant., Conclusions: This exploratory study suggests perineuromal hydrodissection may improve residual limb pain and to a lesser degree phantom limb pain, particularly when implemented early in the course of postamputation pain. The study provides preliminary effect size estimates and identifies acute pain as a potential characteristic of patients who may respond more favorably to this intervention. Randomized controlled trials are needed to confirm these findings and control for the confounding variables identified., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2025. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ Group.)

Background/importance: Driving under the influence of drugs (DUID) refers to operating a vehicle after consuming drugs or medications other than alcohol that impair the ability to drive safely. There is no consensus on legal limits for drug intoxication while driving in the USA. Balancing the benefits of prescription medications, such as opioids, with traffic safety remains an ongoing public health challenge., Objective: This article examines DUID policy and provides recommendations for policy improvement and unification grounded in scientific evidence on opioid-related impairment and driving risks., Evidence Review: A literature review of epidemiologic data, psychomotor effects, and public policy related to opioid use and driving was conducted. A total of 38 epidemiological studies, 21 studies on psychomotor effects, and pertinent laws and policies were reviewed., Findings: Epidemiological data reveal an increasing prevalence of opioid-positive drivers and an association between opioid use and elevated risk of motor vehicle collisions. Psychomotor studies show mixed results, with some indicating impairment in opioid users and others suggesting minimal effects on driving ability. State laws regarding DUID remain heterogeneous, with trends toward expanded testing powers, lower impairment thresholds, and limitations on prescription-based defenses. The lack of standardized opioid testing limits and inconsistent policy approaches across states hinder effective management of opioid-related impaired driving., Conclusions: A balanced public health approach can reduce opioid-involved crashes through education, prevention, enhanced enforcement tools, and rehabilitation. In drafting future DUID laws, policymakers must analyze evolving opioid research when balancing the pain relief of opioids with public roadway safety., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Despite humanity's long experience with amputations, postamputation pain remains a highly prevalent, incompletely understood, and clinically challenging condition. There are two main types of postamputation pain: residual limb pain (including but not limited to the "stump") and phantom limb pain. Despite considerable overlap between the two, they also have distinct clinical features, risk factors, and pathophysiological mechanisms. Central, peripheral, and spinal mechanisms may all contribute to the protean manifestations of persistent postamputation pain; an improved understanding of these mechanisms will be essential to identify the most promising interventions for the prevention and treatment of postamputation pain. Although there are currently no standardized prevention or treatment recommendations for any type of postamputation pain, an evidence-based, multimodal strategy including pharmacological agents, nonsurgical procedures, surgery, complementary and integrative techniques, and assistive technologies may prevent the development of chronic postamputation pain after amputation and/or optimize treatment outcomes., Competing Interests: Competing interests: SPC has served as a consultant to SPR, which manufactures a peripheral nerve stimulation system studied in PAP. All other authors report no relevant competing interests or financial disclosures., (© American Society of Regional Anesthesia & Pain Medicine 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Marasmius crinis-equi , known as the horse hair fungus, is a litter-decomposing fungus that is opportunistically pathogenic on various plants. We sequenced the genome of M. crinis-equi strain GH-76 isolated from thread blight disease-infected cacao leaves in Ghana. The genome is 72.8 Mbp in size and 91.2% complete via benchmarking universal single-copy orthologs (BUSCO).

Introduction: Pain from the cervical facet joints, either due to degenerative conditions or due to whiplash-related trauma, is very common in the general population. Here, we provide an overview of the literature on the diagnosis and treatment of cervical facet-related pain with special emphasis on interventional treatment techniques., Methods: A literature search on the diagnosis and treatment of cervical facet joint pain and whiplash-associated disorders (WAD) was performed using PubMed, Cochrane, and Embase databases. All relevant literature was retrieved and summarized., Results: Facet-related pain is typically diagnosed based on history and physical examination of the patients, combined with a diagnostic block (eg, with local anesthetic) of the medial branches innervating the joints. There is no additive value for imaging techniques to diagnose cervical facet pain, but imaging may be used for procedure planning. First-line therapy for pain treatment includes focused exercise, graded activity, and range-of-motion training. Pharmacological treatment may be considered for acute facet joint pain; however, for chronic facet joint pain, evidence for pharmacological treatment is lacking. Considering the lack of evidence for treatment with botulinum toxin, intra-articular steroid injections, or surgery, these interventions are not recommended. Diagnostic blocks are not considered a viable treatment option, though some patients may experience a prolonged analgesic effect. Long-term analgesia (>6 months) has been observed for radiofrequency treatment of the medial branches., Conclusions: Cervical facet pain is diagnosed based on history, physical examination, and a diagnostic block of the medial branches innervating the painful joints. Conservative management, including exercise therapy, is the first line of treatment. When conservative management does not result in adequate improvement of pain, radiofrequency treatment of the medial branches should be considered, which often results in adequate pain relief., (© 2025 The Author(s). Pain Practice published by Wiley Periodicals LLC on behalf of World Institute of Pain.)

Background: Pulmonary hypertension in children is progressive with wide variability in prognosis. This document provides an evidence-based clinical practice guideline for the management of children with progressive pulmonary hypertension despite optimal therapy. Methods: A multidisciplinary panel identified pertinent questions regarding the management of children with pulmonary hypertension that has progressed despite optimal therapy, conducted systematic reviews of the relevant literature, and applied the Grading of Recommendations, Assessment, Development and Evaluation approach to develop clinical recommendations. Results: After reviewing the research evidence, the panel considered the balance of desirable (benefits) and undesirable (harms and burdens) effects of the interventions in each proposed question. Valuation of our main outcomes was also considered, together with resources required, equity, acceptability, and feasibility. Recommendations were developed for or against interventional strategies specific to children with pulmonary hypertension that has progressed despite optimal therapy. Conclusions: Although there is a growing population of children with pulmonary hypertension, there is a striking lack of empirical evidence regarding management of those whose disease has progressed despite optimal pharmacotherapy. The panel formulated and provided the rationale for clinical recommendations for or against interventional strategies on the basis of this limited empirical evidence, coupled with expert opinion, to aid clinicians in the management of these complex pediatric patients. In addition, we identified important areas for future research.

The recent SARS-CoV-2 pandemic has underscored the significance of viral infections, affecting billions of lives and costing trillions of dollars globally. Even beyond SARS-CoV-2, common infections with viruses like influenza, HIV, and herpesviruses have profound impacts beyond their typical manifestations, often triggering acute and chronic pain syndromes that can be life-altering. These virally induced pain states can arise through direct viral replication within neurons, or indirectly, via immune responses to infection in both the contexts of afferent signaling in the dorsal root ganglion (DRG) or subsequent higher order integration in intracranial systems. Varicella-zoster virus (VZV), influenza virus, and SARS-CoV-2 each provide a unique lens through which to examine the interplay between viral activity and pain. This perspective paper is not meant to be an exhaustive review of virally-induced neuropathic pain states. It seeks to explore curated aspects of the complexities of these pain states, identify research gaps, and suggest solutions using nanoscale molecular understanding and psychoneuroimmunological and biopsychosocial frameworks. Each subheading is accompanied by a list of related issues for study which we think will lead to advances in our understanding of the vexing pain phenotype associated with viral infection., Competing Interests: The 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., (© 2025 Dochnal, Cohen, Hutchinson, Miller and Yaksh.)

Background: Checkpoint inhibitor pneumonitis (CIP) that develops following immune checkpoint inhibitor (ICI) treatment can be difficult to distinguish from other common etiologies of lung inflammation in cancer patients. Here, we evaluate the bronchoalveolar lavage fluid (BAL) for potential biomarkers specific to CIP., Methods: We conducted a retrospective study of patients who underwent standard of care bronchoscopy to compare the cytokines of interest between patients with and without CIP and with and without immune-mediated pulmonary diseases. Pulmonary diagnoses were determined by the treating clinician at the time of bronchoscopy and retroactively reviewed for agreement by the study team., Results: Thirty-seven patients were included, and 24 (64.9%) had pulmonary infection, 2 (5.4%) had pulmonary edema, 6 (16.2%) had non-CIP drug-induced pneumonitis, 3 (8.1%) had CIP, 5 (13.5%) had immune-mediated ILD or autoimmune vasculitis, 4 (10.8%) had cancer progression, and 4 (10.8%) had nonimmune-mediated interstitial lung disease (ILD). IL-6 from the BAL was significantly higher in patients with CIP compared to those with cancer progression and nonimmune-mediated ILD, and IL-6 was significantly higher in patients with immune-mediated pulmonary diseases compared to cancer progression, nonimmune-mediated ILD, and infection., Conclusions: BAL IL-6 distinguished CIP from other common, important causes of pulmonary infiltrates in patients with cancer, suggesting it may give insight into the pathophysiology of CIP and has potential as a biomarker., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: The study protocol was approved by the Ohio State University Institutional Board (2023C0071), and a waiver of consent was granted due to the retrospective nature of analysis., (© 2024. The Author(s).)

Objective: To determine variables associated with difficult clinical encounters., Patients and Methods: This was a cross-sectional study of 428 new patients evaluated from 2022 to 2023. Demographic, clinical, social (eg, missed appointments, prior felony conviction, prior pain physicians, medical assistance) and visit-related (eg, visit took longer than expected, difficulty communicating) information was recorded, supplemented by in-person history gathered by the trainee and attending whose demographic data were also recorded. Physicians independently rated the "difficulty" of the encounter on a 6-point Likert scale from 1 = very easy/pleasant, 2 = easy/pleasant, 3 = neutral/average, 4 = difficult, 5 = very difficult, to 6 = extremely difficult. A difficult encounter was a combined trainee and attending rating of one IQR above the median of 2.0±1.75., Results: Among 428 participants, mean ± SD age was 54.2±15.8 years and 261 (61.0%) were female. Attending gender, gender concordance, race and racial concordance, and years of physician experience were not associated with difficulty. In multivariable analysis, requesting opioids (P=.001), lengthier than expected visit (P<.001), hostile/demanding behavior (P=.003), refusal to try recommended treatment (P=.002), unrealistic expectations (P<0.001), and difficulty communicating (P=.02) were associated with difficult encounters., Conclusion: Most variables associated with physician impressions of difficult encounters were visit-related, suggesting some patient-related factors (eg, prior substance abuse, translator requirement) may be less relevant in pain patients. Future research should evaluate interventions designed to decrease the difficulty of encounters and determine their effect on patients and physicians., (Published by Elsevier Inc.)

Introduction: Chronic knee pain is defined as pain that persists or recurs over 3 months. The most common is degenerative osteoarthritis (OA). This review represents a comprehensive description of the pathology, diagnosis, and treatment of OA of the knee., Methods: The literature on the diagnosis and treatment of chronic knee pain was retrieved and summarized. A modified Delphi approach was used to formulate recommendations on interventional treatments., Results: Patients with knee OA commonly present with insidious, chronic knee pain that gradually worsens. Pain caused by knee OA is predominantly nociceptive pain, with occasional nociplastic and infrequent neuropathic characteristics occurring in a diseased knee. A standard musculoskeletal and neurological examination is required for the diagnosis of knee OA. Although typical clinical OA findings are sufficient for diagnosis, medical imaging may be performed to improve specificity. The differential diagnosis should exclude other causes of knee pain including bone and joint disorders such as rheumatoid arthritis, spondylo- and other arthropathies, and infections. When conservative treatment fails, intra-articular injections of corticosteroids and radiofrequency (conventional and cooled) of the genicular nerves have been shown to be effective. Hyaluronic acid infiltrations are conditionally recommended. Platelet-rich plasma infiltrations, chemical ablation of genicular nerves, and neurostimulation have, at the moment, not enough evidence and can be considered in a study setting. The decision to perform joint-preserving and joint-replacement options should be made multidisciplinary., Conclusions: When conservative measures fail to provide satisfactory pain relief, a multidisciplinary approach is recommended including psychological therapy, integrative treatments, and procedural options such as intra-articular injections, radiofrequency ablation, and surgery., (© 2024 The Author(s). Pain Practice published by Wiley Periodicals LLC on behalf of World Institute of Pain.)

Introduction: Complex regional pain syndrome (CRPS) is a clinical disorder that can develop following surgery or trauma. Based on the most prominent underlying pathophysiological mechanisms, CRPS can be classified into different subtypes, namely inflammatory, nociplastic/neuropathic, vasomotor, and motor. Depending on the subtype, personalized treatment can be applied. If conservative treatments are insufficient or ineffective, more invasive treatments may be recommended. This article provides an overview of the most recent insights into CRPS and discusses the most common invasive treatments., Methods: The literature regarding interventional treatments for CRPS has been systematically reviewed and summarized., Results: Bisphosphonates are effective in treating the inflammatory subtype, while ketamine can provide pain relief for the nociplastic/neuropathic subtype. Sympathetic blocks are effective in addressing vasomotor disturbances. For patients with refractory symptoms, neurostimulation is a viable option due to its multimechanistic properties for all subtypes. End-of-line motor disturbances may benefit from intrathecal baclofen., Conclusions: CRPS is a debilitating condition with an unpredictable course. The effectiveness of treatment varies from patient to patient. When conservative approaches prove insufficient, gradual progression to invasive treatments based on the underlying subtype is recommended., (© 2024 The Author(s). Pain Practice published by Wiley Periodicals LLC on behalf of World Institute of Pain.)

Background: Many conditions, including autoimmune disease and idiopathic pulmonary hemosiderosis (IPH), can cause diffuse alveolar hemorrhage (DAH). Little is known about the epidemiology and outcomes in children., Objectives: This retrospective cohort study sought to describe the etiologies and outcomes of DAH in pediatric patients at a tertiary care center., Methods: This study involved review of patient records with diagnostic codes or bronchoscopy reports suggestive of pulmonary hemorrhage at a large children's hospital over 11 years (2010-2020). Patients were included if they met criteria for DAH, defined as bilateral pulmonary infiltrates and at least one of the following: (1) hemoptysis, (2) blood visible on bronchoscopic exam without apparent airway source, or (3) DAH noted on biopsy or autopsy. Infants less than 10 days corrected gestational age were excluded., Results: Seventy-one children with DAH were included in the analysis. Cardiovascular disease was the most common etiology. Bleeding diathesis was common, but all patients had other causes of DAH. Patients with IPH were younger than those with autoimmune disease (p < .001). Most (77%) patients required mechanical ventilation, though this was less common among patients with autoimmune disease. Overall mortality was high (37%) but varied based on underlying etiology; mortality was higher in patients with cardiovascular disease (65%) while no deaths were seen in patients with autoimmune disease or IPH (p = .002). Survivors of DAH who performed pulmonary function tests had normal lung function., Conclusions: DAH frequently causes respiratory failure in children. In our cohort, mortality was highest in patients with cardiovascular disease., (© 2024 The Author(s). Pediatric Pulmonology published by Wiley Periodicals LLC.)

Background: The smallest meaningful improvement in pain scores (minimal clinically important difference [MCID]) after an analgesic intervention is essential information when both interpreting published data and designing a clinical trial. However, limited information is available for patients with chronic pain conditions, and what is published is derived from studies involving pharmacologic and psychological interventions. We here calculate these values based on data collected from 144 participants of a previously published multicenter clinical trial investigating the effects of a single treatment with percutaneous cryoneurolysis., Methods: In the original trial, we enrolled patients with a lower-limb amputation and established phantom pain. Each received a single-injection femoral and sciatic nerve block with lidocaine and was subsequently randomized to receive either ultrasound-guided percutaneous cryoneurolysis or sham treatment at these same locations. Investigators, participants, and clinical staff were masked to treatment group assignment with the exception of the treating physician performing the cryoneurolysis, who had no subsequent participant interaction. At both baseline and 4 months (primary end point), participants rated their phantom limb pain based on a numeric rating scale (NRS) and their interference of pain on physical and emotional functioning as measured with the Brief Pain Inventory's interference subscale. They subsequently qualitatively defined the change using the 7-point ordinal Patient Global Impression of Change (PGIC). The smallest clinically meaningful improvements in phantom limb pain and Brief Pain Inventory scores were calculated using an anchor-based method based on the PGIC., Results: The median (interquartile range [IQR]) phantom pain NRS (0-10) improvements at 4 months considered small, medium, and large were 1 [1-1], 3 [3-4], and 4 [3-6], respectively. The median improvements in the Brief Pain Inventory interference subscale (0-70) associated with a small, medium, and large analgesic changes were 16 [6-18], 24 [22-31], and 34 [22-46]. The proportions of patients that experienced PGIC ≥5 were 33% and 36% in the active and placebo groups, respectively. The relative risk of a patient experiencing PGIC ≥5 in the active group compared to the sham group with 95% confidence interval was 0.9 (0.6-1.4), P = .667., Conclusions: Amputees with phantom limb pain treated with percutaneous cryoneurolysis rate analgesic improvements as clinically meaningful similar to pharmacologic treatments, although their MCID for the Brief Pain Inventory was somewhat larger than previously published values. This information on patient-defined clinically meaningful improvements will facilitate interpretation of available studies and guide future trial design., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2024 International Anesthesia Research Society.)

Pain is the leading reason people seek orthopedic and rheumatological care. By definition, most pain can be classified as nociceptive, or pain resulting from non-neural tissue injury or potential injury, with between 15% and 50% of individuals suffering from concomitant neuropathic pain or the newest category of pain, nociplastic pain, defined as "pain arising from altered nociception despite no clear evidence of actual or threatened tissue damage, or of a disease or lesion affecting the somatosensory system." Pain classification is important because it affects treatment decisions at all levels of care. Although several instruments can assist with classifying treatment, physician designation is the reference standard. The appropriate treatment of pain should ideally involve multidisciplinary care including physical therapy, psychotherapy and integrative therapies when appropriate, and pharmacotherapy with non-steroidal anti-inflammatory drugs for acute, mechanical pain, membrane stabilizers for neuropathic and nociplastic pain, and serotonin-norepinephrine reuptake inhibitors and tricyclic antidepressants for all types of pain. For nonsurgical interventions, there is evidence to support a small effect for epidural steroid injections for an intermediate-term duration, and conflicting evidence for radiofrequency ablation to provide at least 6months of benefit for facet joint pain, knee osteoarthritis, and sacroiliac joint pain. Since pain and disability represent the top reason for elective surgery, it should be reserved for patients who fail conservative interventions. Risk factors for procedural failure are the same as risk factors for conservative treatment failure and include greater disease burden, psychopathology, opioid use, central sensitization and multiple comorbid pain conditions, poorly controlled preoperative and postoperative pain, and secondary gain., (Copyright © 2024. Published by Elsevier Masson SAS.)

Trial Registration: ClinicalTrials.gov Identifier: NCT03372161., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Background: Race/ethnicity and gender concordance between patients and providers is a potential strategy to improve health care interventions. In digital health, where human interactions occur both synchronously and asynchronously, the effect of concordance between patients and providers is unknown., Objective: This study aimed to evaluate the impact of race/ethnicity or gender concordance between patients and physical therapists (PTs) in engagement and the clinical outcomes following a digital care program (DCP) in patients with musculoskeletal (MSK) conditions., Methods: This secondary analysis of 2 prospective longitudinal studies (originally focused on assessing the acceptance, engagement, and clinical outcomes after a remote DCP) examined the impact of both race/ethnicity concordance and gender concordance between patients and PTs on outcomes for a digital intervention for MSK conditions. Outcomes included engagement (measured by the completion rate and communication, assessed by text interactions), satisfaction, and clinical outcomes (response rate, ie, percentage of patients achieving at least a minimal clinically important change in pain, measured by the Numerical Pain Rating Scale [NPRS]; anxiety, measured by the Generalized Anxiety Disorder 7-item scale [GAD-7]; depression, measured by the Patient Health Questionnaire 9-item [PHQ-9]; and daily activity impairment, measured by the Work Productivity and Activity Impairment [WPAI] questionnaire)., Results: Of 71,201 patients, 63.9% (n=45,507) were matched with their PT in terms of race/ethnicity, while 61.2% (n=43,560) were matched for gender. Concordant dyads showed a higher completion rate among White (adjusted odds ratio [aOR] 1.11, 95% CI 1.05-1.19, P<.001) and Hispanic (aOR 1.27, 95% CI 1.08-1.54, P=.009) groups, as well as women (aOR 1.10, 95% CI 1.06-1.18, P<.001), when compared to discordant dyads. High and similar levels of interaction between patients and PTs were observed across race/ethnicity and gender dyads, except for Asian concordant dyads (adjusted β coefficient 5.32, 95% CI 3.28-7.36, P<.001). Concordance did not affect satisfaction, with high values (>8.52, 95% CI 8.27-8.77) reported across all dyads. Response rates for pain, anxiety, and daily activity impairment were unaffected by race/ethnicity concordance. An exception was observed for depression, with White patients reporting a higher response rate when matched with PTs from other races/ethnicities (aOR 1.20, 95% CI 1.02-1.39, P=.02). In terms of gender, men had a slightly higher pain response rate in discordant dyads (aOR 1.08, 95% CI 1.01-1.15, P=.03) and a higher depression response rate in concordant dyads (aOR 1.23, 95% CI 1.05-1.47, P=.01)., Conclusions: Race/ethnicity and gender concordance between patients and PTs does not translate into higher satisfaction or improvement for most clinical outcomes, aside from a positive effect on treatment completion. These results highlight the importance of other PT characteristics, in addition to race/ethnicity or gender concordance, suggesting the potential benefit of experience, languages spoken, and cultural safety training as ways to optimize care., Trial Registration: ClinicalTrials.gov NCT04092946, NCT05417685; https://clinicaltrials.gov/study/NCT05417685, https://clinicaltrials.gov/study/NCT04092946., (©Anabela C Areias, Dora Janela, Maria Molinos, Virgílio Bento, Carolina Moreira, Vijay Yanamadala, Steven P Cohen, Fernando Dias Correia, Fabíola Costa. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 29.10.2024.)

Here, we report a hybrid genome of Marasmius tenuissimus strain MS-2, a cacao thread blight disease causing isolate that was collected from cacao leaves in Tafo, Eastern region, Ghana. The final assembly consists of 2,083 contigs spanning 69,843,039 bp, with 49.21% GC content, 92.6% BUSCO completeness, and scaffold N50 186,871., Competing Interests: The authors declare no conflict of interest.

Introduction: Patients suffering from postherpetic neuralgia (PHN) report unilateral chronic pain in one or more dermatomes after an acute herpes zoster (HZ) infection. The incidence of acute HZ ranges between three and five patients per 1000 person-years. In one out of four patients, acute HZ-related pain will transition into PHN. PHN can be very disabling for patients and reduce quality of life. Additionally, the treatment of PHN is characterized by high failure rates. The aim of this review is to give an update on the previous practical guideline published in 2011 and revised in 2015 (published in 2019) and to provide an overview of current interventional treatment options for HZ infection and PHN., Methods: The literature on the diagnosis and treatment of HZ and PHN was systematically reviewed and summarized., Results: The most important treatment for acute HZ-related pain is antiviral therapy within 72 h of symptom onset. Additional symptomatic treatment options are analgesic drugs according to the WHO pain ladder, tricyclic antidepressants (eg, nortriptyline), and antiepileptic drugs (eg, gabapentin). If pain is not sufficiently reduced, interventional treatment such as an epidural injection with local anesthetics and corticosteroids or pulsed radiofrequency of the dorsal root ganglion (DRG) are options. Treatment for PHN is preferably transdermal capsaicin, lidocaine, or oral drugs such as antidepressants or antiepileptics., Conclusions: Treatment of acute HZ-related pain especially PHN is challenging. Besides the conventional treatment for PHN, interventional management is considered a new treatment option. PRF of DRG seems to be the most promising interventional management., (© 2024 The Author(s). Pain Practice published by Wiley Periodicals LLC on behalf of World Institute of Pain.)

Purpose of Review: To provide an evidence-informed review weighing the pros and cons of particulate vs. nonparticulate steroids for lumbar transforaminal epidural steroid injections (TFESI)., Recent Findings: The relative use of nonparticulate vs. particulate steroids for lumbar TFESI has risen recently in light of catastrophic consequences reported for the latter during cervical TFESI. Among various causes of spinal cord infarct, an exceedingly rare event in the lower lumbar spine, embolization of particulate steroid is among the least likely. Case reports have documented cases of spinal cord infarct during lower lumbar TFESI with both particulate and nonparticulate steroids, with database reviews finding no difference in complication rates. There is some evidence for superiority of particulate over nonparticulate steroids in well-designed studies, which could lead to increase steroid exposure (i.e. more injections) and treatment failure resulting in surgical and/or opioid management when nonparticulate steroids are utilized., Summary: Similar to a paradigm shift in medicine, a personalized approach based on a shared decision model and the consequences of treatment failure, should be utilized in deciding which steroid to utilize. Alternatives to ESI include high-volume injections with nonsteroid solutions, and the use of hypertonic saline, which possesses anti-inflammatory properties and has been shown to be superior to isotonic saline in preliminary clinical studies., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Peripheral artery diseases (PAD) and Raynaud's syndrome are associated with substantial morbidity. PAD, through the restriction of blood flow to the extremities, may lead to critical limb ischemia with symptoms of pain at rest which may eventually progress to severe limb ischemia with gangrene. This serious and painful clinical condition requires extensive medical care, is limb-threatening and, in case of delayed or unsuccessful treatment, is associated with a high mortality rate. In Raynaud's syndrome, the blood supply to certain parts of the body, usually the fingers and toes and less frequently the nose or ears, is restricted because of vasculopathy of the smaller vessels at acral sites. Under certain circumstances, with cold as the most well-known provoking factor, blood flow restriction occurs, leading to demarcated color changes and symptoms such as pain, paresthesia, and numbness. In severe cases of Raynaud syndrome tissue ischemia may lead to necrosis and the need for amputation of the affected area., Methods: In this narrative review, the literature on the diagnosis and interventional pain treatment of PAD and Raynaud's syndrome was updated and summarized., Objectives: This review focused on interventional pain treatment. In PAD, the effects of the intervention on limb salvage, ulcer healing, and ischemic pain were summarized. Additionally, results with respect to skin microcirculation and quality of life were reported if available. In Raynaud's syndrome, we focused on the effect of the intervention on peripheral blood flow metrics and pain intensity during attacks., Results: In PAD, prevention and treatment of risk factors are important. Initially, conservative treatment and pharmacological therapy are preferred first-line therapies. However, when disease progression occurs, interventional management may be considered. The literature search yielded conflicting evidence for sympathectomy as a treatment for PAD. Spinal cord stimulation (SCS) as a treatment modality for advanced PAD had high-quality evidence for limb salvage in subgroups of patients but conflicting evidence for other outcome measures such as pain, wound healing, and quality of life. The literature search for interventional pain management in Raynaud's syndrome was limited to only one randomized controlled trial (RCT) studying the effect of thoracic sympathectomy. This study had several limitations and hence the level of evidence for this interventional treatment is very low. No RCTs studying SCS in patients with Raynaud's syndrome were found., Conclusions: In both PAD and Raynaud's syndrome, additional RCTs are needed to substantiate interventional (pain) management and bolster the evidence base for sympathectomy and SCS as treatment options., (© 2024 The Author(s). Pain Practice published by Wiley Periodicals LLC on behalf of World Institute of Pain.)

Introduction: Persistent Spinal Pain Syndrome (PSPS) refers to chronic axial pain and/or extremity pain. Two subtypes have been defined: PSPS-type 1 is chronic pain without previous spinal surgery and PSPS-type 2 is chronic pain, persisting after spine surgery, and is formerly known as Failed Back Surgery Syndrome (FBSS) or post-laminectomy syndrome. The etiology of PSPS-type 2 can be gleaned using elements from the patient history, physical examination, and additional medical imaging. Origins of persistent pain following spinal surgery may be categorized into an inappropriate procedure (eg a lumbar fusion at an incorrect level or for sacroiliac joint [SIJ] pain); technical failure (eg operation at non-affected levels, retained disk fragment, pseudoarthrosis), biomechanical sequelae of surgery (eg adjacent segment disease or SIJ pain after a fusion to the sacrum, muscle wasting, spinal instability); and complications (eg battered root syndrome, excessive epidural fibrosis, and arachnoiditis), or undetermined., Methods: The literature on the diagnosis and treatment of PSPS-type 2 was retrieved and summarized., Results: There is low-quality evidence for the efficacy of conservative treatments including exercise, rehabilitation, manipulation, and behavioral therapy, and very limited evidence for the pharmacological treatment of PSPS-type 2. Interventional treatments such as pulsed radiofrequency (PRF) of the dorsal root ganglia, epidural adhesiolysis, and spinal endoscopy (epiduroscopy) might be beneficial in patients with PSPS-type 2. Spinal cord stimulation (SCS) has been shown to be an effective treatment for chronic, intractable neuropathic limb pain, and possibly well-selected candidates with axial pain., Conclusions: The diagnosis of PSPS-type 2 is based on patient history, clinical examination, and medical imaging. Low-quality evidence exists for conservative interventions. Pulsed radiofrequency, adhesiolysis and SCS have a higher level of evidence with a high safety margin and should be considered as interventional treatment options when conservative treatment fails., (© 2024 The Authors. Pain Practice published by Wiley Periodicals LLC on behalf of World Institute of Pain.)

Background: Up to 30% of patients with knee osteoarthritis (KOA) have evidence of sensitization, with a similar proportion experiencing severe pain during procedures. Most patients with KOA are elderly and often develop side effects from intravenous sedation. Our study investigated the effectiveness of a methoxyflurane inhaler combined with local anesthesia in reducing procedural pain from genicular nerve block compared with local anesthesia alone., Methods: 42 adults with refractory KOA were randomized into two groups. Methoxyflurane group received a self-titrated methoxyflurane inhaler with local anesthesia whereas lidocaine group received local anesthesia only. The primary outcome was pain score on a 0-10 verbal numerical rating scale (VNRS) during the procedure. Secondary outcomes included changes in VNRS and behavioral pain scale (critical care pain observational tool) during the procedure, hemodynamic changes, anxiety level, sedation score, and adverse events., Results: 42 patients with a mean age of 66±12 years participated in this study. There were no significant baseline differences. During the procedure, the methoxyflurane group experienced a significantly greater VNRS pain reduction from baseline (2 (1, 4) vs -1 (-2, 0); p<0.01) and greater VNRS reduction over time (p=0.01) compared with the lidocaine group, with a higher sedation score (p<0.01). Immediately postprocedure, anxiety levels were lower in the methoxyflurane group compared with the lidocaine group (median State-Trait Anxiety Inventory score 21 (IQR 20, 24) vs 27 (23, 29); p=0.02), but the median reduction in anxiety level was not significant (6 (1, 12) vs 5 (0, 14); p=0.61). There were no differences in behavioral pain scores, hemodynamic parameters, recovery or discharge times, and adverse effects between the two groups., Conclusion: A methoxyflurane inhaler combined with local anesthesia provided better procedural pain control than local anesthesia alone with no observable differences in adverse effects. Future studies evaluating the impact of a methoxyflurane inhaler on different types of painful procedures are warranted., Competing Interests: Competing interests: SPC is a consultant for Avanos, SPR Therapeutics, Persica, and SWORD, and has previously served as a consultant for Clearing and Scilex in the past 3 years. Currently, SPC is the editorial board member of RAPM. SS, PK, WI, NT, SL, RS, and KP have no conflicts of interest to declare., (© American Society of Regional Anesthesia & Pain Medicine 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Objective: To compare preparation for transition in adolescents in the United States prior to and during the COVID-19 pandemic., Study Design: We used data from the 2019 and 2021 National Survey of Children's Health to compare transition preparation before and after the COVID-19 pandemic among adolescents who had a medical care visit within the preceding year, controlled for relevant potential confounders. The association of demographic factors and survey year with a composite measure of adequate transition preparation was evaluated using univariable analysis and multivariable logistic regression., Results: The difference in transition preparation was not significant when comparing 2019 to 2021 (9.25 % in 2019 vs. 8.67 % in 2021, p = .556), despite changes in potential confounders, such as worse caregiver mental or emotional health and fewer adolescents having insurance or a usual source of preventive care. Older adolescents (odds ratio for each year 1.321, 95 % confidence interval 1.196 - 1.459), females (odds ratio 1.153, 95 % confidence interval 1.02 - 1.304) were more likely to have received adequate transition preparation. Adolescents from Spanish-speaking homes were less likely than adolescents from English-speaking homes to have received adequate transition preparation (odds ratio 0.529, 95 % confidence interval 0.329 - 0.849)., Conclusions: The proportion of adolescents in the United States who received adequate preparation to transition to adult care did not change during the COVID-19 pandemic. However, in both years studied, only a small minority of adolescents in the United States were adequately prepared., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: There is potential for adverse events from corticosteroid injections, including increase in blood glucose, decrease in bone mineral density and suppression of the hypothalamic-pituitary axis. Published studies note that doses lower than those commonly injected provide similar benefit., Methods: Development of the practice guideline was approved by the Board of Directors of American Society of Regional Anesthesia and Pain Medicine with several other societies agreeing to participate. The scope of guidelines was agreed on to include safety of the injection technique (landmark-guided, ultrasound or radiology-aided injections); effect of the addition of the corticosteroid on the efficacy of the injectate (local anesthetic or saline); and adverse events related to the injection. Based on preliminary discussions, it was decided to structure the topics into three separate guidelines as follows: (1) sympathetic, peripheral nerve blocks and trigger point injections; (2) joints; and (3) neuraxial, facet, sacroiliac joints and related topics (vaccine and anticoagulants). Experts were assigned topics to perform a comprehensive review of the literature and to draft statements and recommendations, which were refined and voted for consensus (≥75% agreement) using a modified Delphi process. The United States Preventive Services Task Force grading of evidence and strength of recommendation was followed., Results: This guideline deals with the use and safety of corticosteroid injections for sympathetic, peripheral nerve blocks and trigger point injections for adult chronic pain conditions. All the statements and recommendations were approved by all participants after four rounds of discussion. The Practice Guidelines Committees and Board of Directors of the participating societies also approved all the statements and recommendations. The safety of some procedures, including stellate blocks, lower extremity peripheral nerve blocks and some sites of trigger point injections, is improved by imaging guidance. The addition of non-particulate corticosteroid to the local anesthetic is beneficial in cluster headaches but not in other types of headaches. Corticosteroid may provide additional benefit in transverse abdominal plane blocks and ilioinguinal/iliohypogastric nerve blocks in postherniorrhaphy pain but there is no evidence for pudendal nerve blocks. There is minimal benefit for the use of corticosteroids in trigger point injections., Conclusions: In this practice guideline, we provided recommendations on the use of corticosteroids in sympathetic blocks, peripheral nerve blocks, and trigger point injections to assist clinicians in making informed decisions., Competing Interests: Competing interests: HTB, MD: NIH NIAMS P30AR072579. AC, MD: Research Funding: RM1NS128956-01A1; Consultant: Swing Therapeutics, Scilex Pharmaceuticals. SS, MD: Consultant: SPR Therapeutics, Allergan, Inc. DS, MD: Advisory Board, Funded research: Scilex; Speaker: AbbVie. AN, MD: Speaker: Averitas Pharmaceuticals; Research: Saol Therapeutics. AA-E, MD: Consultant: Curonix. TD, MD: Research support: Biohaven, NIH; Consultant: Guidepoint Global; Speaker honorarium: Remedy Health Media. MSE, MD: Funded research: SPR Therapeutics; Consultant: Avanos, Abbott. TH, MD: Acella: Advisory board, speaker: Acella. CH, MD: Research grant: Nevro, Inc. CP, MD: Consulting: Mainstay Medical; Royalties, UpToDate. BS, MD: Consultant: State Farm, Carelon. AS, MD: NIH R34AR080279. MM, MD: Consultant: Juris Medicus. JAH, MD: Grants: Neiman Health Policy Institute (there is no number associated with this foundation grant; Consulting (last 12 months): Medtronic, Relievant, Persica; DMC Chair: Balt, Rapid Medical, Arsenal. AW, MD: Investigator-initiated grant, Goodblends, PA. DAP, MD: Consulting: Avanos, Boston Scientific, Medtronic, Nevro, and SI Bone. Research support: Avanos, Boston Scientific, Medtronic, Nevro, Stimgenics, Abbott. SPC, MD: Consulting (past 2 years): Avanos, Scilex, SPR, SWORD, Releviate (ended), Clearing (ended), Persica (inactive); Research funds paid to institution: Scilex, Avanos. TM, MD: Consultant, Interventional AnalgesiX. The remaining authors declare no competing interests., (© American Society of Regional Anesthesia & Pain Medicine 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The acute respiratory distress syndrome (ARDS) is a common complication of severe COVID-19 and contributes to patient morbidity and mortality. ARDS is a heterogeneous syndrome caused by various insults, and results in acute hypoxemic respiratory failure. Patients with ARDS from COVID-19 may represent a subgroup of ARDS patients with distinct molecular profiles that drive disease outcomes. Here, we hypothesized that longitudinal transcriptomic analysis may identify distinct dynamic pathobiological pathways during COVID-19 ARDS., Methods: We identified a patient cohort from an existing ICU biorepository and established three groups for comparison: 1) patients with COVID-19 ARDS that survived hospitalization (COVID survivors, n = 4), 2) patients with COVID-19 ARDS that did not survive hospitalization (COVID non-survivors, n = 5), and 3) patients with ARDS from other causes as a control group (ARDS controls, n = 4). RNA was isolated from peripheral blood mononuclear cells (PBMCs) at 4 time points (Days 1, 3, 7, and 10 following ICU admission) and analyzed by bulk RNA sequencing., Results: We first compared transcriptomes between groups at individual timepoints and observed significant heterogeneity in differentially expressed genes (DEGs). Next, we utilized the likelihood ratio test to identify genes that exhibit different patterns of change over time between the 3 groups and identified 341 DEGs across time, including hemoglobin subunit alpha 2 ( HBA1, HBA2 ), hemoglobin subunit beta ( HBB ), von Willebrand factor C and EGF domains ( VWCE ), and carbonic anhydrase 1 ( CA1 ), which all demonstrated persistent upregulation in the COVID non-survivors compared to COVID survivors. Of the 341 DEGs, 314 demonstrated a similar pattern of persistent increased gene expression in COVID non-survivors compared to survivors, associated with canonical pathways of iron homeostasis signaling, erythrocyte interaction with oxygen and carbon dioxide, erythropoietin signaling, heme biosynthesis, metabolism of porphyrins, and iron uptake and transport., Discussion: These findings describe significant differences in gene regulation during patient ICU course between survivors and non-survivors of COVID-19 ARDS. We identified multiple pathways that suggest heme and red blood cell metabolism contribute to disease outcomes. This approach is generalizable to larger cohorts and supports an approach of longitudinal sampling in ARDS molecular profiling studies, which may identify novel targetable pathways of injury and resolution., Competing Interests: The 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 © 2024 Eltobgy, Johns, Farkas, Leuenberger, Cohen, Ho, Karow, Swoope, Pannu, Horowitz, Mallampalli, Englert and Bednash.)

Chronic pain begins with acute pain. Physicians tend to classify pain by duration (acute vs chronic) and mechanism (nociceptive, neuropathic and nociplastic). Although this taxonomy may facilitate diagnosis and documentation, such categories are to some degree arbitrary constructs, with significant overlap in terms of mechanisms and treatments. In clinical practice, there are myriad different definitions for chronic pain and a substantial portion of chronic pain involves mixed phenotypes. Classification of pain based on acuity and mechanisms informs management at all levels and constitutes a critical part of guidelines and treatment for chronic pain care. Yet specialty care is often siloed, with advances in understanding lagging years behind in some areas in which these developments should be at the forefront of clinical practice. For example, in perioperative pain management, enhanced recovery protocols are not standardized and tend to drive treatment without consideration of mechanisms, which in many cases may be incongruent with personalized medicine and mechanism-based treatment. In this educational document, we discuss mechanisms and classification of pain as it pertains to commonly performed surgical procedures. Our goal is to provide a clinical reference for the acute pain physician to facilitate pain management decision-making (both diagnosis and therapy) in the perioperative period., Competing Interests: Competing interests: SPC: serves as a consultant for Avanos and SPR, which make radiofrequency equipment and peripheral nerve stimulators, that have been studied for perioperative pain., (© American Society of Regional Anesthesia & Pain Medicine 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Transforaminal epidural steroid injections (TFESI) are commonly employed to treat lumbosacral radiculopathy. Despite anti-inflammatory properties, the addition of 3% hypertonic saline has not been studied., Objective: Compare the effectiveness of adding 0.9% NaCl (N-group) vs. 3% NaCl (H-group) in TFESI performed for lumbosacral radiculopathy., Methods: This retrospective study compared TFESI performed with lidocaine, triamcinolone and 0.9% NaCl vs. lidocaine, triamcinolone and 3% NaCl. The primary outcome was the proportion of patients who experienced a ≥ 30% reduction in pain on a verbal rating scale (VRS; 0-100) at 3 months. Secondary outcome measures included the proportion of patients who improved by at least 30% for pain at 1 and 6 months, and who experienced ≥15% from baseline on the Oswestry disability index (ODI) at follow-up., Results: The H-group experienced more successful pain outcomes than the N-group at 3 months (59.09% vs. 41.51%; P = .002) but not at 1 month (67.53% vs. 64.78%; P = .61) or 6 months (27.13% vs 21.55%: P = .31). For functional outcome, there was a higher proportion of responders in the H-group than the N-group at 3 months (70.31% vs. 53.46%; P = .002). Female, age ≤ 60 years, and duration of pain ≤ 6 months were associated with superior outcomes at the 3-month endpoint. Although those with a herniated disc experienced better outcomes in general with TFESI, the only difference favoring the H-group was for spondylolisthesis patients., Conclusions: 3% hypertonic saline is a viable alternative to normal saline as an adjunct for TFESI, with randomized studies needed to compare its effectiveness to steroids as a possible alternative., Registration: Thai Clinical Trials Registry ID TCTR 20231110006., (Published by Oxford University Press on behalf of the American Academy of Pain Medicine.)

Background: Peer review represents a cornerstone of the scientific process, yet few studies have evaluated its association with scientific impact. The objective of this study is to assess the association of peer review scores with measures of impact for manuscripts submitted and ultimately published., Methods: 3173 manuscripts submitted to Regional Anesthesia & Pain Medicine (RAPM) between August 2018 and October 2021 were analyzed, with those containing an abstract included. Articles were categorized by topic, type, acceptance status, author demographics and open-access status. Articles were scored based on means for the initial peer review where each reviewer's recommendation was assigned a number: 5 for 'accept', 3 for 'minor revision', 2 for 'major revision' and 0 for 'reject'. Articles were further classified by whether any reviewers recommended 'reject'. Rejected articles were analyzed to determine whether they were subsequently published in an indexed journal, and their citations were compared with those of accepted articles when the impact factor was < 1.4 points lower than RAPM 's 5.1 impact factor. The main outcome measure was the number of Clarivate citations within 2 years from publication. Secondary outcome measures were Google Scholar citations within 2 years and Altmetric score., Results: 422 articles met inclusion criteria for analysis. There was no significant correlation between the number of Clarivate 2-year review citations and reviewer rating score (r=0.038, p=0.47), Google Scholar citations (r=0.053, p=0.31) or Altmetric score (p=0.38). There was no significant difference in 2-year Clarivate citations between accepted (median (IQR) 5 (2-10)) and rejected manuscripts published in journals with impact factors > 3.7 (median 5 (2-7); p=0.39). Altmetric score was significantly higher for RAPM -published papers compared with RAPM -rejected ones (median 10 (5-17) vs 1 (0-2); p<0.001)., Conclusions: Peer review rating scores were not associated with citations, though the impact of peer review on quality and association with other metrics remains unclear., Competing Interests: Competing interests: BDS, MD and SPC receive support for editorial work at Regional Anesthesia & Pain Medicine. SPC received research support from Avanos and Scilex (paid to institution) and serves as a consultant for Scilex, Avanos, SPR Therapeutics, Persica and Sword., (© American Society of Regional Anesthesia & Pain Medicine 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The use of sedation during interventional procedures has continued to rise resulting in increased costs, complications and reduced validity during diagnostic injections, prompting a search for alternatives. Virtual reality (VR) has been shown to reduce pain and anxiety during painful procedures, but no studies have compared it to a control and active comparator for a pain-alleviating procedure. The main objective of this study was to determine whether VR reduces procedure-related pain and other outcomes for epidural steroid injections (ESI)., Methods: A randomized controlled trial was conducted in 146 patients undergoing an ESI at 6 hospitals in Thailand and the United States. Patients were allocated to receive immersive VR with local anesthetic, sedation with midazolam and fentanyl plus local anesthetic, or local anesthetic alone. The primary outcome was procedure-related pain recorded on a 0-10 scale. Other immediate-term outcome measures were pain from a standardized subcutaneous skin wheal, procedure-related anxiety, ability to communicate, satisfaction, and time to discharge. Intermediate-term outcome measures at 4 weeks included back and leg pain scores, function, and success defined as a ≥2-point decrease in average leg pain coupled with a score ≥5/7 on a Patient Global Impression of Change scale., Findings: Procedure-related pain scores with both VR (mean 3.7 (SD 2.5)) and sedation (mean 3.2 (SD 3.0)) were lower compared to control (mean 5.2 (SD 3.1); mean differences -1.5 (-2.7, -0.4) and -2.1 (-3.3, -0.9), respectively), but VR and sedation scores did not significantly differ (mean difference 0.5 (-0.6, 1.7)). Among secondary outcomes, communication was decreased in the sedation group (mean 3.7 (SD 0.9)) compared to the VR group (mean 4.1 (SD 0.5); mean difference 0.4 (0.1, 0.6)), but neither VR nor sedation was different than control. The trends favoring sedation and VR over control for procedure-related anxiety and satisfaction were not statistically significant. Post-procedural recovery time was longer for the sedation group compared to both VR and control groups. There were no meaningful intermediate-term differences between groups except that medication reduction was lowest in the control group., Interpretation: VR provides comparable benefit to sedation for procedure-related pain, anxiety and satisfaction, but with fewer side effects, superior communication and a shorter recovery period., Funding: Funded in part by grants from MIRROR, Uniformed Services University of the Health Sciences, U.S. Dept. of Defense, grant # HU00011920011. Equipment was provided by Harvard MedTech, Las Vegas, NV., Competing Interests: SPC is a consultant for Avanos, SPR Therapeutics, Persica, Scilex and SWORD, and has previously served as a consultant for Relieviate and Clearing in the past 3 years. The views expressed in this manuscript are those of the authors and do not reflect the official policy of the Uniformed Services University, the Departments of Army and Navy, Department of Defense, the Department of Veterans Affairs, or the U.S. Government. The identification of specific products or scientific instrumentation is considered an integral part of the scientific endeavor and does not constitute endorsement or implied endorsement on the part of the authors, DoD, or any component agency.

Theobroma cacao, the chocolate tree, is indigenous to the Amazon basin, the greatest biodiversity hotspot on earth. Recent advancement in plant genomics highlights the importance of de novo sequencing of multiple reference genomes to capture the genome diversity present in different cacao populations. In this study, three high-quality chromosome-level genomes of wild cacao were constructed, de novo assembled with HiFi long reads sequencing, and scaffolded using a reference-free strategy. These genomes represent the three most important genetic clusters of cacao trees from the Upper Amazon region. The three wild cacao genomes were compared with two reference genomes of domesticated cacao. The five cacao genetic clusters were inferred to have diverged in the early and middle Pleistocene period, approximately 1.83-0.69 million years ago. The results shown here serve as an example of understanding how the Amazonian biodiversity was developed. The three wild cacao genomes provide valuable resources for studying genetic diversity and advancing genetic improvement of this species., (© 2024. The Author(s).)

Objectives: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) commonly presents with diffuse alveolar haemorrhage (DAH) and/or glomerulonephritis. Patients who present with DAH but without kidney involvement have been understudied., Methods: Patients with DAH diagnosed by bronchoscopy and attributed to AAV over 8.5 years were retrospectively identified through electronic medical records and bronchoscopy reporting software. Patients with end-stage kidney disease (ESKD) or prior kidney transplant were excluded. Characteristics, treatments, and outcomes were abstracted., Results: 30 patients were identified with DAH secondary to AAV. Five with ESKD or prior kidney transplant, and one with concomitant anti-glomerular basement membrane disease, were excluded, leaving 24 patients for analysis. At the time of qualifying bronchoscopy, six patients had no apparent kidney involvement by AAV, while eight of 18 with kidney involvement required dialysis. Of the eight patients dialysed during the initial hospitalisation, four were declared to have ESKD and three died in the subsequent year (one of whom did both). None of the 16 patients without initial dialysis requirement developed kidney involvement requiring dialysis in the subsequent year, though three of the six without initial evidence of kidney involvement by AAV ultimately developed it. No patient without initial kidney involvement died during follow-up., Conclusions: In our cohort, patients with DAH due to AAV without initial kidney involvement did not develop kidney involvement requiring dialysis or die during the follow-up period, though half of patients without initial evidence of kidney involvement subsequently developed it. Larger studies are warranted to better characterise this population and guide medical management.

Introduction: Sacroiliac (SI) joint pain is defined as pain localized in the anatomical region of the SI joint. The reported prevalence of SI joint pain among patients with mechanical low back pain varies between 15% and 30%., Methods: In this narrative review, the literature on the diagnosis and treatment of SI joint pain was updated and summarized., Results: Patient's history provides clues on the source of pain. The specificity and sensitivity of provocative maneuvers are relatively high when three or more tests are positive, though recent studies have questioned the predictive value of single or even batteries of provocative tests. Medical imaging is indicated only to rule out red flags for potentially serious conditions. The diagnostic value of SI joint infiltration with local anesthetic remains controversial due to the potential for false-positive and false-negative results. Treatment of SI joint pain ideally consists of a multidisciplinary approach that includes conservative measures as first-line therapies (eg, pharmacological treatment, cognitive-behavioral therapy, manual medicine, exercise therapy and rehabilitation treatment, and if necessary, psychological support). Intra- and extra-articular corticosteroid injections have been documented to produce pain relief for over 3 months in some people. Radiofrequency ablation (RFA) of the L5 dorsal ramus and S1-3 (or 4) lateral branches has been shown to be efficacious in numerous studies, with extensive lesioning strategies (eg, cooled RFA) demonstrating the strongest evidence. The reported rate of complications for SI joint treatments is low., Conclusions: SI joint pain should ideally be managed in a multidisciplinary and multimodal manner. When conservative treatment fails, corticosteroid injections and radiofrequency treatment can be considered., (© 2023 The Authors. Pain Practice published by Wiley Periodicals LLC on behalf of World Institute of Pain.)

Pain that accompanies deafferentation is one of the most mysterious and misunderstood medical conditions. Prevalence rates for the assorted conditions vary considerably but the most reliable estimates are greater than 50% for strokes involving the somatosensory system, brachial plexus avulsions, spinal cord injury, and limb amputation, with controversy surrounding the mechanistic contributions of deafferentation to ensuing neuropathic pain syndromes. Deafferentation pain has also been described for loss of other body parts (e.g., eyes and breasts) and may contribute to between 10% and upwards of 30% of neuropathic symptoms in peripheral neuropathies. There is no pathognomonic test or sign to identify deafferentation pain, and part of the controversy surrounding it stems from the prodigious challenges in differentiating cause and effect. For example, it is unknown whether cortical reorganization causes pain or is a byproduct of pathoanatomical changes accompanying injury, including pain. Similarly, ascertaining whether deafferentation contributes to neuropathic pain, or whether concomitant injury to nerve fibers transmitting pain and touch sensation leads to a deafferentation-like phenotype can be clinically difficult, although a detailed neurologic examination, functional imaging, and psychophysical tests may provide clues. Due in part to the concurrent morbidities, the physical, psychologic, and by extension socioeconomic costs of disorders associated with deafferentation are higher than for other chronic pain conditions. Treatment is symptom-based, with evidence supporting first-line antineuropathic medications such as gabapentinoids and antidepressants. Studies examining noninvasive neuromodulation and virtual reality have yielded mixed results., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

Introduction: Low back pain is the leading cause of disability worldwide, with sacroiliac joint pain comprising up to 30% of cases of axial lower back pain. Conservative therapies provide only modest relief. Although placebo-controlled trials show efficacy for sacral lateral branch cooled radiofrequency ablation, there are no comparative effectiveness studies., Methods: In this randomized, multicenter comparative effectiveness study, 210 patients with clinically suspected sacroiliac joint pain who obtained short-term benefit from diagnostic sacroiliac joint injections and prognostic lateral branch blocks were randomly assigned to receive cooled radiofrequency ablation of the L5 dorsal ramus and S1-S3 lateral branches or standard medical management consisting of pharmacotherapy, injections and integrative therapies. The primary outcome measure was mean reduction in low back pain score on a 0-10 Numeric Rating Scale at 3 months. Secondary outcomes included measures of quality of life and function., Results: 3 months post-treatment, the mean Numeric Rating Scale pain score for the cooled radiofrequency ablation group was 3.8±2.4 (mean reduction 2.5±2.5) compared with 5.9±1.7 (mean reduction 0.4±1.7) in the standard medical management group (p<0.0001). 52.3% of subjects in the cooled radiofrequency ablation group experienced > 2 points or 30% pain relief and were deemed responders versus 4.3% of standard medical management patients (p<0.0001). Comparable improvements favoring cooled radiofrequency ablation were noted in Oswestry Disability Index score (mean 29.7±15.2 vs 41.5+13.6; p<0.0001) and quality of life (mean EuroQoL-5 score 0.68±0.22 vs 0.47±0.29; p<0.0001)., Conclusions: In patients with sacroiliac joint pain, cooled radiofrequency ablation provided statistically superior improvements across the spectrum of patient outcomes compared with standard medical management., Trial Registration Number: NCT03601949., Competing Interests: Competing interests: All authors received institutional research funding. SPC, LKa, LKo, SL, DPB and MJD are consultants for Avanos (which makes radiofrequency equipment). Currently, SPC is the editorial board member of RAPM., (© American Society of Regional Anesthesia & Pain Medicine 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Background: There are few efficacious treatments for mechanical neck pain, with controlled trials suggesting efficacy for muscle relaxants and topical nonsteroidal anti-inflammatory drugs. Although studies evaluating topical lidocaine for back pain have been disappointing, the more superficial location of the cervical musculature suggests a possible role for topical local anesthetics., Methods: This study was a randomized, double-blind, placebo-controlled crossover trial performed at four U.S. military, Veterans Administration, academic, and private practice sites, in which 76 patients were randomized to receive either placebo followed by lidocaine patch for 4-week intervals (group 1) or a lidocaine-then-placebo patch sequence. The primary outcome measure was mean reduction in average neck pain, with a positive categorical outcome designated as a reduction of at least 2 points in average neck pain coupled with at least a 5-point score of 7 points on the Patient Global Impression of Change scale at the 4-week endpoint., Results: For the primary outcome, the median reduction in average neck pain score was -1.0 (interquartile range, -2.0, 0.0) for the lidocaine phase versus -0.5 (interquartile range, -2.0, 0.0) for placebo treatment (P = 0.17). During lidocaine treatment, 27.7% of patients experienced a positive outcome versus 14.9% during the placebo phase (P = 0.073). There were no significant differences between treatments for secondary outcomes, although a carryover effect on pain pressure threshold was observed for the lidocaine phase (P = 0.015). A total of 27.5% of patients in the lidocaine group and 20.5% in the placebo group experienced minor reactions, the most common of which was pruritis (P = 0.36)., Conclusions: The differences favoring lidocaine were small and nonsignificant, but the trend toward superiority of lidocaine suggests more aggressive phenotyping and applying formulations with greater penetrance may provide clinically meaningful benefit.

Introduction: Patients suffering lumbosacral radicular pain report radiating pain in one or more lumbar or sacral dermatomes. In the general population, low back pain with leg pain extending below the knee has an annual prevalence that varies from 9.9% to 25%., Methods: The literature on the diagnosis and treatment of lumbosacral radicular pain was reviewed and summarized., Results: Although a patient's history, the pain distribution pattern, and clinical examination may yield a presumptive diagnosis of lumbosacral radicular pain, additional clinical tests may be required. Medical imaging studies can demonstrate or exclude specific underlying pathologies and identify nerve root irritation, while selective diagnostic nerve root blocks can be used to confirm the affected level(s). In subacute lumbosacral radicular pain, transforaminal corticosteroid administration provides short-term pain relief and improves mobility. In chronic lumbosacral radicular pain, pulsed radiofrequency (PRF) treatment adjacent to the spinal ganglion (DRG) can provide pain relief for a longer period in well-selected patients. In cases of refractory pain, epidural adhesiolysis and spinal cord stimulation can be considered in experienced centers., Conclusions: The diagnosis of lumbosacral radicular pain is based on a combination of history, clinical examination, and additional investigations. Epidural steroids can be considered for subacute lumbosacral radicular pain. In chronic lumbosacral radicular pain, PRF adjacent to the DRG is recommended. SCS and epidural adhesiolysis can be considered for cases of refractory pain in specialized centers., (© 2023 The Authors. Pain Practice published by Wiley Periodicals LLC on behalf of World Institute of Pain.)

The oomycete Phytophthora palmivora infects the fruit of cacao trees (Theobroma cacao) causing black pod rot and reducing yields. Cacao genotypes vary in their resistance levels to P. palmivora, yet our understanding of how cacao fruit respond to the pathogen at the molecular level during disease establishment is limited. To address this issue, disease development and RNA-Seq studies were conducted on pods of seven cacao genotypes (ICS1, WFT, Gu133, Spa9, CCN51, Sca6 and Pound7) to better understand their reactions to the post-penetration stage of P. palmivora infection. The pod tissue-P. palmivora pathogen assay resulted in the genotypes being classified as susceptible (ICS1, WFT, Gu133 and Spa9) or resistant (CCN51, Sca6 and Pound7). The number of differentially expressed genes (DEGs) ranged from 1625 to 6957 depending on genotype. A custom gene correlation approach identified 34 correlation groups. De novo motif analysis was conducted on upstream promoter sequences of differentially expressed genes, identifying 76 novel motifs, 31 of which were over-represented in the upstream sequences of correlation groups and associated with gene ontology terms related to oxidative stress response, defense against fungal pathogens, general metabolism and cell function. Genes in one correlation group (Group 6) were strongly induced in all genotypes and enriched in genes annotated with defense-responsive terms. Expression pattern profiling revealed that genes in Group 6 were induced to higher levels in the resistant genotypes. An additional analysis allowed the identification of 17 candidate cis-regulatory modules likely to be involved in cacao defense against P. palmivora. This study is a comprehensive exploration of the cacao pod transcriptional response to P. palmivora spread after infection. We identified cacao genes, promoter motifs, and promoter motif combinations associated with post-penetration resistance to P. palmivora in cacao pods and provide this information as a resource to support future and ongoing efforts to breed P. palmivora-resistant cacao., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: Pain as a symptom of diabetic polyneuropathy (DPN) significantly lowers quality of life, increases mortality and is the main reason for patients with diabetes to seek medical attention. The number of people suffering from painful diabetic polyneuropathy (PDPN) has increased significantly over the past decades., Methods: The literature on the diagnosis and treatment of diabetic polyneuropathy was retrieved and summarized., Results: The etiology of PDPN is complex, with primary damage to peripheral nociceptors and altered spinal and supra-spinal modulation. To achieve better patient outcomes, the mode of diagnosis and treatment of PDPN evolves toward more precise pain-phenotyping and genotyping based on patient-specific characteristics, new diagnostic tools, and prior response to pharmacological treatments. According to the Toronto Diabetic Neuropathy Expert Group, a presumptive diagnosis of "probable PDPN" is sufficient to initiate treatment. Proper control of plasma glucose levels, and prevention of risk factors are essential in the treatment of PDPN. Mechanism-based pharmacological treatment should be initiated as early as possible. If symptomatic pharmacologic treatment fails, spinal cord stimulation (SCS) should be considered. In isolated cases, where symptomatic pharmacologic treatment and SCS are unsuccessful or cannot be used, sympathetic lumbar chain neurolysis and/or radiofrequency ablation (SLCN/SLCRF), dorsal root ganglion stimulation (DRGs) or posterior tibial nerve stimulation (PTNS) may be considered. However, it is recommended that these treatments be applied only in a study setting in a center of expertise., Conclusions: The diagnosis of PDPN evolves toward pheno-and genotyping and treatment should be mechanism-based., (© 2023 The Authors. Pain Practice published by Wiley Periodicals LLC on behalf of World Institute of Pain.)