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We investigated the kinetics of hydrochloric acid demineralization of human cortical bone with the objective of developing a method of controlled demineralization for structural bone allografts. It is known that the demineralization of cortical bone is a diffusion rate limited process with a sharp advancing reaction front. The demineralization kinetics of human cortical bone, described as the advance of the reaction front versus immersion time, were determined by measuring extraction of bone mineral in both planar and cylindrical geometries. Mathematical models based on diffusional mass transfer were developed to predict this process. The experimental data fit well with the behavior predicted by the model. The model for planar geometry is applicable to controlled demineralization of cortical bone allografts of irregular shapes such as cortical struts. The model for cylindrical geometry is appropriate when curved surfaces are involved such as in diaphyseal bone allografts. This method of demineralization has direct application to clinical modification of cortical bone allografts to potentially enhance their osteoinductive properties.

Background: Recently, there has been a significant evolution in our understanding of the molecular pathways causing the genesis and progression of cancer via the inter-individual variations. Thus, one-size-fits-all methods for cancer treatment have been replaced by precision oncology (PO) targeting individual cancer symptoms, offering increased effectiveness, and decreased safety concerns and cost load., Objective: The identification of novel actionable indications, rapid, precise, and comprehensive detection of complex phenotypes in every individual, pioneering clinical trial projects with enhanced response feedback, and widespread availability of innovative targeted anticancer management for every patient are vital for the effective implementation of next-generation precision oncology. Additionally, the emergence of precision medicine has altered the perspective of oncologic biomarkers, drug discovery, drug development, and, improvements for cancer patients., Method: This paper narratively reviewed to identify actionable abnormalities, Genomic profiling of tumors employing clinical next-generation sequencing (NGS) from both tumor tissues and liquid biopsies along with the multi-omics strategies as the key component of PO., Results: Our increasing information on tumor biology, specifically microenvironment and heterogeneity- associated data, would improve our understanding of the resistance of targeted drugs and specific mechanisms of action, as well as help enhance existing metastatic colorectal cancer (mCRC) treatment strategies., Conclusion: Collectively, this paper indicated the current and innovative strategies for prognosis, diagnosis, and treatment of various cancer types based on PO overview with a groundbreaking emphasis on CRC suggesting the integrations of multi-omics, highlighting Genomics, and utilizing AL and ML algorithms with targeted therapies. Notably, these findings can help improve the life-span and ageing of the predisposed people., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The International Society for the Advancement of Spine Surgery hosted the first of a series of 4 webinars on endoscopic spine surgery techniques, focusing on end§oscopic discectomy, foraminotomy, instrumented endoscopic fusion, standalone lumbar interbody fusion with innovative materials, and the role of patient feedback in awake procedures. This series aims to share knowledge and discuss the complexities and clinical evidence of modern endoscopic spine surgery., Objective: To analyze the level of surgeon endorsement for the presented endoscopic spine surgery techniques before and after the webinar, utilizing polytomous Rasch analysis, and to evaluate the potential for these insights to inform clinical guideline recommendations., Methods: A survey was available to 1311 potential respondents during the Zoom webinar, collecting data on surgeon endorsements using a Likert scale. The polytomous Rasch model was employed to analyze responses, considering the complexity of decisions against surgeon expertise, developing a logarithmic measurement scale, allowing objective statistical analysis of categorical variables, highlighting incongruent or out-of-order items vs congruent and in-order items, and driving improvement in clinical guidelines., Results: All 4 topics received higher confidence ratings demonstrated by descriptive statistics, highlighting the webinar's effective role in surgeon education and in identifying ongoing trends in spine surgery. The logarithmic transformation of these data during Rasch analysis showed noticeable shifts in surgeon confidence levels postwebinar, with increased endorsement for transforaminal full-endoscopic thoracolumbar interbody fusion for hard disc herniation and standalone endoscopic lumbar interbody fusion. The Wright plot and person-item map analyses demonstrated that the webinar effectively targeted areas of initial low confidence, significantly impacting surgeons' perceptions. Disordered endorsement thresholds remained in the topics of uniportal transforaminal discectomy/foraminotomy and patient feedback during endoscopic spine surgery, indicating issues in response category discrimination or confounding factors not captured by the survey. Ongoing controversies were highlighted by the influence of confounding factors, stemming from preconceived notions and limited familiarity with high-grade evidence., Conclusion: The first in the 4-part webinar series effectively shifted professional confidence and acceptance of innovative surgical approaches among spine surgeons. Observations indicated a high level of interest in applying the endoscopic surgery platform with other advanced technologies. The polytomous Rasch analysis provided nuanced insights into ongoing trends and areas in need of further clarification., Clinical Relevance: Assessing surgeon confidence and acceptance of endoscopic spinal surgeries using polytomous Rasch analysis., Level of Evidence: Level 2 (inferential) and 3 (observational) evidence because Rasch analysis provides statistical validation of instruments rather than direct clinical outcomes., Competing Interests: Declaration of Conflicting Interests : The authors declare no conflict of interest relevant to this research, and there was no personal circumstance or interest that may be perceived as inappropriately influencing the representation or interpretation of reported research results. This research was not compiled to enrich anyone., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2024 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Competing Interests: Declaration of Conflicting Interests : The author reports no conflicts of interest in this work.

Objective: To compare clinical and radiographic outcomes between 2 motion preservation surgeries, cervical disc replacement (CDR) and posterior endoscopic cervical decompression (PECD), for unilateral cervical radiculopathy., Methods: Between February 2018 and December 2020, 60 patients with unilateral cervical radiculopathy who underwent either CDR or PECD were retrospectively recruited as matched pairs. Clinical outcomes included visual analogue scale (VAS) scores for neck and arm pain, Neck Disability Index (NDI), and satisfaction rates. The radiographic outcome was index level motion. Intraoperative data, complications, and hospital stay were collected. Preoperative and postoperative outcomes were compared., Results: Patients undergoing CDR or PECD were included, with 30 cases in each group. Matched pairs were compared in terms of demographic data and preoperative measurements. CDR was associated with shorter operative times, whereas PECD resulted in less intraoperative blood loss. The total complication rate was 5%. NDI and VAS for neck and arm were significantly improved in both groups, with no significant differences between the 2 groups. Satisfaction rates of good and excellent exceeded 87% in both groups. CDR was superior to PECD in the restoration of disc height. Early postoperative follow-up showed no significant difference in terms of index level motion. PECD demonstrated significantly shorter hospital stays and quicker return-to-work times (p<0.05)., Conclusion: PECD achieved equivalent clinical and radiologic outcomes compared with CDR when the certain criteria for surgery were met. Both techniques demonstrated the potential to maintain index level motion. Additionally, PECD resulted in less blood loss, shorter hospital stays, and faster return-to-work times. Conversely, CDR offered shorter operative times and better restoration of disc height.

Competing Interests: Conflict of Interest KB holds patents both domestic and foreign related to pro-dopamine regulation complexes and genetic testing for addiction risk. Through his company Synaptamine inc., licensed patents on KB220Z to Victory nutrition international, LLC., There are no other conflicts to report.

Background and Objectives: Fibromyalgia (FM) is a chronic musculoskeletal pain syndrome characterized by widespread pain and a variety of other symptoms, including fatigue, cognitive dysfunction, and sleep disturbances. Recent research has highlighted the potential role of pro-inflammatory cytokines and neurotransmitters in the pathophysiology of FM. This study aimed to investigate the relationship between serum levels of interleukin-6 (IL-6) and serotonin with the clinical parameters observed in patients with fibromyalgia. Additionally, it sought to analyze the similarities and differences among the different groups classified by symptom severity., Materials and Methods: This cross-sectional study included 26 female patients aged 20-70 diagnosed with FM according to the American College of Rheumatology (ACR) 2016 criteria and 14 healthy controls (HCs). Serum levels of IL-6 and serotonin were measured using electrochemiluminescence and high-performance liquid chromatography (HPLC), respectively., Results: FM patients exhibited significantly higher pain scores (VAS), anxiety, and depression levels compared to HCs. FIQ-R scores were significantly elevated in FM patients, with stratification showing 3.8% mild, 65.4% moderate, 23.1% severe, and 7.7% very severe cases. While no significant difference in IL-6 levels was observed between the FM patients and HCs, a trend towards increased IL-6 levels in patients with higher FIQ-R scores was noted. Serum serotonin levels were significantly lower in the FM patients than in the HCs, with moderate patients having lower levels than those classified as severe and very severe., Conclusions: The study underscores the potential role of IL-6 and serotonin in the pathophysiology of FM, suggesting that these biomarkers could be relevant in assessing the severity and impact of FM. Further research is needed to elucidate these relationships and their implications for developing personalized treatment strategies.

Background: The traditional open midline posterior cervical spine fusion procedure has several shortcomings. It can cause soft tissue damage, muscle atrophy, compromise of the lateral masses and painful prominent posterior cervical instrumentation or spinous process if there is dehiscence of the fascia. Additionally, patients frequently experience the rapid development of adjacent segment disease, which can result in the reemergence of debilitating pain and functional impairment. Clinical relevance: Tissue-sparing posterior cervical fusion is an alternative method for treating patients with symptomatic cervical degenerative disc disease. However, widespread clinical adoption has been challenged by ambiguity, misunderstandings and misinterpretations regarding appropriate procedural reimbursement coding. Technological advancement : The tissue-sparing posterior cervical fusion procedure was approved by the US Food and Drug Administration (FDA) in 2018 (CORUS™ Spinal System and CAVUX ® Facet Fixation System (CORUS/CAVUX); Providence™ Medical Technology). This technique addresses the concerns with traditional spine fusion methods by achieving the stability and outcomes of posterior cervical fusion without the morbidity associated with significant muscle stripping in the traditional approach. This technology uses specialized implants and instrumentation to perform all of the steps required to facilitate bone fusion and provide stability while minimizing tissue disruption. The technique involves extensive bone preparation for fusion and placement of specialized stabilization implants that span the facet joint, promoting natural bone growth and fusion while reducing the need for extensive exposure. This procedure provides an effective, less invasive solution for patients with cervical degenerative disc disease. Reimbursement and coding clarity: The article provides a comprehensive rationale for appropriate reimbursement coding for tissue-sparing posterior cervical fusion. This is a critical aspect for the adoption and accessibility of medical technologies. This information is crucial for practitioners and healthcare administrators, ensuring that innovative procedures are accurately coded and reimbursed. Procedural details and clinical evidence: By detailing the procedural steps, instruments used and the physiological basis for the procedure, this article serves as a valuable educational resource for spine surgeons and payers to appropriately code for this procedure. Conclusions: The description of work for CORUS/CAVUX is equivalent to the current surgical standard of lateral mass screw fixation with decortication and onlay posterior grafting to facilitate posterior fusion. Thus, it is recommended that CPT codes 22600/22840 be used, as they best reflect the surgical approach, instrumentation, decortication, posterior cervical fusion and bone grafting procedures.

Several trends toward patient-centered multi-care models employing translational research strategies are currently emerging in orthopaedics. These align seamlessly with epigenetics discussions in pain, a clinical approach to pain management that prioritizes tailoring healthcare to individual needs, preferences, and circumstances. Recognizing the unique genetic and epigenetic factors influencing pain perception, healthcare providers can integrate personalized insights into their patient-centered approach, offering more targeted and effective pain management strategies tailored to each individual's experience. Custom 3D-printing technologies may also become increasingly relevant to more effectively and reliably treat painful degenerative structural abnormalities. They are expected to go hand-in-hand with the precision medicine redefinition of musculoskeletal care. More effective analysis of surgeons' clinical decision-making and patients' perception of high-value orthopaedic care is needed. Shared Decision Making (SDM) is critical to identifying the best solution for each patient and improving stakeholders' understanding of factors influencing the diverse prioritizing values of surgical or non-surgical treatments by payers, systems, and other providers. Identifying high-value orthopaedic surgeries via effective SDM in orthopedic surgery requires more than just presenting patients with information. The Rasch analysis of patient expectations can provide this nuanced approach that involves understanding patient values, addressing misconceptions, and aligning surgical recommendations with patient-specific goals. Optimizing orthopaedic treatment within the patient-centered framework can drive innovation in reimbursement policies that support the field more broadly. Research on separating high-value from low-value orthopaedic procedures may likely impact healthcare decision- makers' resource allocation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The severity and invasiveness of clinical outcomes from organic responses to trauma are influenced by individual, surgical, and anesthetic factors. A stress response elicits neuroendocrine and immune reactions that may lead to multi-organ dysfunction. The degree of neuroinflammatory reflex activation from trauma can increase pro-inflammatory cytokine production, leading to endothelial dysfunction, glycocalyx damage, neutrophil activation, and multisystem tissue destruction. A shift in patient treatment towards a neuroinflammatory perspective has prompted a new evaluation protocol for surgical patients, required to understand surgical pathogenesis and its link to chosen anesthetic-surgical methods. The goal of this study is to summarize and disseminate the present knowledge about the mechanisms involved in immune and neuroendocrine responses, focusing on video laparoscopic surgeries. This article outlines various measures cited in the literature aimed at reducing the burden of surgical trauma. It reviews anesthetic drugs, anesthetic techniques, and intensive care procedures that are known to have immunomodulatory effects. The results show a preference for more sensitive inflammatory mediators to tissue trauma serving as care tools, indicators for prognosis, and therapeutic outcomes.

3D-printing technology has revolutionized spinal implant manufacturing, particularly in developing personalized and custom-fit titanium interbody fusion cages. These cages are pivotal in supporting inter-vertebral stability, promoting bone growth, and restoring spinal alignment. This article reviews the latest advancements in 3D-printed titanium interbody fusion cages, emphasizing their relevance in modern personalized surgical spine care protocols applied to common clinical scenarios. Furthermore, the authors review the various printing and post-printing processing technologies and discuss how engineering and design are deployed to tailor each type of implant to its patient-specific clinical application, highlighting how anatomical and biomechanical considerations impact their development and manufacturing processes to achieve optimum osteoinductive and osteoconductive properties. The article further examines the benefits of 3D printing, such as customizable geometry and porosity, that enhance osteointegration and mechanical compatibility, offering a leap forward in patient-specific solutions. The comparative analysis provided by the authors underscores the unique challenges and solutions in designing cervical, and lumbar spine implants, including load-bearing requirements and bioactivity with surrounding bony tissue to promote cell attachment. Additionally, the authors discuss the clinical outcomes associated with these implants, including the implications of improvements in surgical precision on patient outcomes. Lastly, they address strategies to overcome implementation challenges in healthcare facilities, which often resist new technology acquisitions due to perceived cost overruns and preconceived notions that hinder potential savings by providing customized surgical implants with the potential for lower complication and revision rates. This comprehensive review aims to provide insights into how modern 3D-printed titanium interbody fusion cages are made, explain quality standards, and how they may impact personalized surgical spine care.

The Continuous Visual Attention Test (CVAT) is a test that detects visuomotor reaction time (RT, alertness), variability of reaction time (VRT, sustained attention), omission errors (OE, focused attention), and commission errors (CE, response inhibition). The standard test takes 15 min, while the ultrafast version only 90 s. Besides overall task length, the two versions differ by target probability (20% and 80% in the 15-min vs. only 80% in the 90-s test) and stimulus-onset asynchrony (SOA) (1, 2, and 4 s in the 15-min vs. only 1 s in the 90-s test. We aimed to analyze the effect of target probability, SOA, and time length on the CVAT variables across the 15-min task and to verify correlations and agreements between the 15-min and the 90-s CVATs. 205 healthy participants performed the two CVATs on the same day. Considering the 15-min task, RT and CE were strongly affected by target probability. Conversely, VRT was not affected. When the 15-min task was compared to the 90-s task, we found no significant difference in the VRT variable. Additionally, a significant agreement between the two tasks was found for the VRT variable. We concluded that sustained attention can be measured with the 90-s CVAT., (© 2024. The Author(s).)

The advent of ultra-minimally invasive endoscopic spine surgery, characterized by significantly reduced surgery times, minimal blood loss, and minimal tissue trauma, has precipitated a paradigm shift in the preoperative management of patients with cardiac disease undergoing elective spine procedures. This perspective article explores how these advancements have influenced the requirements for preoperative cardiac workups and the protocols surrounding the cessation of anticoagulation and antiplatelet therapies. Traditionally, extensive cardiac evaluations and the need to stop anticoagulation and antiplatelet agents have posed challenges, increasing the risk of cardiac events and delaying surgical interventions. However, the reduced invasiveness of endoscopic spine surgery presents a safer profile for patients with cardiac comorbidities, potentially minimizing the necessity for rigorous cardiac clearance and allowing for more flexible anticoagulation management. This perspective article synthesizes current research and clinical practices to provide a comprehensive overview of these evolving protocols. It also discusses the implications of these changes for patient safety, surgical outcomes, and overall healthcare efficiency. Finally, the article suggests directions for future research, emphasizing the need for updated guidelines that reflect the reduced perioperative risk associated with these innovative surgical techniques. This discussion is pivotal for primary care physicians, surgeons, cardiologists, and the broader medical community in optimizing care for this high-risk patient population.

Purpose: Bone and joint infections, complicated by the burgeoning challenge of antimicrobial resistance (AMR), pose significant public health threats by amplifying the disease burden globally. We leveraged results from the 2019 Global Burden of Disease Study (GBD) to explore the impact of AMR attributed to bone and joint infections in terms of disability-adjusted life years (DALYs), elucidating the contemporary status and temporal trends., Methods: Utilizing GBD 2019 data, we summarized the burden of bone and joint infections attributed to AMR across 195 countries and territories in the 30 years from 1990 to 2019. We review the epidemiology of AMR in terms of age-standardized rates, the estimated DALYs, comprising years of life lost (YLLs) and years lived with disability (YLDs), as well as associations between DALYs and socio-demographic indices., Results: The GBD revealed that DALYs attributed to bone and joint infections associated with AMR have risen discernibly between 1990 and 2019 globally. Significant geographical disparities and a positive correlation with socio-demographic indicators were observed. Staphylococcus aureus infections, Group A Streptococcus, Group B Streptococcus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter-related bone and joint infections were associated with the highest DALYs because of a high proportion of antimicrobial resistance. Countries with limited access to healthcare, suboptimal sanitary conditions, and inconsistent antibiotic stewardship were markedly impacted., Conclusions: The GBD underscores the escalating burden of bone and joint infections exacerbated by AMR, necessitating urgent, multi-faceted interventions. Strategies to mitigate the progression and impact of AMR should emphasize prudent antimicrobial usage and robust infection prevention and control measures, coupled with advancements in diagnostic and therapeutic modalities., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Considering the variability in individual responses to opioids and the growing concerns about opioid addiction, prescribing opioids for postoperative pain management after spine surgery presents significant challenges. Therefore, this study undertook a novel pharmacogenomics-based in silico investigation of FDA-approved opioid medications. The DrugBank database was employed to identify all FDA-approved opioids. Subsequently, the PharmGKB database was utilized to filter through all variant annotations associated with the relevant genes. In addition, the dpSNP ( https://www.ncbi.nlm.nih.gov/snp/ ), a publicly accessible repository, was used. Additional analyses were conducted using STRING-MODEL (version 12), Cytoscape (version 3.10.1), miRTargetLink.2, and NetworkAnalyst (version 3). The study identified 125 target genes of FDA-approved opioids, encompassing 7019 variant annotations. Of these, 3088 annotations were significant and pertained to 78 genes. During variant annotation assessments (VAA), 672 variants remained after filtration. Further in-depth filtration based on variant functions yielded 302 final filtered variants across 56 genes. The Monoamine GPCRs pathway emerged as the most significant signaling pathway. Protein-protein interaction (PPI) analysis revealed a fully connected network comprising 55 genes. Gene-miRNA Interaction (GMI) analysis of these 55 candidate genes identified miR-16-5p as a pivotal miRNA in this network. Protein-Drug Interaction (PDI) assessment showed that multiple drugs, including Ibuprofen, Nicotine, Tramadol, Haloperidol, Ketamine, L-Glutamic Acid, Caffeine, Citalopram, and Naloxone, had more than one interaction. Furthermore, Protein-Chemical Interaction (PCI) analysis highlighted that ABCB1, BCL2, CYP1A2, KCNH2, PTGS2, and DRD2 were key targets of the proposed chemicals. Notably, 10 chemicals, including carbamylhydrazine, tetrahydropalmatine, Terazosin, beta-methylcholine, rubimaillin, and quinelorane, demonstrated dual interactions with the aforementioned target genes. This comprehensive review offers multiple strong, evidence-based in silico findings regarding opioid prescribing in spine pain management, introducing 55 potential genes. The insights from this report can be applied in exome analysis as a pharmacogenomics (PGx) panel for pain susceptibility, facilitating individualized opioid prescribing through genotyping of related variants. The article also points out that African Americans represent an important group that displays a high catabolism of opioids and suggest the need for a personalized therapeutic approach based on genetic information., (© 2024. The Author(s).)

Background: In anticipation of Food and Drug Administration (FDA) approval of the Total Posterior Spine (TOPS) system, the International Society for the Advancement of Spine Surgery (ISASS) conducted a study to estimate the work relative value units (RVUs) for facet arthroplasty. The purpose of this study was to establish a valuation of work RVU for Current Procedural Terminology (CPT) Code 0202T in the interim until the Relative Value Scale Update Committee (RUC) can determine an appropriate value. The valuation established from this survey will assist surgeons to establish appropriate procedure reimbursement from third-party payers., Methods: A survey was created and sent to 52 surgeons who had experience implanting the TOPS system during the investigational device exemption clinical trial. The survey included a patient vignette, a description of CPT Code 0202T along with a video of the TOPS system, and a confirmation question about the illustration's effectiveness. Respondents were asked to compare the work involved in CPT Code 0202T to 8 lumbar spine procedures. A Rasch analysis was performed to estimate the relative difficulty of CPT 0202T using the work RVUs of the comparable procedures., Results: Forty-one surgeons responded to the survey. Of all the procedures, CPT Code 0202T received the most responses for equal work compared with posterior osteotomy (46%) followed by transforaminal lumbar interbody fusion (41%). The results of the regression analysis indicate a work RVU for CPT 0202T of 39.47., Conclusion: The study found an estimated work RVU of 39.47 for CPT Code 0202T using Rasch analysis. As an alternative to this Rasch methodology, one may consider a crosswalk methodology to the work RVUs for transforaminal lumbar interbody fusion procedurally, not as an alternative code., Clinical Relevance: These recommendations are not a substitute for RUC methodology but serve as a reference for physicians and third-party payers to understand work RVU similarities for charge and payment purposes temporarily until RUC methodology provides accurate RVUs for the procedure., Competing Interests: Declaration of Conflicting Interests : The authors report no conflicts of interest in this work., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2024 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Background: Effective 1 January 2017, single-level endoscopic lumbar discectomy received a Category I Current Procedural Terminology (CPT) code 62380. However, no work relative value units (RVUs) are currently assigned to the procedure. An international team of endoscopic spine surgeons conducted a study, endorsed by several spine societies, analyzing the learning curve, difficulty, psychological intensity, and estimated work RVUs of endoscopic lumbar spinal decompression compared with other common lumbar spine surgeries., Methods: A survey comparing CPT 62380 to 10 other comparator CPT codes reflective of common spine surgeries was developed to assess the work RVUs in terms of learning curve, difficulty, psychological intensity, and work effort using a paired Rasch method., Results: The survey was sent to 542 spine specialists. Of 322 respondents, 150 completed the survey for a 43.1% completion rate. Rasch analysis of the submitted responses statistically corroborated common knowledge that the learning curve with lumbar endoscopic spinal surgery is steeper and more complex than with traditional translaminar lumbar decompression surgeries. It also showed that the psychological stress and mental and work effort with the lumbar endoscopic decompression surgery were perceived to be higher by responding spine surgeons compared with posterior comparator decompression and fusion surgeries and even posterior interbody and posterolateral fusion surgeries. The regression analysis of work effort vs procedural difficulty showed the real-world evaluation of the lumbar endoscopic decompression surgery described in CPT code 62380 with a calculated work RVU of 18.2464., Conclusion: The Rasch analysis suggested the valuation for the endoscopic lumbar decompression surgery should be higher than for standard lumbar surgeries: 111.1% of the laminectomy with exploration and/or decompression of spinal cord and/or cauda equina (CPT 63005), 118.71% of the laminectomy code (CPT 63047), which includes foraminotomy and facetectomy, 152.1% of the hemilaminectomy code (CPT 63030), and 259.55% of the interlaminar or interspinous process stabilization/distraction without decompression code (CPT 22869). This research methodology was endorsed by the Interamerican Society for Minimally Invasive Spine Surgery (SICCMI), the Mexican Society of Spinal Surgeons (AMCICO), the International Society For Minimally Invasive Spine Surgery (ISMISS), the Brazilian Spine Society (SBC), the Society for Minimally Invasive Spine Surgery (SMISS), the Korean Minimally Invasive Spine Surgery (KOMISS), and the International Society for the Advancement of Spine Surgery (ISASS)., Clinical Relevance: This study provides an updated reimbursement recommendation for endoscopic spine surgery., Level of Evidence: Level 3., Competing Interests: Declaration of Conflicting Interests : There was no formal funding by private, government, or commercial funders. The participating spine centers and their authors (Center For Advanced Spine Care of Southern Arizona, Tucson, Arizona; Desert Institute of Spine Care, Phoenix, Arizona; Department of Orthopedics, Fundación Universitaria Sanitas, Bogotá, D.C., Colombia; Department of Neurosurgery, Orthopedics and Thoracic Surgery at Hospital Universitário Gaffre e Guinle, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil; Department of Orthopedic Surgery USP, Riberao Preto Brazil, Universitätsklinikum des Saarlandes, Klinik für Orthopädie and Neurochirurgie, Department of Orthopedic Surgery, Arabellaklinik, Munich, Germany, the Atualli Spine Care Clinica, Sao Paulo, Brazil; Cape Cod Health care, Hyannis, MA, USA; Department of Neurosurgery, Azienda Ospedaliero Universitaria Pisana, University of Pisa, Italy; Clínica Articulare, Belem, Brazil; Comprehensive Specialty Care, Clinical Radiology of Oklahoma, Department of Orthopedics, First Medical Center, PLA General Hospital, Beijing; Spinartus Hospital Chungdam, Korea; Department of Neurosurgery, Seoul; St. Mary’s Hospital, College of Medicine, The Catholic University of Korea) volunteered their time and internal resources to support the design and conduction of this research study. All authors aided in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. The authors declare no conflict of interest relevant to this research, and there was no personal circumstance or interest that may be perceived as inappropriately influencing the representation or interpretation of reported research results. This research was not compiled to enrich anyone. It was merely intended to advance the understanding of the learning curve, difficulty, psychological intensity, and estimated work relative value units of endoscopic lumbar spinal decompression surgery in comparison to other common lumbar spine surgeries., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2024 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

While achieving premarket approval from the US Food and Drug Administration represents a significant milestone in the development and commercialization of a Class III medical device, the aftermath endeavor of gaining market access can be daunting. This article provides a case study of the Barricaid annular closure device (Barricaid), a reherniation reduction device, which has been demonstrated to decrease the risk of suffering a recurrent lumbar intervertebral disc herniation. Following Food and Drug Administration approval, clinical adoption has been slow due to barriers to market access, including the perception of low-quality clinical evidence, questionable significance of the medical necessity of the procedure, and imaging evidence of increased likelihood of vertebral endplate changes. The aim of this article is to provide appropriate examination, rationale, and rebuttal of these concerns. Weighing the compendium of evidence, we offer a definition of a separate and unique current procedural terminology code to delineate this procedure. Adoption of this code will help to streamline the processing of claims and support the conduct of research, the evaluation of health care utilization, and the development of appropriate medical guidelines., Competing Interests: Declaration of Conflicting Interests : The authors report no conflicts of interest in this work., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2024 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Background: With the growing prevalence of lumbar spinal stenosis, endoscopic surgery, which incorporates techniques such as transforaminal, interlaminar, and unilateral biportal (UBE) endoscopy, is increasingly considered. However, the patient selection criteria are debated among spine surgeons., Objective: This study used a polytomous Rasch analysis to evaluate the factors influencing surgeon decision-making in selecting patients for endoscopic surgical treatment of lumbar spinal stenosis., Methods: A comprehensive survey was distributed to a representative sample of 296 spine surgeons. Questions encompassed various patient-related and clinical factors, and responses were captured on a logit scale graphically displaying person-item maps and category probability curves for each test item. Using a Rasch analysis, the data were subsequently analyzed to determine the latent traits influencing decision-making., Results: The Rasch analysis revealed that surgeons' preferences for transforaminal, interlaminar, and UBE techniques were easily influenced by comfort level and experience with the endoscopic procedure and patient-related factors. Harder-to-agree items included technological aspects, favorable clinical outcomes, and postoperative functional recovery and rehabilitation. Descriptive statistics suggested interlaminar as the best endoscopic spinal stenosis decompression technique. However, logit person-item analysis integral to the Rasch methodology showed highest intensity for transforaminal followed by interlaminar endoscopic lumbar stenosis decompression. The UBE technique was the hardest to agree on with a disordered person-item analysis and thresholds in category probability curve plots., Conclusion: Surgeon decision-making in selecting patients for endoscopic surgery for lumbar spinal stenosis is multifaceted. While the framework of clinical guidelines remains paramount, on-the-ground experience-based factors significantly influence surgeons' selection of patients for endoscopic lumbar spinal stenosis surgeries. The Rasch methodology allows for a more granular psychometric evaluation of surgeon decision-making and accounts better for years-long experience that may be lost in standardized clinical guideline development. This new approach to assessing spine surgeons' thought processes may improve the implementation of evidence-based protocol change dictated by technological advances was endorsed by the Interamerican Society for Minimally Invasive Spine Surgery (SICCMI), the International Society for Minimal Intervention in Spinal Surgery (ISMISS), the Mexican Spine Society (AMCICO), the Brazilian Spine Society (SBC), the Society for Minimally Invasive Spine Surgery (SMISS), the Korean Minimally Invasive Spine Society (KOMISS), and the International Society for the Advancement of Spine Surgery (ISASS)., Competing Interests: Declaration of Conflicting Interests : There was no formal funding by private, government, or commercial funders. The participating spine centers and their authors (Center For Advanced Spine Care of Southern Arizona – Tucson, Arizona, Desert Institute of Spine Care – Phoenix, Arizona, Department of Orthopedics, Fundación Universitaria Sanitas – Bogotá, D.C., Colombia, Department of Neurosurgery, Orthopedics and Thoracic Surgery at Hospital Universitário Gaffre e Guinle, Universidade Federal do Estado do Rio de Janeiro – Rio de Janeiro, Brazil, Department of Orthopedic Surgery USP, Riberao Preto Brazil, Universitätsklinikum des Saarlandes, Klinik für Orthopädie and Neurochirurgie, Department of Orthopedic Surgery, Arabellaklinik, Munich, Germany, the Atualli Spine Care Clinica – Sao Paulo, Brazil, Cape Cod Healthcare, Hyannis, MA, USA, Department of Neurosurgery, Azienda Ospedaliero Universitaria Pisana, University of Pisa, Italy, Clínica Articulare, Belem, Brazil, Comprehensive Specialty Care, Clinical Radiology of Oklahoma, Department of Orthopedics, First Medical Center, PLA General Hospital, Beijing, Spinartus Hospital Chungdam, Korea, Department of Neurosurgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea) volunteered their time and internal resources to support the design and conduction of this research study. All authors aided in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. The authors declare no conflict of interest relevant to this research, and there was no personal circumstance or interest that may be perceived as inappropriately influencing the representation or interpretation of reported research results. This research was not compiled to enrich anyone., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2024 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Background: There is an increasing acceptance of conducting minimally invasive transforaminal lumbar interbody fusion (TLIF) in ambulatory surgical centers (ASCs). The Centers for Medicare and Medicaid Services (CMS) introduced the Hospitals Without Walls (HWW) program in March 2020. This program granted hospitals regulatory flexibility to offer services and procedures in nontraditional locations, including ASCs. However, implementation hurdles persist., Methods: A survey was sent to 235 surgeons regarding the use of ASCs for performing TLIF surgeries on elderly patients. Multiple-choice questions covering various aspects of TLIF practice preferences, including surgical indications, decision factors for choosing ASCs over hospitals, implementation hurdles, reimbursement concerns, staffing issues, and the impact of CMS rules and regulations on TLIF in ASCs, particularly concerning physician ownership and self-referral conflicts governed by the Stark law, were asked., Results: The survey completion rate was 25.8% (Figure 1). The most common surgical indications for TLIF in ASCs were spondylolisthesis (80%), spinal stenosis (62.5%), and low back pain (47.5%). Most surgeons (78%) believed TLIF could be safely performed in ASCs. Streamlined workflow, lower infection rates, and cost-effectiveness were advantages listed by 58.5% of surgeons. Patient's medical history (75.8%), followed by ASC resources and capabilities (61%) and surgeon preference (61%), were relevant factors. Higher efficiencies at ASCs (14.6%), contractual issues (9.8%), and ownership issues (7.3%) were less relevant to surgeons. About 65.9% of surgeons reported lower reimbursement in ASCs, and 43.9% said it was an implementation hurdle. Lower direct costs were reported by 53.7% of surgeons. Other hurdles included a lack of trained staff (24.4%), inadequate staffing (22.0%), cost overruns (26.8%), high Joint Commission or the Accreditation Association for Ambulatory Health Care credentialing costs, and surgeons feeling uncomfortable performing TLIF in ASCs (22.0%). Only 17.1% listed medical problems as a reason their patient was considered unsuitable for the ASC environment. A majority (53.7%) stated that their ASCs complied with strict Stark requirements by disclosing physician ownership interests. However, 22% of surgeons reported self-referrals under the "In-Office Ancillary Services Exception" allowed by the Stark law., Conclusion: Our survey data show that surgeons' perceptions of current CMS rules and regulations may hinder the transition into the ASC setting because they think the reimbursement is too low and the regulatory burden is too high. ASCs have disproportionally higher initial acquisition and ongoing costs related to staff training and maintenance of the TLIF technology that CMS should consider when determining the appropriate financial remuneration for these complex procedures., Clinical Relevance: ASC offers a viable and attractive option for their TLIF procedure with the advantage of same-day discharge and at-home recovery., Competing Interests: Declaration of Conflicting Interests : This manuscript is not intended to endorse any products or push any agenda other than the associated clinical outcomes with TLIF spine surgery in ASC or hospital settings. None of the authors received anything of value in return for this publication. None of the authors are paid consultants of Wenzel Spine., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2024 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Exercise promotes health and wellness, including its operation as a protective factor against a variety of psychological, neurological, and chronic diseases. Selenium and its biomarker, selenoprotein P (SEPP1), have been implicated in health, including cancer prevention, neurological function, and dopamine signaling. SEPP1 blood serum levels were compared with a one-way ANOVA between sedentary (SED), moderately exercised (MOD) [10 m/min starting at 10 min, increasing to 60 min], and high-intensity interval training (HIIT) exercised rats [30 min in intervals of 2-min followed by a 1-min break, speed progressively increased from 10 to 21 m/min]. HIIT rats showed significantly higher serum SEPP1 concentrations compared to MOD and SED. More specifically, HIIT exercise showed an 84% increase in SEPP1 levels compared to sedentary controls. MOD rats had greater serum SEPP1 concentrations compared to SED, a 33% increase. The results indicated that increased exercise intensity increases SEPP1 levels. Exercise-induced increases in SEPP1 may indicate an adaptive response to the heightened oxidative stress. Previous studies found a significant increase in dopamine D2 receptor (D2R) binding in these same rats, suggesting a potential association between SEPP1 and dopamine signaling during exercise. Modulating antioxidants like SEPP1 through personalized therapies, including exercise, has broad implications for health, disease, and addiction.

The widespread adoption of Glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of obesity and diabetes has raised concerns about their potential adverse effects, including the induction of depression and suicide ideation. We report on a male patient in his early 50s with a complex medical history, including adult Attention-Deficit/Hyperactive Disorder, narcolepsy with cataplexy, and major depressive disorder in remission, who experienced exacerbated hemiplegic migraines after initiating treatment with an injectable GLP-1 agonist (Saxenda) for weight loss. Despite a previous history of experiencing hemiplegic migraines once or twice a year, the patient reported daily occurrences of migraines, many of which were hemiplegic, during the 60 days of GLP-1 agonist treatment. The migraines abated only upon discontinuation of the medication. This case underscores the need to carefully consider patient history and potential genetic predispositions when prescribing GLP-1 agonists, highlighting the complex interactions between these medications, existing comorbidities, and the dopaminergic and calcitonin gene-related peptide pathways. Our findings suggest that GLP-1 agonists, while beneficial for some, may pose significant risks for patients with specific genetic backgrounds or neurological conditions, calling for personalized approaches to treatment and increased awareness of potential adverse effects., Competing Interests: Conflict of Interest KB is the inventor and through his company synaptamine and Transplicegen Holdings Inc owns USA and foreign patents related KB220 a pro dopamine regulator.

Background:  Minimally invasive spinal surgery (ESS) are both well-established surgical techniques for lumbar spinal stenosis; however, there is limited literature comparing the efficacy of the two techniques with respect to radiologic decompression data., Methods:  In this review, PubMed, Google Scholar, and Scopus databases were systematically searched from inception until July 2022 for studies that reported the radiologic outcomes of endoscopic and minimally invasive approaches for decompressive spinal surgery, namely, the spinal canal area, neural foraminal area, and neural foraminal heights., Results:  Of the 378 articles initially retrieved using MeSH and keyword search, 9 studies reporting preoperative and postoperative spinal areas and foraminal areas and heights were finally included in our review. Of the total 581 patients, 391 (67.30%) underwent MISS and 190 (32.70%) underwent ESS. The weighted mean difference between the spinal canal diameter in pre- and postoperative conditions was 56.64 ± 7.11 and 79.52 ± 21.31 mm 2 in the MISS and ESS groups, respectively. ESS was also associated with a higher mean difference in the foraminal area postoperatively (72 ± 1 vs. 35.81 ± 11.3 mm 2 in the MISS and ESS groups, respectively), but it was comparable to MISS in terms of the foraminal height (0.32 ± 0.037 vs. 0.29 ± 0.03 cm in the MISS and endoscopic groups, respectively)., Conclusions:  Compared with MISS, ESS was associated with improved radiologic parameters, including spinal canal area and neural foraminal area in the lumbar spinal segments. Both techniques led to the same endpoint of neural decompression when starting with a more severe compression. However, the present data do not allow the correlation of the radiographic results with the related clinical outcomes., Competing Interests: None declared., (Thieme. All rights reserved.)

Clonidine operates through agonism at the alpha-2A receptor, a specific subtype of the alpha-2-adrenergic receptor located predominantly in the prefrontal cortex. By inhibiting the release of norepinephrine, which is responsible for withdrawal symptoms, clonidine effectively addresses withdrawal-related conditions such as anxiety, hypertension, and tachycardia. The groundbreaking work by Gold et al . demonstrated clonidine's ability to counteract the effects of locus coeruleus stimulation, reshaping the understanding of opioid withdrawal within the field. In the 1980s, the efficacy of clonidine in facilitating the transition to long-acting injectable naltrexone was confirmed for individuals motivated to overcome opioid use disorders (OUDs), including physicians and executives. Despite challenges with compliance, naltrexone offers sustained blockade of opioid receptors, reducing the risk of overdose, intoxication, and relapse in motivated patients in recovery. The development of clonidine and naltrexone as treatment modalities for OUDs, and potentially other addictions, including behavioral ones, underscores the potential for translating neurobiological advancements from preclinical models (bench) to clinical practice (bedside), ushering in innovative approaches to addiction treatment., Competing Interests: Conflict of interest Dr. Blum is the inventor of GARS® and Pro-dopamine Regulation (KB220Z™). There are no other conflicts of interest.

Background: Duchene Muscular Disorder (DMD) is a severe X-linked recessive neuromuscular disease. Previous reports predicted that one-third of cases with a fatal X-linked recessive disease will be caused by a novel mutation, and the mutation rate for DMD seems to be higher in males., Objective: A novel mutation in the DMD gene DMD (NM&#95;004006.3):c.92A>G (p.Lys31Arg) is suggested for males because of their heterozygous mothers carrying the mutant alleles., Method: Whole Exome Sequencing (WES) was done for a 25-year-old female followed by the screening of the novel mutation in her parents and her brother by the Sanger sequencing technique. Some in silico analyses were run to find the putative alterations in wild-type and mutant structures by PolyPhen-2 and Mupro. Notably, SWISS-MODEL was performed to build a reliable model for the mutant allele based on the PDB ID: 1DXX structure. Also, superimposition was done by PyMol., Results: WES analysis revealed three novel mutations including DLD (exon13:c.G1382A:p. G461E), ABCA3 (exon12:c.G1404C:p.W468C), and DMD (exon2:c.A92G:p.K31R) in the case. Focusing on DMD mutation, Sanger sequencing of the patient's parents and brother indicated no mutant allele in her mother and brother but a mutant allele in her father as a hemizygous pattern. In silico analyses showed no considerable change regarding pathogenic impact., Conclusion: In conclusion, our findings revealed no pathogenic effect of the new mutation (K31R) of the DMD gene in an Iranian 25-year-old woman. Because of the DMD importance in preclinical diagnosis, these data may shed a light on the diagnosis of this mutation in future pregnancies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Methotrexate (MTX), sulfonamides, hydroxychloroquine, and leflunomide have consistently resulted in remission with relatively mild to moderate adverse effects in patients with rheumatoid arthritis (RA). Modern medications outperform traditional treatments in that they target the pathological processes that underlie the development of RA., Methods: Following PRISMA guidelines, the authors accomplished a systematic review of the clinical efficacy of RA drugs, including the biologics such as Tumor Necrosis Factor-alpha inhibitors (TNF-α i) like Etanercept, Infliximab, Golimumab, and Adalimumab, kinase inhibitors (JAK inhibitors including Baricitinib and Tofacitanib), SyK inhibitors like Fos-tamatinib, MAPK inhibitors such as Talmapimod, T-cell inhibitors (Abatacept), IL6 blockers (Tocilizumab), and B cells depleters (Rituximab). These drugs have been found to increase remission rates when combined with MTX. A bioinformatics-based network was designed applying STRING-MODEL and the DrugBank database for the aforementioned drugs and MTX and, finally, employed for this systematic review., Results: Current research demonstrates that non-TNF-α inhibitor biologicals are particularly helpful in treating patients who did not respond well to conventional medications and TNF-α inhibitors. Despite being effective, these innovative drugs have a higher chance of producing hazardous side effects. The in silico investigations suggested an uncovered molecular interaction in combining MTX with other biological drugs. The STRING-MODEL showed that DHFR, TYMS, and ATIC, as the receptors of MTX, interact with each other but are not connected to the major interacted receptors., Conclusions: New game-changing drugs including Mavrilimumab, Iguratimod, Upadacitinib, Fenebrutinib, and nanoparticles may be crucial in controlling symptoms in poorly managed RA patients. Emerging therapeutic targets like Toll-like 4 receptors, NLRP3 inflammasome complexes, and mesenchymal stem cells can further transform RA therapy.

Endoscopic surgery of the cervical spine is constantly evolving and the spectrum of its indications has expanded in recent decades. Full-endoscopic techniques have standardized the procedures for posterior and anterior access. The full-endoscopic approach was developed to treat degenerative diseases with the least possible invasion and without causing instability of the cervical spine. The posterior full-endoscopic approach is indicated for the treatment of diseases of the lateral part of the vertebral segment, such as herniations and stenoses of the lateral recess and vertebral foramen. There has been little discussion of this approach to the treatment of central stenosis of the cervical spine. This technical note describes a step-by-step surgical technique for central and over-the-top full-endoscopic decompression in the cervical spine, using a 3.7 mm working channel endoscope. This technique has already been shown to be effective in a recent case series with a 4.7 mm working channel endoscope, and may represent a new treatment option for central or bilateral lateral recess stenosis. There is also the possibility of a bilateral full-endoscopic approach, but this may be associated with greater muscle damage and a longer operative time. Case series and comparative studies should be encouraged to confirm the safety and utility of this technique.

This International Society for the Advancement of Spine Surgery statement has been generated to respond to growing requests for background, supporting literature and evidence, and proper coding for restorative neurostimulation for chronic low back pain. Chronic low back pain describes the diverse experience of a significant proportion of the population. Conservative management of these patients remains the predominant care pathway, but for many patients, symptom relief is poor. The application of new techniques in patients who have exhausted traditional care paradigms should be undertaken with a detailed understanding of the pathology being treated, the mechanisms involved, and the data supporting efficacy. This statement on restorative neurostimulation places this technology in the context of the current understanding of the etiology of mechanical low back pain and the currently available evidence for this technique. In an appropriately selected cohort with a specific subset of chronic low back pain symptoms, this technique may provide benefit to payers and patients., Competing Interests: Declaration of Conflicting Interests : The authors report no conflicts of interest in this work., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2023 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Background: The microsurgical anterior approach to the cervical spine is commonplace. Fewer surgeons perform posterior cervical microsurgical procedures on a routine basis for lack of indication, more bleeding, persistent postoperative neck pain, and risk of progressive misalignment. In comparison, the endoscopic technique is preferentially performed through the posterior approach. Many spine surgeons and even surgeons versed in lumbar endoscopy are often reluctant to consider endoscopic procedures in the cervical spine. We report the results of a surgeon survey to find out why., Methods: A questionnaire of 10 questions was sent to spine surgeons by email and chat groups in social media networks including Facebook, WeChat, WhatsApp, and LinkedIn to collect practice pattern data about microscopic and endoscopic spine surgery in the lumbar and cervical spine. The responses were cross-tabulated by surgeons' demographic data. Pearson Chi-Square measures, Kappa statistics, and linear regression analysis of agreement or disagreement were performed by analyzing the distribution of variances using the statistical package SPSS Version 27.0., Results: The survey response rate was 39.7%, with 50 of the 126 surgeons who started the survey submitting a completed questionnaire. Of the 50 surgeons, 56.2% were orthopedic, and 42% neurological surgeons. Most surgeons worked in private practice (42%). Another 26% were university-employed, 18% were in private practice affiliated with a university, and the remaining 14% were hospital employed. The majority of surgeons (55.1%) were autodidacts. The largest responding surgeon groups were between 35-44 years (38%) and between 45-54 years of age (34%). Half of the responding surgeons were routinely performing endoscopic cervical spine surgery. The other half did not perform it for the main hurdle of fear of complications (50%). Lack of appropriate mentorship was listed as second most reason (25.4%). More concerns for not performing cervical endoscopic approaches were the perception of lack of technology (20.8%) and suitable surgical indication (12.5%). Only 4.2% considered cervical endoscopy too risky. Nearly a third (30.6%) of the spine surgeons treated over 80% of their cervical spine patients with endoscopic surgeries. Most commonly performed were posterior endoscopic cervical discectomy (PECD; 52%), posterior endoscopic cervical foraminotomy (PECF; 48%), anterior endoscopic cervical discectomy (AECD; 32%), cervical endoscopic unilateral laminotomy for bilateral decompression (CE-ULBD; 30%), respectively., Conclusion: Cervical endoscopic spine surgery is gaining traction among spine surgeons. However, by far most surgeons performing cervical endoscopic spine surgery work in private practice and are autodidacts. This lack of a teacher to shorten the learning curve as well as fear of complications are two of the major impediments to the successful implementation of cervical endoscopic procedures., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Previous studies have documented pain as an important concern for quality of life (QoL) and one of the most challenging manifestations for cancer patients. Thus, cancer pain management (CPM) plays a key role in treating pain related to cancer. The aim of this systematic review was to investigate CPM, with an emphasis on personalized medicine, and introduce new pharmacogenomics-based procedures for detecting and treating cancer pain patients., Methods: This study systematically reviewed PubMed from 1990 to 2023 using keywords such as cancer, pain, and personalized medicine. A total of 597 publications were found, and after multiple filtering processes, 75 papers were included. In silico analyses were performed using the GeneCards, STRING-MODEL, miRTargetLink2, and PharmGKB databases., Results: The results reveal that recent reports have mainly focused on personalized medicine strategies for CPM, and pharmacogenomics-based data are rapidly being introduced. The literature review of the 75 highly relevant publications, combined with the bioinformatics results, identified a list of 57 evidence-based genes as the primary gene list for further personalized medicine approaches. The most frequently mentioned genes were CYP2D6, COMT, and OPRM1. Moreover, among the 127 variants identified through both the literature review and data mining in the PharmGKB database, 21 variants remain as potential candidates for whole-exome sequencing (WES) analysis. Interestingly, hsa-miR-34a-5p and hsa-miR-146a-5p were suggested as putative circulating biomarkers for cancer pain prognosis and diagnosis., Conclusions: In conclusion, this study highlights personalized medicine as the most promising strategy in CPM, utilizing pharmacogenomics-based approaches to alleviate cancer pain.

Proving clinical superiority of personalized care models in interventional and surgical pain management is challenging. The apparent difficulties may arise from the inability to standardize complex surgical procedures that often involve multiple steps. Ensuring the surgery is performed the same way every time is nearly impossible. Confounding factors, such as the variability of the patient population and selection bias regarding comorbidities and anatomical variations are also difficult to control for. Small sample sizes in study groups comparing iterations of a surgical protocol may amplify bias. It is essentially impossible to conceal the surgical treatment from the surgeon and the operating team. Restrictive inclusion and exclusion criteria may distort the study population to no longer reflect patients seen in daily practice. Hindsight bias is introduced by the inability to effectively blind patient group allocation, which affects clinical result interpretation, particularly if the outcome is already known to the investigators when the outcome analysis is performed (often a long time after the intervention). Randomization is equally problematic, as many patients want to avoid being randomly assigned to a study group, particularly if they perceive their surgeon to be unsure of which treatment will likely render the best clinical outcome for them. Ethical concerns may also exist if the study involves additional and unnecessary risks. Lastly, surgical trials are costly, especially if the tested interventions are complex and require long-term follow-up to assess their benefit. Traditional clinical testing of personalized surgical pain management treatments may be more challenging because individualized solutions tailored to each patient's pain generator can vary extensively. However, high-grade evidence is needed to prompt a protocol change and break with traditional image-based criteria for treatment. In this article, the authors review issues in surgical trials and offer practical solutions.

Background: Ossification of the posterior longitudinal ligament (OPLL) may cause cervical myelopathy. In its multilevel form, it may not be easy to manage. Minimally invasive endoscopic posterior cervical decompression may be an alternative to traditional laminectomy surgery., Methods: Thirteen patients with multilevel OPLL and symptomatic cervical myelopathy were treated with endoscopic spine surgery from January 2019 to June 2020. In this consecutive observational cohort study, pre- and postoperative Japanese Orthopaedic Association (JOA) score and Neck Disability Index (NDI) were analyzed at a final follow-up of 2 years postoperatively., Results: There were 13 patients consisting of 3 women and 10 men. The patient's average age was 51.15 years. At the final 2-year follow-up, the JOA score improved from a preoperative value of 10.85 ± 2.91 to 14.77 ± 2.13 postoperatively ( P < 0.001). The corresponding NDI scores decreased from 26.61 ± 12.88 to 11.12 ± 10.85 ( P < 0.001). There were no infections, wound complications, or reoperations., Conclusion: Direct posterior endoscopic decompression for multilevel OPLL is feasible in symptomatic patients when executed at a high skill level. While 2-year outcomes were encouraging and on par with historic data obtained with traditional laminectomy, future studies will need to show whether any long-term shortcomings exist., Competing Interests: Declaration of Conflicting Interests : The authors have no direct or indirect conflicts. This manuscript is not meant for or intended to endorse any products or push any other agenda other than the associated clinical outcomes with endoscopic spine surgery. The motive for compiling this clinically relevant information is by no means created and/or correlated to directly enrich anyone due to its publication. This publication was intended to substantiate cervical endoscopic spinal surgery concepts to facilitate technology advancements., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2023 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Background: Due to its ultraminimally invasive nature, endoscopic spinal surgery is an attractive tool in spinal oncologic care. To date, there has been no comprehensive review of this topic. The authors therefore present a thorough search of the medical literature on endoscopic techniques for spinal oncology., Methods: A systematic review using PubMed was conducted using the following keywords: endoscopic spine surgery, spinal oncology, and spinal tumors., Results: Collectively, 19 cases described endoscopic spine surgery for spinal oncologic care. Endoscopic spine surgery has been employed for the care of patients with spinal tumors under the following 4 circumstances: (1) to obtain a reliable tissue diagnosis; (2) to serve as an adjunct during traditional open surgery; (3) to achieve targeted debulking; or (4) to perform definitive resection. These cases employing endoscopic techniques highlight the versatility of this approach and its utility when applied to the right patient and with an experienced surgeon., Conclusions: Our systematic review suggests that, given the right patient and an experienced surgeon, endoscopic spine surgery should be considered in the armamentarium for spinal oncologic care for both staging and definitive resection., Clinical Relevance: This systematic literature review showed that endoscopic techniques have been successfully applied across the spectrum of care in spinal oncology, from diagnosis to definitive treatment., Competing Interests: Declaration of Conflicting Interests : The authors report no conflicts of interest in this work., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2023 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Background: Durotomy during endoscopic spine surgery can cause a patient's neurological or cardiovascular status to deteriorate unexpectedly intra- or postoperatively. There is currently limited literature regarding appropriate fluid management strategies, irrigation-related risk factors, and clinical consequences of incidental durotomy during spinal endoscopy, and no validated irrigation protocol exists for endoscopic spine surgery. Thus, the present article sought to (1) describe 3 cases of durotomy, (2) investigate standard epidural pressure measurements, and (3) survey endoscopic spine surgeons on the incidence of adverse effects believed to result from durotomy., Materials and Methods: The authors first reviewed clinical outcomes and analyzed complications in 3 patients with intraoperatively recognized incidental durotomy. Second, the authors conducted a small case series with intraoperative epidural pressure measurements during gravity-assisted irrigated video endoscopy of the lumbar spine. Measurements were conducted on 12 patients with a transducer assembly that was introduced through the endoscopic working channel of the RIWOSpine Panoview Plus and Vertebris endoscope to the decompression site in the spine. Third, the authors conducted a retrospective, multiple-choice survey of endoscopic spine surgeons to better understand the frequency and seriousness of problems they attributed to irrigation fluid escaping from the surgical decompression site into the spinal canal and neural axis. Descriptive and correlative statistical analyses were performed on the surgeons' responses., Results: In the first part of this study, durotomy-related complications during irrigated spinal endoscopy were observed in 3 patients. Postoperative head computed tomographic (CT) images revealed massive blood in the intracranial subarachnoid space, the basal cisterns, the III and IV ventricle, and the lateral ventricles characteristic of an arterial fisher grade IV subarachnoid hemorrhage, and hydrocephalus without evidence of aneurysms or angiomas. Two additional patients developed intraoperative seizures, cardiac arrhythmia, and hypotension. The head CT image in 1 of these 2 patients had intracranial air entrapment.In the second part, epidural pressure measurements in 12 patients who underwent uneventful routine lumbar interlaminar decompression for L4-L5 and L5-S1 disc herniation showed an average epidural pressure of 24.5 mm Hg.In the third part, the online survey was accessed by 766 spine surgeons worldwide and had a response rate of 43.6%. Irrigation-related problems were reported by 38% of responding surgeons. Only 11.8% used irrigation pumps, with 90% running the pump above 40 mm Hg. Headaches (4.5%) and neck pain (4.9%) were observed by nearly a 10th (9.4%) of surgeons. Seizures in combination with headaches, neck and abdominal pain, soft tissue edema, and nerve root injury were reported by another 5 surgeons. One surgeon reported a delirious patient. Another 14 surgeons thought that they had patients with neurological deficits ranging from nerve root injury to cauda equina syndrome related to irrigation fluid. Autonomic dysreflexia associated with hypertension was attributed by 19 of the 244 responding surgeons to the noxious stimulus of escaped irrigation fluid that migrated from the decompression site in the spinal canal. Two of these 19 surgeons reported 1 case associated with a recognized incidental durotomy and another with postoperative paralysis., Conclusions: Patients should be educated preoperatively about the risk of irrigated spinal endoscopy. Although rare, intracranial blood, hydrocephalus, headaches, neck pain, seizures, and more severe complications, including life-threatening autonomic dysreflexia with hypertension, may arise if irrigation fluid enters the spinal canal or the dural sac and migrates from the endoscopic site along the neural axis rostrally. Experienced endoscopic spine surgeons suspect a correlation between durotomy and irrigation-related extra- and intradural pressure equalization that could be problematic if associated with high volumes of irrigation fluid LEVEL OF EVIDENCE: 3., Competing Interests: Declaration of Conflicting Interests : The authors report no conflicts of interest in this work., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2023 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Competing Interests: Declaration of Conflicting Interests : This manuscript is not meant for or intended to endorse any products or push any other agenda other than the clinical utilization data associated with the presented research. This research was not compiled to enrich anyone. It was merely intended to highlight the common problems encountered in community spine care in Brazil and the United States.

Background: In clinical outcome studies, patient input into the factors that drive higher satisfaction with lumbar minimally invasive spinal surgery (MISS) is rare. The skin incision is often the only visible consequence of surgery that patients can assess. The authors were interested in patients' opinions about the type of lumbar paramedian minimally invasive spinal (MIS) skin incision employed during MISS and how novel skin incisions could impact patients' interpretation of the outcome. The authors wanted to compare traditional lumbar stab incisions to three novel lumbar paramedian (MIS) skin incisions to determine if further study is indicated. The primary objective was to examine patient satisfaction and perceptions regarding lumbar paramedian MIS skin incisions., Methods: We reviewed the literature and conducted a patient opinion survey. Responses were solicited from back pain patients from a single chiropractic office. Survey questions regarding novel skin incisions for minimally invasive spine surgery (NSIMISS) were conceptualized. The three novel skin incisions were designed using Langer's lines to reduce the total number of incisions; improve patient satisfaction; increase ease of surgical approach/fixation; and reduce operative time/radiation exposure., Results: One hundred and six participants were surveyed. When shown traditional lumbar paramedian MIS skin stab incisions, 76% of respondents indicated negative responses, n = 65. The majority of patients chose traditional stab incisions ( n = 41) followed by novel larger intersecting incisions ( n = 37). The least popular incisions were the novel horizontal ( n = 20) and the novel mini oblique ( n = 5) incisions. Female patients worried more than male patients about how their incision looked. However, there was no statistically significant difference ( p value of 0.0418 via Mann-Whitney U one-tailed test and p value of 0.0836 via Mann-Whitney U two-tailed test). Patients less than or equal to 50 years of age worried more than patients over 51 years of age, which was statistically significant ( p value of 0.0104 via Mann-Whitney U one-tailed test and p value of 0.0208 via Mann-Whitney U two-tailed test)., Conclusions: Patients do have opinions on the type of lumbar paramedian MIS skin incision used. It appears that younger patients and female patients worry most about how the incision on their back looks after surgery. A larger population of patients across many demographics is needed to validate these findings.

Personalized care models are dominating modern medicine. These models are rooted in teaching future physicians the skill set to keep up with innovation. In orthopedic surgery and neurosurgery, education is increasingly influenced by augmented reality, simulation, navigation, robotics, and in some cases, artificial intelligence. The postpandemic learning environment has also changed, emphasizing online learning and skill- and competency-based teaching models incorporating clinical and bench-top research. Attempts to improve work-life balance and minimize physician burnout have led to work-hour restrictions in postgraduate training programs. These restrictions have made it particularly challenging for orthopedic and neurosurgery residents to acquire the knowledge and skill set to meet the requirements for certification. The fast-paced flow of information and the rapid implementation of innovation require higher efficiencies in the modern postgraduate training environment. However, what is taught typically lags several years behind. Examples include minimally invasive tissue-sparing techniques through tubular small-bladed retractor systems, robotic and navigation, endoscopic, patient-specific implants made possible by advances in imaging technology and 3D printing, and regenerative strategies. Currently, the traditional roles of mentee and mentor are being redefined. The future orthopedic surgeons and neurosurgeons involved in personalized surgical pain management will need to be versed in several disciplines ranging from bioengineering, basic research, computer, social and health sciences, clinical study, trial design, public health policy development, and economic accountability. Solutions to the fast-paced innovation cycle in orthopedic surgery and neurosurgery include adaptive learning skills to seize opportunities for innovation with execution and implementation by facilitating translational research and clinical program development across traditional boundaries between clinical and nonclinical specialties. Preparing the future generation of surgeons to have the aptitude to keep up with the rapid technological advances is challenging for postgraduate residency programs and accreditation agencies. However, implementing clinical protocol change when the entrepreneur-investigator surgeon substantiates it with high-grade clinical evidence is at the heart of personalized surgical pain management.

There is an enormous body of literature that has identified the intervertebral disc as a potent pain generator. However, with regard to lumbar degenerative disc disease, the specific diagnostic criteria lack clarity and fail to capture the primary components which include axial midline low back pain with or without non-radicular/non-sciatic referred leg pain in a sclerotomal distribution. In fact, there is no specific ICD-10-CM diagnostic code to classify and define discogenic pain as a unique source of pain distinct from other recognized sources of chronic low back pain including facetogenic, neurocompressive including herniation and/or stenosis, sacroiliac, vertebrogenic, and psychogenic. All of these other sources have well-defined ICD-10-CM codes. Corresponding codes for discogenic pain remain absent from the diagnostic coding vernacular. The International Society for the Advancement of Spine Surgery (ISASS) has proposed a modernization of ICD-10-CM codes to specifically define pain associated with lumbar and lumbosacral degenerative disc disease. The proposed codes would also allow the pain to be characterized by location: lumbar region only, leg only, or both. Successful implementation of these codes would benefit both physicians and payers in distinguishing, tracking, and improving algorithms and treatments for discogenic pain associated with intervertebral disc degeneration.

Pain generator-based lumbar spinal decompression surgery is the backbone of modern spine care. In contrast to traditional image-based medical necessity criteria for spinal surgery, assessing the severity of neural element encroachment, instability, and deformity, staged management of common painful degenerative lumbar spine conditions is likely to be more durable and cost-effective. Targeting validated pain generators can be accomplished with simplified decompression procedures associated with lower perioperative complications and long-term revision rates. In this perspective article, the authors summarize the current concepts of successful management of spinal stenosis patients with modern transforaminal endoscopic and translaminar minimally invasive spinal surgery techniques. They represent the consensus statements of 14 international surgeon societies, who have worked in collaborative teams in an open peer-review model based on a systematic review of the existing literature and grading the strength of its clinical evidence. The authors found that personalized clinical care protocols for lumbar spinal stenosis rooted in validated pain generators can successfully treat most patients with sciatica-type back and leg pain including those who fail to meet traditional image-based medical necessity criteria for surgery since nearly half of the surgically treated pain generators are not shown on the preoperative MRI scan. Common pain generators in the lumbar spine include (a) an inflamed disc, (b) an inflamed nerve, (c) a hypervascular scar, (d) a hypertrophied superior articular process (SAP) and ligamentum flavum, (e) a tender capsule, (f) an impacting facet margin, (g) a superior foraminal facet osteophyte and cyst, (h) a superior foraminal ligament impingement, (i) a hidden shoulder osteophyte. The position of the key opinion authors of the perspective article is that further clinical research will continue to validate pain generator-based treatment protocols for lumbar spinal stenosis. The endoscopic technology platform enables spine surgeons to directly visualize pain generators, forming the basis for more simplified targeted surgical pain management therapies. Limitations of this care model are dictated by appropriate patient selection and mastering the learning curve of modern MIS procedures. Decompensated deformity and instability will likely continue to be treated with open corrective surgery. Vertically integrated outpatient spine care programs are the most suitable setting for executing such pain generator-focused programs.

Aim: Digital and robotic technology applications in laparoscopic surgery have revolutionized routine cholecystectomy. Insufflation of the peritoneal space is vital for its safety but comes at the cost of ischemia-reperfusion-induced intraabdominal organ compromise before the return of physiologic functions. Dexmedetomidine in general anesthesia promotes controlling the response to trauma by altering the neuroinflammatory reflex. This strategy may improve clinical outcomes in the postoperative period by reducing postoperative narcotic use and lowering the risk of subsequent addiction. In this study, the authors aimed to evaluate dexmedetomidine's therapeutic and immunomodulatory potential on perioperative organ function., Methods: Fifty-two patients were randomized 1:1: group A-sevoflurane and dexmedetomidine (dexmedetomidine infusion [1 µg/kg loading, 0.2-0.5 µg/kg/h maintenance dose]), and group B-sevoflurane with saline 0.9% infusion as a placebo control. Three blood samples were collected: preoperatively (T0 h), 4-6 h after surgery (T4-6 h), and 24 h postoperatively (T24 h). The primary outcome was the level analysis of inflammatory and endocrine mediators. Secondary outcome measures were the time to return to normal preoperative hemodynamic parameters, spontaneous ventilation, and postoperative narcotic requirements to control surgical pain., Results: A reduction of Interleukin 6 was found at 4-6 h after surgery in group A with a mean of 54.76 (27.15-82.37; CI 95%) vs. 97.43 (53.63-141.22); p = 0.0425) in group B patients. Systolic and diastolic blood pressure and heart rate were lower in group A patients, who also had a statistically significantly lower opioid consumption in the first postoperative hour when compared to group B patients ( p < 0.0001). We noticed a similar return to spontaneous ventilation pattern in both groups., Conclusions: Dexmedetomidine decreased interleukin-6 4-6 h after surgery, likely by providing a sympatholytic effect. It provides good perioperative analgesia without respiratory depression. Implementing dexmedetomidine during laparoscopic cholecystectomy has a good safety profile and may lower healthcare expenditure due to faster postoperative recovery.

Background : Effective 1 January 2017, single-level endoscopic lumbar discectomy received a Category I Current Procedural Terminology (CPT ® ) code 62380. However, no work relative value units (wRVUs) are currently assigned to the procedure. A physician's payment needs to be updated to commensurate with the work involved in the modern version of the lumbar endoscopic decompression procedure with and without the use of any implants to stabilize the spine. In the United States, the American Medical Association (AMA) and its Specialty Society Relative Value Scale Update Committee (RUC) proposes to the Centers for Medicare and Medicaid Services (CMS) what wRVUs to assign for any endoscopic lumbar surgery codes. Methods : The authors conducted an independent survey between May and June 2022 which reached 210 spine surgeons using the TypeForm survey platform. The survey link was sent to them via email and social media. Surgeons were asked to assess the endoscopic procedure's technical and physical effort, risk, and overall intensity without focusing just on the time required to perform the surgery. Respondents were asked to compare the work involved in modern comprehensive endoscopic spine care with other commonly performed lumbar surgeries. For this purpose, respondents were provided with the verbatim descriptions of 12 other existing comparator CPT ® codes and associated wRVUs of common spine surgeries, as well as a typical patient vignette describing an endoscopic lumbar decompression surgery scenario. Respondents were then asked to select the comparator CPT ® code most reflective of the technical and physical effort, risk, intensity, and time spent on patient care during the pre-operative, peri- and intra-operative, and post-operative periods of a lumbar endoscopic surgery. Results: Of the 30 spine surgeons who completed the survey, 85.8%, 46.6%, and 14.3% valued the appropriate wRVU for the lumbar endoscopic decompression to be over 13, over 15, and over 20, respectively. Most surgeons (78.5%; <50th percentile) did not think they were adequately compensated. Regarding facility reimbursement, 77.3% of surgeons reported that their healthcare facility struggled to cover the cost with the received compensation. The majority (46.5%) said their facility received less than USD 2000, while another 10.7% reported less than USD 1500 and 17.9% reported less than USD 1000. The professional fee received by surgeons was ® 62380 with the complexity and intensity of a laminectomy and interbody fusion preparation, considering the work in the epidural space using the contemporary outside-in and interlaminar technique and the work inside the interspace using the inside-out technique. Modern endoscopic spine surgery goes beyond the scope of a simple soft-tissue discectomy. The current iterations of the procedure must be considered to avoid undervaluing its complexity and intensity. Additional undervalued payment scenarios could be created if technological advances continue to replace traditional lumbar spinal fusion protocols with less burdensome, yet no less complex, endoscopic surgeries that necessitate a high surgeon effort in terms of time required to perform the operation and its intensity. These undervalued payment scenarios of physician practices, as well as the facility and malpractice expenses, should be further discussed to arrive at updated CPT ® codes reflective of modern comprehensive endoscopic spine care.

In the last decade, several studies have demonstrated Cutibacterium acnes colonization in intervertebral discs (IVDs) in patients with lumbar disc degeneration (LDD) and low back pain (LBP), but the meaning of these findings remains unclear. Being aware of this knowledge gap, we are currently conducting a prospective analytical cohort study with LBP and LDD patients undergoing lumbar microdiscectomy and posterior fusion. The IVDs samples collected during the surgeries are subjected to a stringent analytical protocol using microbiological, phenotypic, genotypic, and multiomic techniques. Additionally, pain-related scores and quality-of-life indexes are monitored during patient follow-up. Our preliminary results for 265 samples (53 discs from 23 patients) revealed a C. acnes prevalence of 34.8%, among which the phylotypes IB and II were the most commonly isolated. The incidence of neuropathic pain was significantly higher in the colonized patients, especially between the third and sixth postoperative months, which strongly suggests that the pathogen plays an important role in the chronicity of LBP. The future results of our protocol will help us to understand how C. acnes contributes to transforming inflammatory/nociceptive pain into neuropathic pain and, hopefully, will help us to find a biomarker capable of predicting the risk of chronic LBP in this scenario.