A Pharmacogenomics-Based In Silico Investigation of Opioid Prescribing in Post-operative Spine Pain Management and Personalized Therapy.

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.

Disability-adjusted life years from bone and joint infections associated with antimicrobial resistance: an insight from the 2019 Global Burden of Disease Study.

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.

Surgeon reported practice patterns related to full endoscopic cervical decompression procedures.

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.

Patient selection criteria for percutaneous anterior cervical laser versus endoscopic discectomy.

BACKGROUND: Percutaneous anterior laser and anterior endoscopic cervical spine surgery are associated with less approach trauma than conventional open cervical spine surgery. The literature illustrating their appropriate use corroborated with objective outcome evidence is scarce. The authors were interested in comparing the clinical outcomes following percutaneous laser disc decompression (PLDD) versus percutaneous endoscopic disc decompression (PEDD). © 2021 Wiley Periodicals LLC. MATERIALS AND METHODS: Thirty patients with soft contained symptomatic cervical disc herniations and an average age of 50.5 years (range 26 - 68 years; 16 males and 14 females) were prospectively enrolled in 2 groups of 15 patients to be either treated with PLDD or PEDD. All patients underwent PLDD or PEDD under local anesthesia and sedation. Clinical outcomes were assessed with the Macnab criteria VAS score for arm pain. Complications and reoperations were recorded. RESULTS: There were significant reductions in the VAS score for arm pain from preoperative 8.4 ± 2.5 to 3.1 ± 1.2 in the PLDD group (P < 0.03), and from preoperative 8.6 ± 2.7 to 2.4 ± 1.1 (P < 0.01) in the PEDD group. In the PLDD group, Macnab outcomes were excellent in 21% of patients, good in 44%, fair in 21%, and poor in 14%. In the PEDD group, Macnab outcomes were excellent in 14% of patients, good in 32%, fair in 12%, and poor in the remaining 12%. There were no statistically significant differences in clinical outcomes between the PLDD and the PEDD group. There were no approach-related or surgical complications. CONCLUSIONS: Tissue trauma is significantly reduced with laser and endoscopic surgery techniques. PLDD and PEDD are both suitable for the specific indication of soft, symptomatic contained cervical disc herniations. The authors' small prospective cohort study indicates that PLDD and PEDD are options for cervical decompression surgery when medical comorbidities or preferences by patients and surgeons dictate more minimally invasive strategies.

Minimally invasive debridement and drainage using intraoperative CT-Guide in multilevel spondylodiscitis: a long-term follow-up study.

BACKGROUND: Spondylodiscitis is an unusual infectious disease, which usually originates as a pathogenic infection of intervertebral discs and then spreads to neighboring vertebral bodies. The objective of this study is to evaluate percutaneous debridement and drainage using intraoperative CT-Guide in multilevel spondylodiscitis. METHODS: From January 2002 to May 2017, 23 patients with multilevel spondylodiscitis were treated with minimally invasive debridement and drainage procedures in our department. The clinical manifestations, evolution, and minimally invasive debridement and drainage treatment of this refractory vertebral infection were investigated. RESULTS: Of the enrolled patients, the operation time ranged from 30 minutes to 124 minutes every level with an average of 48 minutes. Intraoperative hemorrhage was minimal. The postoperative follow-up period ranged from 12 months to 6.5 years with an average of 3.7 years. There was no reactivation of infection in the treated vertebral segment during follow-up, but two patients with fungal spinal infection continued to progress by affecting adjacent segments prior to final resolution. According to the classification system of Macnab, one patient had a good outcome at the final follow-up, and the rest were excellent. CONCLUSIONS: Minimally invasive percutaneous debridement and irrigation using intraoperative CT-Guide is an effective minimally invasive method for the treatment of multilevel spondylodiscitis.

Worldwide research productivity in the field of full-endoscopic spine surgery: a bibliometric study.

PURPOSE: To investigate the quantity and quality of articles in the field of full-endoscopic spine surgery (FESS) from different countries and assess characteristics of worldwide research productivity. METHODS: Articles published from 1997 to July 23, 2018, were screened using the Web of Science database. All studies were assessed for the following parameters: the number of total publications, h-index, contribution of countries, authors, journals, and institutions. RESULTS: A total of 408 articles were identified between 1997 and 2018. Between 1997 and 2017, the number of published articles tended to increase by 41 times. The largest number of articles was from China (30.15%), followed by South Korea (28.68%), the USA (13.97%), Germany (9.31%), and Japan (4.90%). The highest h-index was found for articles from South Korea (23), followed by the USA (18), Germany (16), China (11), and Japan (7). The highest number of articles was published in World Neurosurgery (12.50%), followed by Pain Physician (10.29%), Spine (6.62%), European Spine Journal (4.66%), and Journal of Neurosurgery: Spine (4.17%). Wooridul Spine Hospital published the largest number of articles (10.29%), followed by Tongji University (5.88%), University of Witten/Herdecke (5.39%), Brown University (5.15%), and Third Military Medical University (3.43%). CONCLUSIONS: The number of articles published in the field of FESS has increased rapidly in the past 20 years. In terms of quantity, China is the most contributive country based on the number of publications. High-quality papers as measured by h-index and the large quantity is from South Korea (second only to China). These slides can be retrieved under Electronic Supplementary Material.

Intradiscal Expandable Balloon Distraction During Transforaminal Decompression for Lumbar Foraminal and Lateral Recess Stenosis.

Advanced videoendoscopic equipment (such as motorized drills, chisels, and rongeurs) facilitates the use of modern decompression tools through the inner working channel of the spinal endoscope using the transforaminal approach. Postoperative dysesthetic leg pain, however, is common because of irritation of the dorsal root ganglion. This article presents a novel surgical technique employing an expandable balloon placed into the hollow intervertebral space in patients without any functional disc tissue to distract the stenotic motion segment. This approach improves visualization, facilitates removal of bone during the decompression, and minimizes intraoperative manipulation of the exiting and traversing nerve roots. In a study of 52 targeted patients with symptomatic spinal stenosis at 60 levels (L2/3-1, L3/4-9, L4/5-28, and L5/S1-22) due to advanced degenerative changes of the intervertebral disc and facet joint complex contributing to both foraminal and lateral recess stenosis, only 2 of the 52 patients complained of postoperative dysesthetic leg pain (3.85%) after undergoing this novel procedure. At the final 2-year follow-up, 80.9% of patients showed Excellent and Good outcomes according to modified Macnab criteria.

A Novel Mutation (Lys31Arg) in the DMD Gene Impacts on Neuromuscular Dysfunctions Found by Whole Exome Sequencing and In Silico Analyses in an Iranian Family.

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_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.

Surgeon Perceptions of Performing Transforaminal Lumbar Interbody Fusion in an Ambulatory Surgical Center vs Hospital Setting in the Elderly Population: Results of a Surgeon Survey.

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.

Paired Comparison Survey Analysis Utilizing Rasch Methodology of the Relative Difficulty and Estimated Work Relative Value Units of CPT Code 0202T.

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.

A Mutation in the CACNA1F Gene Found by Whole Exome Sequencing (WES) and In Silico Analysis in an Iranian Family with Consanguineous Relationships.

BACKGROUND: X-linked mutations are highly important in clinical diagnosis, and at least 533 disorders are related to the genes located on the X chromosome. CASE PRESENTATION: A 21-year-old Caucasian woman with a 24-year-old Caucasian man as her fiancé referred Clinical genetic lab for premarital genetic counseling (carrier screening). None of them had any abnormal manifestations. Following genetic counseling, Whole Exome Sequencing (WES) test performed to find the possible pathogenic mutations. Also, after drawing the couple's pedigree, candidate mutations were examined in the woman's parents as well as her uncles. Additionally, in silico investigations were performed through SWISS-MODEL, MolProbity, ProSA, Py- Mol, and FATCAT tools. The most important mutation diagnosed in the woman (R1362Q in the 35th exon of CACNA1F), was observed in her mother and her two uncles. The mutation was also screened in both her father and her fiancé, but they had no mutations. After medical examinations of carriers, there was no sign of any eye impairment. Other mutations were TCTN2 (c.1613-2A>G), TARS (p.K319E), SPEG (p.E3020K), CPS1 (p.A1180V), MYO3A (p.I736M), NNT (p.R968Q), MED23 (p.K406T). Bioinformatics analyses indicated no alteration in the mutant structure of CACNA1F (Q1362) compared with the normal structure (R1362). CONCLUSION: Conclusively, the current study emphasizes the non-pathogenic effect of missense mutation R1362Q in the 35th exon of CACNA1F in association with ocular diseases. This will ensure the reports of this mutation as healthy instead of uncertain in the literature and databanks.

Is Minimally Invasive Spinal Surgery Superior to Endoscopic Spine Surgery in Postoperative Radiologic Outcomes of Lumbar Spine Degenerative Disease? A Systematic Review.

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 mm2 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 mm2 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.

Utilization of Bone-Anchored Annular Defect Closure to Prevent Reherniation Following Lumbar Discectomy: Overcoming Barriers to Clinical Adoption and Market Access.

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.

Selenoprotein P in a Rodent Model of Exercise; Theorizing Its Interaction with Brain Reward Dysregulation, Addictive Behavior, and Aging.

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.

Summary Document Research on RDS Anti-addiction Modeling: Annotated Bibliography.

Annotated bibliography of genetic addiction risk severity (GARS) publications, pro-dopamine regulation in nutraceuticals (KB220 nutraceutical variants), and policy documents. Further research is required to encourage the field to consider "Reward Deficiency Syndrome (RDS) Anti-addiction Modeling" which involves early risk identification by means of genetic assessment similar to GARS, followed by induction of dopamine homeostasis by means of genetically guided pro-dopamine regulation similar to KB220. These results suggest that genetically based treatments may be a missing piece in the treatment of substance use disorder (SUD).

Polytomous Rasch Analyses of Surgeons' Decision-Making on Choice of Procedure in Endoscopic Lumbar Spinal Stenosis Decompression Surgeries.

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).

Comparative Analysis of Learning Curve, Complexity, Psychological Stress, and Work Relative Value Units for CPT 62380 Endoscopic Lumbar Spinal Decompression vs Traditional Lumbar Spine Surgeries: A Paired Rasch Survey Study.

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.

Determination of Work Related to Endoscopic Decompression of Lumbar Spinal Stenosis.

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

International Society for the Advancement of Spine Surgery Statement: Restorative Neurostimulation for Chronic Mechanical Low Back Pain Resulting From Neuromuscular Instability.

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.

Personalized Medicine in Cancer Pain Management.

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.