Disparities in Surgical Intervention and Health-Related Quality of Life Among Racial/Ethnic Groups With Degenerative Lumbar Spondylolisthesis.

BACKGROUND AND OBJECTIVES: Racial and socioeconomic disparities in spine surgery for degenerative lumbar spondylolisthesis persist in the United States, potentially contributing to unequal health-related quality of life (HRQoL) outcomes. This is important as lumbar spondylolisthesis is one of the most common causes of surgical low back pain, and low back pain is the largest disabler of individuals worldwide. Our objective was to assess the relationship between race, socioeconomic factors, treatment utilization, and outcomes in patients with lumbar spondylolisthesis. METHODS: This cohort study analyzed prospectively collected data from 9941 patients diagnosed with lumbar spondylolisthesis between 2015 and 2020 at 5 academic hospitals. Exposures were race, socioeconomic status, health coverage, and HRQoL measures. Main outcomes and measures included treatment utilization rates between racial groups and the association between race and treatment outcomes using logistic regression, adjusting for patient characteristics, socioeconomic status, health coverage, and HRQoL measures. RESULTS: Of the 9941 patients included (mean [SD] age, 67.37 [12.40] years; 63% female; 1101 [11.1%] Black, Indigenous, and People of Color [BIPOC]), BIPOC patients were significantly less likely to use surgery than White patients (odds ratio [OR] = 0.68; 95% CI, 0.62-0.75). Furthermore, BIPOC race was associated with significantly lower odds of reaching the minimum clinically important difference for physical function (OR = 0.74; 95% CI, 0.60; 0.91) and pain interference (OR = 0.77; 95% CI, 0.62-0.97). Medicaid beneficiaries were significantly less likely (OR = 0.65; 95% CI, 0.46-0.92) to reach a clinically important improvement in HRQoL when accounting for race. CONCLUSION: This study found that BIPOC patients were less likely to use spine surgery for degenerative lumbar spondylolisthesis despite reporting higher pain interference, suggesting an association between race and surgical utilization. These disparities may contribute to unequal HRQoL outcomes for patients with lumbar spondylolisthesis and warrant further investigation to address and reduce treatment disparities.

Clinical Outcomes Following Operative and Nonoperative Management of Odontoid Fractures Among Elderly Individuals with Dementia.

BACKGROUND: The incidence of odontoid fractures among the elderly population has been increasing in recent years. Elderly individuals with dementia may be at increased risk for inferior outcomes following such fractures. Although surgical intervention has been maintained to optimize survival and recovery, it is unclear if this benefit extends to patients with dementia. We hypothesized that patients with dementia who were treated operatively for odontoid fractures would experience improved survival and lower rates of hospice admission but higher rates of delirium and of intensive interventions. METHODS: We used Medicare claims data (2017 to 2018) to identify community-dwelling individuals with dementia who sustained type-II odontoid fractures. We considered treatment strategy (operative or nonoperative) as the primary predictor and survival as the primary outcome. The secondary outcomes consisted of post-treatment delirium, hospice admission, post-treatment intensive intervention, and post-discharge admission to a nursing home or a skilled nursing facility. In all models, we controlled for age, biological sex, race, Elixhauser Comorbidity Index, Frailty Index, admission source, treating hospital, and dual eligibility. Adjusted analyses for survival were conducted using Cox proportional hazards regression. Adjusted analyses for secondary outcomes were performed using generalized estimating equations. To address confounding by indication, we performed confirmatory analyses using inverse probability of treatment weighting. RESULTS: In this study, we included 1,030 patients. The median age of the cohort was 86.5 years (interquartile range, 80.9 to 90.8 years), 60.7% of the patients were female, and 90% of the patients were White. A surgical procedure was performed in 19.8% of the cohort. Following an adjusted analysis, patients treated surgically had a 28% lower hazard of mortality (hazard ratio, 0.72 [95% confidence interval (CI), 0.53 to 0.98]), but higher odds of delirium (odds ratio, 1.64 [95% CI, 1.10 to 2.44]). These findings were preserved in the inverse probability weighted analysis. CONCLUSIONS: We found that, among individuals with dementia who sustain a type-II odontoid fracture, surgical intervention may confer a survival benefit. A surgical procedure may be an appropriate treatment strategy for individuals with dementia whose life-care goals include life prolongation and maximizing quality of life in the short term following an injury. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Establishing case volume benchmarks for ACGME-accredited orthopedic surgery of the spine fellowship training.

BACKGROUND CONTEXT: There has been increasing scrutiny on the standardization of surgical training in the US. PURPOSE: This study provides case volume benchmarks for Accreditation Council for Graduate Medical Education (ACGME)-accredited orthopedic spine surgery fellowship training. STUDY DESIGN/SETTING: This was a retrospective cross-sectional study of fellows at ACGME-accredited orthopedic spine surgery fellowships (2017-2022). PATIENT SAMPLE: N/A. OUTCOME MEASURES: Reported case volume during fellowship training. METHODS: Case volume percentiles were calculated across ACGME-defined case categories and temporal changes assessed via linear regression. Variability between the highest and lowest deciles by case volume was calculated as fold-differences (90th percentile/10th percentile). Sensitivity analyses were performed to identify potential targets for case minimum requirements. RESULTS: A total of 163 spine surgery fellows were included in this study. Total mean reported spine surgery case volume increased from 313.2±122 in 2017 to 382.0±164 in 2022 (p=.19). Most cases were classified as adult (range, 97.2%-98.0%) over pediatric cases (range, 2.0%-2.8%). An average of 322.0 cases were reported and most were classified as laminectomy (32%), posterior arthrodesis (29%), and anterior arthrodesis (20%). Overall variability in total case volume was 2.4 and the greatest variability existed for posterior instrumentation (38.1), application of cage (34.6), anterior instrumentation (20.8), and fractures and dislocations (17.3). If case minimum requirements for total reported cases was assumed at 200 cases, then all spine fellows included in this study would achieve this requirement. However, if case minimum requirements were assumed at 250 total cases, then approximately thirty percent of fellows (n=49) would not achieve this requirement for graduation. CONCLUSIONS: Increasingly, national societies and accrediting bodies for surgical education recognize the need for standardized training. This study provides benchmarks to inform potential case minimum requirements and help reduce variability during spine fellowship training. Future studies are needed to establish case minimum requirements for spine surgery fellowship training across comprehensive and granular case categories that cover the full gamut of orthopedic spine surgery.

Biological Therapeutic Modalities for Intervertebral Disc Diseases: An Orthoregeneration Network (ON) Foundation Review.

Orthoregeneration is defined as a solution for orthopaedic conditions that harnesses the benefits of biology to improve healing, reduce pain, improve function, and, optimally, provide an environment for tissue regeneration. Options include drugs, surgical intervention, scaffolds, biologics as a product of cells, and physical and electromagnetic stimuli. The goal of regenerative medicine is to enhance the healing of tissue after musculoskeletal injuries as both isolated treatment and adjunct to surgical management, using novel therapies to improve recovery and outcomes. Various orthopaedic biologics (orthobiologics) have been investigated for the treatment of pathology involving the spine, including lower back pain, with or without numbness and/or dysfunction in the lower extremities, disc herniation, spinal stenosis, and spondylolisthesis. Promising and established treatment modalities include repair of the annulus fibrosis, injection of expanded or nonexpanded autologous or allogenic cells that are chondrogenic or from a stem cell lineage used to promote matrix tissue regeneration of the intervertebral disc, including nucleus pulpous cells and mesenchymal stem cells isolated from bone marrow, umbilical cord blood, or adipose tissue; and injection of platelet-rich plasma, platelet-rich fibrin, or fibrin sealant. Early clinical studies show promise for pain reduction and functional recovery. LEVEL OF EVIDENCE: Level V, expert opinion.

Analysis of Academic Accomplishments and Demographics for Elected Presidents of National Orthopedic Surgery Organizations in the United States.

This study analyzed the academic accomplishments and demographics of elected presidents of the American Academy of Orthopaedic Surgeons (AAOS), American Orthopaedic Association (AOA), and American Board of Orthopaedic Surgery (ABOS). Curriculum vitae and internet-based resources were reviewed to collect demographics, training characteristics, bibliometrics, and National Institutes of Health (NIH) research funding of contemporary presidents (1990-2020). Eighty presidents were included. Most presidents were men (97%), and 4% of presidents were non-White (3% Black and 1% Hispanic). Few had an additional graduate degree (4% MBA, 3% MS, 1% MPH, 1% PhD). Ten orthopedic surgery residency programs trained 47% of these presidents. Most had fellowship training (59%), and the top three were hand surgery (11%), pediatric orthopedics (11%), and adult reconstruction (10%). Twenty-nine presidents (36%) participated in a traveling fellowship. The mean age at appointment was 58±5 years, which was 27 years since residency graduation. The mean h-index was 36±23, resulting from 150±126 peer-reviewed manuscripts. Orthopedic surgery presidents had more peer-reviewed manuscripts (150±126) than chairs (73±81) and program directors (27±32) (P<.001). AOA presidents had the highest mean h-index (42±21) compared with AAOS (38±27) and ABOS (25±16) presidents (P=.035). Nineteen presidents had NIH funding (24%). More presidents had NIH funding in the AOA (39%) and AAOS (25%) than the ABOS (0%) (P=.007). Orthopedic surgery presidents possess high levels of scholarly output. AOA presidents had the highest h-index values and prevalence of NIH funding. Females and racial minorities remain underrepresented at the highest levels of leadership. [Orthopedics. 2024;47(1):e45-e51.].

Trends in ACGME Accreditation of Orthopedic Surgery Fellowship Training.

Currently, most surgeons pursue subspecialty fellowship training. This study answers the following questions: (1) How does the rate of fellowship training in orthopedic surgery compare with that in other surgical specialties? (2) To what extent did adoption of Accreditation Council for Graduate Medical Education (ACGME) accreditation change from 2013 to 2021? Orthopedic subspecialties were analyzed for total number of fellowship programs and positions in the 2013 and 2021 Match. Rates of ACGME accreditation were analyzed via chi-square tests. In 2021, orthopedic surgery had the highest rate of fellowship selection (94%) relative to general surgery (77%), ophthalmology (66%), plastic surgery (63%), and otolaryngology (55%). Across all orthopedic subspecialties, the percentage of ACGME accreditation decreased among fellowship programs (53% in 2013 to 48% in 2021, P=.166) and positions (58% in 2013 to 50% in 2021, P<.001). Orthopedic sports medicine had the highest adoption of ACGME accreditation (100%), followed by hand surgery (99%), musculoskeletal oncology (67%), and pediatric orthopedics (56%). Significant increases in the adoption of ACGME accreditation were noted for orthopedic sports medicine (93% in 2013 to 100% in 2021, P=.016) and hand surgery (81% in 2013 to 99% in 2021, P<.001). There was a significant decrease in ACGME accreditation for adult reconstructive orthopedics (40% in 2013 to 24% in 2021, P=.042), driven by the increase in unaccredited fellowship programs. Accreditation of orthopedic subspecialty fellowship training has decreased with respect to the proportion of accredited training positions. More research is needed to understand the benefits of ACGME accreditation for fellowship training in orthopedic surgery. [Orthopedics. 2024;47(1):57-63.].

Geriatric Surgery Produces a Hypoactive Molecular Phenotype in the Monocyte Immune Gene Transcriptome.

Surgery is a major challenge for the immune system, but little is known about the immune response of geriatric patients to surgery. We therefore investigated the impact of surgery on the molecular signature of circulating CD14+ monocytes, cells implicated in clinical recovery from surgery, in older patients. We enrolled older patients having elective joint replacement (N = 19) or spine (N = 16) surgery and investigated pre- to postoperative expression changes in 784 immune-related genes in monocytes. Joint replacement altered the expression of 489 genes (adjusted p < 0.05), of which 38 had a |logFC| > 1. Spine surgery changed the expression of 209 genes (adjusted p < 0.05), of which 27 had a |logFC| > 1. In both, the majority of genes with a |logFC| > 1 change were downregulated. In the combined group (N = 35), 471 transcripts were differentially expressed (adjusted p < 0.05) after surgery; 29 had a |logFC| > 1 and 72% of these were downregulated. Notably, 21 transcripts were common across procedures. Thus, elective surgery in older patients produces myriad changes in the immune gene transcriptome of monocytes, with many suggesting development of an immunocompromised/hypoactive phenotype. Because monocytes are strongly implicated in the quality of surgical recovery, this signature provides insight into the cellular and molecular mechanisms of the immune response to surgery and warrants further study as a potential biomarker for predicting poor outcomes in older surgical patients.

Limited number of spine surgeons among recipients of National Institutes of Health grants awarded for degenerative spine disease research.

OBJECTIVE: Surgeon scientists remain underrepresented among recipients of National Institutes of Health (NIH) grants despite their unique ability to perform translational research. This study elucidates the portfolio of NIH grants awarded for degenerative spine diseases and the role of spine surgeons in this portfolio. METHODS: The most common diagnoses and surgical procedures for degenerative spine diseases were queried on the NIH Research Portfolio Online Reporting Tools Expenditures and Results (RePORTER) database (2011-2021). Total NIH funding was extracted for 20 additional clinical areas and compound annual growth rates (CAGRs) were calculated. A retrospective cohort study of principal investigators (PIs) was conducted. NIH grants and funding totals were extracted and compared to those from other clinical areas. RESULTS: The total NIH research budget increased from $31 to $43 billion over the 10-year period (CAGR 3.4%). A total of 273 unique grants equaling $91 million (CAGR 0%) were awarded for degenerative spine diseases. Diabetes ($11.8 billion, CAGR 0%), obesity ($10.6 billion, CAGR 3%), and chronic pain ($5.6 billion, CAGR 7%) received the most funding. Most NIH funding for degenerative spine disease research was awarded through the R01 (66%) and R44 (8%) grant mechanisms. The National Institute of Arthritis and Musculoskeletal and Skin Diseases awarded the most NIH funding (64%). Departments of orthopedic surgery were awarded the most funding (32%). NIH funding supported clinical (28%), translational (37%), and basic science (35%) research. Disease mechanisms (58%), imaging modalities (20%), and emerging technologies (16%) received the most funding. Nineteen spine surgeons were identified as PIs (16%). There were no significant differences in NIH funding totals by PI demographic and academic characteristics (p > 0.05)-except for full professors, who had the most NIH funding (p = 0.007) and highest h-index values (p < 0.001). CONCLUSIONS: Few spine surgeons receive NIH grants for degenerative spine disease research. Future opportunities may exist for spine surgeons to collaborate in identified areas of clinical interest. Additional strategies are needed to increase NIH funding in spine surgery.

Impact of Specialty on Cases Performed During Spine Surgery Training in the United States.

OBJECTIVE: Two general pathways exist for spine surgery training in the United States: orthopedic surgery and neurological surgery. Previous studies have not quantified the impact of fellowship training when comparing case volumes between these 2 training pathways. This study compares reported spine surgery case volume upon graduation from orthopedic surgery and neurological surgery training. METHODS: This was a retrospective cohort study of recent graduates from orthopedic surgery and neurological Surgery training programs in the United States (2018-2021). The Accreditation Council for Graduate Medical Education provided case logs for residents in neurological surgery and orthopedic surgery as well as fellows in orthopedic spine surgery. Case volumes were compared for adult and pediatric spine surgery cases using parametric tests. RESULTS: Case logs from 3146 orthopedic surgery residents, 107 orthopedic spine surgery fellows, and 766 neurological surgery residents were included in this study. Across each cohort, neurological surgery trainees reported more total adult spine surgery cases than orthopedic surgery trainees (514 ± 206 vs. 383 ± 171, P < 0.001). Orthopedic surgery trainees reported more total pediatric spine surgery cases (21 ± 14 vs. 17 ± 12, P = 0.006). CONCLUSIONS: Neurological surgery training affords a greater volume of adult spine surgery cases, but orthopedic surgery affords more pediatric spine surgery cases. Identification of relative strengths and weaknesses can help facilitate multidisciplinary training experiences in spine surgery.

Utility of Spine Surgery Fellowship Training for Orthopaedic Surgeons in the United States.

INTRODUCTION: Orthopaedic spine surgeons gain surgical experience through cases conducted during residency and fellowship training. This study elucidates the incremental benefit in spine surgery volume from orthopaedic spine surgery fellowship training. METHODS: This was a retrospective national cohort study of orthopaedic surgery residents and orthopaedic spine surgery fellows graduating from US Accreditation Council for Graduate Medical Education-accredited training programs during the 2017 to 2020 academic years. Comparisons in spine surgery case volume were made with parametric tests. RESULTS: One hundred fourteen spine surgery fellows and 3,000 orthopaedic surgery residents were included. There was a 3.5-fold increase in total spine surgery cases conducted during fellowship versus residency (314 ± 129 vs. 89 ± 61, P < 0.001). Spine surgery fellows one standard deviation more than the mean reported 443 total spine cases. The largest differences between fellows and residents were Decompression (104 ± 48 vs. 28 ± 23, P < 0.001), Posterior Arthrodesis (94 ± 46 vs. 21 ± 18, P < 0.001), Anterior Arthrodesis (64 ± 31 vs. 13 ± 13, P < 0.001), and Instrumentation (43 ± 25 vs. 22 ± 12, P < 0.001). DISCUSSION: Spine surgery fellowship training affords orthopaedic surgeons the opportunity to increase spine surgery case volume by over threefold. The greatest increases in case volume were reported for Decompression, Posterior Arthrodesis, Anterior Arthrodesis, and Instrumentation.

Appropriate Telemedicine Utilization in Spine Surgery: Results From a Delphi Study.

STUDY DESIGN: Delphi expert panel consensus. OBJECTIVE: To obtain expert consensus on best practices for appropriate telemedicine utilization in spine surgery. SUMMARY OF BACKGROUND DATA: Several studies have shown high patient satisfaction associated with telemedicine during the COVID-19 peak pandemic period as well as after easing of restrictions. As this technology will most likely continue to be employed, there is a need to define appropriate utilization. METHODS: An expert panel consisting of 27 spine surgeons from various countries was assembled in February 2021. A two-round consensus-based Delphi method was used to generate consensus statements on various aspects of telemedicine (separated as video visits or audio visits) including themes, such as patient location and impact of patient diagnosis, on assessment of new patients. Topics with ≥75% agreement were categorized as having achieved a consensus. RESULTS: The expert panel reviewed a total of 59 statements. Of these, 32 achieved consensus. The panel had consensus that video visits could be utilized regardless of patient location and that video visits are appropriate for evaluating as well as indicating for surgery multiple common spine pathologies, such as lumbar stenosis, lumbar radiculopathy, and cervical radiculopathy. Finally, the panel had consensus that video visits could be appropriate for a variety of visit types including early, midterm, longer term postoperative follow-up, follow-up for imaging review, and follow-up after an intervention (i.e., physical therapy, injection). CONCLUSION: Although telemedicine was initially introduced out of necessity, this technology most likely will remain due to evidence of high patient satisfaction and significant cost savings. This study was able to provide a framework for appropriate telemedicine utilization in spine surgery from a panel of experts. However, several questions remain for future research, such as whether or not an in-person consultation is necessary prior to surgery and which physical exam maneuvers are appropriate for telemedicine.Level of Evidence: 4.

Trends and Complications in Spinopelvic Fixation for Deformity for Spinal Surgeons in Early Independent Practice.

STUDY DESIGN: Retrospective case series study. OBJECTIVE: Evaluate trends and complications following posterior spinal instrumented fusion for deformity with/without pelvic fixation using the American Board of Orthopaedic Surgery Part II Oral Examination Candidate Case List data from 2008 to 2017. SUMMARY OF BACKGROUND DATA: Complication rates for cases with pelvic fixation are widely reported in spine deformity literature but are typically derived from practices of senior surgeons. As surgical experience and clinical volume are shown to decrease complication rates, spine surgeons newly in practice may have higher risks of such events. MATERIALS AND METHODS: Surgical cases submitted by candidates taking the American Board of Orthopaedic Surgery Part II Oral Examination between 2008 and 2017 with a self-designated sub-specialty of spine surgery were retrospectively reviewed. Mortality, readmission/reoperation data, and complications as reported by candidates were tracked over time. Bivariate testing and multivariable Poisson analyses, respectively, were used to assess complication rates and time-related trends. RESULTS: A total of 37,539 cases were submitted between 2008 and 2017. Four hundred sixty-one cases (1.2%) were for deformity; of these, 60 cases included pelvic fixation (13% of deformity cases). For all deformity cases, we noted medical, surgical, and overall complication rates to be 17%, 22.3%, and 31.5%. Multivariable analyses demonstrated no difference in surgical/overall complication rates between spinopelvic and nonspinopelvic instrumented groups, but showed a consistently low number of cases using spinopelvic fixation over time. CONCLUSIONS: Newly practicing spinal surgeons consistently performed low numbers of deformity cases with relatively high complication rates which remained stable over time.

Characterizing Health-Related Quality of Life by Ambulatory Status in Patients with Spinal Metastases.

STUDY DESIGN: Retrospective review of prospective longitudinal data. OBJECTIVE: To determine health-related quality of life (HRQL) utilities associated with specific ambulatory states in patients with spinal metastases: independent, ambulatory with assistance, and nonambulatory. SUMMARY OF BACKGROUND DATA: It is assumed that HRQL is aligned with ambulatory ability in patients with spinal metastases. Few studies have effectively considered these parameters while also accounting for clinical confounders. METHODS: We used prospective longitudinal data from patients treated at one of three tertiary medical centers (2017-2019). HRQL was characterized using the Euroquol-5-dimension (EQ5D) inventory. We performed standardized estimations of HRQL stratified by ambulatory state using generalized linear modeling that accounted for patient age at presentation, biologic sex, follow-up duration, operative or nonoperative management, and repeated measures within the same participant. RESULTS: We evaluated 675 completed EQ5D assessments, with 430 for independent ambulators, 205 for ambulators with assistance, and 40 for nonambulators. The average age of the cohort was 61.5. The most common primary cancer was lung (20%), followed by breast (18%). Forty-one percent of assessments were performed for participants treated surgically. Mortality occurred in 51% of the cohort. The standardized EQ5D utility for patients with spinal metastases and independent ambulatory function was 0.76 (95% confidence interval [CI] 0.74, 0.78). Among those ambulatory with assistance, the standardized EQ5D utility was 0.59 (95% CI 0.57, 0.61). For nonambulators, the standardized EQ5D utility was 0.14 (95% CI 0.09, 0.19). CONCLUSION: Patients with spinal metastases and independent ambulatory function have an HRQL similar to patients with primary cancers and no spinal involvement. Loss of ambulatory ability leads to a 22% decrease in HRQL for ambulation with assistance and an 82% reduction among nonambulators. Given prior studies demonstrate superior maintenance of ambulatory function with surgery for spinal metastases, our results support surgical consideration to the extent that it is clinically warranted.Level of Evidence: 3.

Improving Arthroplasty Efficiency and Quality Through Concentrating Service Volume by Complexity: Surviving the Medicare Policy Changes.

We have an academic medical center (AMC), an associated community-based hospital (CBH) and several ambulatory care centers which are being prepared to provide same day discharge (SDD) total joint arthroplasty (TJA) and unicompartmental knee arthroplasty (UKA). The near-capacity AMC cared for medically and technically complicated TJA patients. The CBH wanted to increase volume, improve margins, and become a center of excellence with an efficient hospital outpatient department and SDD TJA experience. METHODS: We transitioned primary, uncomplicated TJA, UKA, and minimally invasive TJA to the CBH. Revision surgeries, patients with extensive comorbidities, and complex primaries were performed at the AMC. Protocols were developed to facilitate SDD UKA and total hip arthroplasty (THA) as well as rapid recovery protocols for total knee arthroplasty (TKA) at both hospitals. A protocol-based system was put in place to make both hospitals ready for the removal of TKA from the Inpatient-Only list to avoid Quality Improvement Organization and possible resultant Recovery Audit Contractor audits if referred after implementation. RESULTS: The CBH volume increased 36.7% (+239). AMC volume slightly decreased (-0.46%, -5) resulting in an increase in margin contribution for the system. CBH quality metrics (surgical site infections, length of stay, readmissions, and mortality) were improved. Surgeon satisfaction improved as their volume, efficiency, quality metrics, and finances were enhanced. Although CBH per case revenue was 80.3% and 74.4% of the AMC for THA and TKA, net margins were 3.6% and 18.8% higher for THA and TKA, respectively. Increased efficiency, lower hospital cost, and higher volume at the CBH allowed for an increase in revenue despite lower reimbursement per case. CONCLUSION: This strategy will help hospital systems improve net margins while improving patient care despite lower net revenue per TJA episode. These strategies will become increasingly important going forward with the transition of higher numbers of TJA patients to outpatient which will be subjected to further decreases in net revenue per patient.

ISSLS prize in basic science 2021: a novel inducible system to regulate transgene expression of TIMP1.

PURPOSE: Inflammatory and oxidative stress upregulates matrix metalloproteinase (MMP) activity, leading to intervertebral disc degeneration (IDD). Gene therapy using human tissue inhibitor of metalloproteinase 1 (hTIMP1) has effectively treated IDD in animal models. However, persistent unregulated transgene expression may have negative side effects. We developed a recombinant adeno-associated viral (AAV) gene vector, AAV-NFκB-hTIMP1, that only expresses the hTIMP1 transgene under conditions of stress. METHODS: Rabbit disc cells were transfected or transduced with AAV-CMV-hTIMP1, which constitutively expresses hTIMP1, or AAV-NFκB-hTIMP1. Disc cells were selectively treated with IL-1ß. NFκB activation was verified by nuclear translocation. hTIMP1 mRNA and protein expression were measured by RT-PCR and ELISA, respectively. MMP activity was measured by following cleavage of a fluorogenic substrate. RESULTS: IL-1ß stimulation activated NFκB demonstrating that IL-1ß was a surrogate for inflammatory stress. Stimulating AAV-NFκB-hTIMP1 cells with IL-1ß increased hTIMP1 expression compared to unstimulated cells. AAV-CMV-hTIMP1 cells demonstrated high levels of hTIMP1 expression regardless of IL-1ß stimulation. hTIMP1 expression was comparable between IL-1ß stimulated AAV-NFκB-hTIMP1 cells and AAV-CMV-hTIMP1 cells. MMP activity was decreased in AAV-NFκB-hTIMP1 cells compared to baseline levels or cells exposed to IL-1ß. CONCLUSION: AAV-NFκB-hTIMP1 is a novel inducible transgene delivery system. NFκB regulatory elements ensure that hTIMP1 expression occurs only with inflammation, which is central to IDD development. Unlike previous inducible systems, the AAV-NFκB-hTIMP1 construct is dependent on endogenous factors, which minimizes potential side effects caused by constitutive transgene overexpression. It also prevents the unnecessary production of transgene products in cells that do not require therapy.

Conditioned open-label placebo for opioid reduction after spine surgery: a randomized controlled trial.

ABSTRACT: Placebo effects have traditionally involved concealment or deception. However, recent evidence suggests that placebo effects can also be elicited when prescribed transparently as "open-label placebos" (OLPs), and that the pairing of an unconditioned stimulus (eg, opioid analgesic) with a conditioned stimulus (eg, placebo pill) can lead to the conditioned stimulus alone reducing pain. In this randomized control trial, we investigated whether combining conditioning with an OLP (COLP) in the immediate postoperative period could reduce daily opioid use and postsurgical pain among patients recovering from spine surgery. Patients were randomized to COLP or treatment as usual, with both groups receiving unrestricted access to a typical opioid-based postoperative analgesic regimen. The generalized estimating equations method was used to assess the treatment effect of COLP on daily opioid consumption and pain during postoperative period from postoperative day (POD) 1 to POD 17. Patients in the COLP group consumed approximately 30% less daily morphine milligram equivalents compared with patients in the treatment as usual group during POD 1 to 17 (-14.5 daily morphine milligram equivalents; 95% CI: [-26.8, -2.2]). Daily worst pain scores were also lower in the COLP group (-1.0 point on the 10-point scale; 95% CI: [-2.0, -0.1]), although a significant difference was not detected in average daily pain between the groups (-0.8 point; 95% CI: [-1.7, 0.2]). These findings suggest that COLP may serve as a potential adjuvant analgesic therapy to decrease opioid consumption in the early postoperative period, without increasing pain.

Orthopaedic Manifestations of Amyloidosis.

Amyloidosis is a disorder of misfolded proteins in human tissues, which can result in morbid cardiac and neurological disease. Historically, the utility of tissue biopsy during orthopaedic procedures to detect amyloidosis has been limited because no disease-modifying therapies were available; however, new drug therapies have recently emerged for the treatment of amyloidosis. Although these novel pharmaceuticals show promise for slowing disease progression, they are primarily effective in the early stages of amyloidosis, underscoring the importance of early diagnosis. Common orthopaedic manifestations of amyloidosis include carpal tunnel syndrome, trigger finger, spontaneous distal biceps tendon rupture, rotator cuff disease, and lumbar spinal stenosis. Carpal tunnel syndrome is frequently the earliest manifestation of amyloidosis, on average preceding a formal diagnosis of amyloidosis by over four years. By recognizing the constellation of musculoskeletal symptoms in the patient with amyloidosis, orthopaedic surgeons can play an active role in patient referral, early detection of systemic disease, and prompt initiation of disease-modifying treatment. There may be a role for selective biopsy for amyloid deposition in at-risk patients during routine orthopaedic procedures.

Trends in Spinal Surgery Performed by American Board of Orthopaedic Surgery Part II Candidates (2008 to 2017).

INTRODUCTION: The American Board of Orthopaedic Surgery (ABOS) Part II Oral Examination is typically taken two calendar years after fellowship completion. Despite previous studies using ABOS Part II Oral Examination data in other subspecialties, types of cases performed by spine surgeons in initial independent practice have not been well-studied. Such data may help trainees anticipate case composition observed in early practice and allow spine fellowship programs to understand emerging trends. METHODS: We retrospectively reviewed surgical cases submitted to the ABOS by candidates taking the Part II Oral Examination between 2008 and 2017 whose designated subspecialty was spine. A hierarchical, restrictive algorithm was used to determine procedures based on candidate-reported International Classification of Diseases 9th/10th Revision and Current Procedural Terminology codes. Adjusted multivariable Poisson regression analyses were used to assess changes in procedure incidence rates over time. RESULTS: We identified 37,539 cases, averaging 3,754 cases/yr, and an average of 49 cases per candidate per 6-month collection period. The most common procedures were lumbar diskectomy (22% of all procedures), posterolateral spinal fusion (PSF) (19%), and anterior cervical diskectomy and fusion (ACDF) (17%). Rates of ACDF and cervical disk arthroplasty significantly increased over time (incidence rate ratios of 1.41 and 23.3 times higher, respectively, at the end of the study period), whereas rates of cervical foraminotomy, lumbar diskectomy, PSF, and structural autograft use decreased (incidence rate ratios of 0.35, 0.84, 0.55, and 0.30). Rates of anterior lumbar interbody fusion/lateral lumbar interbody fusion and transforaminal lumbar interbody fusion did not significantly change over the study period. DISCUSSION: Recent spine fellowship graduates are performing more cervical disk arthroplasties and ACDFs while decreasingly using structural autograft as well as performing fewer PSFs and lumbar diskectomies. Techniques such as anterior lumbar interbody fusion/lateral lumbar interbody fusions and transforaminal lumbar interbody fusions have not changed significantly over the last decade. LEVEL OF EVIDENCE: Level IV (retrospective case series study).

Prospective validation of a clinical prediction score for survival in patients with spinal metastases: the New England Spinal Metastasis Score.

BACKGROUND CONTEXT: The New England Spinal Metastasis Score (NESMS) was proposed as an intuitive and accessible prognostic tool for predicting survival in patients with spinal metastases. We designed an appropriately powered, prospective, longitudinal investigation to validate the NESMS. PURPOSE: To prospectively validate the NESMS. STUDY DESIGN: Prospective longitudinal observational cohort study. PATIENT SAMPLE: Patients, aged 18 and older, presenting for treatment with spinal metastatic disease. OUTCOME MEASURES: One-year mortality (primary); 6-month mortality and mortality at any time point following enrollment (secondary). METHODS: The date of enrollment was set as time zero for all patients. The NESMS was assigned based on data collected at the time of enrollment. Patients were prospectively followed to one of two predetermined end-points: death, or survival at 365 days following enrollment. Survival was visually assessed with Kaplan-Meier curves and then analyzed using multivariable logistic regression, followed by Bayesian regression to assess for robustness of point estimates and 95% confidence intervals (CI). RESULTS: This study included 180 patients enrolled between 2017 and 2018. Mortality within 1-year occurred in 56% of the cohort. Using NESMS 3 as the referent, those with a score of 2 had significantly greater odds of mortality (odds ratio 7.04; 95% CI 2.47, 20.08), as did those with a score of 1 (odds ratio 31.30; 95% CI 8.82, 111.04). A NESMS score of 0 was associated with perfect prediction, as 100% of individuals with this score were deceased at 1-year. Similar determinations were encountered for mortality at 6-months and overall. CONCLUSIONS: This study validates the NESMS and demonstrates its utility in prognosticating survival for patients with spinal metastatic disease, irrespective of selected treatment strategy. This is the first study to prospectively validate a prognostic utility for patients with spinal metastases. The NESMS can be directly applied to patient care, hospital-based practice and health-care policy.