Factors Related to Clinical Performance in Spine Surgery Fellowship: Can We Predict Success.

INTRODUCTION: The factors most important in the spine fellowship match may not ultimately correlate with quality of performance during fellowship. This study examined the spine fellow applicant metrics correlated with high application rank compared with the metrics associated with the strongest clinical performance during fellowship. METHODS: Spine fellow applications at three academic institutions were retrieved from the San Francisco Match database (first available to 2021) and deidentified for application review. Application metrics pertaining to research, academics, education, extracurriculars, leadership, examinations, career interests, and letter of recommendations were extracted. Attending spine surgeons involved in spine fellow selection at their institutions were sent a survey to rank (1) fellow applicants based on their perceived candidacy and (2) the strength of performance of their previous fellows. Pearson correlation assessed the associations of application metrics with theoretical fellow rank and actual performance. RESULTS: A total of 37 spine fellow applications were included (Institution A: 15, Institution B: 12, Institution C: 10), rated by 14 spine surgeons (Institution A: 6, Institution B: 4, Institution C: 4). Theoretical fellow rank demonstrated a moderate positive association with overall research, residency program rank, recommendation writer H-index, US Medical Licensing Examination (USMLE) scores, and journal reviewer positions. Actual fellow performance demonstrated a moderate positive association with residency program rank, recommendation writer H-index, USMLE scores, and journal reviewer positions. Linear regressions identified journal reviewer positions (ß = 1.73, P = 0.002), Step 1 (ß = 0.09, P = 0.010) and Step 3 (ß = 0.10, P = 0.002) scores, recommendation writer H-index (ß = 0.06, P = 0.029, and ß = 0.07, P = 0.006), and overall research (ß = 0.01, P = 0.005) as predictors of theoretical rank. Recommendation writer H-index (ß = 0.21, P = 0.030) and Alpha Omega Alpha achievement (ß = 6.88, P = 0.021) predicted actual performance. CONCLUSION: Residency program reputation, USMLE scores, and a recommendation from an established spine surgeon were important in application review and performance during fellowship. Research productivity, although important during application review, was not predictive of fellow performance. LEVEL OF EVIDENCE: III. STUDY DESIGN: Cohort Study.

Transthyretin amyloidosis in spinal canal stenosis: A systematic review.

We systematically review literature regarding the contribution of transthyretin amyloidosis to spinal stenosis. Amyloidosis is a protein misfolding condition that causes systemic deposition of amyloid and commonly leads to heart failure and nephropathy. A growing body of literature suggests that amyloid deposits within the ligamentum flavum are frequently associated with spinal stenosis with subsequent myelopathy. Our search identified 67 publications from the PubMed database for literature review. After evaluating the inclusion and exclusion criteria, a total of 18 articles were included in the review. Each article was evaluated for country, study type, sample size, amyloidosis subtype, spinal level, systemic symptoms, treatment, patient outcome, and conclusions. Many studies concluded that lumbar ligamentum flavum hypertrophy is more severe in patients with amyloidosis due to associated amyloid deposition. Additionally, patients with systemic amyloidosis are more likely to have recurrence of spinal stenosis. Multiple studies encourage routine screening be performed on spinal stenosis patients to target those needing cardiac surveillance. Amyloid deposition is frequently associated with spinal stenosis, and its presence may provide an earlier opportunity to diagnose or predict systemic amyloidosis. Surgeons should consider obtaining intraoperative biopsy to identify amyloidosis and inform screening postoperatively. Finally, physicians should be aware of this association and counsel patients accordingly on the risks and treatment options available for amyloidosis.

Toward the Development of a Tissue Engineered Gradient Utilizing CRISPR-Guided Gene Modulation.

Cellular, compositional, and mechanical gradients are found throughout biological tissues, especially in transition zones between tissue types. Yet, strategies to engineer such gradients have proven difficult due to the complex nature of these tissues. Current strategies for tissue engineering complex gradients often utilize stem cells; however, these multipotent cells require direction from environmental cues, which can be difficult to control both in vitro and in vivo. In this study, we utilize clustered regularly-interspaced short palindromic repeats (CRISPR)-guided gene modulation to direct the differentiation of multipotent adipose-derived stem cells (ASCs) to demonstrate the effectiveness of CRISPR-engineered cells in tissue engineering applications. Specifically, we screen CRISPR-interference (CRISPRi) constructs targeting the promotors of selected osteogenic inhibitors and demonstrate that ASC osteogenic differentiation and mineral deposition can be regulated with CRISPRi targeting of Noggin without the use of exogenous growth factors in tissue engineered constructs. As a proof of concept, we combine three technologies developed out of our laboratories to demonstrate the controlled deposition of these engineered cells in a gradient with CRISPR-activation multiplex-engineered aggrecan/collagen type-II-chondrogenic ASCs on a high density anisotropic type I collagen construct to create a cell and tissue gradient similar to the fibrocartilage-to-mineralized-fibrocartilage gradient in the enthesis. Our results display the promise of CRISPR-engineered ASCs to produce tissue gradients, similar to what is observed in native tissue.

Therapeutic TNF-alpha Delivery After CRISPR Receptor Modulation in the Intervertebral Disc.

Low back pain (LBP) ranks among the leading causes of disability worldwide and generates a tremendous socioeconomic cost. Disc degeneration, a leading contributor to LBP, can be characterized by the breakdown of the extracellular matrix of the intervertebral disc (IVD), disc height loss, and inflammation. The inflammatory cytokine TNF-α has multiple pathways and has been implicated as a primary mediator of disc degeneration. We tested our ability to regulate the multiple TNF-α inflammatory signaling pathways in vivo utilizing CRISPR receptor modulation to slow the progression of disc degeneration in rats. Sprague-Dawley rats were treated with CRISPRi-based epigenome-editing therapeutics targeting TNFR1 and showed a decrease in behavioral pain in a disc degeneration model. Surprisingly, while treatment with the vectors alone was therapeutic, TNF-α injection itself became therapeutic after TNFR1 modulation. These results suggest direct inflammatory receptor modulation, to harness beneficial inflammatory signaling pathways, as a potent strategy for treating disc degeneration.

Multiplex epigenome editing of ion channel expression in nociceptive neurons abolished degenerative IVD-conditioned media-induced mechanical sensitivity.

Background: Low back pain is a major contributor to disability worldwide and generates a tremendous socioeconomic impact. The degenerative intervertebral disc (IVD) has been hypothesized to contribute to discogenic pain by sensitizing nociceptive neurons innervating the disc to stimuli that is nonpainful in healthy patients. Previously, we demonstrated the ability of degenerative IVDs to sensitize neurons to mechanical stimuli; however, elucidation of degenerative IVDs discogenic pain mechanisms is required to develop therapeutic strategies that directly target these mechanisms. Aims: In this study, we utilized CRISPR epigenome editing of nociceptive neurons to identify mechanisms of degenerative IVD-induced changes to mechanical nociception and demonstrated the ability of multiplex CRISPR epigenome editing of nociceptive neurons to modulate inflammation-induced mechanical nociception. Methods and Results: Utilizing an in vitro model, we demonstrated degenerative IVD-produced IL-6-induced increases in nociceptive neuron activity in response to mechanical stimuli, mediated by TRPA1, ASIC3, and Piezo2 ion channel activity. Once these ion channels were identified as mediators of degenerative IVD-induced mechanical nociception, we developed singleplex and multiplex CRISPR epigenome editing vectors that modulate endogenous expression of TRPA1, ASIC3, and Piezo2 via targeted gene promoter histone methylation. When delivered to nociceptive neurons, the multiplex CRISPR epigenome editing vectors abolished degenerative IVD-induced mechanical nociception while preserving nonpathologic neuron activity. Conclusion: This work demonstrates the potential of multiplex CRISPR epigenome editing as a highly targeted gene-based neuromodulation strategy for the treatment of discogenic pain, specifically; and, for the treatment of inflammatory chronic pain conditions, more broadly.

Multiplex gene editing to promote cell survival using low-pH clustered regularly interspaced short palindromic repeats activation (CRISPRa) gene perturbation.

BACKGROUND AIMS: Lower back pain is the leading cause of disability worldwide and is often linked to degenerative disc disease (DDD), the breakdown of intervertebral discs. The majority of treatment options for DDD are palliative, with clinicians prescribing medication or physical therapy to return the patient to work. Cell therapies are promising treatment options with the potential to restore functional physiological tissue and treat the underlying causes of DDD. DDD is characterized by biochemical changes in the microenvironment of the disc, including changes in nutrient levels, hypoxia, and changes in pH. Stem cell therapies are promising therapies to treat DDD, but the acidic environment in a degenerating disc significantly hinders the viability of stem cells, affecting their efficacy. Clustered regularly interspaced short palindromic repeats (CRISPR) systems allow us to engineer cell phenotypes in a well-regulated and controlled manner. Recently, CRISPR gene perturbation screens have assessed fitness, growth and provided a means for specific cell phenotype characterization. METHODS: In this study, we use a CRISPR-activation (a) gene perturbation screen to identify gene upregulation targets that enhance adipose-derived stem cell survival in acidic culture conditions. RESULTS: We identified 1213 prospective pro-survival genes and systematically narrowed these down to 20 genes for validation. We further narrowed down our selection to the top five prospective genes using Cell Counting Kit-8 cell viability assays in naïve adipose-derived stem cells and ACAN/Col2 CRISPRa upregulated stem cells. Finally, we examined the extracellular matrix-producing abilities of multiplex ACAN/Col2-pro-survival edited cells in pellet culture. CONCLUSIONS: Using the results from the CRISPRa screen, we are able to engineer desirable cell phenotypes to improve cell viability for the potential treatment of DDD and other disease states that expose cell therapies to acidic environments, while also providing broader knowledge on genes regulating low-pH cell survival.

Response to Preoperative Steroid Injections Predicts Surgical Outcomes in Patients Undergoing Fusion for Isthmic Spondylolisthesis.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The decision to pursue operative intervention for patients with isthmic spondylolisthesis is complex. Although steroid injections are a well-accepted therapeutic modality that may delay or obviate surgery, little is known regarding their ability to predict surgical outcomes. SUMMARY OF BACKGROUND DATA: Here, we examine whether improvement after preoperative steroid injections can accurately predict clinical outcomes after surgery. METHODS: A retrospective cohort analysis was performed on adult patients undergoing primary posterolateral lumbar fusion for isthmic spondylolisthesis between 2013 and 2021. Data were stratified into a control (no preoperative injection) group and an injection group (received a preoperative diagnostic and therapeutic injection). We collected demographic data, peri-injection visual analog pain scores (VAS) pain scores, PROMIS pain interference and physical function scores, Oswestry Disability Index, and VAS pain (back and leg). Student t test was utilized to compare baseline group characteristics. Linear regression was performed comparing changes in peri-injection VAS pain scores and postoperative measures. RESULTS: Seventy-three patients did not receive a preoperative injection and were included in the control group. Fifty-nine patients were included in the injection group. Of patients who received an injection, 73% had >50% relief of their preinjection VAS pain score. Linear regression revealed a positive interaction between the injection efficacy and postoperative pain relief as measured by VAS leg scores ( P <0.05). There was also an association between injection efficacy and back pain relief, though this did not achieve statistical significance ( P =0.068). No association was found between injection efficacy and improvement in Oswestry Disability Index or PROMIS measures. CONCLUSIONS: Steroid injections are often utilized in the nonoperative therapeutic management of patients with lumbar spine disease. Here, we demonstrate the diagnostic value of steroid injections in predicting postoperative leg pain relief in patients undergoing posterolateral fusion for isthmic spondylolisthesis.

Hypoalbuminemia as a Predictor of Mortality, Disability, and Readmission in Patients Undergoing Spine Surgery: A Retrospective Analysis.

STUDY DESIGN: This was a retrospective cohort study. OBJECTIVE: The objective of this study was to clarify the association between preoperative albumin status and mortality and morbidity in lumbar spine surgery. SUMMARY OF BACKGROUND DATA: Hypoalbuminemia is a known marker of inflammation and is associated with frailty. Hypoalbuminemia is an identified risk factor for mortality following spine surgery for metastases, yet has not been well studied among spine surgical cohorts outside of metastatic cancer. MATERIALS AND METHODS: We identified patients with preoperative serum albumin laboratory values who underwent lumbar spine surgery at a US public university health system between 2014 and 2021. Demographic, comorbidity, and mortality data were collected along with preoperative and postoperative Oswestry Disability Index (ODI) scores. Any cause readmission within 1 year of surgery was recorded. Hypoalbuminemia was defined as <3.5 g/dL in serum. We examined the Kaplan-Meier survival plots based on serum albumin. Multivariable regression models were used to identify the association between preoperative hypoalbuminemia with mortality, readmission, and ODI, while controlling for age, sex, race, ethnicity, procedure, and Charlson Comorbidity Index. RESULTS: Of 2573 patients, 79 were identified as hypoalbuminemic. Hypoalbuminemic patients had a significantly greater adjusted risk of mortality through 1 year (odds ratio=10.2; 95% CI: 3.1-33.5; P <0.001), and 7 years (hazard ratio=4.18; 95% CI: 2.29-7.65; P <0.001). Hypoalbuminemic patients had ODI scores 13.5 points higher (95% CI: 5.7-21.4; P <0.001) at baseline. Adjusted readmission rates were not different between groups through 1 year (odds ratio=1.15; 95% CI: 0.5-2.62; P =0.75) or through full surveillance (hazard ratio=0.82; 95% CI: 0.44-1.54; P =0.54). CONCLUSIONS: Preoperative hypoalbuminemia was strongly associated with postoperative mortality. Hypoalbuminemic patients did not have demonstrably worse outcomes in their functional disability beyond 6 months. Within the first 6 months following surgery, the hypoalbuminemic group improved at a similar rate to the normoalbuminemic group despite having a greater preoperative disability. However, causal inference is limited in this retrospective study.

Preoperative Fluoroscopically Guided Regional Erector Spinae Plane Blocks Reduce Opioid Use, Increase Mobilization, and Reduce Length of Stay Following Lumbar Spine Fusion.

STUDY DESIGN: Retrospective review. OBJECTIVE: To determine the effectiveness of erector spinae plane (ESP) blocks at improving perioperative pain control and function following lumbar spine fusions. METHODS: A retrospective analysis was performed on patients undergoing < 3 level posterolateral lumbar fusions. Data was stratified into a control group and a block group. We collected postop MED (morphine equivalent dosages), physical therapy ambulation, and length of stay. PROMIS pain interference (PI) and physical function (PF) scores, ODI, and VAS were collected preop and at the first postop visit. Chi-square and student's t-test (P = .05) were used for analysis. We also validated a novel fluoroscopic technique for ESP block delivery. RESULTS: There were 37 in the block group and 39 in the control group. There was no difference in preoperative opioid use (P = .22). On postop day 1, MED was reduced in the block group (32 vs 51, P < .05), and more patients in the block group did not utilize any opioids (22% vs 5%, P < .05). The block group ambulated further on postop day 1 (312 ft vs 204 ft, P < .05), and had reduced length of stay (2.4 vs 3.2 days, P < .05). The block group showed better PROMIS PI scores postoperatively (58 vs 63, P < .05). The novel delivery technique was validated and successful in targeting the correct level and plane. CONCLUSIONS: ESP blocks significantly reduced postop opioid use following lumbar fusion. Block patients ambulated further with PT, had reduced length of stay, and had improved PROMIS PI postoperatively. Validation of the block demonstrated the effectiveness of a novel fluoroscopic delivery technique. ESP blocks represent an underutilized method of reducing opioid consumption, improving postoperative mobilization and reducing length of stay following lumbar spine fusion.

Risk Factors for Postoperative Ileus in Patients Undergoing Spine Surgery.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVES: Postoperative ileus (POI) is a common complication following elective spinal surgeries. The aim of this study was to determine the incidence of POI and identify demographic and surgical risk factors for developing POI after elective instrumented fusion of the thoracolumbar spine. METHODS: The University of Utah Institutional Review Board (IRB) approved this retrospective study. The study does not require informed consent given the data reviewed was deidentified and collected in accordance with the institution's standard of care. A designated IRB committee determined that study is exempt under exemption category 7. IRB approval number 00069703. Patients undergoing instrumented thoracolumbar fusion for one or more levels were retrospectively identified from an internal spine surgery database. Cases performed for trauma, infection, or tumors were excluded. Demographics, medical comorbidities, surgical variables, and opioid medication administration (morphine milligram equivalents, MME) were abstracted from the electronic medical record. Univariate analysis was used to identify variables associated with POI. These variables were then tested for independent association with POI using multivariate logistic regression. RESULTS: 418 patients were included in the current study. The incidence of POI was 9.3% in this cohort. There was no significant relationship between development of POI and patient age, gender, BMI, diabetes mellitus, thyroid dysfunction, lung disease, CKD, GERD, smoking status, alcohol abuse, anemia, or prior abdominal surgery. Univariate analysis demonstrated significant association between POI and fusion ≥7 levels compared to fusions of fewer levels (P = .001), as well as intraoperative sufentanil compared to other opioids (35.9% vs 20.1%, P = .02). POI was not significantly associated with total intraoperative MME, approach, use of interbody cage, or osteotomy. Multivariate logistic regression confirmed total 24-hour postoperative MME as an independent risk factor for POI (OR 1.004, P = .04), however, intraoperative sufentanil administration was not an independent risk factor for POI when controlling for other variables. CONCLUSIONS: This retrospective cohort study demonstrates that greater postoperative MME is an independent risk factor for POI after thoracolumbar spine fusion when accounting for demographic, medical, and surgical variables with multiple logistic regression. Prospective studies are warranted to evaluate clinical measures to decrease the risk of POI among patients undergoing instrumented thoracolumbar spinal fusions.

What Does Your PROMIS Score Mean? Improving the Utility of Patient-Reported Outcomes at the Point of Care.

STUDY DESIGN: Prospective cohort. OBJECTIVES: Patient-Reported Outcome Measurement Information System (PROMIS) has been validated for lumbar spine. Use of patient-reported outcome (PRO) measures can improve clinical decision making and health literacy at the point of care. Use of PROMIS, however, has been limited in part because clinicians and patients lack plain language understanding of the meaning of scores and it remains unclear how best to use them at the point of care. The purpose was to develop plain language descriptions to apply to PROMIS Physical Function (PF) and Pain Interference (PI) scores and to assess patient understanding and preferences in presentation of their individualized PRO information. METHODS: Retrospective analysis of prospectively collected PROMIS PF v1.2 and PI v1.1 for patients presenting to a tertiary spine center for back/lower extremity complaints was performed. Patients with missing scores, standard error >0.32, and assessments with <4 or >12 questions were excluded. Scores were categorized into score groups, specifically PROMIS PF groups were: <18, 20 ± 2, 25 ± 2, 30 ± 2, 35 ± 2, 40 ± 2, 45 ± 2, 50 ± 2, 55 ± 2, 60 ± 2, and >62; and PROMIS PI groups were: <48, 50 ± 2, 55 ± 2, 60 ± 2, 65 ± 2, 70 ± 2, 75 ± 2, 80 ± 2, and >82. Representative questions and answers from the PROMIS PI and PROMIS PF were selected for each score group, where questions with <25 assessments or representing <15% of assessments were excluded. Two fellowship-trained spine surgeons further trimmed the questions to create a streamlined clinical tool using a consensus process. Plain language descriptions for PROMIS PF were then used in a prospective assessment of 100 consecutive patients. Patient preference for consuming the score data was recorded and analyzed. RESULTS: In total, 12 712 assessments/5524 unique patients were included for PF and 14 823 assessments/6582 unique patients for PI. More than 90% of assessments were completed in 4 questions. The number of assessments and patients per scoring group were normally distributed. The mean PF score was 37.2 ± 8.2 and the mean PI was 63.3 ± 7.4. Plain language descriptions and compact clinical tool was were generated. Prospectively 100 consecutive patients were surveyed for their preference in receiving their T-score versus plain language description versus graphical presentation. A total of 78% of patients found receiving personalized PRO data helpful, while only 1% found this specifically not helpful. Overall, 80% of patients found either graphical or plain language more helpful than T-score alone, and half of these preferred plain language and graphical descriptions together. In total, 89% of patients found the plain language descriptions to be accurate. CONCLUSIONS: Patients at the point of care are interested in receiving the results of their PRO measures. Plain language descriptions of PROMIS scores enhance patient understanding of PROMIS numerical scores. Patients preferred plain language and/or graphical representation rather than a numerical score alone. While PROs are commonly used for assessing outcomes in research, use at point of care is a growing interest and this study clarifies how they might be utilized in physician-patient communication.

Degenerative IVD conditioned media and acidic pH sensitize sensory neurons to cyclic tensile strain.

Low back pain is among the leading causes of disability worldwide. The degenerative intervertebral disc (IVD) environment contains pathologically high levels of inflammatory cytokines and acidic pH hypothesized to contribute to back pain by sensitizing nociceptive neurons to stimuli that would not be painful in healthy patients. We hypothesized that the degenerative IVD environment drives discogenic pain by sensitizing nociceptive neurons to mechanical loading. To test this hypothesis, we developed an in vitro model that facilitated the investigation of interactions between the degenerative IVD environment, nociceptive neurons innervating the IVD and mechanical loading of the disc; and, the identification of the underlying mechanism of degenerative IVD induced nociceptive neuron sensitization. In our model, rat dorsal root ganglia (DRG) neurons were seeding onto bovine annulus fibrosus tissue, exposed to degenerative IVD conditioned media and/or acidic pH, and subjected to cyclic tensile strain (1 Hz; 1%-6% strain) during measurement of DRG sensory neuron activity via calcium imaging. Using this model, we demonstrated that both degenerative IVD conditioned media and degenerative IVD acidic pH levels induced elevated nociceptive neuron activation in response to physiologic levels of mechanical strain. In addition, interleukin 6 (IL-6) was demonstrated to mediate degenerative IVD conditioned media induced elevated nociceptive neuron activation. These results demonstrate IL-6 mediates degenerative IVD induced neuron sensitization to mechanical loading and further establishes IL-6 as a potential therapeutic target for the treatment of discogenic pain. Data further suggests the degenerative IVD environment contains multiple neuron sensitization pathways (IL-6, pH) that may contribute to discogenic pain.

Response to the Coronavirus Disease 2019 Pandemic by the Spine Division at a Level-I Academic Referral Center.

Coronavirus disease 2019 (COVID-19) is a ubiquitous health concern and a global pandemic. In an effort to slow the disease spread and protect valuable healthcare resources, cessation of nonessential surgery, including many orthopaedic procedures, has become commonplace. This crisis has created a unique situation in the care of spine patients as we must balance the urgency of patient evaluation, surgical intervention, and continued training against the risk of disease exposure and resource management. The spine division of an orthopaedic surgery department has taken an active role in enacting protocol changes in anticipation of COVID-19. In the initial 4 weeks of the COVID-19 pandemic the spine division went from an average of 60.4 cases to 10 cases during the same timeframe. Clinic visits decreased from 417.4 to 322 with new patient visits decreasing from 28% to 20%. Three hundred eighteen of the 322 (98.7%) clinic visits were performed via telehealth. Although these changes have been forced upon us by necessity, we feel that our division and department will emerge in a more responsive, agile, and stronger state. As we look to the coming months and beyond, it will be important to continue to adapt to the changing landscape during unprecedented times.

Hangman's Fracture.

STUDY DESIGN: Review article. OBJECTIVE: A review and update of the treatment of Hangman's fractures including the indications for both nonoperative and operative treatment of typical and atypical fractures. SUMMARY OF BACKGROUND DATA: Hangman's fractures are the second most common fracture pattern of the C2 vertebrae following odontoid fractures. Many of the stable extension type I and II fractures can be treated with external immobilization, whereas the predominant flexion type IIa and III fractures require surgical stabilization. METHODS: A review of the literature. RESULTS: The clinical and radiographic outcomes of the treatment of Hangman's fractures lend a good overall prognosis when the correct diagnosis is made. The nonoperative treatment of stable type I and II fractures with external immobilization leads to excellent long-term outcomes as does the operative treatment of the unstable type IIa and III fractures. CONCLUSIONS: Hangman's fractures can be classified as stable (type I and most II) or unstable (type IIa and III) and the optimal treatment depends upon this distinction. Stable injuries do well with rigid immobilization and rarely require operative intervention. In contrast, unstable injuries do poorly if treated nonoperatively but do well with surgical intervention. When treating atypical Hangman's variants, great vigilance and close clinical observation is paramount if nonoperative treatment is indicated given the potential for neurological compression in this fracture pattern. Properly identifying and treating these injuries represents an opportunity for the spine surgeon to optimize patient outcomes.

The Impact of Preoperative Mindfulness-Based Stress Reduction on Postoperative Outcomes in Lumbar Spine Degenerative Disease: 3-Month and 12-Month Results of a Pilot Study.

BACKGROUND: We previously reported inpatient and 30-day postoperative patient-reported outcomes (PROs) of a controlled, noncrossover pilot study using preoperative mindfulness-based stress reduction (MBSR) training for lumbar spine surgery. Our goal here was to assess 3-month and 12-month postoperative PROs of preoperative MBSR in lumbar spine surgery for degenerative disease. METHODS: Intervention group participants were prospectively enrolled in a preoperative online MBSR course. A comparison standard care only group was one-to-one matched retrospectively by age, sex, surgery type, and prescription opioid use. Three-month and 12-month postoperative PROs for pain, disability, quality of life, and opioid use were compared within and between groups. Regression models were used to assess whether MBSR use predicted outcomes. RESULTS: Twenty-four participants were included in each group. At 3 months, follow-up was 87.5% and 95.8% in the comparison and intervention groups, respectively. In the intervention group, mean Patient-Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF) was significantly higher, whereas mean Patient-Reported Outcomes Measurement Information System-Pain Interference (PROMIS-PI) and Oswestry Disability Index were significantly lower. The change from baseline in mean PROMIS-PF and PROMIS-PI was significantly greater than in the comparison group. At 12 months, follow-up was 58.3% and 83.3% in the comparison and intervention groups, respectively. In the intervention group, mean PROMIS-PI was significantly lower and change in mean PROMIS-PI from baseline was significantly greater. MBSR use was a significant predictor of change in PROMIS-PF at 3 months and in PROMIS-PI at 12 months. No adverse events were reported. CONCLUSIONS: Three-month and 12-month results suggest that preoperative MBSR may have pain control benefits in lumbar spine surgery.

The impact of the lordosis distribution index on failure after surgical treatment of adult spinal deformity.

BACKGROUND CONTEXT: Proximal junctional failure (PFJ) is a common and dreaded complication of adult spinal deformity. Previous research has identified parameters associated with the development of PJF and the search for radiographic and clinical variables continues in an effort to decrease the incidence of PFJ. The lordosis distribution index (LDI) is a parameter not based on pelvic incidence. Ideal values for LDI have been established in prior literature with demonstrated association with PJF. PURPOSE: The purpose of this study is compare PJF and mechanical failure rates between patients with ideal and nonideal LDI cohort. STUDY DESIGN: This is a retrospective, single-center case-controlled study. PATIENT SAMPLE: Adult patients who underwent surgical treatment for spinal deformity as defined by the SRS-Schwab criteria between 2001 and 2016 were included. Furthermore, fusion constructs spanned at least four vertebral segments with the upper instrumented vertebra (UIV) T9 or caudal. Patients who were under the age of 18, those with radiographic data less than 1 year, and those with neoplastic or trauma etiologies were excluded. Prior thoracolumbar spine surgery was not an exclusion criterion. OUTCOME MEASURES: The outcome measures were physiologic in nature: The primary outcome was defined as PFJ. The International Spine Study Group (ISSG) definition for PJF was used, which includes postoperative fracture of the UIV or UIV+1, instrumentation failure at UIV, PJA increase greater than 15° from preoperative baseline or extension of the construct needed within 6 months. Secondary outcomes included extension of the construct after 6 months or revision due to instrumentation failure, pseudarthrosis or distal junctional failure. METHODS: A portion of this project was funded through National Institute of Health Grant 5UL1TR001067-05. The authors have no conflict of interest related to this study. The records of patients meeting the inclusion criteria were reviewed. Clinical and radiographic data were extracted and analyzed. Univariate cox proportional hazard models were used to identify factors associated with mechanical failure and included in a multivariate Cox proportional hazards model. RESULTS: There were 187 patients that met the inclusion criteria. Univariate analysis demonstrated the number of levels fused, instrumentation to the sacrum or pelvis, PI-LL difference between pre- and postoperative states, T1-SPI, T9-SPI, and postoperative LDI (treated as a continuous variable). When LDI was treated as a categorical variable using an LDI cutoff of less than 0.5 for hypolordotic, 0.5 to 0.8 for aligned and greater than 0.8 for hyperlordotic, there was no difference in failure rates between the two groups. CONCLUSIONS: Lumbar lordosis is an important parameter in adult deformity. However, the LDI is an imperfect variable and previously developed categories did not show differences in failure rates in this cohort.

Potential Selection Bias in Observational Studies Comparing Cervical Disc Arthroplasty to Anterior Cervical Discectomy and Fusion.

STUDY DESIGN: Retrospective study using a national administrative database. OBJECTIVE: To define the cohort differences in patient characteristics between patients undergoing cervical disc arthroplasty (CDA) and anterior cervical discectomy and fusion (ACDF) in a large national sample, and to describe the impact of those baseline patient characteristics on analyses of costs and complications. SUMMARY OF BACKGROUND DATA: CDA was initially studied in high quality, randomized trials with strict inclusion criteria. Recently a number of non-randomized, observational studies have been published an attempt to expand CDA indications. These trials are predisposed to falsely attributing differences in outcomes to an intervention due to selection bias. METHODS: Adults undergoing ACDF or CDA between 2004 and 2014 were identified using International Classification of Diseases, 9, Clinical Modification (ICD-9-CM) diagnosis and procedure codes. Perioperative demographics, comorbidities, complications, and costs were queried. Patient characteristics were compared via chi-square and t tests. Cost, mortality, and complications were compared between ACDF and CDA cohorts using models that adjusted for demographics and comorbidities, as well as "naïve" models that did not. RESULTS: A total of 290,419 procedures, 98.2% ACDF and 1.8% CDA, were included in the sample. Compared with ACDF patients, CDA patients were younger, healthier as evidenced by number of comorbidities, and had an improved socioeconomic status as measured by income and insurance. The naïve logistic regression model showed that hospital costs for CDA were $549 lower than ACDF. In the fully specified model, CDA was $574 more expensive. The naïve model for medical complications suggests a protective advantage for CDA over ACDF, odds ratio of 0.627, P < 0.01. No statistically significant difference was found in the fully specified model in terms of complications. CONCLUSION: Patients undergoing CDA were younger and healthier with higher socioeconomic statuses compared with ACDF patients. Accounting for these baseline differences significantly attenuated the apparent benefit for CDR on costs and medical complications. LEVEL OF EVIDENCE: 3.

Defining Instability in Degenerative Spondylolisthesis: Surgeon Views.

STUDY DESIGN: Surgeon survey. OBJECTIVE: To examine factors influencing surgeons' definition of instability in grade 1 degenerative spondylolisthesis (DS) and assess treatment preferences for both stable and unstable DS. SUMMARY OF BACKGROUND DATA: DS treatment options are broadly classified as decompression with or without fusion. In surgical decision-making, "instability" is frequently considered as a key factor. However, no consensus on the definition of instability exists. METHODS: A survey was conducted to ascertain the minimum amounts of static translation, dynamic translation, and angulation change that surgeons considered significant for determining instability. The importance of other clinical and radiographic features were also assessed, and respondents' standard treatment for stable and unstable DS. RESULTS: Out of 226 respondents, 99% deemed dynamic translation moderately to extremely influential for determining instability, whereas only 55% found static translation as important. The most prevalent cut-off values for dynamic (57%) and static translation (32%) were at least 2-4 mm and for angulation change at least 10-15 degrees (43%). Facet angulation was considered moderately to extremely important to determine instability by 69% of the surgeons, disk height by 67%, patient age by 64%, severity of stenosis by 55%, severity of back pain by 50%, patient-reported function by 49%, pelvic incidence by 47%, and severity of neurogenic claudication by 42%.Decompression with fusion was the preferred treatment method for unstable DS in 99% of the respondents. For stable DS, 40% would still perform fusion, whereas 60% preferred treatment with decompression-alone. Those who preferred fusion for stable DS reported significantly lower thresholds for static (P<0.001) and dynamic translation (P=0.004) for their determination of instability. CONCLUSIONS: Clear consensus regarding the definition of instability does not exist. Dynamic translation is the most agreed-upon parameter of influence. Treatment preferences vary for stable DS, but for unstable cases there is broad consensus to perform fusion. LEVEL OF EVIDENCE: Level II.

Multiplex Epigenome Editing of Dorsal Root Ganglion Neuron Receptors Abolishes Redundant Interleukin 6, Tumor Necrosis Factor Alpha, and Interleukin 1ß Signaling by the Degenerative Intervertebral Disc.

Back pain is the leading cause of disability worldwide and contributes to significant socioeconomic impacts. It has been hypothesized that the degenerative intervertebral disc (IVD) contributes to back pain by sensitizing nociceptive neurons innervating the IVD to stimuli that would not be painful to healthy patients. However, the inflammatory signaling networks mediating this sensitization remain poorly understood. A better understanding of the underlying mechanisms of degenerative IVD-induced changes in nociception is required to improve the understanding and treatment of back pain. Toward these ends, a novel in vitro model was developed to investigate degenerative IVD-induced changes in dorsal root ganglion (DRG) neuron activation by measuring DRG neuron activity following neuron seeding on human degenerative IVD tissue collected from patients undergoing surgical treatment for back pain. Lentiviral clustered regularly interspaced palindromic repeat (CRISPR) epigenome editing vectors were built to downregulate the inflammatory receptors TNFR1, IL1R1, and IL6st in DRG neurons in single- and multiplex. Multiplex CRISPR epigenome editing of inflammatory receptors demonstrated that degenerative IVD tissue drives thermal sensitization through the simultaneous and redundant signaling of interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), and IL-1ß. This work elucidates redundant signaling pathways in neuron interactions with the degenerative IVD and suggests the need for multiplex targeting of IL-6, TNF-α, and IL-1ß for pain modulation in the degenerative IVD.