Indiana Spine Group

Prospective, multicenter, single-blind, randomized, controlled pivotal study. To evaluate whether P-15L (PearlMatrix P-15 Peptide Enhanced Bone Graft) is noninferior in effectiveness to local autograft when applied in single-level instrumented transforaminal lumbar interbody fusion (TLIF). P-15L, an FDA-designated Breakthrough Drug-Device, is a composite drug-device combination bone graft containing P-15, a 15-amino acid polypeptide, which enhances cell binding, proliferation, and differentiation, resulting in bone formation. Skeletally mature patients, aged 22 to 80 years, with degenerative disc disease (DDD) were randomized 1:1 to P-15L (investigational) or to the local autograft (control) during single-level TLIF with a polyetheretherketone (PEEK) cage and supplemental pedicle screw fixation. The primary outcome was composite clinical success (CCS) at 24 months, defined as: no index level secondary surgical procedures; achievement of fusion; ≥15-point improvement in Oswestry low back pain disability questionnaire (ODI) from baseline; no new or worsening persistent neurological deficit relative to baseline; and no device-related serious adverse events (SAEs). A total of 290 patients were enrolled at 33 sites: 141 (48.6%) received P-15L, and 149 (51.3%) received local autograft. P-15L was noninferior ( P <0.0001) and superior ( P =0.002) to autograft with respect to CCS, with 55.5% of the investigational group achieving composite clinical success compared with 37.5% of the control group. P-15L had a 25.8% higher fusion rate as compared with autograft for the CCS at 24 months (84.3% vs. 58.5%, respectively). Device-related SAE rates were similar in both groups. P-15L was superior to local autograft in achieving clinical success at 24 months. Furthermore, P-15L produced a significantly higher fusion rate as compared with autograft. No meaningful clinical differences were found in the incidence of device-related SAEs. P-15L appears to be a safe and effective option for TLIF. Level I.

Study Design.Prospective, multicenter, single-blind, randomized, and controlled pivotal study.Objective.Compare time-to-fusion in patients treated with P-15L (PearlMatrixTM P-15 peptide enhanced bone graft) versus local autograft over 24 months and evaluate changes in pain and quality of life at 24 months relative to baseline.Summary of Background Data.P-15L, an FDA-designated breakthrough device, is a composite bone graft with P-15, a 15-amino acid polypeptide that promotes cellular adhesion, proliferation, and differentiation to support bone formation.Methods.Patients (22–80 y) with degenerative disc disease were randomized to the investigational (P-15L) or control (local autograft) group during single-level transforaminal lumbar interbody fusion (TLIF) with a PEEK cage and supplemental pedicle screw fixation. Fusion assessments occurred at 6, 12, and 24 months. Time-to-fusion was tested for superiority as compared with the control using Kaplan-Meier survival analysis. Back and leg pain were measured using the Visual Analog Scale (VAS) and quality of life was assessed using the Short Form Survey (SF-12).Results.The analysis included 290 patients from 33 sites; 141 (48.6%) received P-15L and 149 (51.3%) received local autograft. At randomization, at least one risk factor for pseudoarthrosis (obesity, nicotine use, or diabetes) was reported in 58.9% (83/141) of the investigational group and 60.4% (90/149) of the control group. More patients in the investigational group than the control group achieved fusion at 6 months (Kaplan-Meier fusion rates 57.6% vs. 26.9%, respectively), 12 months (68.8% vs. 41.5%, respectively), and 24 months (81.1% vs. 54.9%, respectively). P-15L was statistically superior to autograft for time-to-fusion (hazard ratio=1.87, 95% CI: 1.47–2.38; P < 0.0001). There was marked improvement in VAS and SF-12 relative to baseline in both groups at 24 months.Conclusion.P-15L promotes statistically superior earlier time-to-fusion than local autograft in instrumented TLIF. Both treatments resulted in clinically meaningful improvements in pain and quality of life at 24 months.Level of Evidence.Level I.

Incarcerated individuals in state and federal prisons demonstrate disproportionately high rates of cardiovascular disease, especially hypertension and tobacco use. 1 As a result, in comparison with the United States general population, inmates are faced with a more than three-fold risk of acute ischemic stroke (AIS). 2 Unfortunately, some evidence suggests that incarcerated individu-als receive suboptimal medical care due to structural barriers in healthcare delivery as well as discrimination based on incarcerated status, 3 which underscores a public health and human rights concern.To the best of our knowledge, no studies to date have evaluated treatment rates and clinical outcomes of AIS in this specialized population, in whom healthcare outcomes in general are woefully understudied.Herein, we aim to evaluate treatment rates of reperfusion therapies as well as clinical outcomes of in-

Coexisting medical conditions are increasingly prevalent in surgical populations. The impact of multiple comorbidities on patient-reported outcomes (PROs) and endotypes of frequently co-occurring conditions for cervical spondylotic myelopathy (CSM) remain unclear. This study explores whether CSM patients with multimorbidity have worse baseline and postoperative PROs and less functional improvement after surgery compared to those with few or no comorbidities. The authors also investigated whether distinct comorbidity endotypes exist among CSM surgical patients and whether they influence postoperative outcomes. The prospective Quality Outcomes Database (QOD) was used to assess patients undergoing surgery for CSM. Multimorbidity was defined as ≥ 2 chronic conditions, including diabetes, coronary artery disease, peripheral vascular disease, arthritis, chronic renal disease, chronic obstructive pulmonary disease, Parkinson's disease, multiple sclerosis, depression, and anxiety. Baseline characteristics and 24-month PROs were assessed across multiple-comorbidity status, including modified Japanese Orthopaedic Association (mJOA), Neck Disability Index (NDI), visual analog scale for neck and arm pain, EQ-5D, and patient satisfaction scores. Clusters were identified from the full cohort using k-medoids, revealing subgroups with similar comorbidity endotypes. The final cohort included 1141 CSM patients (83.1% reaching 24-month follow-up), with 761 (66.7%) having 0 or 1 comorbidity and 380 (33.3%) ≥ 2 comorbidities. The multimorbidity cohort was older (mean age 62.6 ± 11.2 vs 59.5 ± 12.0 years, p < 0.001), more likely to be female (52.9% vs 44.7%, p = 0.011), and had a higher BMI (mean 31.1 ± 6.7 vs 29.7 ± 6.2 kg/m2, p < 0.001). Multimorbidity patients exhibited worse mJOA, NDI, and EQ-5D scores at baseline and 24 months (p < 0.05). On multivariable analysis, the total number of comorbidities was not significantly associated with any PRO measures. Four comorbidity clusters were identified: low burden, arthritis, diabetes, and high burden. On one-way ANOVA, the baseline mJOA score was significantly different across clusters (p = 0.003). At 24 months, the mJOA score was significantly lower in the diabetes and high-burden endotypes. Twenty-four-month score change and minimal clinically important difference (MCID) achievement of all PROs remained similar across clusters (p > 0.05). While patients with multimorbidity have worse baseline and postoperative PROs, they achieve similar functional and pain-related improvements following CSM surgery. Similarly, the comorbidity endotypes identified in this QOD cohort suggest that certain patterns of coexisting chronic conditions, such as overlapping diabetes and arthritis, are associated with different levels of disability but may not diminish the effectiveness of surgical intervention.

Background: Posterior circulation (PC) large-vessel occlusion (LVO) strokes have significant morbidity and mortality, but patient selection for acute interventions remains understudied. Multiple computed tomography (CT)-based scores exist, including the CT-perfusion-based CAPS score, CT-angiogram(CTA)-based BATMAN and PC-CTA scores, and CTA source image or non-contrast-CT-based PC-ASPECTS score, but their predictive values for long-term outcomes after thrombectomy have not been directly compared. Methods: We conducted a retrospective multicenter cohort study of patients with basilar artery occlusions treated with endovascular thrombectomy. Four CT-based scores were assessed: PC-ASPECTS, BATMAN, PC-CTA, and CAPS. The primary outcome of interest for the study was favourable functional outcome at 3 months (mRS of 0-3). We generated receiver operating characteristic curves measuring area under the curve (AUC) for poor functional outcomes and compared AUCs with non-parametric methods. Results: 98 patients were included for analysis, with an average age of 64.9±15.6 years. The median National Institute of Health Stroke Severity Score (NIHSS) was 13.5 (IQR 7.0 – 23.0). AUC values were highest for the CAPS score (AUC 0.72 (95%CI 0.63 – 82)), and lowest for the pc-CTA score (AUC 0.57 (95%CI 0.45 – 0.68)), p=0.019. There was a trend towards the CAPS score outperforming the BATMAN (AUC 0.66 (95%CI 0.55 – 0.77) and PC-ASPECTS scores (AUC 0.63 (95%CI 0.52 – 0.75)), though this difference was not statistically significant (p=0.29 and p=0.23, respectively). However, the CAPS score was the only score with 100% specificity for predicting inability to achieve good functional outcome after thrombectomy: 0/12 patients with CAPS score of 4-6 went on to have a good functional outcome at 3 months after thrombectomy. Conclusion: Our analysis demonstrated that the CT-perfusion-based CAPS score outperformed three other imaging-based scores for predicting outcomes after 3 months. The CAPS score could be implemented to inform patient selection for endovascular thrombectomy in basilar artery occlusions.

Cervical spondylotic myelopathy (CSM) shows varying levels of improvement after surgical treatment. While some patients improve soon after surgery, others may take months to years to show any signs of improvement. The goal of this study was to evaluate postoperative improvement, patient-reported outcomes, and patient satisfaction up to 2 years after surgical treatment for CSM, which will help optimize the current treatment strategies and effectively manage patient expectations. This was a retrospective study of prospectively collected data using the Quality Outcomes Database. The primary outcomes of interest were achievement of the minimal clinically important difference (MCID) for the numeric rating scale for neck and arm pain, modified Japanese Orthopaedic Association, Neck Disability Index, and EQ-5D scores and postoperative satisfaction (North American Spine Society scale). Early and sustained improvement was defined as MCID achievement in at least one patient-reported outcome measure (PROM) at the 3-, 12-, and 24-month follow-ups. Transient improvement was defined as MCID achievement only at the 3-month and/or 12-month follow-up but not at the 24-month follow-up. Late improvement was defined as MCID achievement in at least one PROM only at the 24-month follow-up. There were 630 patients included in the comparative analysis. A total of 463 (73.5%) patients achieved early and sustained improvement, 105 (16.7%) patients experienced transient improvement with subsequent decline, 25 (4.0%) patients reported late improvement, and 37 (5.9%) patients did not report any clinically meaningful improvement after surgery. Patients with an anterior approach were more likely to be in the early and sustained improvement group. African American patients (OR 2.98, 95% CI 1.14-7.76; p = 0.03) were more likely to report late improvement when compared with White patients. The overall satisfaction rate at the 24-month follow-up was 87.8%. These findings indicate that 73.5% of patients achieve early and sustained improvement, and 87.8% of patients are satisfied with surgery 24 months postoperatively.

Lumbar decompression and/or fusion surgery is a common operation for symptomatic lumbar spondylolisthesis refractory to conservative management. Multiyear follow-up of patient outcomes can be difficult to obtain but allows for identification of preoperative patient characteristics associated with durable pain relief, improved functional outcome, and higher patient satisfaction. A query of the Quality Outcomes Database (QOD) low-grade spondylolisthesis module for patients who underwent surgery for grade 1 lumbar spondylolisthesis (from July 2014 to June 2016 at the 12 highest-enrolling sites) was used to identify patient satisfaction, as measured with the North American Spine Society (NASS) questionnaire, which uses a scale of 1-4. Patients were considered satisfied if they had a score ≤ 2. Multivariable logistic regression was performed to identify baseline demographic and clinical predictors of long-term satisfaction 5 years after surgery. Of 573 eligible patients from a cohort of 608, patient satisfaction data were available for 81.2%. Satisfaction (NASS score of 1 or 2) was reported by 389 patients (83.7%) at 5-year follow-up. Satisfied patients were predominantly White and ambulation independent and had lower baseline BMI, lower back pain levels, lower Oswestry Disability Index (ODI) scores, and greater EQ-5D index scores at baseline when compared to the unsatisfied group. No significant differences in reoperation rates between groups were reported at 5 years. On multivariate analysis, patients who were independently ambulating at baseline had greater odds of long-term satisfaction (OR 1.12, p = 0.04). Patients who had higher 5-year ODI scores (OR 0.99, p < 0.01) and were uninsured (OR 0.43, p = 0.01) were less likely to report long-term satisfaction. Lumbar surgery for the treatment of grade 1 spondylolisthesis can provide lasting pain relief with high patient satisfaction. Baseline independent ambulation is associated with a higher long-term satisfaction rate after surgery. Higher ODI scores at 5-year follow-up and uninsured status are associated with lower postoperative long-term satisfaction.

BACKGROUND: Lumbar disc herniation (LDH) occurs when the central disc material, primarily the nucleus pulposus, is displaced beyond the outer annulus, compressing the spinal nerve roots. LDH symptoms, including radicular leg pain, radiculopathy, and low back pain, are associated with considerable disease burden and the significant utilization of health care resources. OBJECTIVES: Provide overview of the current treatment landscape for LDH, identify unmet needs, and describe emerging treatments. STUDY DESIGN: Narrative literature review. METHODS: A review of literature concerning available LDH treatments and associated outcomes was conducted in PubMed to identify areas of unmet need. Some key words included “lumbar disc herniation,” “radicular leg pain,” “sciatica,” “treatment,” “therapy,” and “burden.” RESULTS: For patients who do not respond to conservative therapy, epidural steroid injections (ESIs) are widely used for persistent LDH symptoms. While ESIs provide short-term improvements in radicular pain, evidence that ESIs bestow sustained benefits is limited. ESIs are not approved by the US Food and Drug Administration (FDA) and, in rare cases, carry risks of infection and neurological injury, as well as the potential for long-term systemic effects of glucocorticoids. In cases when nonsurgical treatment fails to relieve symptoms, lumbar discectomy can provide rapid pain relief; however, in addition to the risk of intraoperative complications, the long-term consequences of lumbar discectomy may include recurrent pain or herniation, revision discectomy, loss of disc height, and Modic changes. Treatments for LDH in late-stage clinical development include sustained-release ESI formulations and a novel agent for chemonucleolysis, a nonsurgical method of minimizing the volume of the displaced nucleus pulposus. Emerging minimally invasive therapies that address the underlying pathophysiology of the disease have the potential to bridge the gap between symptomatic treatments and surgery. LIMITATIONS: Because this paper was a narrative review, literature search and selection processes were not systematic in nature. The evidence regarding the long-term efficacy of some treatments, such as discectomy, was limited by the high rates of crossover between the treatment groups. CONCLUSIONS: The lack of sustained benefits associated with ESIs and the risks associated with surgery underscore the unmet need for novel, minimally invasive interventional therapies able to address the underlying nerve root compression in LDH. KEY WORDS: Lumbar disc herniation, radicular leg pain, lumbar radiculopathy, epidural steroid injection, surgery, microdiscectomy, chemonucleolysis, condoliase, intradiscal therapy, minimally invasive treatment