Lumbar Facet Arthroplasty Versus Fusion for Grade-I Degenerative Spondylolisthesis with Stenosis: A Prospective Randomized Controlled Trial.

BACKGROUND: The comparative effectiveness of decompression plus lumbar facet arthroplasty versus decompression plus instrumented lumbar spinal fusion in patients with lumbar spinal stenosis and grade-I degenerative spondylolisthesis is unknown. METHODS: In this randomized, controlled, Food and Drug Administration Investigational Device Exemption trial, we assigned patients who had single-level lumbar spinal stenosis and grade-I degenerative spondylolisthesis to undergo decompression plus lumbar facet arthroplasty (arthroplasty group) or decompression plus fusion (fusion group). The primary outcome was a predetermined composite clinical success score. Secondary outcomes included the Oswestry Disability Index (ODI), visual analog scale (VAS) back and leg pain, Zurich Claudication Questionnaire (ZCQ), Short Form (SF)-12, radiographic parameters, surgical variables, and complications. RESULTS: A total of 321 adult patients were randomized in a 2:1 fashion, with 219 patients assigned to undergo facet arthroplasty and 102 patients assigned to undergo fusion. Of these, 113 patients (51.6%) in the arthroplasty group and 47 (46.1%) in the fusion group who had either reached 24 months of postoperative follow-up or were deemed early clinical failures were included in the primary outcome analysis. The arthroplasty group had a higher proportion of patients who achieved composite clinical success than did the fusion group (73.5% versus 25.5%; p < 0.001), equating to a between-group difference of 47.9% (95% confidence interval, 33.0% to 62.8%). The arthroplasty group outperformed the fusion group in most patient-reported outcome measures (including the ODI, VAS back pain, and all ZCQ component scores) at 24 months postoperatively. There were no significant differences between groups in surgical variables or complications, except that the fusion group had a higher rate of developing symptomatic adjacent segment degeneration. CONCLUSIONS: Among patients with lumbar spinal stenosis and grade-I degenerative spondylolisthesis, lumbar facet arthroplasty was associated with a higher rate of composite clinical success than fusion was at 24 months postoperatively. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Is Upper Extremity or Lower Extremity Function More Important for Patient Satisfaction? An Analysis of 24-Month Outcomes from the QOD Cervical Spondylotic Myelopathy Cohort.

STUDY DESIGN: Retrospective analysis of a prospective, multicenter registry. OBJECTIVE: To assess whether upper or lower limb mJOA improvement more strongly associates with patient satisfaction after surgery for cervical spondylotic myelopathy (CSM). SUMMARY OF BACKGROUND DATA: The modified Japanese Orthopaedic Association (mJOA) is commonly used to assess functional status in patients with CSM. Patients present with upper and/or lower extremity dysfunction, and it is unclear whether improvement in one and/or both symptoms drives postoperative patient satisfaction. METHODS: This study utilizes the prospective Quality Outcomes Database (QOD) CSM data set. Clinical outcomes included mJOA and North American Spine Society (NASS) satisfaction. The upper limb mJOA score was defined as upper motor plus sensory mJOA, and the lower limb mJOA as lower motor plus sensory mJOA. Ordered logistic regression was used to determine whether upper or lower limb mJOA was more closely associated with NASS satisfaction, adjusting for other covariates. RESULTS: Overall, 1141 patients were enrolled in the QOD CSM cohort. In all, 780 had both preoperative and 24-month mJOA scores, met inclusion criteria, and were included for analysis. The baseline mJOA was 12.1±2.7, and postoperatively, 85.6% would undergo surgery again (NASS 1 or 2, satisfied). Patients exhibited mean improvement in both upper (baseline:3.9±1.4 vs. 24 mo:5.0±1.1, P<0.001) and lower limb mJOA (baseline:3.9±1.4 vs. 24 mon:4.5±1.5, P<0.001); however, the 24-month change in the upper limb mJOA was greater (upper:1.1±1.6 vs. lower:0.6±1.6, P<0.001). Across 24-month NASS satisfaction, the baseline upper and lower limb mJOA scores were similar (pupper=0.28, plower=0.092). However, as satisfaction decreased, the 24-month change in upper and lower limb mJOA decreased as well (pupper<0.001, plower<0.001). Patients with NASS scores of 4 (lowest satisfaction) did not demonstrate significant differences from baseline in upper or lower limb mJOA (P>0.05). In ordered logistic regression, NASS satisfaction was independently associated with upper limb mJOA improvement (OR=0.81; 95% CI: 0.68-0.97; P=0.019) but not lower limb mJOA improvement (OR=0.84; 95% CI: 0.70-1.0; P=0.054). CONCLUSIONS: As the magnitude of upper and lower mJOA improvement decreased postoperatively, so too did patient satisfaction with surgical intervention. Upper limb mJOA improvement was a significant independent predictor of patient satisfaction, whereas lower limb mJOA improvement was not. These findings may aid preoperative counseling, stratified by patients' upper and lower extremity treatment expectations. LEVEL OF EVIDENCE: Level-III.

Evaluating potential developmental toxicity of perfluoroalkyl and polyfluoroalkyl substances in Xenopus laevis embryos and larvae.

As part of the US Environmental Protection Agency's perfluoroalkyl and polyfluoroalkyl substances (PFAS) Action Plan, the agency is committed to increasing our understanding of the potential ecological effects of PFAS. The objective of these studies was to examine the developmental toxicity of PFAS using the laboratory model amphibian species Xenopus laevis. We had two primary aims: (1) to understand the developmental toxicity of a structurally diverse set of PFAS compounds in developing embryos and (2) to characterize the potential impacts of perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), and hexafluoropropylene oxide-dimer acid (HFPO-DA a.k.a. GenX), on growth and thyroid hormone-controlled metamorphosis. We employed a combination of static renewal and flow-through exposure designs. Embryos were exposed to 17 structurally diverse PFAS starting at the midblastula stage through the completion of organogenesis (96 h). To investigate impacts on PFOS, PFOA, PFHxS, and HFPO-DA on development and metamorphosis, larvae were exposed from premetamorphosis (Nieuwkoop Faber stage 51 or 54) through pro metamorphosis. Of the PFAS tested in embryos, only 1H,1H,10H,10H-perfluorodecane-1,10-diol (FC10-diol) and perfluorohexanesulfonamide (FHxSA) exposure resulted in clear concentration-dependent developmental toxicity. For both of these PFAS, a significant increase in mortality was observed at 2.5 and 5 mg/L. For FC10-diol, 100% of the surviving embryos were malformed at 1.25 and 2.5 mg/L, while for FHxSA, a significant increase in malformations (100%) was observed at 2.5 and 5 mg/L. Developmental stage achieved was the most sensitive endpoint with significant effects observed at 1.25 and 0.625 mg/L for FC10-diol and FHxSA, respectively. In larval studies, we observed impacts on growth following exposure to PFHxS and PFOS at concentrations of 100 and 2.5 mg/L, respectively, while no impacts were observed in larvae when exposed to PFOA and HFPO-DA at concentration of 100 mg/L. Further, we did not observe impacts on thyroid endpoints in exposed larvae. These experiments have broadened our understanding of the impact of PFAS on anuran development.

What predicts the best 24-month outcomes following surgery for cervical spondylotic myelopathy? A QOD prospective registry study.

OBJECTIVE: The aim of this study was to identify predictors of the best 24-month improvements in patients undergoing surgery for cervical spondylotic myelopathy (CSM). For this purpose, the authors leveraged a large prospective cohort of surgically treated patients with CSM to identify factors predicting the best outcomes for disability, quality of life, and functional status following surgery. METHODS: This was a retrospective analysis of prospectively collected data. The Quality Outcomes Database (QOD) CSM dataset (1141 patients) at 14 top enrolling sites was used. Baseline and surgical characteristics were compared for those reporting the top and bottom 20th percentile 24-month Neck Disability Index (NDI), EuroQol-5D (EQ-5D), and modified Japanese Orthopaedic Association (mJOA) change scores. A multivariable logistic model was constructed and included candidate variables reaching p ≤ 0.20 on univariate analyses. Least important variables were removed in a stepwise manner to determine the significant predictors of the best outcomes (top 20th percentile) for 24-month NDI, EQ-5D, and mJOA change. RESULTS: A total of 948 (83.1%) patients with 24-month follow-up were included in this study. For NDI, 204 (17.9%) had the best NDI outcome and 200 (17.5%) had the worst NDI outcome. Factors predicting the best NDI outcomes included symptom duration less than 12 months (OR 1.5, 95% CI 1.1-1.9; p = 0.01); procedure other than posterior fusion (OR 1.5, 95% CI 1.03-2.1; p = 0.03); higher preoperative visual analog scale neck pain score (OR 1.2, 95% CI 1.1-1.3; p < 0.001); and higher baseline NDI (OR 1.06, 95% CI 1.05-1.07; p < 0.001). For EQ-5D, 163 (14.3%) had the best EQ-5D outcome and 169 (14.8%) had the worst EQ-5D outcome. Factors predicting the best EQ-5D outcomes included arm pain-only complaints (compared to neck pain) (OR 1.9, 95% CI 1.3-2.9; p = 0.002) and lower baseline EQ-5D (OR 167.7 per unit lower, 95% CI 85.0-339.4; p < 0.001). For mJOA, 222 (19.5%) had the best mJOA outcome and 238 (20.9%) had the worst mJOA outcome. Factors predicting the best mJOA outcomes included lower BMI (OR 1.03 per unit lower, 95% CI 1.004-1.05; p = 0.02; cutoff value of ≤ 29.5 kg/m2); arm pain-only complaints (compared to neck pain) (OR 1.7, 95% CI 1.1-2.5; p = 0.02); and lower baseline mJOA (OR 1.6 per unit lower, 95% CI 1.5-1.7; p < 0.001). CONCLUSIONS: Compared to the worst outcomes for EQ-5D, the best outcomes were associated with patients with arm pain-only complaints. For mJOA, lower BMI and arm pain-only complaints portended the best outcomes. For NDI, those with the best outcomes had shorter symptom durations, higher preoperative neck pain scores, and less often underwent posterior spinal fusions. Given the positive impact of shorter symptom duration on outcomes, these data suggest that early surgery may be beneficial for patients with CSM.

Does the number of social factors affect long-term patient-reported outcomes and satisfaction in those with cervical myelopathy? A QOD study.

OBJECTIVE: It is not clear whether there is an additive effect of social factors in keeping patients with cervical spondylotic myelopathy (CSM) from achieving both a minimum clinically important difference (MCID) in outcomes and satisfaction after surgery. The aim of this study was to explore the effect of multiple social factors on postoperative outcomes and satisfaction. METHODS: This was a multiinstitutional, retrospective study of the prospective Quality Outcomes Database (QOD) CSM cohort, which included patients aged 18 years or older who were diagnosed with primary CSM and underwent operative management. Social factors included race (White vs non-White), education (high school or below vs above), employment (employed vs not), and insurance (private vs nonprivate). Patients were considered to have improved from surgery if the following criteria were met: 1) they reported a score of 1 or 2 on the North American Spine Society index, and 2) they met the MCID in patient-reported outcomes (i.e., visual analog scale [VAS] neck and arm pain, Neck Disability Index [NDI], and EuroQol-5D [EQ-5D]). RESULTS: Of the 1141 patients included in the study, 205 (18.0%) had 0, 347 (30.4%) had 1, 334 (29.3%) had 2, and 255 (22.3%) had 3 social factors. The 24-month follow-up rate was > 80% for all patient-reported outcomes. After adjusting for all relevant covariates (p < 0.02), patients with 1 or more social factors were less likely to improve from surgery in all measured outcomes including VAS neck pain (OR 0.90, 95% CI 0.83-0.99) and arm pain (OR 0.88, 95% CI 0.80-0.96); NDI (OR 0.90, 95% CI 0.83-0.98); and EQ-5D (OR 0.90, 95% CI 0.83-0.97) (all p < 0.05) compared to those without any social factors. Patients with 2 social factors (outcomes: neck pain OR 0.86, arm pain OR 0.81, NDI OR 0.84, EQ-5D OR 0.81; all p < 0.05) or 3 social factors (outcomes: neck pain OR 0.84, arm pain OR 0.84, NDI OR 0.84, EQ-5D OR 0.84; all p < 0.05) were more likely to fare worse in all outcomes compared to those with only 1 social factor. CONCLUSIONS: Compared to those without any social factors, patients who had at least 1 social factor were less likely to achieve MCID and feel satisfied after surgery. The effect of social factors is additive in that patients with a higher number of factors are less likely to improve compared to those with only 1 social factor.

What factors influence surgical decision-making in anterior versus posterior surgery for cervical myelopathy? A QOD analysis.

OBJECTIVE: The aim of this study was to explore the preoperative patient characteristics that affect surgical decision-making when selecting an anterior or posterior operative approach in patients diagnosed with cervical spondylotic myelopathy (CSM). METHODS: This was a multi-institutional, retrospective study of the prospective Quality Outcomes Database (QOD) Cervical Spondylotic Myelopathy module. Patients aged 18 years or older diagnosed with primary CSM who underwent multilevel (≥ 2-level) elective surgery were included. Demographics and baseline clinical characteristics were collected. RESULTS: Of the 841 patients with CSM in the database, 492 (58.5%) underwent multilevel anterior surgery and 349 (41.5%) underwent multilevel posterior surgery. Surgeons more often performed a posterior surgical approach in older patients (mean 64.8 ± 10.6 vs 58.5 ± 11.1 years, p < 0.001) and those with a higher American Society of Anesthesiologists class (class III or IV: 52.4% vs 46.3%, p = 0.003), a higher rate of motor deficit (67.0% vs 58.7%, p = 0.014), worse myelopathy (mean modified Japanese Orthopaedic Association score 11.4 ± 3.1 vs 12.4 ± 2.6, p < 0.001), and more levels treated (4.3 ± 1.3 vs 2.4 ± 0.6, p < 0.001). On the other hand, surgeons more frequently performed an anterior surgical approach when patients were employed (47.2% vs 23.2%, p < 0.001) and had intervertebral disc herniation as an underlying pathology (30.7% vs 9.2%, p < 0.001). CONCLUSIONS: The selection of approach for patients with CSM depends on patient demographics and symptomology. Posterior surgery was performed in patients who were older and had worse systemic disease, increased myelopathy, and greater levels of stenosis. Anterior surgery was more often performed in patients who were employed and had intervertebral disc herniation.

Greater improvement in Neck Disability Index scores in women after surgery for cervical myelopathy: an analysis of the Quality Outcomes Database.

OBJECTIVE: There is a high prevalence of cervical myelopathy that requires surgery; as such, it is important to identify how different groups benefit from surgery. The American Association of Neurological Surgeons launched the Quality Outcomes Database (QOD), a prospective longitudinal registry, that includes demographic, clinical, and patient-reported outcome data to measure the safety and quality of neurosurgical procedures. In this study, the authors assessed the impact of gender on patient-reported outcomes in patients who underwent surgery for cervical myelopathy. METHODS: The authors analyzed 1152 patients who underwent surgery for cervical myelopathy and were included in the QOD cervical module. Univariate comparison of baseline patient characteristics between males and females who underwent surgery for cervical spondylotic myelopathy was performed. Baseline characteristics that significantly differed between males and females were included in a multivariate generalized linear model comparing baseline and 1-year postoperative Neck Disability Index (NDI) scores. RESULTS: This study included 546 females and 604 males. Females demonstrated significantly greater improvement in NDI score 1 year after surgery (p = 0.036). In addition to gender, the presence of axial neck pain and insurance status were also significantly predictive of improvement in NDI score after surgery (p = 0.0013 and p = 0.0058, respectively). CONCLUSIONS: Females were more likely to benefit from surgery for cervical myelopathy compared with males. It is important to identify gender differences in postoperative outcomes after surgery in order to deliver more personalized and patient-centric care.

Three-level ACDF versus 3-level laminectomy and fusion: are there differences in outcomes? An analysis of the Quality Outcomes Database cervical spondylotic myelopathy cohort.

OBJECTIVE: The authors sought to compare 3-level anterior with posterior fusion surgical procedures for the treatment of multilevel cervical spondylotic myelopathy (CSM). METHODS: The authors analyzed prospective data from the 14 highest enrolling sites of the Quality Outcomes Database CSM module. They compared 3-level anterior cervical discectomy and fusion (ACDF) and posterior cervical laminectomy and fusion (PCF) surgical procedures, excluding surgical procedures crossing the cervicothoracic junction. Rates of reaching the minimal clinically important difference (MCID) in patient-reported outcomes (PROs) were compared at 24 months postoperatively. Multivariable analyses adjusted for potential confounders elucidated in univariable analysis. RESULTS: Overall, 199 patients met the inclusion criteria: 123 ACDF (61.8%) and 76 PCF (38.2%) patients. The 24-month follow-up rates were similar (ACDF 90.2% vs PCF 92.1%, p = 0.67). Preoperatively, ACDF patients were younger (60.8 ± 10.2 vs 65.0 ± 10.3 years, p < 0.01), and greater proportions were privately insured (56.1% vs 36.8%, p = 0.02), actively employed (39.8% vs 22.8%, p = 0.04), and independently ambulatory (14.6% vs 31.6%, p < 0.01). Otherwise, the cohorts had equivalent baseline modified Japanese Orthopaedic Association (mJOA), Neck Disability Index (NDI), numeric rating scale (NRS)-arm pain, NRS-neck pain, and EQ-5D scores (p > 0.05). ACDF patients had reduced hospitalization length (1.6 vs 3.9 days, p < 0.01) and a greater proportion had nonroutine discharge (7.3% vs 22.8%, p < 0.01), but they had a higher rate of postoperative dysphagia (13.5% vs 3.5%, p = 0.049). Compared with baseline values, both groups demonstrated improvements in all outcomes at 24 months (p < 0.05). In multivariable analyses, after controlling for age, insurance payor, employment status, ambulation status, and other potential clinically relevant confounders, ACDF was associated with a greater proportion of patients with maximum satisfaction on the North American Spine Society Patient Satisfaction Index (NASS) (NASS score of 1) at 24 months (69.4% vs 53.7%, OR 2.44, 95% CI 1.17-5.09, adjusted p = 0.02). Otherwise, the cohorts shared similar 24-month outcomes in terms of reaching the MCID for mJOA, NDI, NRS-arm pain, NRS-neck pain, and EQ-5D score (adjusted p > 0.05). There were no differences in the 3-month readmission (ACDF 4.1% vs PCF 3.9%, p = 0.97) and 24-month reoperation (ACDF 13.5% vs PCF 18.6%, p = 0.36) rates. CONCLUSIONS: In a cohort limited to 3-level fusion surgical procedures, ACDF was associated with reduced blood loss, shorter hospitalization length, and higher routine home discharge rates; however, PCF resulted in lower rates of postoperative dysphagia. The procedures yielded comparably significant improvements in functional status (mJOA score), neck and arm pain, neck pain-related disability, and quality of life at 3, 12, and 24 months. ACDF patients had significantly higher odds of maximum satisfaction (NASS score 1). Given comparable outcomes, patients should be counseled on each approach's complication profile to aid in surgical decision-making.

Cervical laminoplasty versus laminectomy and posterior cervical fusion for cervical myelopathy: propensity-matched analysis of 24-month outcomes from the Quality Outcomes Database.

OBJECTIVE: Compared with laminectomy with posterior cervical fusion (PCF), cervical laminoplasty (CL) may result in different outcomes for those operated on for cervical spondylotic myelopathy (CSM). The aim of this study was to compare 24-month patient-reported outcomes (PROs) for laminoplasty versus PCF by using the Quality Outcomes Database (QOD) CSM data set. METHODS: This was a retrospective study using an augmented data set from the prospectively collected QOD Registry Cervical Module. Patients undergoing laminoplasty or PCF for CSM were included. Using the nearest-neighbor method, the authors performed 1:1 propensity matching based on age, operated levels, and baseline modified Japanese Orthopaedic Association (mJOA) and visual analog scale (VAS) neck pain scores. The 24-month PROs, i.e., mJOA, Neck Disability Index (NDI), VAS neck pain, VAS arm pain, EQ-5D, EQ-VAS, and North American Spine Society (NASS) satisfaction scores, were compared. Only cases in the subaxial cervical region were included; those that crossed the cervicothoracic junction were excluded. RESULTS: From the 1141 patients included in the QOD CSM data set who underwent anterior or posterior surgery for cervical myelopathy, 946 (82.9%) had 24 months of follow-up. Of these, 43 patients who underwent laminoplasty and 191 who underwent PCF met the inclusion criteria. After matching, the groups were similar for baseline characteristics, including operative levels (CL group: 4.0 ± 0.9 vs PCF group: 4.2 ± 1.1, p = 0.337) and baseline PROs (p > 0.05), except for a higher percentage involved in activities outside the home in the CL group (95.3% vs 81.4%, p = 0.044). The 24-month follow-up for the matched cohorts was similar (CL group: 88.4% vs PCF group: 83.7%, p = 0.534). Patients undergoing laminoplasty had significantly lower estimated blood loss (99.3 ± 91.7 mL vs 186.7 ± 142.7 mL, p = 0.003), decreased length of stay (3.0 ± 1.6 days vs 4.5 ± 3.3 days, p = 0.012), and a higher rate of routine discharge (88.4% vs 62.8%, p = 0.006). The CL cohort also demonstrated a higher rate of return to activities (47.2% vs 21.2%, p = 0.023) after 3 months. Laminoplasty was associated with a larger improvement in 24-month NDI score (-19.6 ± 18.9 vs -9.1 ± 21.9, p = 0.031). Otherwise, there were no 3- or 24-month differences in mJOA, mean NDI, VAS neck pain, VAS arm pain, EQ-5D, EQ-VAS, and distribution of NASS satisfaction scores (p > 0.05) between the cohorts. CONCLUSIONS: Compared with PCF, laminoplasty was associated with decreased blood loss, decreased length of hospitalization, and higher rates of home discharge. At 3 months, laminoplasty was associated with a higher rate of return to baseline activities. At 24 months, laminoplasty was associated with greater improvements in neck disability. Otherwise, laminoplasty and PCF shared similar outcomes for functional status, pain, quality of life, and satisfaction. Laminoplasty and PCF achieved similar neck pain scores, suggesting that moderate preoperative neck pain may not necessarily be a contraindication for laminoplasty.

Ventricular Parasystole in Cardiomyopathy Patients: A Link Between His-Purkinje System Damage and Ventricular Fibrillation.

BACKGROUND: The clinical relevance and prognostic implications of ventricular parasystole are unknown. OBJECTIVES: This study sought to assess the prevalence of ventricular parasystole in patients with implantable cardioverter-defibrillators (ICDs) and ventricular parasystole's association with ventricular arrhythmias and conduction system abnormalities. METHODS: This study retrospectively evaluated patients who underwent ICD interrogation at a single center between June 1, 2019, and August 31, 2020, and reviewed all available ICD and electrocardiogram data. This study identified patients with ventricular parasystole and compared the prevalence of ventricular fibrillation (VF), ventricular tachycardia (VT), and new conduction system abnormalities in those with ≥5 years of intrinsic QRS-complex electrocardiograms to those without parasystole. RESULTS: This study included 374 patients (age 57 ± 21 years, 72% male, 45% nonischemic, 32% ischemic cardiomyopathy), of which, 104 (28%) had VT only, 39 (10%) VF only, and 10 (3%) both VT/VF. Ventricular parasystole was identified in 33 patients (9%); parasystolic foci were predominantly from the His-Purkinje system. Compared with those without parasystole, patients with parasystole had a significantly higher rate of VF (36% vs 11%; P < 0.01), but not VT (42% vs 29%; P = 0.12). Patients with parasystole, compared with those without parasystole, had a higher prevalence of new conduction abnormalities, particularly progressive intraventricular conduction delay (11 of 18 [61%] vs 12 of 83 [14%]; P < 0.01) and new right bundle branch block (4 of 18 [22%] vs 1 of 83 [1%]; P < 0.01). CONCLUSIONS: Ventricular parasystole was strongly associated with new conduction system abnormalities and VF in patients who have cardiomyopathy with ICDs, suggesting a potential link between VF and His-Purkinje damage in this patient population.

Which supervised machine learning algorithm can best predict achievement of minimum clinically important difference in neck pain after surgery in patients with cervical myelopathy? A QOD study.

OBJECTIVE: The purpose of this study was to evaluate the performance of different supervised machine learning algorithms to predict achievement of minimum clinically important difference (MCID) in neck pain after surgery in patients with cervical spondylotic myelopathy (CSM). METHODS: This was a retrospective analysis of the prospective Quality Outcomes Database CSM cohort. The data set was divided into an 80% training and a 20% test set. Various supervised learning algorithms (including logistic regression, support vector machine, decision tree, random forest, extra trees, gaussian naïve Bayes, k-nearest neighbors, multilayer perceptron, and extreme gradient boosted trees) were evaluated on their performance to predict achievement of MCID in neck pain at 3 and 24 months after surgery, given a set of predicting baseline features. Model performance was assessed with accuracy, F1 score, area under the receiver operating characteristic curve, precision, recall/sensitivity, and specificity. RESULTS: In total, 535 patients (46.9%) achieved MCID for neck pain at 3 months and 569 patients (49.9%) achieved it at 24 months. In each follow-up cohort, 501 patients (93.6%) were satisfied at 3 months after surgery and 569 patients (100%) were satisfied at 24 months after surgery. Of the supervised machine learning algorithms tested, logistic regression demonstrated the best accuracy (3 months: 0.76 ± 0.031, 24 months: 0.773 ± 0.044), followed by F1 score (3 months: 0.759 ± 0.019, 24 months: 0.777 ± 0.039) and area under the receiver operating characteristic curve (3 months: 0.762 ± 0.027, 24 months: 0.773 ± 0.043) at predicting achievement of MCID for neck pain at both follow-up time points, with fair performance. The best precision was also demonstrated by logistic regression at 3 (0.724 ± 0.058) and 24 (0.780 ± 0.097) months. The best recall/sensitivity was demonstrated by multilayer perceptron at 3 months (0.841 ± 0.094) and by extra trees at 24 months (0.817 ± 0.115). Highest specificity was shown by support vector machine at 3 months (0.952 ± 0.013) and by logistic regression at 24 months (0.747 ± 0.18). CONCLUSIONS: Appropriate selection of models for studies should be based on the strengths of each model and the aims of the studies. For maximally predicting true achievement of MCID in neck pain, of all the predictions in this balanced data set the appropriate metric for the authors' study was precision. For both short- and long-term follow-ups, logistic regression demonstrated the highest precision of all models tested. Logistic regression performed consistently the best of all models tested and remains a powerful model for clinical classification tasks.

Do comorbid self-reported depression and anxiety influence outcomes following surgery for cervical spondylotic myelopathy?

OBJECTIVE: Depression and anxiety are associated with inferior outcomes following spine surgery. In this study, the authors examined whether patients with cervical spondylotic myelopathy (CSM) who have both self-reported depression (SRD) and self-reported anxiety (SRA) have worse postoperative patient-reported outcomes (PROs) compared with patients who have only one or none of these comorbidities. METHODS: This study is a retrospective analysis of prospectively collected data from the Quality Outcomes Database CSM cohort. Comparisons were made among patients who reported the following: 1) either SRD or SRA, 2) both SRD and SRA, or 3) neither comorbidity at baseline. PROs at 3, 12, and 24 months (scores for the visual analog scale [VAS] for neck pain and arm pain, Neck Disability Index [NDI], modified Japanese Orthopaedic Association [mJOA] scale, EQ-5D, EuroQol VAS [EQ-VAS], and North American Spine Society [NASS] patient satisfaction index) and achievement of respective PRO minimal clinically important differences (MCIDs) were compared. RESULTS: Of the 1141 included patients, 199 (17.4%) had either SRD or SRA alone, 132 (11.6%) had both SRD and SRA, and 810 (71.0%) had neither. Preoperatively, patients with either SRD or SRA alone had worse scores for VAS neck pain (5.6 ± 3.1 vs 5.1 ± 3.3, p = 0.03), NDI (41.0 ± 19.3 vs 36.8 ± 20.8, p = 0.007), EQ-VAS (57.0 ± 21.0 vs 60.7 ± 21.7, p = 0.03), and EQ-5D (0.53 ± 0.23 vs 0.58 ± 0.21, p = 0.008) than patients without such disorders. Postoperatively, in multivariable adjusted analyses, baseline SRD or SRA alone was associated with inferior improvement in the VAS neck pain score and a lower rate of achieving the MCID for VAS neck pain score at 3 and 12 months, but not at 24 months. At 24 months, patients with SRD or SRA alone experienced less change in EQ-5D scores and were less likely to meet the MCID for EQ-5D than patients without SRD or SRA. Furthermore, patient self-reporting of both psychological comorbidities did not impact PROs at all measured time points compared with self-reporting of only one psychological comorbidity alone. Each cohort (SRD or SRA alone, both SRD and SRA, and neither SRD nor SRA) experienced significant improvements in mean PROs at all measured time points compared with baseline (p < 0.05). CONCLUSIONS: Approximately 12% of patients who underwent surgery for CSM presented with both SRD and SRA, and 29% presented with at least one symptom. The presence of either SRD or SRA was independently associated with inferior scores for 3- and 12-month neck pain following surgery, but this difference was not significant at 24 months. However, at long-term follow-up, patients with SRD or SRA experienced lower quality of life than patients without SRD or SRA. The comorbid presence of both depression and anxiety was not associated with worse patient outcomes than either diagnosis alone.

Sleep Disturbances in Cervical Spondylotic Myelopathy: Prevalence and Postoperative Outcomes-an Analysis From the Quality Outcomes Database.

STUDY DESIGN: Prospective observational study, level of evidence 1 for prognostic investigations. OBJECTIVES: To evaluate the prevalence of sleep impairment and predictors of improved sleep quality 24 months postoperatively in cervical spondylotic myelopathy (CSM) using the quality outcomes database. SUMMARY OF BACKGROUND DATA: Sleep disturbances are a common yet understudied symptom in CSM. MATERIALS AND METHODS: The quality outcomes database was queried for patients with CSM, and sleep quality was assessed through the neck disability index sleep component at baseline and 24 months postoperatively. Multivariable logistic regressions were performed to identify risk factors of failure to improve sleep impairment and symptoms causing lingering sleep dysfunction 24 months after surgery. RESULTS: Among 1135 patients with CSM, 904 (79.5%) had some degree of sleep dysfunction at baseline. At 24 months postoperatively, 72.8% of the patients with baseline sleep symptoms experienced improvement, with 42.5% reporting complete resolution. Patients who did not improve were more like to be smokers [adjusted odds ratio (aOR): 1.85], have osteoarthritis (aOR: 1.72), report baseline radicular paresthesia (aOR: 1.51), and have neck pain of ≥4/10 on a numeric rating scale. Patients with improved sleep noted higher satisfaction with surgery (88.8% vs 72.9%, aOR: 1.66) independent of improvement in other functional areas. In a multivariable analysis including pain scores and several myelopathy-related symptoms, lingering sleep dysfunction at 24 months was associated with neck pain (aOR: 1.47) and upper (aOR: 1.45) and lower (aOR: 1.52) extremity paresthesias. CONCLUSION: The majority of patients presenting with CSM have associated sleep disturbances. Most patients experience sustained improvement after surgery, with almost half reporting complete resolution. Smoking, osteoarthritis, radicular paresthesia, and neck pain ≥4/10 numeric rating scale score are baseline risk factors of failure to improve sleep dysfunction. Improvement in sleep symptoms is a major driver of patient-reported satisfaction. Incomplete resolution of sleep impairment is likely due to neck pain and extremity paresthesia.

How closely are outcome questionnaires correlated to patient satisfaction after cervical spine surgery for myelopathy?

OBJECTIVE: Patient-reported outcomes (PROs) have become the standard means to measure surgical outcomes. Insurers and policy makers are also increasingly utilizing PROs to assess the value of care and measure different aspects of a patient's condition. For cervical myelopathy, it is currently unclear which outcome measure best reflects patient satisfaction. In this investigation, the authors evaluated patients treated for cervical myelopathy to determine which outcome questionnaires best correlate with patient satisfaction. METHODS: The Quality Outcomes Database (QOD), a prospectively collected multi-institutional database, was used to retrospectively analyze patients undergoing surgery for cervical myelopathy. The North American Spine Society (NASS) satisfaction index, Neck Disability Index (NDI), numeric rating scales for neck pain (NP-NRS) and arm pain (AP-NRS), EQ-5D, and modified Japanese Orthopaedic Association (mJOA) scale were evaluated. RESULTS: The analysis included 1141 patients diagnosed with myelopathy, of whom 1099 had an NASS satisfaction index recorded at any of the follow-up time points. Concomitant radiculopathy was an indication for surgery in 368 (33.5%) patients, and severe neck pain (NP-NRS ≥ 7) was present in 471 (42.8%) patients. At the 3-month follow-up, NASS patient satisfaction index scores were positively correlated with scores for the NP-NRS (r = 0.30), AP-NRS (r = 0.32), and NDI (r = 0.36) and negatively correlated with EQ-5D (r = -0.38) and mJOA (r = -0.29) scores (all p < 0.001). At the 12-month follow-up, scores for the NASS index were positively correlated with scores for the NP-NRS (r = 0.44), AP-NRS (r = 0.38), and NDI (r = 0.46) and negatively correlated with scores for the EQ-5D (r = -0.40) and mJOA (r = -0.36) (all p < 0.001). At the 24-month follow-up, NASS index scores were positively correlated with NP-NRS (r = 0.49), AP-NRS (r = 0.36), and NDI (r = 0.49) scores and negatively correlated with EQ-5D (r = -0.44) and mJOA (r = -0.38) scores (all p < 0.001). CONCLUSIONS: Neck pain was highly prevalent in patients with myelopathy. Notably, improvement in neck pain-associated disability rather than improvement in myelopathy was the most prominent PRO factor for patients. This finding may reflect greater patient concern for active pain symptoms than for neurological symptoms caused by myelopathy. As commercial payers begin to examine novel remuneration strategies for surgical interventions, thoughtful analysis of PRO measurements will have increasing relevance.

A Prospective Study of Lumbar Facet Arthroplasty in the Treatment of Degenerative Spondylolisthesis and Stenosis: Results from the Total Posterior Spine System (TOPS) IDE Study.

STUDY DESIGN: Prospective randomized Food and Drug Administration investigational device exemption clinical trial. OBJECTIVE: The purpose of the present study is to report the 1-year clinical and radiographic outcomes and safety profile of patients who underwent lumbar facet arthroplasty through implantation of the Total Posterior Spine System (TOPS) device. SUMMARY OF BACKGROUND DATA: Lumbar facet arthroplasty is one proposed method of dynamic stabilization to treat grade-1 spondylolisthesis with stenosis; however, there are currently no Food and Drug Administration-approved devices for facet arthroplasty. METHODS: Standard demographic information was collected for each patient. Radiographic parameters and patient-reported outcome measures were assessed preoperatively and at regular postoperative intervals. Complication and reoperation data were also collected for each patient. RESULTS: At the time of this study, 153 patients had undergone implantation of the TOPS device. The mean surgical time was 187.8 minutes and the mean estimated blood loss was 205.7cc. The mean length of hospital stay was 3.0 days. Mean Oswestry Disability Index, Visual Analog Score leg and back, and Zurich Claudication Questionnaire scores improved significantly at all postoperative time points ( P >0.001). There were no clinically significant changes in radiographic parameters, and all operative segments remained mobile at 1-year follow-up. Postoperative complications occurred in 11 patients out of the 153 patients (7.2%) who underwent implantation of the TOPS device. Nine patients (5.9%) underwent a total of 13 reoperations, 1 (0.6%) of which was for device-related failure owing to bilateral L5 pedicle screw loosening. CONCLUSIONS: Lumbar facet arthroplasty with the TOPS device demonstrated a statistically significant improvement in all patient-reported outcome measures and the ability to maintain motion at the index level while limiting sagittal translation with a low complication rate.

Cervical spondylotic myelopathy with severe axial neck pain: is anterior or posterior approach better?

OBJECTIVE: The aim of this study was to determine whether multilevel anterior cervical discectomy and fusion (ACDF) or posterior cervical laminectomy and fusion (PCLF) is superior for patients with cervical spondylotic myelopathy (CSM) and high preoperative neck pain. METHODS: This was a retrospective study of prospectively collected data using the Quality Outcomes Database (QOD) CSM module. Patients who received a subaxial fusion of 3 or 4 segments and had a visual analog scale (VAS) neck pain score of 7 or greater at baseline were included. The 3-, 12-, and 24-month outcomes were compared for patients undergoing ACDF with those undergoing PCLF. RESULTS: Overall, 1141 patients with CSM were included in the database. Of these, 495 (43.4%) presented with severe neck pain (VAS score > 6). After applying inclusion and exclusion criteria, we compared 65 patients (54.6%) undergoing 3- and 4-level ACDF and 54 patients (45.4%) undergoing 3- and 4-level PCLF. Patients undergoing ACDF had worse Neck Disability Index scores at baseline (52.5 ± 15.9 vs 45.9 ± 16.8, p = 0.03) but similar neck pain (p > 0.05). Otherwise, the groups were well matched for the remaining baseline patient-reported outcomes. The rates of 24-month follow-up for ACDF and PCLF were similar (86.2% and 83.3%, respectively). At the 24-month follow-up, both groups demonstrated mean improvements in all outcomes, including neck pain (p < 0.05). In multivariable analyses, there was no significant difference in the degree of neck pain change, rate of neck pain improvement, rate of pain-free achievement, and rate of reaching minimal clinically important difference (MCID) in neck pain between the two groups (adjusted p > 0.05). However, ACDF was associated with a higher 24-month modified Japanese Orthopaedic Association scale (mJOA) score (ß = 1.5 [95% CI 0.5-2.6], adjusted p = 0.01), higher EQ-5D score (ß = 0.1 [95% CI 0.01-0.2], adjusted p = 0.04), and higher likelihood for return to baseline activities (OR 1.2 [95% CI 1.1-1.4], adjusted p = 0.002). CONCLUSIONS: Severe neck pain is prevalent among patients undergoing surgery for CSM, affecting more than 40% of patients. Both ACDF and PCLF achieved comparable postoperative neck pain improvement 3, 12, and 24 months following 3- or 4-segment surgery for patients with CSM and severe neck pain. However, multilevel ACDF was associated with superior functional status, quality of life, and return to baseline activities at 24 months in multivariable adjusted analyses.

Prospective, randomized controlled multicenter study of posterior lumbar facet arthroplasty for the treatment of spondylolisthesis.

OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of a posterior facet replacement device, the Total Posterior Spine (TOPS) System, for the treatment of one-level symptomatic lumbar stenosis with grade I degenerative spondylolisthesis. Posterior lumbar arthroplasty with facet replacement is a motion-preserving alternative to lumbar decompression and fusion. The authors report the preliminary results from the TOPS FDA investigational device exemption (IDE) trial. METHODS: The study was a prospective, randomized controlled FDA IDE trial comparing the investigational TOPS device with transforaminal lumbar interbody fusion (TLIF) and pedicle screw fixation. The minimum follow-up duration was 24 months. Validated patient-reported outcome measures included the Oswestry Disability Index (ODI) and visual analog scale (VAS) for back and leg pain. The primary outcome was a composite measure of clinical success: 1) no reoperations, 2) no device breakage, 3) ODI reduction of ≥ 15 points, and 4) no new or worsening neurological deficit. Patients were considered a clinical success only if they met all four measures. Radiographic assessments were made by an independent core laboratory. RESULTS: A total of 249 patients were evaluated (n = 170 in the TOPS group and n = 79 in the TLIF group). There were no statistically significant differences between implanted levels (L4-5: TOPS, 95% and TLIF, 95%) or blood loss. The overall composite measure for clinical success was statistically significantly higher in the TOPS group (85%) compared with the TLIF group (64%) (p = 0.0138). The percentage of patients reporting a minimum 15-point improvement in ODI showed a statistically significant difference (p = 0.037) favoring TOPS (93%) over TLIF (81%). There was no statistically significant difference between groups in the percentage of patients reporting a minimum 20-point improvement on VAS back pain (TOPS, 87%; TLIF, 64%) and leg pain (TOPS, 90%; TLIF, 88%) scores. The rate of surgical reintervention for facet replacement in the TOPS group (5.9%) was lower than the TLIF group (8.8%). The TOPS cohort demonstrated maintenance of flexion/extension range of motion from preoperatively (3.85°) to 24 months (3.86°). CONCLUSIONS: This study demonstrates that posterior lumbar decompression and dynamic stabilization with the TOPS device is safe and efficacious in the treatment of lumbar stenosis with degenerative spondylolisthesis. Additionally, decompression and dynamic stabilization with the TOPS device maintains segmental motion.

Scalable Generation of Multiphoton Entangled States by Active Feed-Forward and Multiplexing.

Multiphoton entangled quantum states are key to advancing quantum technologies such as multiparty quantum communications, quantum sensing, or quantum computation. Their scalable generation, however, remains an experimental challenge. Current methods for generating these states rely on stitching together photons from probabilistic sources, and state generation rates drop exponentially in the number of photons. Here, we implement a system based on active feed-forward and multiplexing that addresses this challenge. We demonstrate the scalable generation of four-photon and six-photon Greenberger-Horne-Zeilinger states, increasing generation rates by factors of 9 and 35, respectively. This is consistent with the exponential enhancement compared to the standard nonmultiplexed approach that is predicted by our theory. These results facilitate the realization of practical multiphoton protocols for photonic quantum technologies.

A split ß-lactamase sensor for the detection of DNA modification by cisplatin and ruthenium-based chemotherapeutic drugs.

Here we present a split-enzyme sensor approach for the sequence-specific detection of metal-based drug adducts of DNA. Split ß-lactamase reporters were constructed using domain A of the High Mobility Group Box 1 protein (HMGB1a) in conjunction with zinc finger DNA-binding domains. As a proof of concept, the sensors were characterized with the well-known drug cisplatin, which forms 1,2-intrastrand crosslinks with DNA that are recognized by HMGB1a. After promising results with cisplatin, five ruthenium-based drugs were studied, four of which produced significant signal over background. These results highlight the utility of our approach for rapid screening of novel metal-based chemotherapeutic drug candidates and provide evidence that HMGB1a likely binds to DNA adducts formed by NAMI-A (imidazolium trans-tetrachlorodimethylsulfoxideimidazoleruthenate(III)), KP1019 (indazolium trans-tetrachlorodiindazoleruthenate(III)), KP418 (imidazolium trans-tetrachlorodiimidazoleruthenate(III)), and RAPTA-C (dichloro(η6-p-cymene)(1,3,5-triaza-7-phosphaadamantane)ruthenium(II)). These results thus imply a potential biologically relevant mode of action for the ruthenium-based drugs investigated herein.

Correlation of the Modified Japanese Orthopedic Association With Functional and Quality-of-Life Outcomes After Surgery for Degenerative Cervical Myelopathy: A Quality Outcomes Database Study.

BACKGROUND: The modified Japanese Orthopedic Association (mJOA) score is a widely used and validated metric for assessing severity of myelopathy. Its relationship to functional and quality-of-life outcomes after surgery has not been fully described. OBJECTIVE: To quantify the association of the mJOA with the Neck Disability Index (NDI) and EuroQol-5 Dimension (EQ-5D) after surgery for degenerative cervical myelopathy. METHODS: The cervical module of the prospectively enrolled Quality Outcomes Database was queried retrospectively for adult patients who underwent single-stage degenerative cervical myelopathy surgery. The mJOA score, NDI, and EQ-5D were assessed preoperatively and 3 and 12 months postoperatively. Improvement in mJOA was used as the independent variable in univariate and multivariable linear and logistic regression models. RESULTS: Across 14 centers, 1121 patients were identified, mean age 60.6 ± 11.8 years, and 52.5% male. Anterior-only operations were performed in 772 patients (68.9%). By univariate linear regression, improvements in mJOA were associated with improvements in NDI and EQ-5D at 3 and 12 months postoperatively (all P < .0001) and with improvements in the 10 NDI items individually. These findings were similar in multivariable regression incorporating potential confounders. The Pearson correlation coefficients for changes in mJOA with changes in NDI were -0.31 and -0.38 at 3 and 12 months postoperatively. The Pearson correlation coefficients for changes in mJOA with changes in EQ-5D were 0.29 and 0.34 at 3 and 12 months. CONCLUSION: Improvements in mJOA correlated weakly with improvements in NDI and EQ-5D, suggesting that changes in mJOA may not be a suitable proxy for functional and quality-of-life outcomes.