Discovery of circulating blood biomarkers in patients with and without Modic changes of the lumbar spine: a preliminary analysis.

PURPOSE: The following study aimed to determine the existence of blood biomarkers in symptomatic patients with or without lumbar Modic changes (MC). METHODS: A cross-sectional sub-analyses of a prospective cohort was performed. Fasting blood samples were collected from patients with and without lumbar MC who had undergone spinal fusion or microdiscectomy. An 80-plex panel and CCL5/RANTES were used to assess preoperative plasma cytokine concentrations. Patient demographics and imaging phenotypes were also assessed. RESULTS: Thirty-one subjects were analysed (n = 18 no MC; n = 13 MC). No significant differences were found in age, sex, body mass index, smoking and alcohol history, and surgical procedure (i.e. fusion, decompression) between the two groups (p > 0.05). Several statistically significant blood biomarkers in MC patients were identified, including elevated levels of C-C Motif Chemokine Ligand 5 (CCL5, p = 0.0006), while Macrophage Migration Inhibitory Factor (MIF) was significantly lower (p = 0.009). Additionally, C-X-C Motif Chemokine Ligand 5 (CXCL5, p = 0.052), Pentraxin 3 (PTX3, p = 0.06) and Galectin-3 (Gal-3, p = 0.07) showed potential relevance. Moreover, MC patients exhibited significantly higher levels of disc degeneration (p = 0.0001) and displacement severity (p = 0.020). Based on multivariate analyses and controlling for disc degeneration/displacement, CCL5 (OR 1.02; 95% CI 1.002-1.033; p = 0.028) and MIF (OR 0.60; 95% CI 0.382-0.951; p = 0.030) were independently associated with MC patients. CONCLUSION: This "proof-of-concept" study is the first to identify specific and significantly circulating blood biomarkers associated with symptomatic patients with lumbar MC, independent of disc alterations of degeneration and/or bulges/herniations. Specifically, differences in CCL5 and MIF protein levels were significantly noted in MC patients compared to those without MC.

A flow cytometry-based neutralization assay for simultaneous evaluation of blocking antibodies against SARS-CoV-2 variants.

Vaccines against SARS-CoV-2 have alleviated infection rates, hospitalization and deaths associated with COVID-19. In order to monitor humoral immunity, several serology tests have been developed, but the recent emergence of variants of concern has revealed the need for assays that predict the neutralizing capacity of antibodies in a fast and adaptable manner. Sensitive and fast neutralization assays would allow a timely evaluation of immunity against emerging variants and support drug and vaccine discovery efforts. Here we describe a simple, fast, and cell-free multiplexed flow cytometry assay to interrogate the ability of antibodies to prevent the interaction of Angiotensin-converting enzyme 2 (ACE2) and the receptor binding domain (RBD) of the original Wuhan-1 SARS-CoV-2 strain and emerging variants simultaneously, as a surrogate neutralization assay. Using this method, we demonstrate that serum antibodies collected from representative individuals at different time-points during the pandemic present variable neutralizing activity against emerging variants, such as Omicron BA.1 and South African B.1.351. Importantly, antibodies present in samples collected during 2021, before the third dose of the vaccine was administered, do not confer complete neutralization against Omicron BA.1, as opposed to samples collected in 2022 which show significant neutralizing activity. The proposed approach has a comparable performance to other established surrogate methods such as cell-based assays using pseudotyped lentiviral particles expressing the spike of SARS-CoV-2, as demonstrated by the assessment of the blocking activity of therapeutic antibodies (i.e. Imdevimab) and serum samples. This method offers a scalable, cost effective and adaptable platform for the dynamic evaluation of antibody protection in affected populations against variants of SARS-CoV-2.

Pediatric Back Pain: A Scoring System to Guide Use of Magnetic Resonance Imaging.

BACKGROUND: The prevalence of back pain in the pediatric population is increasing, and the workup of these patients presents a clinical challenge. Many cases are selflimited, but failure to diagnose a pathology that requires clinical intervention can carry severe repercussions. Magnetic resonance imaging (MRI) carries a high cost to the patient and health care system, and may even require procedural sedation in the pediatric population. The aim of this study was to develop a scoring system based on pediatric patient factors to help determine when an MRI will change clinical management. METHODS: This is a retrospective cohort analysis of consecutive pediatric patients who presented to clinic with a chief complaint of back pain between 2010 and 2018 at single orthopaedic surgery practice. Comprehensive demographic and presentation variables were collected. A predictive model of factors that influence whether MRI results in a change in management was then generated using cross-validation least absolute shrinkage and selection operator logistic regression analysis. RESULTS: A total of 729 patients were included, with a mean age of 15.1 years (range: 3 to 20 y). Of these, 344 (47.2%) had an MRI. A predictive model was generated, with nocturnal symptoms (5 points), neurological deficit (10 points), age (0.7 points per year), lumbar pain (2 points), sudden onset of pain (3.25 points), and leg pain (3.75 points) identified as significant predictors. A combined score of greater than 9.5 points for a given patient is highly suggestive that an MRI will result in a change in clinical management (specificity: 0.93; positive predictive value: 0.92). CONCLUSIONS: A predictive model was generated to help determine when ordering an MRI may result in a change in clinical management for workup of back pain in the pediatric population. The main factors included the presence of a neurological deficit, nocturnal symptoms, sudden onset, leg pain, lumbar pain, and age. Care providers can use these findings to better determine if and when an MRI might be appropriate. LEVEL OF EVIDENCE: Level III-diagnostic study.

Patients Undergoing 3-Level-or-Greater Decompression-Only Surgery for Lumbar Spinal Stenosis Have Similar Outcomes to Those Undergoing Single-Level Surgery at 2 Years.

BACKGROUND: Stability following multilevel decompressive laminectomy without fusion has been debated using in vitro biomechanical and radiographic models. However, there is a lack of information regarding clinical outcomes for these patients. The aim of the present study was to determine the association between clinical outcomes and number of levels decompressed via laminectomy for treatment of lumbar spinal stenosis. METHODS: We performed a retrospective cohort analysis of patients who underwent a primary lumbar laminectomy between 2009 and 2015 by senior orthopedic spine surgeons for lumbar spinal stenosis. Patients were divided into 2 groups based on the number of decompression levels: single level or 3 or more levels. Patient-reported outcomes were obtained in the form of Oswestry Disability Index (ODI) scores, visual analog scale (VAS) scores for the back and leg, 12-Item Short Form Mental and Physical Survey scores, and Veterans Rand 12-Item Health Mental and Physical Survey scores. RESULTS: Overall, 138 consecutive patients were assessed, of which 106 underwent a single-level and 32 underwent a 3-or-more-level laminectomy. Average follow-up was 24.2 months. There were no significant differences in the preoperative VAS back, VAS leg, or ODI scores between the single-level laminectomy and 3-or-more-level laminectomy groups. Both groups of patients experienced significant improvements in these clinical outcomes postoperatively with no clinically significant difference in the degree of improvement. Reoperation rates were low and similar between the 2 groups. CONCLUSIONS: Patients undergoing decompression of 3 or more levels present with similar postoperative outcomes to those who undergo a single-level decompression for lumbar spinal stenosis. Under specific clinical and radiographic criteria, a multilevel decompression of 3 or more levels may be a safe and effective procedure with acceptable outcomes at 2 years after surgery. LEVEL OF EVIDENCE: 3.

Cervical spine MRI phenotypes and prediction of pain, disability and adjacent segment degeneration/disease after ACDF.

Degenerative spine imaging findings have been extensively studied in the lumbar region and are associated with pain and adverse clinical outcomes after surgery. However, few studies have investigated the significance of these imaging "phenotypes" in the cervical spine. Patients with degenerative cervical spine pathology undergoing anterior cervical discectomy and fusion (ACDF) from 2008 to 2015 were retrospectively and prospectively assessed using preoperative MRI for disc degeneration, narrowing, and displacement, high-intensity zones, endplate abnormalities, Modic changes, and osteophyte formation from C2-T1. Points were assigned for these phenotypes to generate a novel Cervical Phenotype Index (CPI). Demographics were evaluated for association with phenotypes and the CPI using forward stepwise regression. Bootstrap sampling and multiple imputations assessed phenotypes and the CPI in association with patient-reported outcomes (Neck Disability Index [NDI], Visual Analog Scale [VAS]-neck, VAS-arm) and adjacent segment degeneration (ASDeg) and disease (ASDz). Of 861 patients, disc displacement was the most common (99.7%), followed by osteophytes (92.0%) and endplate abnormalities (57.3%). Most findings were associated with age and were identified at similar cervical vertebral levels; at C5-C7. Imaging phenotypes demonstrated both increased and decreased associations with adverse patient-reported outcomes and ASDeg/Dz. However, the CPI consistently predicted worse NDI (P = .012), VAS-neck (P = .007), and VAS-arm (P = .013) scores, in addition to higher odds of ASDeg (P = .002) and ASDz (P = .004). The CPI was significantly predictive of postoperative symptoms of pain/disability and ASDeg/Dz after ACDF, suggesting that the totality of degenerative findings may be more clinically relevant than individual phenotypes and that this tool may help prognosticate outcomes after surgery.

Risk Factors Associated With Development of Urinary Retention Following Posterior Lumbar Spinal Fusion: Special Attention to the Use of Glycopyrrolate in Anesthesia Reversal.

STUDY DESIGN: The study is designed as a retrospective cohort study. OBJECTIVE: The aim of this study was to identify modifiable and nonmodifiable risk factors of postoperative urinary retention in spine surgery patients. SUMMARY OF BACKGROUND DATA: Postoperative urinary retention is a common complication in patients undergoing operative procedures requiring anesthesia. Current studies have shown significant risk factors for postoperative urinary retention, but most are nonmodifiable and subsequently of limited usefulness in preventing this complication. Several new studies have shown possible modifiable risk factors, but current data are inconsistent in terms of their statistical significance. METHODS: A total of 814 consecutive patients who underwent open posterior lumbar laminectomy and fusion were included in the retrospective cohort study. Pre, intra-, and postoperative characteristics were collected in all patients to identify risk factors for postoperative urinary retention. RESULTS: Glycopyrrolate use (odds ratio [OR] 2.60; P = 0.001), decreased body mass index (OR 0.96; P = 0.018), previous diagnosis of benign prostate hyperplasia (OR 3.34; P ≤ 0.001), and postoperative urinary tract infection (OR 5.60, P = 0.005) were associated with postoperative urinary retention. Previous history of lumbar spine surgery (OR 0.55; P = 0.019) was associated with decreased rates of postoperative urinary retention. CONCLUSION: Glycopyrrolate use, benign prostate hyperplasia, and postoperative urinary tract infection were independent risk factors for postoperative urinary retention. The use of glycopyrrolate is a potentially modifiable risk factor for postoperative urinary retention.Level of Evidence: 3.

Development and validation of a novel scoring tool for predicting facility discharge after elective posterior lumbar fusion.

BACKGROUND CONTEXT: Discharge to acute/intermediate care facilities is a common occurrence after posterior lumbar fusion and can be associated with increased costs and complications after these procedures. This is particularly relevant with the growing popularity of bundled payment plans, creating a need to identify patients at greatest risk. PURPOSE: To develop and validate a risk-stratification tool to identify patients at greatest risk for facility discharge after open posterior lumbar fusion. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: Patients were queried using separate databases from the institution of study and the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) for all patients undergoing open lumbar fusion between 2011 and 2018. OUTCOME MEASURES: Discharge to intermediate care and/or rehabilitation facilities. METHODS: Using an 80:20 training and testing NSQIP data split, collected preoperative demographic and operative variables were used in a multivariate logistic regression to identify potential risk factors for postoperative facility discharge, retaining those with a p value <.05. A nomogram was generated to develop a scoring system from this model, with probability cutoffs determined for facility discharge. This model was subsequently validated within the NSQIP database, in addition to external validation at the institution of study. Overall model performance and calibration was assessed using the Brier score and calibration plots, respectively. RESULTS: A total of 11,486 patients (10,453 NSQIP, 1,033 local cohort) were deemed eligible for study, of which 16.1% were discharged to facilities (16.7% NSQIP, 9.6% local cohort). Utilizing training data, age (p<.001), body mass index (p<.001), female sex (p<.001), diabetes (p=.043), peripheral vascular disease (p=.001), cancer (p=.010), revision surgery (p<.001), number of levels fused (p<.001), and spondylolisthesis (p=.049) were identified as significant risk factors for facility discharge. The area under the receiver operating characteristic curve (AUC) indicated a strong predictive model (AUC=0.750), with similar predictive ability in the testing (AUC=0.757) and local data sets (AUC=0.773). Using this tool, patients identified as low- and high-risk had a 7.94% and 33.28% incidence of facility discharge in the testing data set, while rates of 4.44% and 16.33% were observed at the institution of study. CONCLUSIONS: Using preoperative variables as predictors, this scoring system demonstrated high efficiency in risk-stratifying patients with an approximate four to fivefold difference in rates of facility discharge after posterior lumbar fusion. This tool may help inform medical decision-making and guide reimbursement under bundled-care repayment plans.

Does the Duration of Cervical Radicular Symptoms Impact Outcomes After Anterior Cervical Discectomy and Fusion?

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To compare clinical outcomes after anterior cervical discectomy and fusion (ACDF) based on preoperative duration of radiculopathy symptoms. SUMMARY OF BACKGROUND DATA: There is no clear indication of when outcomes after ACDF become less effective in the setting of acute versus chronic symptoms from cervical nerve root compression. MATERIALS AND METHODS: A retrospective cohort study of consecutive patients who underwent an ACDF between 2008 and 2015 for radiculopathy was performed. Patients were divided into 3 groups: radicular symptoms lasting for <6 months, symptoms lasting for 6-12 months, and those with symptoms for ≥12 months. Neck Disability Index (NDI) and Visual Analog Scale (VAS) scores for both the neck and arms were obtained at preoperative and final postoperative visits. Radiographs were assessed for adjacent segment degeneration, fusion, and subsidence. Bivariate and multivariate regressions were subsequently used to compare outcomes between groups. RESULTS: A total of 379 patients were included. Patients with symptoms lasting for 6-12 months and those with symptoms lasting for ≥12 months had worse preoperative VAS neck pain compared with patients with symptoms lasting for < 6 months (P=0.000 and P=0.004, respectively). Patients with symptoms lasting for ≥12 months had worse baseline functional status compared with patients with symptoms lasting for <6 months (P=0.009). At final follow-up, there were no significant differences in VAS neck, VAS arm, or NDI between symptom duration groups. However, differences in outcomes were noted when considering the type of preoperative symptom. Patients with pain symptoms of ≥12 months had worse preoperative VAS neck (P=0.001), VAS arm (P=0.008), and NDI (P<0.001) and had significantly worse final VAS arm (P=0.019) and NDI (P=0.016) compared with patients with preoperative pain symptoms lasting for <6 months. The overall reoperation rate was 4.5%. Fusion was achieved in 97.6% of the patients, and subsidence was observed in 5.5%. There were no significant differences in the risk of adjacent segment degeneration, reoperations, fusion rates, or subsidence rates based on preoperative symptom duration. CONCLUSIONS: Despite worse preoperative neck pain and functional status in patients with preoperative duration of symptoms >6 months, there were no differences in final clinical outcomes across groups.

Comparing Allografts to Autografts for Maintenance of Cervical Sagittal Parameters and Clinical Outcomes Following Anterior Cervical Discectomy and Fusion With Anterior Cervical Plating.

OBJECTIVE: Current literature has not shown if using either allograft or autograft differentially affects postoperative cervical sagittal parameters. The goal of this study was to compare sagittal alignment and patient-reported outcomes following anterior cervical discectomy and fusion (ACDF) with allograft versus autograft. METHODS: A retrospective cohort analysis of patients who underwent single-level ACDF was conducted. Preoperative, immediate postoperative, and final follow-up radiographic assessments were conducted and included: change in C2-7 lordosis, T1 slope, levels fused, sagittal vertical axis (SVA), fusion mass lordosis, and proximal and distal adjacent segment degeneration (ASD). Patient-reported outcomes were obtained using the Neck Disability Index and visual analogue scale scores for neck and arm. RESULTS: A total of 404 patients were assessed; 353 using allograft and 51 using autograft. No significant differences existed in demographics. Cervical lordosis improved in both groups without significant changes in SVA. Autograft group had a significantly greater amount of lordosis at the proximal segment on immediate postoperative radiographs and less overall cervical lordosis at final follow-up. Sagittal parameters were similar at each time point without significant changes between the 3-time points. No significant differences existed in radiographic ASD or reoperation rates. Fusion rates exceeded 96% in both groups. No significant differences existed between preoperative, postoperative, or change in patient-reported outcomes between the 2 groups. CONCLUSION: Sagittal alignment is maintained following ACDF when using either allograft or autograft. Radiographic evidence of ASD is present in both groups; however, this was not considered clinically significant, given low rates of pseudarthrosis or reoperation. No significant differences exist between groups in terms of patient-reported outcomes.

Obesity does not impact clinical outcome but affects cervical sagittal alignment and adjacent segment degeneration in short term follow-up after an anterior cervical decompression and fusion.

BACKGROUND CONTEXT: Obesity increases complications and cost following spine surgery. However, the impact on sagittal alignment and adjacent segment degeneration (ASD) after anterior cervical decompression and fusion is less understood. PURPOSE: To compare clinical and radiographic outcomes after anterior cervical decompression and fusion between obese and nonobese patients. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: In all, 467 patients that underwent an anterior cervical decompression and fusion procedure from January 2008 through December 2015 were assessed. Surgery indications were radiculopathy, myelopathy, or myeloradiculopathy that had failed nonoperative treatments. Exclusion criteria included patients who had postoperative follow-up less than 6 months. Of 467 patients originally identified, 399 fulfilled the inclusion and exclusion criteria. OUTCOME MEASURES: The following patient-reported outcomes were obtained: Neck Disability Index and Visual Analog Scale scores for the neck and arm pain. Radiographic assessments included: C2-C7 lordosis, T1 angle, levels fused, sagittal vertical axis (SVA), fusion mass lordosis, proximal and distal adjacent segment lordosis, ASD, and presence of fusion. METHODS: Plain radiographs were performed preoperatively, immediately postoperatively, and final follow-up. Demographic information was collected on all patients. Baseline patient characteristics were compared using chi-squared analysis and independent sample t tests for categorical and continuous data, respectively. For analysis, patients were divided into 4 groups based on obesity stratification as defined by Center for Disease Control: body mass index (BMI) <25 kg/m2 (normal weight), BMI≥25 kg/m2 to <30 kg/m2 (overweight), ≥30 kg/m2 to <35 kg/m2 (Class I obesity), BMI≥35 kg/m2 to <40 kg/m2 (Class II obesity), and BMI≥40 kg/m2 (Class III obesity). Additionally, obese (≥30 kg/m2) and nonobese (<30 kg/m2) patients were compared in a separate analysis. Multivariate analysis was used to compare clinical and radiographic outcomes among all BMI classes, as well as between BMI≥30 kg/m2 versus BMI<30 kg/m2 study groups. Multivariate analyses controlled for differences in baseline patient characteristics and included age, sex, smoking, American Society of Anesthesiologists Physical Status Score, diabetes mellitus, and number of levels. RESULTS: Of the 399 patients assessed, 97 were identified as normal weight, 157 as overweight, 81 with Class I obesity, 45 with Class II obesity, and 19 with Class III obesity. On multivariate analysis, despite having similar SVA measurements on preoperative radiographs, increase in BMI was associated with increase in postoperative SVA (p=0.041) along with significantly larger SVA in immediate postoperative (p=0.004) and final follow-up radiographs (p=0.003) for patients with BMI≥30 kg/m2 versus BMI<30 kg/m2. Furthermore, patients with BMI≥30 kg/m2 had smaller preoperative (p=0.012), immediate postoperative (p=0.017), and final lordosis (p<0.001) in addition to smaller immediate postoperative (p=0.025) and final fusion segment lordosis (p=0.015) and smaller preoperative (p=0.024) and final distal lordosis (p=0.021) compared with patients with BMI<30 kg/m2. Additionally, greater BMI was associated with lower final Visual Analog Scale neck scores (p=0.008). Radiographic early ASD rates were higher in patients BMI≥30 kg/m2 versus BMI<30 kg/m2 (p=0.028). CONCLUSIONS: Overall, obese patients who underwent anterior cervical decompression and fusion had similar patient-reported outcomes compared with nonobese patients but had worse radiographic parameters and higher rates of ASD development compared with nonobese patients. This underscores the importance of patient selection and surgical approach for both patient populations.

The Duration of Symptoms Does Not Impact Clinical Outcomes Following Lumbar Decompression Surgery.

STUDY DESIGN: A retrospective cohort analysis. OBJECTIVE: The aim of this study was to assess whether duration of symptoms (DOS) has an effect on clinical outcomes in patients undergoing lumbar decompression. SUMMARY OF BACKGROUND DATA: The success of surgical interventions for lumbar spinal stenosis varies depending on numerous factors, including DOS. However, existing literature does not provide a clear indication of the outcome of lumbar decompression surgery in regard to DOS secondary to nerve root compression. METHODS: Analysis of patients who underwent primary lumbar laminectomy from 2008 through 2015 by one of two senior orthopedic spine surgeons was conducted. Exclusion criteria were as follows: previous lumbar surgery, patient under 18 years of age at time of surgery, or postoperative follow-up less than 3 months. Patients were divided into groups on the basis of preoperative DOS: less than 1 year and 1 year or greater. Patient-reported outcomes were obtained using Oswestry Disability Index (ODI) scores, Visual Analog Scales (VAS) scores for the back and leg, 12-Item Short Form Mental and Physical Survey (SF-12) scores, and Veterans Rand 12-Item Health Mental and Physical Survey (VR-12) scores. Patients were surveyed about expectations and postoperative satisfaction. RESULTS: Two hundred ten patients were assessed; 108 with DOS of less than 1 year and 102 with DOS of 1 year or more. On multivariate analysis, patients with DOS of 1 year or greater presented with significantly lower SF-12 scores (P = 0.043). No significant differences existed in other outcome survey scores. Reoperation rates were not significantly different (P = 0.904). Both groups reported high levels of satisfaction (odds ratio 0.42, P = 0.483) and that surgery met or exceeded their expectations (odds ratio 1.00, P = 0.308). CONCLUSION: Symptom chronicity did not significantly affect postoperative clinical outcomes, reoperation rates, or patient satisfaction. Nonoperative treatment of lumbar spinal stenosis is often successful but may delay operative intervention. However, results of this study suggest that the delay does not negatively impact surgical outcomes. LEVEL OF EVIDENCE: 3.

Multi- versus single-level anterior cervical discectomy and fusion: comparing sagittal alignment, early adjacent segment degeneration, and clinical outcomes.

PURPOSE: The purpose of this study was to compare the rates of adjacent segment degeneration (ASD), sagittal alignment parameters, and patient-reported outcomes in patients who underwent multi-level versus single-level anterior cervical discectomy and fusion (ACDF). METHODS: A retrospective cohort analysis was performed on consecutive patients who underwent an ACDF. Pre- and post-operative radiographic assessment included ASD, change in C2-C7 lordosis, T1 angle, levels fused, sagittal vertical axis (SVA), fusion mass lordosis, proximal and distal adjacent segment lordosis. Patient-reported outcomes were obtained. RESULTS: Of the 404 that underwent an ACDF with a minimum of 6 months of follow-up (average 28 months), there was no significant difference in the rate of radiographic ASD overall (p = 0.479) or in the proximal or distal adjacent segments on multivariate analysis. Secondarily, the multi-level fusions appear to restore significantly greater amounts of lordosis compared to single-level procedures (p < 0.001) and are able to maintain the corrected cervical lordosis and fusion segment lordosis over time. From the immediate post-operative period to final follow-up, the single-level ACDFs show continuing lordosis improvement (p = 0.005) that is significantly greater than that of the multi-level constructs. There were no significant differences between pre-operative, post-operative, or change in patient-reported outcomes. CONCLUSIONS: Two years following an ACDF, patients who underwent multi-level fusions appear to restore significantly greater amounts of lordosis compared to single-level procedures, while single-level ACDFs show significantly greater amounts of lordosis improvement over time. Multi-level procedures may not be at a significantly greater risk of developing early radiographic evidence of ASD compared to single-level procedure. These slides can be retrieved under Electronic Supplementary Material.

Utilization of multiple spinal cord stimulation (SCS) waveforms in chronic pain patients.

BACKGROUND: Advances in spinal cord stimulation (SCS) have improved patient outcomes, leading to its increased utilization for chronic pain. Chronic pain is dynamic showing exacerbations, variable severity, and evolving pain patterns. Given this complexity, SCS systems that provide a broad range of stimulation waveforms may be valuable. METHODS: The aim of this research was to characterize the usage pattern of stimulation waveforms and field shapes in chronic pain patients implanted with the Spectra System. A review of daily device usage in a cohort of 250 patients implanted for a minimum duration of one month was conducted. RESULTS: With follow-ups ranging between 1 month and 1 year post-implant, 72.8% of patients used Standard Rate, 34.8% Anode Intensification, 23.2% Higher Rate, and 8.4% Burst stimulation waveforms. Collectively, 60% used 1 or more advanced waveforms, either exclusively or along with Standard Rate. A trend showed patients continuing to use up to 3 programs one year post-implant. CONCLUSION: When given a choice, SCS patients often utilize a variety of waveforms, suggesting that patients may benefit from a single system that provides multiple waveforms and field shapes to customize therapy and improve efficacy.

Factors affecting reoperations after anterior cervical discectomy and fusion within and outside of a Federal Drug Administration investigational device exemption cervical disc replacement trial.

BACKGROUND CONTEXT: The excellent clinical results of five US Federal Drug Administration (FDA) trials approved for cervical total disc replacement (TDR) (Prestige [Medtronic Sofamor Danek, Memphis, TN, USA], Bryan [Medtronic Sofamor Danek], ProDisc-C [Synthes, West Chester, PA, USA], Kineflex|C [SpinalMotion, Mountain View, CA, USA], and Mobi-C [LDR Spine, Austin, TX, USA]) have recently been published. In these prospective randomized studies, superiority or equivalency of TDR was claimed, citing an 8.7% (23/265), 9.5% (21/221), 8.5% (9/106), 12.2% (14/115), and 6.2% (5/81) (mean = 9.02%) rate of additional related cervical surgical procedures within 2 years in control anterior cervical discectomy and fusion (ACDF) patients, respectively, compared with 1.8% (5/276), 5.8% (14/242), 1.9% (2/103), 11% (15/136), and 1.2% (2/164) (mean = 4.34%) in patients receiving the cervical TDR. The rate of reoperation within 2 years after ACDF seems unusually high. PURPOSE: To assess the rate of and specific indications for early reoperation after ACDF in a cohort of patients receiving the ACDF as part of their customary care. These results are contrasted with similar patients receiving ACDF as the control arm of five FDA investigational device exemption (IDE) studies. STUDY DESIGN: Multisurgeon retrospective clinical series from a single institution. PATIENT SAMPLE: One hundred seventy-six patients with spondylotic radiculopathy or myelopathy underwent ACDF by three surgeons between 2001 and 2005 as part of their clinical practices. All patients had at least 2 years of follow-up with final follow-up within 6 months of completion of this study. OUTCOME MEASURES: Cervical reoperation rates at 2-year follow-up and at 3.5-year follow-up. METHODS: Review of medical records and telephone conversations were completed to determine the number of patients who had undergone a revision cervical procedure. RESULTS: At final follow-up, complete data were available for 159 ACDF patients. Of the 48 patients who underwent single-level ACDF and met criteria for inclusion in the IDE studies, one patient (2.1%) required additional surgery (adjacent-segment degeneration) within 2 years, the duration of follow-up of the five published IDE studies. Of the 159 patients who received single or multilevel ACDF at a mean follow-up of 3.5 years, 12 patients (7.6%) had undergone revision cervical surgery, with three patients (1.9%) undergoing same-level revisions (posterior fusion) and nine patients (5.7%) undergoing adjacent anterior level fusions. Patients who underwent revision same-level surgery typically had the intervention within the first year (mean, 11 months), whereas those requiring adjacent-level fusions typically had surgery later (mean, 29 months). CONCLUSIONS: The present study identifies a 2.1% rate of repeat surgery within 2 years of a single-level ACDF performed during routine clinical practice, which is lower than that reported in the control arm of the Prestige, ProDisc-C, Bryan, Kineflex|C, and Mobi-C FDA trials (mean=9%). Even with longer follow-up including multilevel cases, our reoperation rate (7.6%) compared favorably with the IDE rates. This discrepancy may reflect different thresholds for reoperation in the control arm of a device IDE study compared with routine clinical practice. Additionally, patients enrolled in the single-level-only IDE trial may have received multilevel procedures outside of the study. This factor could result in a higher rate of subsequent surgeries at adjacent levels not addressed at the index procedure. These data suggest that we need to better understand factors driving treatment and, in particular, decisions to reoperate both in and outside of a device trial.

Multiplexed sensing based on Brownian relaxation of magnetic nanoparticles using a compact AC susceptometer.

A novel multiplexed sensing scheme based on the measurement of the magnetic susceptibility of the affinity captured target molecules on magnetic nanoparticles in liquid suspension is proposed. The AC magnetic susceptibility provides a measurement of Brownian relaxation behavior of biomolecules bound to magnetic nanoparticles (MNPs) that is related to its hydrodynamic size. A room temperature, compact AC susceptometer is designed and developed to measure complex AC magnetic susceptibility of such magnetic nanoparticles. The AC susceptometer exhibits high sensitivity in magnetic fields as low as 10 µT for 1 mg ml(-1) concentration and 5 µl volume, and is fully software programmable. The capability of biological sensing using the proposed scheme has been demonstrated in proof of principle using the binding of biotinylated horseradish peroxidase (HRP) to streptavidin-coated MNPs. The proposed technique and instrument are readily compatible with lab-on-chip applications for point-of-care medical applications.

Characterization of graft subsidence in anterior cervical discectomy and fusion with rigid anterior plate fixation.

This study addressed radiographically the evaluation, presence, location, and degree of subsidence with secondary focus on the various clinical parameters and outcomes in 32 patients who underwent anterior cervical discectomy and fusion (ACDF) with tricortical iliac crest bone grafts and rigid anterior plate fixation. Postoperative follow-up plain radiographs were evaluated to determine subsidence on lateral neutral images by measuring the change in height of interscrew distance (ISD) and anterior (AVD), mid (MVD), and posterior (PVD) vertebral endplate-to-endplate vertical distances. Clinical functional outcome and various risk factors were also addressed. A 100% fusion rate was achieved, no instrumentation-related complications were noted, and mild graft subsidence occurred in each patient after the initial 2 months of surgery. Mean AVD, MVD, and PVD were 1.2 mm, 0.4 mm and 0.6 mm, respectively. Mean ISD was 0.6 mm. Percent change for AVD, MVD, PVD, and ISD was 2.3%, 0.8%, 1.2%, and 1.2%, respectively. Subsidence was more pronounced at the anterior vertebral graft-endplate interface (P < .05). Satisfactory clinical results were reported in 90.9% of the patients. With such a sample size, age, sex, smoking status, plate design, graft type, and operative or number of fused levels did not demonstrate statistically significant differences to the degree of subsidence. This paper has shown that ACDF with tricortical bone grafts and rigid plating is associated with slight subsidence, graft load-sharing, high fusion rate, and excellent clinical outcome.

Sexual dimorphism in degenerative disorders of the spine.

Sexual dimorphism is evident during formation, growth, and development of the spine. Pregnancy alters spine physiology and is a risk factor for back pain. The processes of aging and spinal degeneration adversely affect men and women slightly differently. Although degenerative changes are observed at similar rates in both sexes, women seem to be more susceptible to degenerative changes leading to instability and malalignment, structural deterioration, such a stenosis or disc degeneration. Surgical satisfaction is greater in men, which has been attributed to poorer preoperative function secondary to more advanced disease at time of surgery and lower patient expectations for clinical improvement, both observed in women.

Congenital lumbar spinal stenosis: a prospective, control-matched, cohort radiographic analysis.

BACKGROUND CONTEXT: Degenerative lumbar spinal stenosis manifests primarily after the sixth decade of life as a result of facet hypertrophy and degenerative disc disease. Congenital stenosis, on the other hand, presents earlier in age with similar clinical findings but with multilevel involvement and fewer degenerative changes. These patients may have subtle anatomic variations of the lumbar spine that may increase the likelihood of thecal sac compression. However, to the authors' knowledge, no quantitative studies have addressed various radiographic parameters of symptomatic, congenitally stenotic individuals to normal subjects. PURPOSE: To radiographically quantify and compare the anatomy of the lumbar spine in symptomatic, congenitally stenotic individuals to age- and sex-matched, asymptomatic, nonstenotic controlled individuals. STUDY DESIGN/SETTING: A prospective, control-matched, cohort radiographic analysis. PATIENT SAMPLE: Axial and sagittal magnetic resonance imaging (MRI) and lateral, lumbar, plain radiographs of 20 surgically treated patients who were given a clinical diagnosis of congenital lumbar stenosis by the senior author were randomized with images of 20, asymptomatic age- and sex-matched subjects. OUTCOME MEASURES: MRIs and lateral, lumbar, plain radiographs were independently quantitatively assessed by two individuals. Measurements obtained from the axial MRIs included: midline anterior-posterior (AP) vertebral body diameter, vertebral body width, midline AP canal diameter, canal width, spinal canal cross-sectional area, pedicle length, and pedicle width. From the sagittal MRIs, the following measurements were calculated: AP vertebral body diameter, vertebral body height, and AP canal diameter at the mid-vertebral level. On the lateral, lumbar, plain radiograph (L3 level), the AP diameters of the vertebral body spinal canal were measured. METHODS: The images of these 40 individuals were then randomized and distributed in a blinded fashion to five separate spine surgeons who graded the presence and severity of congenital stenosis utilizing a five-tier scale. Images consisting of 15 symptomatic individuals, graded definitely congenitally stenotic (mean age, 51.7 years; range, 43-65 years), and 15 asymptomatic individuals, graded definitely not stenotic (mean age, 50.7 years; range, 41-55 years), were age- and sex-matched and included for further review. From these 30 patients, a lateral, lumbar, plain radiograph and axial and sagittal MRIs (T1/T2 weighted) from L2-L5 were quantitatively analyzed. Rater reliability was assessed by Kappa coefficient testing. RESULTS: The cross-sectional area of the canal was significantly smaller in the congenitally stenotic patients at all lumbar levels measured (L2: 176 mm(2) vs. 259 mm(2), L3: 177 mm(2) vs. 275 mm(2), L4: 183 mm(2) vs. 283 mm(2), L5: 213 mm(2) vs. 323 mm(2), p<.05). Pedicle length was markedly shorter in the stenosis group at each lumbar level (L2: 5.9 mm vs. 8.9 mm, L3: 6.0 mm vs. 8.8 mm, L4: 6.5 mm vs. 9.2 mm, L5: 5.8 mm vs. 9.1 mm, p<.05). Furthermore, midline, axial AP canal diameter, vertebral body width, and sagittal AP canal diameter were all significantly smaller than the control patients (p<.05). A ratio of the AP diameter of the pedicle length to the vertebral body was also noted to be statistically significant on both the lateral plain radiographs (L3: 0.426 vs. 0.704) and sagittal MRI (L2: 0.343 vs. 0.461, L3: 0.361 vs. 0.461, L4: 0.362 vs. 0.481, L5: 0.354 vs. 0.452, p<.05). No difference was noted comparing the AP diameter of the vertebral body (axial and sagittal images), vertebral body height, canal width, and pedicle width. Kappa testing coefficient indicated a strong rater reliability (k=0.81, 95% confidence interval: 0.62-0.94). CONCLUSIONS: Congenital lumbar stenosis has not been clearly defined radiographically. Clinically, congenitally stenotic patients present at a younger age with fewer degenerative changes and multiple levels of involvement. Radiographically, these patients have a shorter pedicular length and as a result a smaller cross-sectional spinal canal area (mean critical values of 6.5 mm and 213 mm(2) were observed, respectively). The mean critical ratios were 0.43 (2:1 AP vertebral body: pedicle length) on the lateral lumbar radiograph and 0.36 on the sagittal MRI. The altered canal anatomy resulting from a decreased pedicle length may anatomically predispose these patients to earlier complaints of symptomatic neurogenic claudication. Identification of the presence of congenital stenosis should increase the treating surgeon's awareness of the potential need for multilevel treatment.

Is autograft the gold standard in achieving radiographic fusion in one-level anterior cervical discectomy and fusion with rigid anterior plate fixation?

STUDY DESIGN: A review of 66 consecutive patients at a single institution who underwent one-level anterior cervical discectomy and fusion (ACDF) with rigid anterior plate fixation with allograft or autograft. OBJECTIVES: To address the efficacy of allograft to autograft with primary respect to fusion rate and secondary attention to risk factors and clinical outcome in patients undergoing one-level ACDF with rigid anterior plate fixation. SUMMARY OF BACKGROUND DATA: Although autograft is considered the gold standard in achieving optimal fusion, when compared with allograft in noninstrumented one-level ACDF and in plated and nonplated multilevel ACDF, the efficacy of allograft to autograft in one-level ACDF with rigid anterior plate fixation is not thoroughly understood. METHODS: Sixty-six consecutive patients (mean age, 45 years) at a single institution who underwent one-level ACDF with rigid anterior plate fixation with allograft (n = 35) or autograft (n = 31) were reviewed for radiographic fusion (mean, 12 months), risk factors, and clinical outcome (mean, 17 months). Smokers entailed 33.3% of the patients, and 45.5% of all patients presented with a work-related injury. An independent blinded observer reviewed at last follow-up lateral neutral and flexion/extension plain radiographs for radiographic fusion and instrumentation integrity. Clinical outcome was assessed on last follow-up and rated according to the Odom criteria. The threshold for statistical significance was established at P < 0.05. RESULTS: Solid fusion was achieved in 63 patients (95.5%). Fusion was noted in 100% of the allograft patients, whereas 90.3% of the autograft cases achieved fusion. No statistically significant difference was noted between allograft to autograft with regard to fusion rate (P > 0.05). Three patients developed nonunions (1 smoker; 2 nonsmokers) and entailed Orion instrumentation. In the one patient who was a nonsmoker with a nonunion, slight screw penetration into the involved and uninvolved interbody spaces was noted. No other intraoperative, postoperative, or radiographic complication was noted. All of the nonunions occurred early in the series. Postoperatively, excellent results were reported in 19.7%, good results in 71.2%, and fair results in 9.1% of the patients. Satisfactory clinical outcome was noted in all nonunion patients. A nonstatistically significant difference was noted with regard to clinical outcome of fused and nonfused patients, demographics, and the presence of a work-related injury (P > 0.05). The impact of smoking was not a factor influencing fusion or clinical outcome in this series (P > 0.05). A statistically significant difference was noted in plate-type on fusion rate (P < 0.05). CONCLUSION: A 100% and 90.3% radiographic fusion rate was obtained for allograft and autograft in one-level ACDF procedures with rigid anterior plate fixation, respectively. Although autograft achieved a higher incidence of nonunion than allograft, this may be attributed to the use of autograft early in the experience of plate application and fixation in this series. The effects of smoking were not found to be a significant factor influencing fusion in these plated patients. In 90.9% of the patients, excellent and good clinical outcome results were reported. The use of allograft in one-level ACDF with rigid plate fixation yields similar and high fusion rates as autograft. The use of allograft bone eliminates complications and pitfalls associated with autologous donor site harvesting. However, the use of autograft is a viable alternative to avoid the risk of infection, disease transmission, and histocompatibility differences associated with allograft. The use of allograft or autograft bone in properly selected patients for one-level ACDF with rigid anterior plate fixation can result in high fusion rates with excellent and good clinical outcomes.

In vivo bypass of chaperone by extended coiled-coil motif in T4 tail fiber.

The distal-half tail fiber of bacteriophage T4 is made of three gene products: trimeric gp36 and gp37 and monomeric gp35. Chaperone P38 is normally required for folding gp37 peptides into a P37 trimer; however, a temperature-sensitive mutation in T4 (ts3813) that suppresses this requirement at 30 degrees C but not at 42 degrees C was found in gene 37 (R. J. Bishop and W. B. Wood, Virology 72:244-254, 1976). Sequencing of the temperature-sensitive mutant revealed a 21-bp duplication of wild-type gene 37 inserted into its C-terminal portion (S. Hashemolhosseini et al., J. Mol. Biol. 241:524-533, 1994). We noticed that the 21-amino-acid segment encompassing this duplication in the ts3813 mutant has a sequence typical of a coiled coil and hypothesized that its extension would relieve the temperature sensitivity of the ts3813 mutation. To test our hypothesis, we crossed the T4 ts3813 mutant with a plasmid encoding an engineered pentaheptad coiled coil. Each of the six mutants that we examined retained two amber mutations in gene 38 and had a different coiled-coil sequence varying from three to five heptads. While the sequences varied, all maintained the heptad-repeating coiled-coil motif and produced plaques at up to 50 degrees C. This finding strongly suggests that the coiled-coil motif is a critical factor in the folding of gp37. The presence of a terminal coiled-coil-like sequence in the tail fiber genes of 17 additional T-even phages implies the conservation of this mechanism. The increased melting temperature should be useful for "clamps" to initiate the folding of trimeric beta-helices in vitro and as an in vivo screen to identify, sequence, and characterize trimeric coiled coils.