The Effect of Preoperative Symptom Duration on Patient-Reported Outcomes After Anterior Cervical Discectomy and Fusion in Nonmyelopathic Patients: Analyses From the Michigan Spine Surgery Improvement Collaborative (MSSIC).

BACKGROUND: The effect of preoperative symptom duration (PSD) on patient-reported outcomes (PROs) in anterior cervical discectomy and fusion (ACDF) for radiculopathy is unclear. OBJECTIVE: To determine whether PSD is a predictor for PRO after ACDF for radiculopathy. METHODS: The Michigan Spine Surgery Improvement Collaborative registry was queried between March, 2014, and July, 2019, for patients who underwent ACDF without myelopathy and PROs (baseline, 90 days, 1 year, 2 years). PROs were measured by numerical rating scales for neck/arm pain, Patient-Reported Outcomes Measurement Information System Short Form-Physical Function (PROMIS-PF), EuroQol-5D (EQ5D), and North American Spine Society satisfaction. Univariate analyses were used to evaluate the proportion of patients reaching minimal clinically important differences (MCID). PSD was <3 months, 3 month-1 year, or >1 years. Multiple logistic regression models were used to estimate the association between PSD and PRO reaching MCID. The discriminative ability of the model was evaluated by receiver operating characteristic curve. RESULTS: We included 2233 patients who underwent ACDF with PSD <3 months (278, 12.4%), 3 month-1 year (669, 30%), and >1 years (1286, 57.6%). Univariate analyses demonstrated a greater proportion of patients achieving MCID in <3-month cohort for arm numerical rating scales, PROMIS-PF, EQ5D, and North American Spine Society Satisfaction. Multivariable analyses demonstrated using <3 months PSD as a reference, PSD >1 years was associated with decreased odds of achieving MCID for EQ5D (odds ratio 0.5, CI 0.32-0.80, P = .004). Private insurance and increased baseline PRO were associated with significantly higher odds for achieving PROMIS-PF MCID and EQ5D-MCID. CONCLUSION: Preoperative symptom duration greater than 1 year in patients who underwent ACDF for radiculopathy was associated with worse odds of achieving MCID for multiple PROs.

Radiographic and Patient-Reported Outcomes of Lordotic Versus Non-lordotic Static Interbody Devices in Minimally Invasive Transforaminal Lumbar Interbody Fusion: A Longitudinal Comparative Cohort Study.

Introduction Minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) is increasingly used to treat lumbar degenerative pathology. Its effect on sagittal parameters remains controversial. Static and expandable lordotic interbody devices (cages) were developed to improve segmental and overall lumbar lordosis. This study aimed to compare the radiographic and patient-reported outcomes (PROs) between static lordotic and non-lordotic titanium cages in patients undergoing 1-2 level MI-TLIF for degenerative conditions.  Methods We reviewed consecutive eligible patients who underwent 1-2 level MI-TLIF (7/2017-11/2019) at a single institution by multiple surgeons. Standing X-rays and PROs were collected at preoperative, 1-month, and 6-month postoperative intervals. Using univariate analyses, we compared the two cohorts regarding confounders, radiographic parameters, and proportions of patients reaching minimal clinically important difference (MCID) for PROs. Results One-hundred-twenty-five patients were reviewed. Forty-seven had lordotic and seventy-eight non-lordotic cages. The lordotic cohort was significantly younger than the non-lordotic (55.9 years vs. 60.7 years, p= 0.042). The baseline radiographic parameters were not significantly different between cohorts. At the preoperative-6-month interval, the lordotic cohort had significant improvement in lumbar lordosis versus non-lordotic cohort (2.95° ± 7.2° vs. -0.3° ± 7.1°, p=0.024). Both cohorts showed improvement in segmental lordosis, anterior and posterior interspace height, and low subsidence grade with no significant difference between cohorts at all intervals. Overall, 69.1-83.8% of patients achieved MCID in all PROs with no significant difference between cohorts. Conclusions The use of a static lordotic titanium cage in 1-2 level MI-TLIF did not result in significantly different radiographic improvements or PROs compared with a non-lordotic cage.

Impact of Interspace Distraction on Fusion and Clinical Outcomes in Anterior Cervical Discectomy and Fusion: A Longitudinal Cohort Study.

STUDY DESIGN: Longitudinal cohort study. PURPOSE: To determine the effect of change in interspace height on fusion and postoperative neck pain. OVERVIEW OF LITERATURE: The optimal height of a cervical interbody device (cage) in anterior cervical discectomy and fusion (ACDF) is not well defined. In addition, the effect of interspace distraction on fusion and postoperative neck pain remains unclear. METHODS: We retrospectively reviewed the charts of consecutive patients who underwent one- or two-level ACDF using polyetheretherketone cages by multiple surgeons from January 2015 to June 2016. We excluded patients younger than 18 years old, patients who had prior surgery at the same level (s), those with two-stage procedures, and those with less than 3 months of followup. Fusion was determined using the "Song" criteria. Ordinal regression was used to determine predictors of fusion. Patient-reported outcomes (PRO) were analyzed. RESULTS: We identified 323 consecutive patients. Twenty-two patients met the exclusion criteria. A total of 435 operative levels were included in the 301 remaining patients. Interspace fusion did not significantly vary by increasing interspace height with fusion rates between 76.2% and 82.8% at a mean follow-up of 17.9±12.6 months. The effect of an increase in interspace height and neck pain PRO was available for 163 patients who underwent one-level ACDF at a mean follow-up period of 16.2±13.1 months. We found no significant difference in fusion rate or neck pain score with increasing interspace height from 1 to 8 mm. Ordinal regression demonstrated no significant predictors of fusion. CONCLUSIONS: Interspace distraction from 1 to 8 mm did not result in significantly different pseudarthrosis rates or postoperative neck pain.

The effect of ketorolac on posterior minimally invasive transforaminal lumbar interbody fusion: an interim analysis from a randomized, double-blinded, placebo-controlled trial.

BACKGROUND CONTEXT: Postoperative pain control following posterior lumbar fusion continues to be challenging and often requires high doses of opioids for pain relief. The use of ketorolac in spinal fusion is limited due to the risk of pseudarthrosis. However, recent literature suggests it may not affect fusion rates with short-term use and low doses. PURPOSE: We sought to demonstrate noninferiority regarding fusion rates in patients who received ketorolac after undergoing minimally invasive (MIS) posterior lumbar interbody fusion. Additionally, we sought to demonstrate ketorolac's opioid-sparing effect on analgesia in the immediate postoperative period. STUDY DESIGN/SETTING: This is a prospective, randomized, double-blinded, placebo-controlled trial. We are reporting our interim analysis. PATIENT SAMPLE: Adults with degenerative spinal conditions eligible to undergo a one to three-level MIS transforaminal lumbar interbody fusion (TLIF). OUTCOME MEASURES: Six-month and 1-year radiographic fusion as determined by Suk criteria, postoperative opioid consumption as measured by intravenous milligram morphine equivalent, length of stay, and drug-related complications. Self-reported and functional measures include validated visual analog scale, short-form 12, and Oswestry Disability Index. METHODS: A double-blinded, randomized placebo-controlled, noninferiority trial of patients undergoing 1- to 3-level MIS TLIF was performed with bone morphogenetic protein (BMP). Patients were randomized to receive a 48-hour scheduled treatment of either intravenous ketorolac (15 mg every 6 hours) or saline in addition to a standardized pain regimen. The primary outcome was fusion. Secondary outcomes included 48-hour and total postoperative opioid use demonstrated as milligram morphine equivalence, pain scores, length of stay (LOS), and quality-of-life outcomes. Univariate analyses were performed. The present study provides results from a planned interim analysis. RESULTS: Two hundred and forty-six patients were analyzed per protocol. Patient characteristics were comparable between the groups. There was no significant difference in 1-year fusion rates between the two treatments (p=.53). The difference in proportion of solid fusion between the ketorolac and placebo groups did not reach inferiority (p=.072, 95% confidence interval, -.07 to .21). There was a significant reduction in total/48-hour mean opioid consumption (p<.001) and LOS (p=.001) for the ketorolac group while demonstrating equivalent mean pain scores in 48 hours postoperative (p=.20). There was no significant difference in rates of perioperative complications. CONCLUSIONS: Short-term use of low-dose ketorolac in patients who have undergone MIS TLIF with BMP demonstrated noninferior fusion rates. Ketorolac safely demonstrated a significant reduction in postoperative opioid use and LOS while maintaining equivalent postoperative pain control.

Age as a Risk Factor for Complications Following Anterior Cervical Discectomy and Fusion: Analysis From the Michigan Spine Surgery Improvement Collaborative (MSSIC).

STUDY DESIGN: Retrospective analysis of prospectively collected registry data using multivariable analyses of imputed data. OBJECTIVE: We sought to demonstrate that age would not be associated with complications in patients undergoing anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: Elderly patients (≥70 yrs) undergoing ACDF are considered a higher risk for complications. However, conclusive evidence is lacking. The Michigan Spine Surgery Improvement Collaborative (MSSIC) is a quality improvement collaborative with 30 hospitals across Michigan. METHODS: The study included all patients who had 1 to 4 level ACDF (September 2015-August 2019) for 90-day complications. Major and minor complications were defined using a validated classification. Multiple imputations were used to generate complete covariate datasets. Generalized estimating equation model was used to identify associations with complications using the whole cohort and elderly subgroup analyses. Bonferroni correction was used. RESULTS: Nine thousand one hundred thirty five patients (11.1% ≥ 70 yrs and 88.9% <70 yrs) with 2266 complications were analyzed. Comparing elderly versus non-elderly, the elderly had a significantly higher rate of any complications (31.5% vs. 24.0%, P < 0.001) and major complications (14.1% vs. 7.0%, P < 0.001). On multivariable analysis, age was not independently associated with any complication. POD#0 ambulation and preop independent ambulation were independently associated with significantly decreased odds of any complication. In the elderly, independent preoperative ambulation was protective for any complication (odds ratio [OR] 0.53, 0.39-0.73 95% confidence interval [CI]), especially major complications (OR 0.41, 0.27-0.61 95% CI). CONCLUSION: Age was not an independent risk factor for complications in patients that underwent ACDF. In the elderly, independent preoperative ambulation was especially protective for major complications.Level of Evidence: 3.

The Effect of Morbid Obesity on Complications, Readmission, and Patient-Reported Outcomes Following Minimally Invasive Transforaminal Lumbar Interbody Fusion: An Inverse Propensity Score Weighted Analysis.

STUDY DESIGN: Retrospective review of prospectively collected data at a single institution. OBJECTIVE: To compare perioperative and clinical outcomes in morbidly obese patients who underwent minimally invasive transforaminal lumbar interbody fusion (MiTLIF). SUMMARY OF BACKGROUND DATA: Obesity remains a serious public health concern. Obese patients who undergo lumbar fusion have historically thought to be at higher risk for complications and fare worse regarding quality-of-life outcomes. However, recent literature may demonstrate comparable risk and outcomes in obese patients. An increasing number of patients are categorized as morbidly obese (body mass index [BMI] ≥ 40 kg/m2). Perioperative and patient-reported outcomes (PROs) are lacking in this patient population. METHODS: The authors retrospectively reviewed a prospectively collected database of all morbidly obese and non-obese patients that underwent MiTLIF between 2015 and 2018 for degenerative conditions who had minimum 1-year follow-up for outcome assessment. An inverse propensity/probability of treatment weighting was utilized to create a synthetic weighted sample in which covariates were independent of obesity designation to adjust for imbalance between groups. Generalized estimating equations (GEE) was used to estimate the association of morbid obesity and complications and 1-year PROs. RESULTS: A total of 292 patients were analyzed with 234 non-obese patients and 58 morbidly obese patients. Multivariate analysis failed to demonstrate any association between morbid obesity and achieving minimal clinically important difference (MCID) for Oswestry disability index (ODI), visual analog scale (VAS), or short form-12 (SF-12) physical component score. However, morbid obesity was associated with significant decrease in odds of achieving MCID for SF-12 mental component score (P = 0.001). Increased surgery duration was significantly associated with morbid obesity (P = 0.001). Morbid obesity exhibited no statistically significant association with postoperative complications, readmission, pseudarthrosis, or adjacent segment disease (ASD). CONCLUSION: Morbidly obese patients who undergo MiTLIF can achieve meaningful clinical improvement comparable to nonobese patients. Morbid obesity was associated with longer surgical times but was not associated with postoperative complications, readmission, or ASD.Level of Evidence: 3.

Age as a Predictor for Complications and Patient-reported Outcomes in Multilevel Transforaminal Lumbar Interbody Fusions: Analyses From the Michigan Spine Surgery Improvement Collaborative (MSSIC).

STUDY DESIGN: Retrospective review of a multi-institutional data registry. OBJECTIVE: The authors sought to determine the association between age and complications & patient-reported outcomes (PRO) in patients undergoing multilevel transforaminal interbody lumbar fusion (MTLIF). SUMMARY OF BACKGROUND DATA: Elderly patients undergoing MTLIF are considered high risk. However, data on complications and PRO are lacking. Additionally, safety of multilevel lumbar fusion in the elderly remains uncertain. METHODS: Patients ≥50-year-old who underwent MTLIF for degenerative lumbar spine conditions were analyzed. Ninety-day complications and PROs (baseline, 90-d, 1-y, 2-y) were queried using the MSSIC database. PROs were measured by back & leg visual analog scale (VAS), Patient-reported Outcomes Measurement Information System (PROMIS), EuroQol-5D (EQ-5D), and North American Spine Society (NASS) Patient Satisfaction Index. Univariate analyses were used to compare among elderly and complication cohorts. Generalized estimating equation (GEE) was used to identify predictors of complications and PROs. RESULTS: A total of 3120 patients analyzed with 961 (31%) ≥ 70-y-o and 2159 (69%) between 50-69. A higher proportion of elderly experienced postoperative complications (P = .003) including urinary retention (P = <.001) and urinary tract infection (P = .002). Multivariate analysis demonstrated that age was not independently associated with complications. Number of operative levels was associated with any (P = .001) and minor (P = .002) complication. Incurring a complication was independently associated with worse leg VAS and PROMIS scores (P = <.001). Preoperative independent ambulation was independently associated with improved PROMIS, and EQ5D (P = <.001). Within the elderly, preoperative independent ambulation and lower BMI were associated with improved PROMIS (P = <.001). Complications had no significant effect on PROs in the elderly. CONCLUSIONS: Age was not associated with complications nor predictive of functional outcomes in patients who underwent MTLIF. Age alone, therefore, may not be an appropriate surrogate for risk. Furthermore, baseline preoperative independent ambulation was associated with better clinical outcomes and should be considered during preoperative surgical counseling.Level of Evidence: 3.

Big data registries in spine surgery research: the lurking dangers.

Spine surgery research has improved considerably over the last few decades. Its' most recent growth is in large part due to the mounting increase in studies conducted using national databases and registries. With easy access to a large number of patients, the benefit of these registries has become evident. However, as with any research, this type of data must be used responsibly with the appropriate strengths and limitations kept in mind. Inappropriate use of these registries continues to be a growing concern as potentially false or inaccurate conclusions can adversely impact clinical practice. It is, therefore, the author and the readers' responsibility to acknowledge and understand the limitations of this type of data. Knowledge of methodological requirements in the use and analyses of registry data is essential to ensuring quality evidence with proper interpretation.

Full endoscopic unilateral laminotomy for bilateral decompression of the cervical spine: surgical technique and early experience.

BACKGROUND: Full-endoscopic decompression surgery has been shown to be safe and efficacious in the lumbar spine, while its role remains to be determined in the cervical spine. We describe the utility of cervical endoscopic unilateral laminotomy for bilateral decompression (CE-ULBD) in a series of elderly patients with severe central stenosis, significant medical comorbidity, and existing cervical deformity. METHODS: A prospectively collected spine surgery registry at the University of Washington was retrospectively queried for patients with cervical spondylotic myelopathy receiving CE-ULBD. Demographic data, operative details, imaging, and patient reported outcomes, including visual analogue scale (VAS) for neck and upper extremity pain, Nurick grade, and the modified Japanese Orthopedic Association (mJOA) score, were reviewed. Description of the surgical technique is provided. Descriptive statistics were calculated. RESULTS: From 2014 through 2018, 10 patients with an average age of 70.2±5.0 years underwent CE-ULBD for symptomatic upper cervical stenosis due to ligamentum flavum buckling. Half of these patients had one stenotic segment, the other half had two stenotic segments. The most commonly affected segment was C3/4 (5/10 patients). Average length of surgery was 128±18.4 minutes. Average length of stay was 1.2±0.2 days. Average clinical follow-up time was 22.0±4.7 months; clinical outcomes at most recent follow-up were improved via both the Nurick grade (1.2±0.4, P<0.01) and modified Japanese Orthopedic Association (14.6±1.0, P<0.001) compared with pre-operative values. One patient experienced a transient loss of motor evoked potentials intraoperatively, but there were no cases of permanent neurological deficit. CONCLUSIONS: Severe central cervical stenosis is a safe and viable target for full-endoscopic decompression via an interlaminar approach.

Enhanced perioperative care and decreased cost and length of stay after elective major spinal surgery.

OBJECTIVEThe purpose of this study was to compare total cost and length of stay (LOS) between spine surgery patients enrolled in an enhanced perioperative care (EPOC) pathway and patients receiving traditional perioperative care (TRDC).METHODSAll spine surgery candidates were screened for inclusion in the EPOC pathway. This cohort was compared to a retrospective cohort of patients who received TRDC and a concurrent group of patients who met inclusion criteria but did not receive the EPOC (no pathway care [NOPC] group). Direct and indirect costs as well as hospital and intensive care LOSs were analyzed between the 3 groups.RESULTSTotal costs after pathway implementation decreased by $19,344 in EPOC patients compared to a historical cohort of patients who received TRDC and $5889 in a concurrent cohort of patients who did not receive EPOC (NOPC group). Hospital and intensive care LOS were significantly lower in EPOC patients compared to TRDC and NOPC patients.CONCLUSIONSThe implementation of a multimodal EPOC pathway decreased LOS and cost in major elective spine surgeries.

Management of Thoracic Disc Herniations via Posterior Unilateral Modified Transfacet Pedicle-Sparing Decompression With Segmental Instrumentation and Interbody Fusion.

STUDY DESIGN: Retrospective consecutive case series. OBJECTIVE: The objective of this case series was to demonstrate the safety of a modified transfacet pedicle-sparing decompression and instrumented fusion in patients with thoracic disc herniations (TDHs). METHODS: Consecutive patients undergoing operative management of TDH from July 2007 to December 2011 using a posterior unilateral modified transfacet pedicle-sparing approach were identified. All patients underwent open or minimally invasive modified transfacet pedicle-sparing discectomy and segmental instrumentation with interbody fusion, performed by four different surgeons. Pre- and postoperative visual analog scale (VAS) pain scores, Nurick grade, and American Spinal Injury Association Impairment Scale (AIS) were analyzed from a retrospective chart review. Estimated blood loss and complications were also obtained. RESULTS: Fifty-one patients were included that had operations for TDH. Thirty-nine patients had single level decompression and 12 had multilevel decompression. The total number of levels operated on was 64. Five patients were treated with minimally invasive surgery. A herniated disc level of T11-12 (n = 17) was treated most often. One major complication of epidural hematoma occurred. Minor complications such as malpositioned hardware, postoperative hematoma, wound infection, pseudoarthrosis, and pulmonary complications occurred in a few patients. Follow-up ranged from 1 to 46 months with 1 patient lost to follow-up. From preoperative to final postoperative: mean VAS scores improved from 8.31 to 4.05, AIS in all patients remained stable or improved, and Nurick scores improved from 3 to 2.6 on average. No intraoperative or permanent neurological deficit occurred. CONCLUSION: In our surgical series, 51 consecutive patients underwent modified transfacet pedicle-sparing approach to TDHs and experienced improvement of functional status as well as improvement of objective pain scales with no neurological complications. The posterior unilateral modified transfacet pedicle-sparing decompression and instrumented fusion approach to the thoracic spine is a safe and reproducible procedure for the treatment of TDHs.

Complexation Hydrogels for the Oral Delivery of Growth Hormone and Salmon Calcitonin.

The hydrogel system of poly(methacrylic acid-co-N-vinyl pyrrolidone) was evaluated for use as an oral delivery system for growth hormone and salmon calcitonin. These proteins were selected because of their therapeutic importance and the insight provided by evaluating the delivery of a therapeutic agent with a high molecular weight (growth hormone) and a drug with a high isoelectric point (salmon calcitonin). Growth hormone loading and release studies were performed for both P(MAA-co-NVP) and P(MAA-g-PEG). Loading efficiencies for the respective systems were 50.9 ± 1.8% and 57.8 ± 4.1%; weight incorporation of the protein was determined to be 3.5 ± 0.1% and 4.0 ± 0.3%. At pH 7.4, growth hormone release of 90% occurred within 45 min for P(MAA-co-NVP) microparticles; 90% release was not achieved with P(MAA-g-PEG) microparticles until 180 min. At pH 1.2, no release occurred from P(MAA-co-NVP) microparticles but 10% release occurred from P(MAA-g-PEG) microparticles. Salmon calcitonin loading and release were shown to be affected by the negative charges of deprotonated MAA; for systems with monomer molar feed ratios of 4:1, 1:1 and 1:4 MAA:NVP, loading efficiencies were determined to be 70.6 ± 3.0%, 25.3 ± 1.2%, and 1.6 ± 1.3%. Salmon calcitonin release was minimal from the copolymer with 4:1 MAA:NVP monomer feed at pH 7.4. The release improved when the pH was raised above physiological levels. These studies confirmed that P(MAA-co-NVP) was an effective oral delivery system for high molecular weight drugs, but improvements are needed before the system could be utilized for high isoelectric point therapeutic delivery.

Assessment of poly(methacrylic acid-co-N-vinyl pyrrolidone) as a carrier for the oral delivery of therapeutic proteins using Caco-2 and HT29-MTX cell lines.

Hydrogels of poly(methacrylic acid-co-N-vinyl pyrrolidone) were synthesized and evaluated for their use as carriers for oral protein delivery. Insulin loading efficiencies were determined to be near 90% for carriers crosslinked with ethylene glycol dimethacrylate with corresponding weight incorporation levels near 12%. Although no insulin was released in gastric conditions, as desired, near instantaneous release occurred when the pH was raised to values typical of the intestinal area. Cytocompatibility studies with Caco-2 and Caco-2/HT29-MTX cultures demonstrated that microparticles did not elicit toxic effects at concentrations up to 5.0 mg/mL. Insulin transport studies revealed that the carriers did not disrupt the cell layer and thus did not change the insulin permeability in the apical-to-basolateral direction. Therefore, microparticles of this system were best suited for oral delivery of therapeutic agents that do not require transport facilitation.

Molecular structure of physiologically-responsive hydrogels controls diffusive behavior.

Polymeric networks and the ensuing hydrogels of MAA and NVP were successfully synthesized using a UV-initiated free radical polymerization and characterized to assess their applicability as carriers for directed drug delivery. FT-IR spectroscopy revealed shifts in peak absorbances that indicated the presence of hydrogen bonding complexes between functional groups, while SEM imaging showed that the different comonomers affect the surface morphology of the microparticles. Dynamic pH swelling studies demonstrated the pH responsiveness of the carriers in gastric and intestinal conditions and revealed that systems containing higher concentrations of MAA experienced the highest degree of hydrogen bonding complexation in gastric conditions. The presence of NVP in the systems enhanced swelling. Equilibrium swelling studies revealed that the mesh size was sufficiently large to allow drug diffusion across the networks.

Impact of Absorption and Transport on Intelligent Therapeutics and Nano-scale Delivery of Protein Therapeutic Agents.

The combination of materials design and advances in nanotechnology has led to the development of new therapeutic protein delivery systems. The pulmonary, nasal, buccal and other routes have been investigated as delivery options for protein therapy, but none result in improved patient compliances and patient quality of life as the oral route. For the oral administration of these new systems, an understanding of protein transport is essential because of the dynamic nature of the gastrointestinal tract and the barriers to transport that exist.Models have been developed to describe the transport between the gastrointestinal lumen and the bloodstream, and laboratory techniques like cell culture provide a means to investigate the absorption and transport of many therapeutic agents. Biomaterials, including stimuli-sensitive complexation hydrogels, have been investigated as promising carriers for oral delivery. However, the need to develop models that accurately predict protein blood concentration as a function of the material structure and properties still exists.