Opening Side of Unilateral Open-Door Laminoplasty Does Not Impact Improvement in Arm Pain or Space Available for the Spinal Cord.

Background/Objectives: There exists limited data guiding open-door laminoplasty. The objective of this study is to determine if open-door laminoplasty affects radiographic decompression or arm pain outcomes. Methods: Adult patients who underwent unilateral open-door laminoplasty cervical myelopathy were included. The side opened was dependent on surgeon discretion. We recorded preoperative side of symptoms, side of radiographic compression, arm pain scores, and canal diameter. Patients with open-side ipsilateral or contralateral to dominant symptoms or compression were compared to determine any effect on arm pain outcomes or spinal canal diameter. If the symptoms were equal bilaterally, patients were neutral. Results: A total of 167 patients were included, with an average age of 64 ± 11 years and average follow-up time of 64.5 ± 72 weeks. The average preoperative arm pain visual analog score (VAS) was 2.13 ± 2.86, and the average arm VAS after 6 months was 1.52 ± 2.68. For dominant symptoms, the ipsilateral, contralateral, and neutral groups had a significant improvement in arm VAS at >6 months postoperatively. For dominant compression, the ipsilateral and contralateral groups had a significant improvement in both arm VASs and canal diameter at >6 months postoperatively. No differences were seen between groups for either. We observed a significant correlation between size of plate and change in canal diameter; however, no differences were noted for arm pain. Conclusions: Laminoplasty may be effective in addressing radicular arm pain by increasing the spinal canal's diameter and space available for the cord. The laterality of open-door laminoplasty did not affect arm pain improvement or canal expansion.

Incidental durotomy resulting in a postoperative lumbosacral nerve root with eventration into the adjacent facet joint: illustrative cases.

BACKGROUND: Radicular pain after lumbar decompression surgery can result from epidural hematoma/seroma, recurrent disc herniation, incomplete decompression, or other rare complications. A less recognized complication is postoperative nerve root herniation, resulting from an initially unrecognized intraoperative or, more commonly, a spontaneous postoperative durotomy. Rarely, this nerve root herniation can become entrapped within local structures, including the facet joint. The aim of this study was to illustrate our experience with three cases of lumbosacral nerve root eventration into an adjacent facet joint and to describe our diagnostic and surgical approach to this rare complication. OBSERVATIONS: Three patients who had undergone lumbar decompression surgery with or without fusion experienced postoperative radiculopathy. Exploratory revision surgery revealed all three had a durotomy with nerve root eventration into the facet joint. Significant symptom improvement was achieved in all patients following liberation of the neural elements from the facet joints. LESSONS: Entrapment of herniated nerve roots into the facet joint may be a previously underappreciated complication and remains quite challenging to diagnose even with the highest-quality advanced imaging. Thus, clinicians must have a high index of suspicion to diagnose this issue and a low threshold for surgical exploration.

Impact of Preoperative Symptom Duration on Patient-Reported Outcomes Following Cervical Disc Replacement for Cervical Radiculopathy.

STUDY DESIGN: Retrospective review of prospectively collected data. OBJECTIVE: To determine the impact of preoperative symptom duration on postoperative functional outcomes following cervical disc replacement (CDR) for radiculopathy. SUMMARY OF BACKGROUND DATA: CDR has emerged as a reliable and efficacious treatment option for degenerative cervical spine pathologies. The relationship between preoperative symptom duration and outcomes following CDR is not well established. METHODS: Patients with radiculopathy without myelopathy who underwent primary 1- or 2-level CDRs were included and divided into shorter (<6 mo) and prolonged (≥6 mo) cohorts based on preoperative symptom duration. Patient-reported outcome measures (PROMs) included Neck Disability Index (NDI), Visual Analog Scale (VAS) Neck and Arm. Change in PROM scores and minimal clinically important difference (MCID) rates were calculated. Analyses were conducted on the early (within 3 mo) and late (6 mo-2 y) postoperative periods. RESULTS: A total of 201 patients (43.6±8.7 y, 33.3% female) were included. In both early and late postoperative periods, the shorter preoperative symptom duration cohort experienced significantly greater change from preoperative PROM scores compared to the prolonged symptom duration cohort for NDI, VAS-Neck, and VAS-Arm. The shorter symptom duration cohort achieved MCID in the early postoperative period at a significantly higher rate for NDI (78.9% vs. 54.9%, P=0.001), VAS-Neck (87.0% vs. 56.0%, P<0.001), and VAS-Arm (90.5% vs. 70.7%, P=0.002). Prolonged preoperative symptom duration (≥6 mo) was identified as an independent risk factor for failure to achieve MCID at the latest timepoint for NDI (OR: 2.9, 95% CI: 1.2-6.9, P=0.016), VAS-Neck (OR: 9.8, 95% CI: 3.7-26.0, P<0.001), and VAS-Arm (OR: 7.5, 95% CI: 2.5-22.5, P<0.001). CONCLUSIONS: Our study demonstrates improved patient-reported outcomes for those with shorter preoperative symptom duration undergoing CDR for radiculopathy, suggesting delayed surgical intervention may result in poorer outcomes and greater postoperative disability. LEVEL OF EVIDENCE: III.

Targeting Wnt signaling for improved glioma immunotherapy.

Introduction: Despite aggressive standard-of-care therapy, including surgery, radiation, and chemotherapy, glioblastoma recurrence is almost inevitable and uniformly lethal. Activation of glioma-intrinsic Wnt/ß-catenin signaling is associated with a poor prognosis and the proliferation of glioma stem-like cells, leading to malignant transformation and tumor progression. Impressive results in a subset of cancers have been obtained using immunotherapies including anti-CTLA4, anti-PD-1, and anti-PD-L1 or chimeric antigen receptor (CAR) T cell therapies. However, the heterogeneity of tumors, low mutational burden, single antigen targeting, and associated antigen escape contribute to non-responsiveness and potential tumor recurrence despite these therapeutic efforts. In the current study, we determined the effects of the small molecule, highly specific Wnt/CBP (CREB Binding Protein)/ß-catenin antagonist ICG-001, on glioma tumor cells and the tumor microenvironment (TME)-including its effect on immune cell infiltration, blood vessel decompression, and metabolic changes. Methods: Using multiple glioma patient-derived xenografts cell lines and murine tumors (GL261, K-Luc), we demonstrated in vitro cytostatic effects and a switch from proliferation to differentiation after treatment with ICG-001. Results: In these glioma cell lines, we further demonstrated that ICG-001 downregulated the CBP/ß-catenin target gene Survivin/BIRC5-a hallmark of Wnt/CBP/ß-catenin inhibition. We found that in a syngeneic mouse model of glioma (K-luc), ICG-001 treatment enhanced tumor infiltration by CD3+ and CD8+ cells with increased expression of the vascular endothelial marker CD31 (PECAM-1). We also observed differential gene expression and induced immune cell infiltration in tumors pretreated with ICG-001 and then treated with CAR T cells as compared with single treatment groups or when ICG-001 treatment was administered after CAR T cell therapy. Discussion: We conclude that specific Wnt/CBP/ß-catenin antagonism results in pleotropic changes in the glioma TME, including glioma stem cell differentiation, modulation of the stroma, and immune cell activation and recruitment, thereby suggesting a possible role for enhancing immunotherapy in glioma patients.

Intravenous Ketorolac Substantially Reduces Opioid Use and Length of Stay After Lumbar Fusion: A Randomized Controlled Trial.

STUDY DESIGN: A randomized, double-blinded, placebo-controlled trial. OBJECTIVE: To examine the effect of intravenous ketorolac (IV-K) on hospital opioid use compared with IV-placebo (IV-P) and IV acetaminophen (IV-A). SUMMARY OF BACKGROUND DATA: Controlling postoperative pain while minimizing opioid use after lumbar spinal fusion is an important area of study. PATIENTS AND METHODS: Patients aged 18 to 75 years undergoing 1 to 2 level lumbar fusions between April 2016 and December 2019 were included. Patients with chronic opioid use, smokers, and those on systemic glucocorticoids or contraindications to study medications were excluded. A block randomization scheme was used, and study personnel, hospital staff, and subjects were blinded to the assignment. Patients were randomized postoperatively. The IV-K group received 15 mg (age > 65) or 30 mg (age < 65) every six hours (q6h) for 48 hours, IV-A received 1000 mg q6h, and IV-P received normal saline q6h for 48 hours. Demographic and surgical details, opioid use in morphine milliequivalents, opioid-related adverse events, and length of stay (LOS) were recorded. The primary outcome was in-hospital opioid use up to 72 hours. RESULTS: A total of 171 patients were included (58 IV-K, 55 IV-A, and 58 IV-P) in the intent-to-treat (ITT) analysis, with a mean age of 57.1 years. The IV-K group had lower opioid use at 72 hours (173 ± 157 mg) versus IV-A (255 ± 179 mg) and IV-P (299 ± 179 mg; P = 0.000). In terms of opiate use, IV-K was superior to IV-A ( P = 0.025) and IV-P ( P = 0.000) on ITT analysis, although on per-protocol analysis, the difference with IV-A did not reach significance ( P = 0.063). When compared with IV-P, IV-K patients reported significantly lower worst ( P = 0.004), best ( P = 0.001), average ( P = 0.001), and current pain ( P = 0.002) on postoperative day 1, and significantly shorter LOS ( P = 0.009) on ITT analysis. There were no differences in opioid-related adverse events, drain output, clinical outcomes, transfusion rates, or fusion rates. CONCLUSIONS: By reducing opioid use, improving pain control on postoperative day 1, and decreasing LOS without increases in complications or pseudarthrosis, IV-K may be an important component of "enhanced recovery after surgery" protocols.

Differences in imaging and clinical characteristics are associated with higher rates of decompression-fusion versus decompression-alone in women compared to men for lumbar degenerative spondylolisthesis.

PURPOSE: The goals were to ascertain if differences in imaging/clinical characteristics between women and men were associated with differences in fusion for lumbar degenerative spondylolisthesis. METHODS: Patients had preoperative standing radiographs, CT scans, and intraoperative fluoroscopic images. Symptoms and comorbidity were obtained from patients; procedure (fusion-surgery or decompression-alone) was obtained from intraoperative records. With fusion surgery as the dependent variable, men and women were compared in multivariable logistic regression models with clinical/imaging characteristics as independent variables. The sample was dichotomized, and analyses were repeated with separate models for men and women. RESULTS: For 380 patients (mean age 67, 61% women), women had greater translation, listhesis angle, lordosis, and pelvic incidence, and less diastasis and disc height (all p ≤ 0.03). The rate of fusion was higher for women (78% vs. 65%; OR 1.9, p = 0.008). Clinical/imaging variables were associated with fusion in separate models for men and women. Among women, in the final multivariable model, less comorbidity (OR 0.5, p = 0.05), greater diastasis (OR 1.6, p = 0.03), and less anterior disc height (OR 0.8, p = 0.0007) were associated with fusion. Among men, in the final multivariable model, opioid use (OR 4.1, p = 0.02), greater translation (OR 1.4, p = 0.0003), and greater diastasis (OR 2.4, p = 0.0002) were associated with fusion. CONCLUSIONS: There were differences in imaging characteristics between men and women, and women were more likely to undergo fusion. Differences in fusion within groups indicate that decisions for fusion were based on composite assessments of clinical and imaging characteristics that varied between men and women.

Risk factors for failure to achieve minimal clinically important difference following cervical disc replacement.

BACKGROUND CONTEXT: While cervical disc replacement (CDR) has been emerging as a reliable and efficacious treatment option for degenerative cervical spine pathology, not all patients undergoing CDR will achieve minimal clinically important difference (MCID) in patient-reported outcome measures (PROMs) postoperatively-risk factors for failure to achieve MCID in PROMs following CDR have not been established. PURPOSE: To identify risk factors for failure to achieve MCID in Neck Disability Index (NDI, Visual Analog Scale (VAS) neck and arm following primary 1- or 2-level CDRs in the early and late postoperative periods. STUDY DESIGN: Retrospective review of prospectively collected data. PATIENT SAMPLE: Patients who had undergone primary 1- or 2-level CDR for the treatment of degenerative cervical pathology at a single institution with a minimum follow-up of 6 weeks between 2017 and 2022. OUTCOME MEASURES: Patient-reported outcomes: Neck disability index (NDI), Visual analog scale (VAS) neck and arm, MCID. METHODS: Minimal clinically important difference achievement rates for NDI, VAS-Neck, and VAS-Arm within early (within 3 months) and late (6 months to 2 years) postoperative periods were assessed based on previously established thresholds. Multivariate logistic regressions were performed for each PROM and evaluation period, with failure to achieve MCID assigned as the outcome variable, to establish models to identify risk factors for failure to achieve MCID and predictors for achievement of MCID. Predictor variables included in the analyses featured demographics, comorbidities, diagnoses/symptoms, and perioperative characteristics. RESULTS: A total of 154 patients met the inclusion criteria. The majority of patients achieved MCID for NDI, VAS-Neck, and VAS-Arm for both early and late postoperative periods-79% achieved MCID for at least one of the PROMs in the early postoperative period, while 80% achieved MCID for at least one of the PROMs in the late postoperative period. Predominant neck pain was identified as a risk factor for failure to achieve MCID for NDI in the early (OR: 3.13 [1.10-8.87], p-value: .032) and late (OR: 5.01 [1.31-19.12], p-value: .018) postoperative periods, and VAS-Arm for the late postoperative period (OR: 36.63 [3.78-354.56], p-value: .002). Myelopathy was identified as a risk factor for failure to achieve MCID for VAS-Neck in the early postoperative period (OR: 3.40 [1.08-10.66], p-value: .036). Anxiety was identified as a risk factor for failure to achieve MCID for VAS-Neck in the late postoperative period (OR: 6.51 [1.91-22.18], p-value: .003). CDR at levels C5C7 was identified as a risk factor for failure to achieve MCID in NDI for the late postoperative period (OR: 9.74 [1.43-66.34], p-value: .020). CONCLUSIONS: Our study identified several risk factors for failure to achieve MCID in common PROMs following CDR including predominant neck pain, myelopathy, anxiety, and CDR at levels C5-C7. These findings may help inform the approach to counseling patients on outcomes of CDR as the evidence suggests that those with the risk factors above may not improve as reliably after CDR.

Recovery Kinetics After Cervical Spine Surgery.

STUDY DESIGN: Retrospective review of a prospectively maintained multisurgeon registry. OBJECTIVE: To study recovery kinetics and associated factors after cervical spine surgery. SUMMARY OF BACKGROUND DATA: Few studies have described return to activities cervical spine surgery. This is a big gap in the literature, as preoperative counseling and expectations before surgery are important. MATERIALS AND METHODS: Patients who underwent either anterior cervical discectomy and fusion (ACDF) or cervical disk replacement (CDR) were included. Data collected included preoperative patient-reported outcome measures, return to driving, return to working, and discontinuation of opioids data. A multivariable regression was conducted to identify the factors associated with return to driving by 15 days, return to working by 15 days, and discontinuing opioids by 30 days. RESULTS: Seventy ACDF patients and 70 CDR patients were included. Overall, 98.2% of ACDF patients and 98% of CDR patients returned to driving in 16 and 12 days, respectively; 85.7% of ACDF patients and 90.9% of CDR patients returned to work in 16 and 14 days; and 98.3% of ACDF patients and 98.3% of CDR patients discontinued opioids in a median of seven and six days. Though not significant, minimal (odds ratio (OR)=1.65) and moderate (OR=1.79) disability was associated with greater odds of returning to driving by 15 days. Sedentary work (OR=0.8) and preoperative narcotics (OR=0.86) were associated with decreased odds of returning to driving by 15 days. Medium (OR=0.81) and heavy (OR=0.78) intensity occupations were associated with decreased odds of returning to work by 15 days. High school education (OR=0.75), sedentary work (OR=0.79), and retired/not working (OR=0.69) were all associated with decreased odds of discontinuing opioids by 30 days. CONCLUSIONS: Recovery kinetics for ACDF and CDR are comparable. Most patients return to all activities after ACDF and CDR within 16 days. These findings serve as an important compass for preoperative counseling.

Biological and structural phenotypes associated with neurodevelopmental outcomes in congenital heart disease.

Neurodevelopmental disability (NDD) is recognised as one of the most common comorbidities in children with congenital heart disease (CHD) and is associated with altered brain structure and growth throughout the life course. Causes and contributors underpinning the CHD and NDD paradigm are not fully understood, and likely include innate patient factors, such as genetic and epigenetic factors, prenatal haemodynamic consequences as a result of the heart defect, and factors affecting the fetal-placental-maternal environment, such as placental pathology, maternal diet, psychological stress and autoimmune disease. Additional postnatal factors, including the type and complexity of disease and other clinical factors such as prematurity, peri-operative factors and socioeconomic factors are also expected to play a role in determining the final presentation of the NDD. Despite significant advances in knowledge and strategies to optimise outcomes, the extent to which adverse neurodevelopment can be modified remains unknown. Understanding biological and structural phenotypes associated with NDD in CHD are vital for understanding disease mechanisms, which in turn will advance the development of effective intervention strategies for those at risk. This review article summarises our current knowledge surrounding biological, structural, and genetic contributors to NDD in CHD and describes avenues for future research; highlighting the need for translational studies that bridge the gap between basic science and clinical practice.

Emerging Need for PROMs to Measure the Impact of Spine Disorders on Overall Health and Well-being: Measuring Expectations as an Example for Lumbar Degenerative Spondylolisthesis.

Background: Assessing the impact of spine disorders such as lumbar degenerative spondylolisthesis (LDS) on overall health is a component of quality of care that may not be comprehensively captured by spine-specific and single-attribute patient-reported outcome measures (PROMs). Purpose: We sought to compare PROMs to the Lumbar Surgery Expectations Survey ("Expectations Survey"), which addresses multiple aspects of health and well-being, and to compare the relevance of surgeon-selected versus survey-selected Patient-Reported Outcomes Measurement Information System (PROMIS) items to LDS. Methods: In a cross-sectional study, 379 patients with LDS preoperatively completed the Expectations Survey, Numerical Rating Pain Scales, Oswestry Disability Index (ODI), and PROMIS computer-adaptive physical function, pain, and mental health surveys. Expectations Survey scores were compared to PROMs with correlation coefficients (indicating strengths of relationships) and probability values (indicating associations by chance). Surgeons reviewed physical function questions to identify those particularly relevant to LDS. Results: Patients' mean age was 67 years, 64% were women, and 83% had single-level and 17% had multiple-level LDS. Probability values between the Expectations Survey and PROMs were reliable, but strengths of relationships were only mild to moderate, indicating PROMs did not comprehensively capture the impact of LDS. None of the surgeon-selected PROMIS physical function questions were posed to patients. Conclusion: This cross-sectional study found PROMs to be reliably associated but not strongly correlated with the Expectations Survey, which addresses the whole-patient impact of LDS. New measures that complement PROMIS and ODI should be developed to capture the whole-person effects of LDS and permit attribution of LDS treatments to overall health.

Instability Missed by Flexion-Extension Radiographs Subsequently Identified by Alternate Imaging in L4-L5 Lumbar Degenerative Spondylolisthesis.

STUDY DESIGN: Cross-sectional preoperative and intraoperative imaging study of L4-L5 lumbar degenerative spondylolisthesis (LDS). OBJECTIVE: To determine if alternate imaging modalities would identify LDS instability that did not meet the criteria for instability based on comparison of flexion and extension radiographs. SUMMARY OF BACKGROUND DATA: Pain may limit full flexion and extension maneuvers and thereby lead to underreporting of true dynamic translation and angulation in LDS. Alternate imaging pairs may identify instability missed by flexion-extension. MATERIALS AND METHODS: Consecutive patients scheduled for surgery for single-level L4-L5 LDS had preoperative standing radiographs in the lateral, flexion, and extension positions, supine computed tomography (CT) scans, and intraoperative fluoroscopic images in the supine and prone positions after anesthesia but before incision. Instability was defined as translation ≥3.5 mm or angulation ≥11° between the following pairs of images: (1) flexion-extension; (2) CT-lateral; (3) lateral-intraoperative supine; (4) lateral-intraoperative prone; and (5) intraoperative supine-prone. RESULTS: Of 240 patients (mean age 68 y, 54% women) 15 (6%) met the criteria for instability by flexion-extension, and 225 were classified as stable. Of these 225, another 84 patients (35% of total enrollment) were reclassified as unstable by comparison of CT-lateral images (21 patients) and by lateral-intraoperative images (63 patients). Nine of the 15 patients diagnosed with instability by flexion-extension had fusion (60%), and 68 of the 84 patients reclassified as unstable by other imaging pairs had fusion (81%) ( P =0.07). The 84 reclassified patients were more likely to undergo fusion compared with the 141 patients who persistently remained classified as stable (odds ratio=2.6, 95% CI: 1.4-4.9, P =0.004). CONCLUSIONS: Our study provides evidence that flexion and extension radiographs underreport the dynamic extent of LDS and therefore should not be solely relied upon to ascertain instability. These findings have implications for how instability should be established and the extent of surgery that is indicated.

Quantitative CT for Preoperative Assessment of Lumbar Degenerative Spondylolisthesis: The Unique Impact of L4 Bone Mineral Density on Single-Level Disease.

Background: Quantitative computed tomography (qCT) efficiently measures 3-dimensional vertebral bone mineral density (BMD), but its utility in measuring BMD at various vertebral levels in patients with lumbar degenerative spondylolisthesis (LDS) is unclear. Purpose: We sought to determine whether qCT could differentiate BMD at different levels of LDS, particularly at L4-L5, the most common single level for LDS. In addition, we sought to describe patterns of BMD for single-level and multiple-level LDS. Methods: We conducted a study of patients undergoing surgery for LDS who were part of a larger longitudinal study comparing preoperative and intraoperative images. Preoperative patients were grouped as single-level or multiple-level LDS, and qCT BMD was obtained for L1-S1 vertebrae. Mean BMD was compared with literature reports; in multivariable analyses, BMD of each vertebra was assessed according to the level of LDS, controlling for covariates and for BMD of other vertebrae. Results: Of 250 patients (mean age: 67 years, 64% women), 22 had LDS at L3-L4 only, 170 at L4-L5 only, 13 at L5-S1 only, and 45 at multiple levels. Compared with other disorders reported in the literature, BMD in our sample similarly decreased from L1 to L3 then increased from L4 to S1, but mean BMD per vertebra in our sample was lower. Nearly half of our sample met criteria for osteopenia. In multivariable analysis controlling for BMD at other vertebrae, lower L4 BMD was associated with LDS at L4-L5, greater pelvic incidence minus lumbar lordosis, and not having diabetes. In contrast, in similar multivariable analysis, greater L4 BMD was associated with LDS at L3-L4. Bone mineral density of L3 and L5 was not associated with LDS levels. Conclusion: In our sample of preoperative patients with LDS, we observed lower BMD for LDS than for other lumbar disorders. L4 BMD varied according to the level of LDS after controlling for covariates and BMD of other vertebrae. Given that BMD can be obtained from routine imaging, our findings suggest that qCT data may be useful in the comprehensive assessment of and strategy for LDS surgery. More research is needed to elucidate the cause-effect relationships among spinopelvic alignment, LDS, and BMD.

Telemedicine Visits Can Generate Highly Accurate Diagnoses and Surgical Plans for Spine Patients.

STUDY DESIGN: A Retrospective cohort study. OBJECTIVE: To (1) assess whether diagnoses and surgical plans established during a new patient telemedicine visit changed following an in-person evaluation and (2) determine any differences in perioperative outcomes between patients who only had a telemedicine visit before surgery versus those who had a telemedicine visit followed by an in-person evaluation before surgery. SUMMARY OF BACKGROUND DATA: Data on capability of telemedicine to deliver high-quality preoperative assessment without a traditional in-person interaction and physical examination is lacking. MATERIALS AND METHODS: Records of patients who had a new patient telemedicine visit and indicated for surgery with documented specific diagnosis as well as surgical plans from a spine department at an urban tertiary center from April 2020 to April 2021 were reviewed. For a subset of patients that had a follow-up in-person evaluation before surgery, these diagnoses and plans were compared. Perioperative outcomes were compared between patients who only had a telemedicine visit before surgery versus those who had a telemedicine visit followed by an in-person evaluation before surgery. RESULTS: A total of 166 patients were included. Of these, 101 patients (61%) only had a new patient telemedicine visit before surgery while 65 (39%) had a telemedicine visit followed by an in-person evaluation. There were no differences in the rate of case cancellations before surgery and patient-reported outcome measures between these two groups ( P >0.05). Of 65 patients who had both a telemedicine followed by an in-person visit, the diagnosis was unchanged for 61 patients (94%) and the surgical plan did not change for 52 patients (80%). The main reason for surgical plan change was due to updated findings on new imaging, 10 patients, (77%). CONCLUSIONS: The current study suggests that telemedicine evaluations can provide an effective means of preoperative assessment for spine patients. LEVEL OF EVIDENCE: Level 3.

Classification system for cervical spine deformity morphology: a validation study.

OBJECTIVE: The objective of this study was to initially validate a recent morphological classification of cervical spine deformity pathology. METHODS: The records of 10 patients for each of the 3 classification subgroups (flat neck, focal deformity, and cervicothoracic), as well as for 8 patients with coronal deformity only, were extracted from a prospective multicenter database of patients with cervical deformity (CD). A panel of 15 physicians of various training and professional levels (i.e., residents, fellows, and surgeons) categorized each patient into one of the 4 groups. The Fleiss kappa coefficient was utilized to evaluate intra- and interrater reliability. Accuracy, defined as properly selecting the main driver of deformity, was reported overall, by morphotype, and by reviewer experience. RESULTS: The overall classification demonstrated a moderate to substantial agreement (round 1: interrater Fleiss kappa = 0.563, 95% CI 0.559-0.568; round 2: interrater Fleiss kappa = 0.612, 95% CI 0.606-0.619). Stratification by level of training demonstrated similar mean interrater coefficients (residents 0.547, fellows 0.600, surgeons 0.524). The mean intrarater score was 0.686 (range 0.531-0.823). A substantial agreement between rounds 1 and 2 was demonstrated in 81.8% of the raters, with a kappa score > 0.61. Stratification by level of training demonstrated similar mean intrarater coefficients (residents 0.715, fellows 0.640, surgeons 0.682). Of 570 possible questions, reviewers provided 419 correct answers (73.5%). When considering the true answer as being selected by at least one of the two main drivers of deformity, the overall accuracy increased to 86.0%. CONCLUSIONS: This initial validation of a CD morphological classification system reiterates the importance of dynamic plain radiographs for the evaluation of patients with CD. The overall reliability of this CD morphological classification has been demonstrated. The overall accuracy of the classification system was not impacted by rater experience, demonstrating its simplicity.

Cervical Disc Replacement for Radiculopathy Versus Myeloradiculopathy: An MCID Analysis.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: The aim was to compare the minimally clinically important difference (MCID) across multiple patient-reported outcomes (PROs) in patients undergoing cervical disc replacement (CDR) for cervical spondylotic radiculopathy versus myeloradiculopathy. SUMMARY OF BACKGROUND DATA: To date, a limited number of studies have demonstrated mostly similar results in patients with cervical spondylotic radiculopathy or myeloradiculopathy undergoing CDR. However, each of these previous studies have focused on statistically significant differences, which may not correlate with patient perceived improvements in outcomes or success. METHODS: Patients who underwent 1 or 2-level CDR with radiculopathy versus myeloradiculopathy were identified, and prospectively collected data was retrospectively reviewed. Demographic variables, preoperative diagnosis, and operative variables were collected for each patient. The following PROs were prospectively collected: Neck Disability Index (NDI), visual analog scale (VAS)-Neck, VAS-Arm, Short Form-12 Health Survey (SF-12) Physical Component Score (PCS), SF-12 Mental Component Score (MCS), PROMIS Physical Function (PF). An MCID analysis of PROs for each diagnosis group was performed and the percentage of patients achieving the MCID was compared between the two diagnosis groups. RESULTS: Eight-five patients, of which 56% had radiculopathy and 44% had myeloradiculopathy. MCID analysis demonstrated that at 6-week, 12-week, and final postoperative follow-up there was no significant difference in the percentage of patients with radiculopathy or myeloradiculopathy achieving the MCID for each PRO assessed. In both diagnosis groups the percentage of patients achieving the MCID for each PRO continued to increase from the 6-week to final postoperative follow-up except for the SF-12 MCS in patients with myeloradiculopathy. CONCLUSIONS: The percentage of patients achieving the MCID was not significantly different at each postoperative period assessed in the radiculopathy and myeloradiculopathy groups treated with CDR. In addition, the percentage of patients achieving the MCID continued to increase from 6 weeks to final follow-up in both groups for almost all PROs assessed.

Anterior Cervical Discectomy and Fusion Versus Cervical Disc Replacement in Patients With Significant Cervical Spondylosis.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The aim was to compare clinical outcomes in patients with significant cervical spondylosis treated with cervical disc replacement (CDR) compared with anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: As CDR utilization has increased over the past decade, recent studies have investigated the outcomes of CDR in patients with more significant spondylotic changes and demonstrated improved postoperative patient-reported outcomes (PROs). However, no prior study has investigated clinical outcomes of patients with significant spondylotic changes treated with CDR in comparison to ACDF. METHODS: Patients who underwent 1-level or 2-level CDR or ACDF with significant cervical spondylosis, quantified using a validated grading scale, were identified, and prospectively collected data was retrospectively reviewed. The following PROs were analyzed: Neck Disability Index (NDI), visual analog scale-Neck, visual analog scale-Arm, and PROMIS Physical Function (PROMIS-PF) Computer Adaptive Test Score. Demographic, operative, and radiographic variables, and achievement of minimum clinically important difference (MCID) for each PRO were compared between the 2 groups. RESULTS: A total of 66 patients were included in the present study, of which 35 (53%) were treated with CDR and 31 (47%) with ACDF. The preoperative cervical spondylotic grade was similar between the 2 groups (1.8 vs. 2.2, P=0.27). At final follow-up, there was no significant difference in the absolute value for each PRO between the 2 groups (P>0.19) and both groups demonstrated significant improvement in each PRO compared with preoperative values (P<0.01). There was no significant difference in the percentage of patients achieving the MCID for each PRO when comparing CDR to ACDF (P>0.09). CONCLUSIONS: A similar percentage of patients with significant degenerative cervical spondylosis achieved the MCID across multiple PROs when treated with CDR or ACDF. Patients in both treatment groups demonstrated significant improvement in all PROs assessed when compared with preoperative values. LEVEL OF EVIDENCE: Level III.

Enhanced method to select human oogonial stem cells for fertility research.

Alternative methods to obtain mature oocytes are still needed for women with premature ovarian failure (POF). Oogonial stem cells (OSCs), found in adult ovaries, have provided insight into potential paths to treating infertility. Previously, the DDX4 antibody marker alone was utilized to isolate OSCs; however, extensive debate over its location in OSCs versus resulting oocytes (transmembrane or intracytoplasmic) has raised doubt about the identity of these cells. Separate groups, however, have efficiently isolated OSCs using another antibody marker Ifitm3 which is consistently recognized to be transmembrane in location. We hypothesized that by using anti-DDX4 and anti-IFITM3 antibodies, in combination, with MACS, we would improve the yield of isolated OSCs versus using anti-DDX4 antibodies alone. Our study supports earlier findings of OSCs in ovaries during the entire female lifespan: from reproductive age through post-menopausal age. MACS sorting ovarian cells using a the two-marker combination yielded a ~ twofold higher percentage of OSCs from a given mass of ovarian tissue compared to existing single marker methods while minimizing the debate surrounding germline marker selection. During in vitro culture, isolated cells retained the germline phenotype expression of DDX4 and IFITM3 as confirmed by gene expression analysis, demonstrated characteristic germline stem cell self-assembly into embryoid bodies, and formed > 40 µm "oocyte-like" structures that expressed the early oocyte markers GDF9, DAZL, and ZP1. This enhanced and novel method is clinically significant as it could be utilized in the future to more efficiently produce mature, secondary oocytes, for use with IVF/ICSI to treat POF patients.

Differential Expression of Interferon-Alpha Protein Provides Clues to Tissue Specificity Across Type I Interferonopathies.

Whilst upregulation of type I interferon (IFN) signaling is common across the type I interferonopathies (T1Is), central nervous system (CNS) involvement varies between these disorders, the basis of which remains unclear. We collected cerebrospinal fluid (CSF) and serum from patients with Aicardi-Goutières syndrome (AGS), STING-associated vasculopathy with onset in infancy (SAVI), presumed monogenic T1Is (pT1I), childhood systemic lupus erythematosus with neuropsychiatric features (nSLE), non-IFN-related autoinflammation (AI) and non-inflammatory hydrocephalus (as controls). We measured IFN-alpha protein using digital ELISA. Eighty-two and 63 measurements were recorded respectively in CSF and serum of 42 patients and 6 controls. In an intergroup comparison (taking one sample per individual), median CSF IFN-alpha levels were elevated in AGS, SAVI, pT1I, and nSLE compared to AI and controls, with levels highest in AGS compared to all other groups. In AGS, CSF IFN-alpha concentrations were higher than in paired serum samples. In contrast, serum IFN was consistently higher compared to CSF levels in SAVI, pT1I, and nSLE. Whilst IFN-alpha is present in the CSF and serum of all IFN-related diseases studied here, our data suggest the primary sites of IFN production in the monogenic T1I AGS and SAVI are, respectively, the CNS and the periphery. These results inform the diagnosis of, and future therapeutic approaches to, monogenic and multifactorial T1Is.

An Indo-Pacific coral spawning database.

The discovery of multi-species synchronous spawning of scleractinian corals on the Great Barrier Reef in the 1980s stimulated an extraordinary effort to document spawning times in other parts of the globe. Unfortunately, most of these data remain unpublished which limits our understanding of regional and global reproductive patterns. The Coral Spawning Database (CSD) collates much of these disparate data into a single place. The CSD includes 6178 observations (3085 of which were unpublished) of the time or day of spawning for over 300 scleractinian species in 61 genera from 101 sites in the Indo-Pacific. The goal of the CSD is to provide open access to coral spawning data to accelerate our understanding of coral reproductive biology and to provide a baseline against which to evaluate any future changes in reproductive phenology.

Microfluidic Systems for Assisted Reproductive Technologies: Advantages and Potential Applications.

Microfluidic technologies have emerged as a powerful tool that can closely replicate the in-vivo physiological conditions of organ systems. Assisted reproductive technology (ART), while being able to achieve successful outcomes, still faces challenges related to technical error, efficiency, cost, and monitoring/assessment. In this review, we provide a brief overview of the uses of microfluidic devices in the culture, maintenance and study of ovarian follicle development for experimental and therapeutic applications. We discuss existing microfluidic platforms for oocyte and sperm selection and maintenance, facilitation of fertilization by in-vitro fertilization/intracytoplastimc sperm injection, and monitoring, selection and maintenance of resulting embryos. Furthermore, we discuss the possibility of future integration of these technologies onto a single platform and the limitations facing the development of these systems. In spite of these challenges, we envision that microfluidic systems will likely evolve and inevitably revolutionize both fundamental, reproductive physiology/toxicology research as well as clinically applicable ART.