Radiographic Alignment Parameters for Lumbosacral Reconstruction in Patients With Altered S1 Morphology.

STUDY DESIGN: Retrospective quantitative analysis study. OBJECTIVES: Pelvic incidence has been established as central radiographic marker which determines patient-specific correction goals during surgery for adult spinal deformity. In cases with sacral doming or sacral osteotomy where the PI cannot be calculated, reliable radiographic parameters need to be established to determine surgical goals. We aim to determine multiple radiographic parameters and formulas that can be utilized when the S1 superior endplate is obscured. METHODS: Retrospective analysis was performed on 68 healthy volunteers without prior spine surgery with full-length radiographs. Pelvic incidence, sacral slope, and pelvic tilt were calculated for each patient. Additional measurements such as L4, L5, and S2 incidence, tilt, and slope were collected. A new radiographic parameter defined as the L4-Sciatic notch angle was measured. Regression analysis was performed on each value to determine its relationship with S1 based incidence, tilt, and slope. RESULTS: Mean values for L5 incidence, L4 incidence, and L4 sciatic notch angle were 21.8° ± 8.9, 4.4° ± 8.1, and 44.4° ± 12, respectively. The linear regression analysis produced the following formulas which can be utilized to determine deformity correction goals when pelvic incidence can be calculated pre-operatively: L5i = .65*S1i-11.4, L4i = .44*S1i-18.6, and L4SNA = -.34*S1i + 66.5. In settings where pelvic incidence cannot be calculated, the following formulas can be utilized: L5i = .66*S2i-32.3 and L4SNA = -.02*S2i2 + 1.1*S2i + 63.5. P-values for all regression analyses were <.001. CONCLUSION: This study provides target radiographic alignment values that can be utilized for patients with either pre-operative altered S1 endplates or in cases with intraoperative alteration of S1 (sacral osteotomy).

Low-Density Lipoprotein Cholesterol and Statin Usage Are Associated With Rates of Pseudarthrosis Following Single-Level Posterior Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To investigate the relationships of low-density lipoprotein cholesterol and statin usage with pseudarthrosis following single-level posterior or transforaminal lumbar interbody fusion (PLIF/TLIF). SUMMARY OF BACKGROUND DATA: Hypercholesterolemia can lead to atherosclerosis of the segmental arteries, which branch into vertebral bone through intervertebral foramina. According to the vascular hypothesis of disc disease, this can lead to ischemia of the lumbar discs and contribute to lumbar degenerative disease. Yet, little has been reported regarding the effects of cholesterol and statins on the outcomes of lumbar fusion surgery. MATERIALS AND METHODS: TriNetX, a global federated research network, was retrospectively queried to identify 52,140 PLIF/TLIF patients between 2002 and 2021. Of these patients, 2137 had high cholesterol (≥130 mg/dL) and 906 had low cholesterol (≤55 mg/dL). Perioperatively, 18,275 patients used statins, while 33,415 patients did not. One-to-one propensity score matching for age, sex, race, and comorbidities was conducted to balance the analyzed cohorts. The incidence of pseudarthrosis was then assessed in the matched cohorts within the six-month, one-year, and two-year postoperative periods. RESULTS: After propensity score matching, high-cholesterol patients had greater odds of developing pseudarthrosis six months [odds ratio (OR): 1.73, 95% confidence interval (CI): 1.28-2.33], one year (OR: 1.59, 95% confidence interval (CI): 1.20-2.10), and two years (OR: 1.57, 95% CI: 1.20-2.05) following a PLIF/TLIF procedure. Patients with statin usage had significantly lower odds of developing pseudarthrosis six months (OR: 0.74, 95% CI: 0.69-0.79), one year (OR: 0.76, 95% CI: 0.71-0.81), and two years (OR: 0.77, 95% CI: 0.72-0.81) following single-level PLIF/TLIF. CONCLUSIONS: The findings suggest that patients with hypercholesterolemia have an increased risk of developing pseudarthrosis following PLIF/TLIF while statin use is associated with a decreased risk. The data presented may underscore an overlooked opportunity for perioperative optimization in lumbar fusion patients, warranting further investigation in this area.

Opioid and Sedative NarxCare Scores Greater Than 300 Are Associated With Adverse Outcomes After Nonemergent Spine Surgery.

STUDY DESIGN: This was a prospectively captured cohort study. OBJECTIVE: To explore associations between the preoperative opioid-specific NarxCare Scores (NCS) (NCS-opioids) as well as sedative-specific NCS (NCS-sedatives) as measures of patients' prescription drug use and (1) 90-day postoperative readmission; (2) ED visits; (3) reoperation; (4) prolonged (>2 d) hospital length of stay (LOS); and (5) nonhome discharge. In addition, we sought to evaluate the previously suggested 300+ threshold as a cutoff for moderate/high-risk designation. BACKGROUND: The association between preoperative opioids and sedative use and healthcare utilization after nonemergent spine surgery is not well quantified. The NCS is a weighted scalar measure of opioids and sedatives that accounts for the number of prescribing providers, dispensing pharmacies, milligram equivalence doses, and overlapping prescription days. METHODS: A total of 4680 nonemergent spine surgery cases were included. Preoperative NCS-opioids/sedatives were captured. Bivariate and multivariable regression models were constructed to analyze associations between NCS-opioids/sedatives ranges and outcomes while accounting for baseline differences. Spline regression and propensity score matching (PSM) analyses were also implemented. RESULTS: For NCS-opioid, multivariable regression demonstrated higher odds of prolonged LOS starting in the 400 to 499 NCS-opioids category [odds ratio (OR): 1.44; 95% confidence interval (CI): 1.05-1.97; P =0.026] going into the 500+ category (OR: 1.94; 95% CI: 1.29-2.93; P =0.002]. The 500+ categories exhibited higher odds of 90-day readmission (OR: 1.77; 95% CI: 1.01-3.09; P =0.045). PSM comparison demonstrated that patients within the 300+ category had higher incidence of prolonged LOS [n=455 (44%) vs . n=537 (52%); P <0.001], 90-day readmission [n=118 (11%) vs . n=155 (15%); P =0.019] and 90-day reoperation [n=51 (4.9%) vs . n=74 (7.2%); P =0.042]. For NCS-sedative; there was higher odds of prolonged LOS (OR: 1.73; 95% CI: 1.14-2.63; P =0.010) and nonhome discharge(OR: 2.09; 95%CI: 1.22-3.63; P =0.008) within the 400 to 499 NCS-sedatives category. PSM comparison demonstrated significantly higher rates of prolonged LOS within the 300+ NCS-sedative cohort ( vs . scores <300), [n=277 (44%) vs. 319 (50%); P =0.021]. CONCLUSION: Spine surgery continues to advance toward patient-specific care. Higher NCS-opioids/sedatives values may predict up to a twofold increase in postoperative healthcare utilization. High values should prompt an interdisciplinary approach to mitigate deleterious prescription drug use.

Perioperative outcomes of cervical disc arthroplasty: no difference between orthopaedic and neurologic surgeons.

Background: Given differences in residency training background, there has been increasing interest in characterizing differential outcomes between orthopaedic surgeons (OS) and neurosurgeons (NS) with regards to outcomes after cervical disc arthroplasty (CDA). This study aimed to assess if there were differences in perioperative outcomes of CDA between OS and NS. Methods: Patients who underwent a single-level CDA between 2012 and 2019 were identified from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database using current procedural terminology codes. The patients were subsequently stratified into those who underwent CDA with OS versus NS, and propensity score-matched to adjust for differences in patient characteristics. Differences were assessed in medical and surgical complications, as well as operative time and healthcare utilization parameters [reoperations, readmissions, and lengths-of-stay (LOS)]. Results: A total of 2,148 patients were identified (NS: n=1,395; OS: n=753). After 1:1 propensity score matching (n=741 each), there were no differences in characteristics between patients who underwent CDA by OS versus NS (P>0.05). There were no significant differences in any of the medical or surgical complications between the two groups (P>0.05 for each). There was a significant difference in the operative time between NS and OS (103.7±36.18 vs. 98.75±36.69 minutes; P=0.009). There were no significant differences in readmissions, reoperations, or LOS between the two groups (P>0.05 for each). Conclusions: There were no differences in medical or surgical complications, as well as in reoperations, readmissions, and LOS in patients who underwent a single-level CDA between OS and NS. There was a statistically significant shorter operative time of four minutes for OS as compared to NS, which is unlikely to have clinical relevance.

New Imaging Modalities for Degenerative Cervical Myelopathy.

INTRODUCTION: Degenerative cervical myelopathy (DCM) is defined as dysfunction of the spinal cord as a result of compression from degenerative changes to surrounding joints, intervertebral disks, or ligaments. Symptoms can include upper extremity numbness and diminished dexterity, difficulty with fine manipulation of objects, gait imbalance, and incoordination, and compromised bowel and bladder function. Accurate diagnosis and evaluation of the degree of impairment due to degenerative cervical myelopathy remain a challenging clinical endeavor requiring a thorough and accurate history, physical examination, and assessment of imaging findings. METHODS: A narrative review is presented summarizing the current landscape of imaging modalities utilized in DCM diagnostics and the future direction of research for spinal cord imaging. RESULTS AND DISCUSSION: Current imaging modalities, particularly magnetic resonance imaging and, to a lesser extent, radiographs/CT, offer important information to aid in decision making but are not ideal as stand-alone tools. Newer imaging modalities currently being studied in the literature include diffusion tensor imaging, MR spectroscopy, functional magnetic resonance imaging, perfusion imaging, and positron emission tomography. These newer imaging modalities attempt to more accurately evaluate the physical structure, intrinsic connectivity, biochemical and metabolic function, and perfusion of the spinal cord in DCM. Although there are still substantial limitations to implementation, future clinical practice will likely be revolutionized by these new imaging modalities to diagnose, localize, surgically plan and manage, and follow patients with DCM.

Transforming Standard of Care for Spine Surgery: Integration of an Online Single-Session Behavioral Pain Management Class for Perioperative Optimization.

Estimates suggest that 10-40% of lumbar spine surgery patients experience persistent post-surgical pain (PPSP). PPSP is associated with 50% greater healthcare costs, along with risks of emotional distress and impaired quality of life. In 2019, U.S. Health and Human Services identified brief and digital behavioral treatments as important for pain management after surgery. Indeed, brief behavioral pain treatments delivered in the perioperative period may offer patients a low burden opportunity to acquire essential pain coping strategies for enhanced surgical recovery. Additionally, the COVID-19 pandemic has diminished in-person pain treatment access during extended perioperative time frames, thus underscoring the need for on-line options and home based care. This report describes the integration of an online, live-instructor delivered single-session pain self-management intervention (Empowered Relief) into the standard of care for lumbar spine surgery. Here, we apply the RE-AIM framework; describe systems implementation of the Empowered Relief intervention in a large, academic medical center during the COVID-19 pandemic; describe operational challenges and financial considerations; and present patient engagement data. Finally, we discuss the scalable potential of Empowered Relief and other single-session interventions in surgical populations, their importance during extended perioperative periods, practical and scientific limitations, and new directions for future research on this topic.

MPAPASS software enables stitched multiplex, multidimensional EV repertoire analysis and a standard framework for reporting bead-based assays.

Extracellular vesicles (EVs) of various types are released or shed from all cells. EVs carry proteins and contain additional protein and nucleic acid cargo that relates to their biogenesis and cell of origin. EV cargo in liquid biopsies is of widespread interest owing to its ability to provide a retrospective snapshot of cell state at the time of EV release. For the purposes of EV cargo analysis and repertoire profiling, multiplex assays are an essential tool in multiparametric analyte studies but are still being developed for high-parameter EV protein detection. Although bead-based EV multiplex analyses offer EV profiling capabilities with conventional flow cytometers, the utilization of EV multiplex assays has been limited by the lack of software analysis tools for such assays. To facilitate robust EV repertoire studies, we developed multiplex analysis post-acquisition analysis (MPAPASS) open-source software for stitched multiplex analysis, EV database-compatible reporting, and visualization of EV repertoires.

A Retrospective Analysis of the L3-L4 Disc and Spinopelvic Parameters on Outcomes in Thoracolumbar Fusion: Was Art Steffee Right?

OBJECTIVE: To determine whether the L3-L4 disc angle may be a surrogate marker for global lumbar alignment in thoracolumbar fusion surgery and to explore the relationship between radiographic and patient-reported outcomes after thoracolumbar fusion surgery. METHODS: Retrospective chart review was conducted on patients who had undergone a lumbar fusion involving levels from T9 to pelvis. EuroQol-Five Dimension (EQ-5D-3L) scores and adverse events including adjacent-segment disease and degeneration, pseudoarthrosis, proximal junctional kyphosis, stenosis, and reoperation were collected. Pre- and postoperative spinopelvic parameters were measured on weight-bearing radiographs, with the L3-L4 disc angle of novel interest. Univariate logistic and linear regression were performed to assess the associations of radiographic parameters with adverse event incidence and improvement in EQ-5D-3L, respectively. RESULTS: In total, 182 patients met inclusion criteria. Univariable analysis revealed that increased magnitude of L3-L4 disc angle, anterior pelvic tilt, and pelvic incidence measures are associated with increased likelihood of developing postoperative adverse events. Conversely, increased lumbar lordosis demonstrated a decreased incidence of developing a postoperative adverse event. Linear regression showed that radiographic parameters did not significantly correlate with postoperative EQ-5D-3L scores, although scores were significantly improved postfusion in all dimensions except Self-Care (P = 0.51). CONCLUSIONS: L3-L4 disc angle magnitude may serve as a surrogate marker of global lumbar alignment. The degree of spinopelvic alignment did not correlate to improvement in EQ-5D-3L score in the present study, suggesting that quality of life metric change may not be a sensitive or specific marker of postfusion alignment.

Longer operative time associated with prolonged length of stay, non-home discharge and transfusion requirement after anterior cervical discectomy and fusion: an analysis of 24,593 cases.

BACKGROUND: Prolonged operative time of single-level ACDF has been associated with adverse postoperative outcomes. The current literature does not contain a comprehensive quantitative description of these associations PURPOSE: This study characterized the associations between single-level anterior cervical discectomy and fusion(ACDF) operative time and (1)30-day postoperative healthcare utilization, and (2)the incidence of local wound complications, need for transfusion and mechanical ventilation. DESIGN/SETTING: Retrospective database analysis PATIENT SAMPLE: The American College of Surgeons National Surgical Quality Improvement Program(ACS-NSQIP) database was queried for single-level ACDF cases(2012-2018) using current procedural terminology codes. A total of 24,593 cases were included. OUTCOME MEASURES: Primary outcomes included healthcare utilization(lengths of stay[LOS], discharge dispositions, 30-day readmissions, and reoperations) per operative time category. The secondary outcome was the incidence of wound complications, blood transfusion and need for ventilation per operative time category. METHODS: Multivariate regression determined operative time categories associated with increased risk while adjusting for patient demographics and comorbidities. Predictive spline regression models visualized the associations. RESULTS: Compared to the reference operative time of 81-100-minutes, the 101-120-minute category was associated with higher odds of LOS >2 days(OR:1.36,95%CI(1.18-1.568);p<.001) and non-home discharge(OR:1.341,95%CI(1.081-1.664);p=.008). Three-times greater odds of LOS >2 days(OR:3.367,95%CI(2.719-4.169); p<.001) and twice the odds of non-home discharge(OR:2.174,95%CI(1.563-3.022);p<.001) were detected at 181-200-minutes. The highest operative time category(≥221 minutes) was associated with the highest odds of LOS>2 days(OR:4.838,95%CI(4.032-5.804);p<.001), non-home discharge(OR:2.687,95%CI(2.045-3.531);p<.001) and reoperation(OR:1.794,95%CI(1.094-2.943);p=.021). Patients within the 201-220 and the ≥221-minute categories exhibited a significant association with greater odds of transfusion(OR:8.57,95%CI(2.321-31.639);p<.001, and OR:11.699, 95%CI(4.179-32.749);p=.001, respectively). Spline regression demonstrated that the odds of LOS >2 days, non-home discharge disposition, reoperation and bleeding requiring transfusion events began to rise, starting at 94, 91.6, 91.6, and 93.3 minutes of operative time, respectively. CONCLUSION: This study demonstrated that prolonged operative time is associated with increased odds of healthcare utilization and transfusion after single-level ACDF. Operative times greater than 91 minutes may carry higher odds of postoperative complications.

Predicting Reciprocal Thoracic Change, Proximal Junctional Kyphosis, and Revision Surgery in Adult Spinal Deformity.

BACKGROUND: Compensatory mechanisms in patients with adult spinal deformity (ASD) that lead to poor quality of life include positive sagittal balance and pelvic retroversion. The objective of this retrospective review was to identify demographic and radiographic parameters of sagittal alignment that are correlated with thoracic kyphosis (TK), PJK, and reoperation in patients undergoing surgical correction for ASD. METHODS: A single-center database of 155 patients with ASD undergoing surgery from 2008 to 2015 was reviewed. Patients >18 years old who underwent multilevel thoracolumbar fusion or fusion of thoracic vertebrae to the pelvis were included. Demographics and radiographic measurements of sagittal alignment were collected preoperatively, 6 weeks postoperatively, and 1 year postoperatively. Statistical analysis was performed to compare groups that did or did not develop change in thoracic kyphosis or PJK at early or late follow-up. Additionally, patients requiring reoperation were evaluated. RESULTS: Increased thoracic kyphosis was associated with older age, hypolordosis, and comorbid PJK. Early PJK was associated with older age, hypolordosis, and increased T1 pelvic angle. Reoperation was associated with older age, higher positive sagittal balance, hypolordosis, and pelvic retroversion; PJK and thoracic kyphosis did not increase risk for reoperation. CONCLUSIONS: Thoracic reciprocal change following surgical correction of ASD is highly associated with PJK, although neither increased risk of reoperation. PJK may be predicted by older age, hypolordosis, and increased T1 pelvic angle. Reoperation in patients with ASD is more likely in older patients with positive sagittal balance, a compensatory flat lower back, and compensatory pelvic retroversion.

Late-week surgery and discharge to specialty care associated with higher costs and longer lengths of stay after elective lumbar laminectomy.

OBJECTIVE: In a healthcare landscape in which costs increasingly matter, the authors sought to distinguish among the clinical and nonclinical drivers of patient length of stay (LOS) in the hospital following elective lumbar laminectomy-a common spinal surgery that may be reimbursed using bundled payments-and to understand their relationships with patient outcomes and costs. METHODS: Patients ≥ 18 years of age undergoing laminectomy surgery for degenerative lumbar spinal stenosis within the Cleveland Clinic health system between March 1, 2016, and February 1, 2019, were included in this analysis. Generalized linear modeling was used to assess the relationships between the day of surgery, patient discharge disposition, and hospital LOS, while adjusting for underlying patient health risks and other nonclinical factors, including the hospital surgery site and health insurance. RESULTS: A total of 1359 eligible patients were included in the authors' analysis. The mean LOS ranged between 2.01 and 2.47 days for Monday and Friday cases, respectively. The LOS was also notably longer for patients who were ultimately discharged to a skilled nursing facility (SNF) or rehabilitation center. A prolonged LOS occurring later in the week was not associated with greater underlying health risks, yet it nevertheless resulted in greater costs of care: the average total surgical costs for lumbar laminectomy were 20% greater for Friday cases than for Monday cases, and 24% greater for late-week cases than for early-week cases ultimately transferred to SNFs or rehabilitation centers. A Poisson generalized linear model fit the data best and showed that the comorbidity burden, surgery at a tertiary care center versus a community hospital, and the incidence of any postoperative complication were associated with significantly longer hospital stays. Discharge to home healthcare, SNFs, or rehabilitation centers, and late-week surgery were significant nonclinical predictors of LOS prolongation, even after adjusting for underlying patient health risks and insurance, with LOSs that were, for instance, 1.55 and 1.61 times longer for patients undergoing their procedure on Thursday and Friday compared to Monday, respectively. CONCLUSIONS: Late-week surgeries are associated with a prolonged LOS, particularly when discharge is to an SNF or rehabilitation center. These findings point to opportunities to lower costs and improve outcomes associated with elective surgical care. Interventions to optimize surgical scheduling and perioperative care coordination could help reduce prolonged LOSs, lower costs, and, ultimately, give service line management personnel greater flexibility over how to use existing resources as they remain ahead of healthcare reforms.

Caloric Restriction Impairs Regulatory T cells Within the Tumor Microenvironment After Radiation and Primes Effector T cells.

Outcomes for triple negative breast cancer (TNBC) are poor and may be improved by increasing CD8+ tumor infiltrating lymphocytes (TIL) to augment antitumor immunity. Radiation (RT) can promote immunogenic cell death with increased antitumor T cell activity but also stimulates suppressive regulatory T cells (Tregs). Because metabolic alterations affect immune homeostasis and prior studies show caloric restriction (CR) combined with RT improves preclinical TNBC outcomes, we hypothesized that CR augments RT, in part, by altering intratumoral immunity. Using an in vivo model of TNBC, we treated mice with ad libitum (AL) diet, radiation, a CR diet, or CR + RT, and demonstrated an immune suppressive environment with a significant increase in CD4+ CD25+Foxp3+ Tregs after RT but not in CR-fed mice. CD8:Treg ratio in CR + RT TIL increased 4-fold compared with AL + RT mice. In vivo CD8 depletion was performed to assess the role of effector T cells in mitigating the effects of CR, and it was found that in mice undergoing CR, depletion of CD8 T cells resulted in increased tumor progression and decreased median survival compared with isotype control-treated mice. In addition, PD-1 expression on CD3+CD8+ T cells within the tumor microenvironment was significantly increased in CR + RT versus AL + RT treated mice as per immunofluorescence. Serum from breast cancer patients undergoing RT alone or CR and RT was collected pre- and postintervention, and a cytokine array demonstrated that patients treated with CR + RT had notable decreases in immunosuppressive cytokines such as IL-2Rγ, IL-10Rß, and TGF-ß2 and 3 compared with patients receiving RT alone. In conclusion, combining CR with RT decreases intratumoral Tregs, increases CD8:Treg, and increases PD-1 expression via a process dependent on CD8 T cells in a TNBC model. Breast cancer patients undergoing CR concurrently with RT also had significant reduction in immunosuppressive cytokine levels compared with those receiving RT alone.

miR-21 Plays a Dual Role in Tumor Formation and Cytotoxic Response in Breast Tumors.

Breast cancer (BrCa) relies on specific microRNAs to drive disease progression. Oncogenic miR-21 is upregulated in many cancers, including BrCa, and is associated with poor survival and treatment resistance. We sought to determine the role of miR-21 in BrCa tumor initiation, progression and treatment response. In a triple-negative BrCa model, radiation exposure increased miR-21 in both primary tumor and metastases. In vitro, miR-21 knockdown decreased survival in all BrCa subtypes in the presence of radiation. The role of miR-21 in BrCa initiation was evaluated by implanting wild-type miR-21 BrCa cells into genetically engineered mouse models where miR-21 was intact, heterozygous or globally ablated. Tumors were unable to grow in the mammary fat pads of miR-21-/- mice, and grew in ~50% of miR-21+/- and 100% in miR-21+/+ mice. The contribution of miR-21 to progression and metastases was tested by crossing miR-21-/- mice with mice that spontaneously develop BrCa. The global ablation of miR-21 significantly decreased the tumorigenesis and metastases of BrCa, while sensitizing tumors to radio- and chemotherapeutic agents via Fas/FasL-dependent apoptosis. Therefore, targeting miR-21 alone or in combination with various radio or cytotoxic therapies may represent novel and efficacious therapeutic modalities for the future treatment of BrCa patients.

A simple, high-throughput method of protein and label removal from extracellular vesicle samples.

Evidence continues to increase of the clinical utility extracellular vesicles (EVs) as translational biomarkers. While a wide variety of EV isolation and purification methods have been implemented, few techniques are high-throughput and scalable for removing excess fluorescent reagents (e.g. dyes, antibodies). EVs are too small to be recovered from routine cell-processing procedures, such as filtration or centrifugation. The lack of suitable methods for removing unbound labels, especially in optical assays, is a major roadblock to accurate EV phenotyping and utilization of EV assays in a translational or clinical setting. Therefore, we developed a method for using a multi-modal resin, referred to as EV-Clean, to remove unbound labels from EV samples, and we demonstrate improvement in flow cytometric EV analysis with the use of this EV-Clean method.

A phase I trial of lenalidomide and radiotherapy in children with diffuse intrinsic pontine gliomas or high-grade gliomas.

PURPOSE: This study was performed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of the immunomodulatory agent, lenalidomide, when administered daily during 6 weeks of radiation therapy to children with newly diagnosed diffuse intrinsic pontine glioma (DIPG) or high-grade glioma (HGG) PATIENTS & METHODS: Children and young adults < 22 years of age with newly diagnosed disease and no prior chemotherapy or radiation therapy were eligible. Children with HGG were required to have an inoperable or incompletely resected tumor. Eligible patients received standard radiation therapy to a prescription dose of 54-59.4 Gy, with concurrent administration of lenalidomide daily during radiation therapy in a standard 3 + 3 Phase I dose escalation design. Following completion of radiation therapy, patients had a 2-week break followed by maintenance lenalidomide at 116 mg/m2/day × 21 days of a 28-day cycle. RESULTS: Twenty-nine patients (age range 4-19 years) were enrolled; 24 were evaluable for dose finding (DIPG, n = 13; HGG, n = 11). The MTD was not reached at doses of lenalidomide up to 116 mg/m2/day. Exceptional responses were noted in DIPG and malignant glioma (gliomatosis cerebri) notably at higher dose levels and at higher steady state plasma concentrations. The primary toxicity was myelosuppression. CONCLUSION: The RP2D of lenalidomide administered daily during radiation therapy is 116 mg/m2/day. Children with malignant gliomas tolerate much higher doses of lenalidomide during radiation therapy compared to adults. This finding is critical as activity was observed primarily at higher dose levels suggesting a dose response.

Epidemiology, Treatment, and Performance-Based Outcomes in American Professional Baseball Players With Symptomatic Spondylolysis and Isthmic Spondylolisthesis.

BACKGROUND: Repetitive lumbar hyperextension and rotation during athletic activity affect the structural integrity of the lumbar spine. While many sports have been associated with an increased risk of developing a pars defect, few previous studies have systematically investigated spondylolysis and spondylolisthesis in professional baseball players. PURPOSE: To characterize the epidemiology and treatment of symptomatic lumbar spondylolysis and isthmic spondylolisthesis in American professional baseball players. We also sought to report the return-to-play (RTP) and performance-based outcomes associated with the diagnosis of a pars defect in this elite athlete population. STUDY DESIGN: Descriptive epidemiology study. METHODS: A retrospective cohort study was conducted among all Major and Minor League Baseball (MLB and MiLB, respectively) players who had low back pain and underwent lumbar spine imaging between 2011 and 2016. Players with radiological evidence of a pars defect (with or without listhesis) were included. Analyses were conducted to assess the association between player-specific characteristics and RTP time. Baseball performance metrics were also compared before and after the injury episode to determine whether there was an association between the diagnosis of a pars defect and diminished player performance. RESULTS: During the study period of 6 MLB seasons, 272 professional baseball players had low back pain and underwent lumbar spine imaging. Overall, 75 of these athletes (27.6%) received a diagnosis of pars defect. All affected athletes except one (98.7%) successfully returned to professional baseball, with a median RTP time of 51 days. Players with spondylolisthesis returned to play faster than those with spondylolysis, MLB athletes returned faster than MiLB athletes, and position players returned faster than pitchers. Athletes with a diagnosed pars defect did not show a significant decline in performance after returning to competition after their injury episode. CONCLUSION: Lumbar pars defects were a common cause of low back pain in American professional baseball players. The vast majority of affected athletes were able to return to competition without demonstrating a significant decline in baseball performance.

Dietary alterations modulate the microRNA 29/30 and IGF-1/AKT signaling axis in breast Cancer liver metastasis.

BACKGROUND: Metastatic cancer is incurable and understanding the molecular underpinnings is crucial to improving survival for our patients. The IGF-1/Akt signaling pathway is often impaired in cancer leading to its progression and metastases. Diet modification is known to alter the IGF-1/Akt pathway and affect the expression of microRNA involved in tumor initiation, growth and metastases. Liver metastases are one of the most common type of metastases in breast and colon cancer. In the present study, we looked at the effect of diet modification on the expression of microRNA in normal liver and liver with breast cancer metastases using in vivo model. METHODOLOGY: 6-month-old C57BL/6 J mice were put on either an ad libitum (AL) diet, or 40% calorie restricted (CR) diet or were fasted for 24 h (FA) before sacrifice. MicroRNA array analysis, western blot and qRT-PCR were performed using liver tissue to compare the treatment groups. A breast cancer model was also used to study the changes in microRNA expression in liver of a group of BALB/c mice orthotopically injected with 4 T1 cells in the mammary fat pad, put on either an AL or 30% CR diet. Liver and primary tumor tissues were used to perform qRT-PCR to compare the treatment groups. RESULTS: MicroRNA array analysis showed significant changes in miRNA expression in both CR and FA conditions in normal liver. Expression of miR-29 and miR-30 family members was increased in both CR and FA. Western blot analysis of the normal liver tissue showed that CR and FA downregulated the IGF-1/Akt pathway and qRT-PCR showed that the expression of miR-29b, miR-29c, miR-30a and miR-30b were increased with CR and FA. Liver tissue collected from mice in the breast cancer model showed an increase in expression of miR-29b, miR-29c and miR-30b while tumor tissue showed increased expression of miR-29c, miR-30a and miR-30b. DISCUSSION: Members of the miR-29 family are known to target and suppress IGF-1, while members of the miR-30 family are known to target and suppress both IGF-1 and IGF-1R. In the present study, we observe that calorie restriction increased the expression of miR-29 and miR-30 in both the normal liver as well as the liver with breast cancer metastases. These findings suggest that dietary alterations may play a role in the treatment of liver metastasis, which should be evaluated further.

The perceived efficacy and utility of spine bioskills curricula for resident and fellow education.

The purpose of this study is to assess the role of bioskills in orthopaedic and neurosurgical resident education. A survey of the utilization and perceived efficacy of bioskills was submitted to Lumbar Spine Research Society (LSRS) members. 36/104 surgeons responded, including 25 orthopaedic, 7 neurosurgical, and 4 integrated respondents. 63% of orthopaedic and 83% of neurosurgery faculty, reported using bioskills. When asked if completion of bioskills modules would encourage advancing trainees' participation (1-10 scale, 10 greatly increase), neurosurgical faculty reported 4.00 versus orthopaedics 6.43. Although orthopaedic faculty perceive greater efficacy of bioskills, the clinical impact of this difference remains uncertain.

Effects of Operating Room Size on Surgical Site Infection Following Lumbar Fusion Surgery.

BACKGROUND: Surgical site infections (SSIs) represent a devastating complication after spine surgery. Many factors have been identified, but the influence of operating room (OR) size on infection rate has not been assessed. METHODS: Two thousand five hundred and twenty-three patients who underwent open lumbar spine fusion at a single institution between 2010 and 2016 were included. Patients were dichotomized into large versus small groups based on OR volume. Bivariate logistic regression and a final multivariate model following a multicollinearity check were used to calculate odds of infection for all variables. RESULTS: A total of 63 patients (2.5%) developed SSIs with 46 (73%) in the larger OR group and 17 (27%) in the smaller OR group. The rate of SSIs in larger ORs was 3.02% compared with 1.81% in smaller ORs. Significant parameters impacting SSI in bivariate analysis included an earlier year of surgery, BMI > 30, more comorbidities, more levels decompressed and fused, smoking, and larger OR volumes. Multivariate analysis identified BMI > 30, Elixhauser scores, smoking, and increasing levels decompressed as significant predictors. Topical vancomycin was found to significantly decrease rate of infection in both analyses. CONCLUSIONS: OR size (large versus small) was ultimately not a significant predictor of infection related to rates of SSIs, although it did show a clinical trend toward significance, suggesting association. Future prospective analysis is warranted. LEVEL OF EVIDENCE: 3.