Elucidating differences in concussion subtype symptomatology in sports-related versus non-sports-related concussions: a retrospective cohort study.

OBJECTIVE: Postconcussive symptom questionnaires (PCSQs) are often used in concussion patient assessment, yet there is a lack of knowledge as to whether symptom subtype prevalence is dependent on the mechanism of injury (MOI). These subtypes can be defined as cognitive, atlanto-occipital/cervical spine, autonomic, balance, low energy/fatigue/sleep, emotional changes, eyes, and somatic. Using an institutional PCSQ that quantitatively addressed these subtypes, this retrospective study aimed to provide insight into differences in subtype symptomatology between sports-related (SR) and non-sports-related (NSR) injuries. METHODS: Consecutive concussion patients with Glasgow Coma Scale (GCS) score ≥ 13 and ≥ 16 years of age who were treated at a concussion clinic affiliated with an academic level I trauma center in the United States between December 2009 and January 2020 were eligible for inclusion. The authors extracted data on MOI, comorbidities, habits, prior injuries, and PCSQ results. Multivariate analysis of covariance was then conducted to determine the correlations between subtype scores and MOI while considering covariates. RESULTS: Of the 194 patients remaining after applying inclusion and exclusion criteria, analysis included 91 patients in the SR group consisting of 54 (59%) males with mean ± SD (range) age of 20.9 ± 7.3 (16-58) years and 103 patients in the NSR group consisting of 38 (37%) males with mean age of 39.2 ± 14.8 (17-71) years. Demographic characteristics differed significantly between groups. Estimated marginal mean scores were significantly lower in the SR injury group compared to the NSR injury group (with comparing main effects) for the cognitive (p < 0.001), autonomic (p < 0.000), balance (p < 0.025), energy (p < 0.006), emotional (p < 0.000), and total score (p < 0.001) subtypes. Multivariate tests identified three comorbidities that contributed to differences in subtype scores between groups: migraines (p < 0.012), vertigo (p < 0.004), and anxiety (p < 0.038). No significant results were found for the remaining comorbidities of (but not limited to) depression, neuropsychiatric disorders, seizures, syncope, sleep disorder, or none. CONCLUSIONS: The findings indicate that patients who sustain a concussion via an NSR injury present with more severe symptoms but similar concussion subtype frequency as those presenting with SR concussion. This suggests that the MOI may correlate more closely to symptom severity than concussion subtype composition, although larger patient populations with more definitive control of MOI are needed to further elucidate these claims.

Histologic Assessment of Lumbosacral Transitional Vertebrae Pseudoarticulation as a Source of Pain in Bertolotti Syndrome.

BACKGROUND: Bertolotti syndrome (BS) is characterized by chronic pain and functional impairment associated with lumbosacral transitional vertebrae (LSTVs). The study aimed to investigate the histologic characteristics of the pseudoarticulation between the enlarged transverse process and sacrum seen in Castellvi 2a LSTV and explore the involvement of nervous tissue in pain generation. METHODS: Immunohistochemical analysis using S100 protein staining was performed to assess the presence of nerve tissue. RESULTS: These changes included fibrillation, chondrocyte cloning, alterations in the proteoglycan matrix, and focal chondrocyte necrosis. Notably, no nerve tissue was observed in any of the specimens, as confirmed by negative S100 protein staining. CONCLUSIONS: The study findings suggest that nerve tissue is not involved in the nociceptive mechanisms underlying pain in BS. The histologic similarities between the pseudoarticulation and osteoarthritic joints indicate that pseudoarticulation itself may be a significant source of pain in BS. These insights contribute to our understanding of the pathophysiology of BS and support treatment paradigms prioritizing pain control with medications such as NSAIDs before considering surgical intervention. Future studies with larger sample sizes and in vivo models are needed to further validate these findings and explore the changes in joint histology under biomechanical forces in LSTVs.

An Interdisciplinary Protocol for Ventriculoperitoneal Shunt Patient Selection in Normal Pressure Hydrocephalus.

BACKGROUND: Normal pressure hydrocephalus can be treated with ventriculoperitoneal shunt (VPS) placement, but no broadly implemented indication for VPS exists. METHODS: Our protocol consists of physical therapy and occupational therapy practitioners administering validated tests of gait, balance, and cognition before and after lumbar drain placement. Specific tests include: Timed "Up & Go", Tinetti Gait and Balance Assessment, Berg Balance Scale, Mini Mental Status Exam, Trail Making Test Part B, and the Rey Auditory and Visual Learning Test. Minimal clinically important difference values for each test were determined from literature review. A retrospective review of patients treated under this protocol was performed. The primary outcomes were candidacy for VPS based on the protocol and patient-reported symptomatic improvement after VPS placement. RESULTS: A total of 48/75 (64%) patients received VPS. A total of 43/48 (89.6%) of those shunted reported improved symptoms at 6-week follow-up. However, 10/22 (45.5%) reported worsening symptoms at 1-year follow-up. The mean Tinetti score significantly increased after lumbar drain in patients who improved with VPS compared to the no shunt group (4.27 vs. -0.48, P < 0.001). A total of 6/33 (18%) patients with postoperative imaging had a subdural fluid collection identified and 3/49 (6%) had other complications, including 1 seizure, 1 intracerebral hemorrhage, and 1 stroke. CONCLUSIONS: Standardized assessment of gait, balance, and cognition before and after temporary cerebrospinal fluid diversion identifies patients with normal pressure hydrocephalus likely to benefit from VPS placement with a low complication rate. One year after VPS, approximately one half of patients had symptoms recurrence.

Matching Patients to Accelerate Clinical Trials (MPACT): Enabling Technology for Oncology Clinical Trial Workflow.

Clinical trial enrollment is impeded by the significant time burden placed on research coordinators screening eligible patients. With 50,000 new cancer cases every year, the Veterans Health Administration (VHA) has made increased access for Veterans to high-quality clinical trials a priority. To aid in this effort, we worked with research coordinators to build the MPACT (Matching Patients to Accelerate Clinical Trials) platform with a goal of improving efficiency in the screening process. MPACT supports both a trial prescreening workflow and a screening workflow, employing Natural Language Processing and Data Science methods to produce reliable phenotypes of trial eligibility criteria. MPACT also has a functionality to track a patient's eligibility status over time. Qualitative feedback has been promising with users reporting a reduction in time spent on identifying eligible patients.

Cannabis Use is Associated With Higher Rates of Pseudarthrosis Following TLIF: A Multi-Institutional Matched-Cohort Study.

STUDY DESIGN: This was a retrospective cohort study. OBJECTIVE: To compare the rates of pseudarthrosis in patients undergoing 1 to 3 level transforaminal lumbar interbody fusion (TLIF) procedures between cannabis users and noncannabis users. SUMMARY OF BACKGROUND DATA: Recreational use of cannabis is common, though it remains poorly studied and legally ambiguous in the United States. Patients with back pain may turn to adjunctive use of cannabis to manage their pain. However, the implications of cannabis use on the achievement of bony fusion are not well-characterized. METHODS: Patients who underwent 1 to 3 level TLIF for degenerative disc disease or degenerative spondylolisthesis between 2010 and 2022 were identified using the PearlDiver Mariner all-claims insurance database. Cannabis users were identified with ICD 10 code F12.90. Patients undergoing surgery for nondegenerative pathologies such as tumors, trauma, or infection were excluded. 1:1 exact matching was performed using demographic factors, medical comorbidities, and surgical factors which were significantly associated with pseudarthrosis in a linear regression model. The primary outcome measure was development of pseudarthrosis within 24 months after 1 to 3 level TLIF. The secondary outcomes were the development of all-cause surgical complications as well as all-cause medical complications. RESULTS: A 1:1 exact matching resulted in two equal groups of 1593 patients who did or did not use cannabis and underwent 1 to 3 level TLIF. Patients who used cannabis were 80% more likely to experience pseudarthrosis compared with patients who do not [relative risk (RR): 1.816, 95% CI: 1.291-2.556, P <0.001]. Similarly, cannabis use was associated with significantly higher rates of all-cause surgical complications (RR: 2.350, 95% CI: 1.399-3.947, P =0.001) and all-cause medical complications (RR: 1.934, 95% CI: 1.516-2.467, P <0.001). CONCLUSION: After 1:1 exact matching to control for confounding variables, the findings of this study suggest that cannabis use is associated with higher rates of pseudarthrosis, as well as higher rates of all-cause surgical and all-cause medical complications. Further studies are needed to corroborate our findings.

TLIF is Associated With Lower Rates of Adjacent Segment Disease and Complications Compared to ALIF: A Matched-Cohort Analysis.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: To compare the rate of adjacent segment disease (ASD) in patients undergoing anterior lumbar interbody fusion (ALIF) versus transforaminal lumbar interbody fusion (TLIF) for the treatment of degenerative stenosis and spondylolisthesis. SUMMARY OF BACKGROUND DATA: ALIF and TLIF are frequently used to treat Lumbar stenosis and spondylolisthesis. While both approaches have distinct advantages, it is unclear whether there are any differences in rates of ASD and postoperative complications. METHODS: A retrospective cohort study of patients who underwent index 1-3 levels ALIF or TLIF between 2010 and 2022, using the PearlDiver Mariner Database, an all-claims insurance database (120 million patients). Patients with a history of prior lumbar surgery and those undergoing surgery for cancer, trauma, or infection were excluded. Exact 1:1 matching was performed using demographic factors, medical comorbidities, and surgical factors found to be significantly associated with ASD in a linear regression model. The primary outcome was a new diagnosis of ASD within 36 months of index surgery, and secondary outcomes were all-cause medical and surgical complications. RESULTS: Exact 1:1 matching resulted in 2 equal groups of 106,451 patients undergoing TLIF and ALIF. The TLIF approach was associated with a lower risk of ASD (RR 0.58, 95% CI 0.56-0.59, P < 0.001) and all-cause medical complications (RR 0.94, 95% CI 0.91-0.98, P =0.002). All-cause surgical complications were not significantly different between both groups. CONCLUSION: After 1:1 exact matching to control for confounding variables, this study suggests that for patients with symptomatic degenerative stenosis and spondylolisthesis, a TLIF procedure (compared to ALIF) is associated with a decreased risk of developing ASD within 36 months of index surgery. Future prospective studies are needed to corroborate these findings. LEVEL OF EVIDENCE: Level-3.

Lumbar Arthroplasty Is Associated With a Lower Incidence of Adjacent Segment Disease Compared With ALIF: A Propensity-matched Analysis.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVE: The objective of this study was to compare the rate of adjacent segment disease (ASD) between lumbar disk arthroplasty (LDA) and anterior lumbar interbody fusion (ALIF). SUMMARY OF BACKGROUND DATA: LDA and ALIF are alternative surgical approaches used to treat lumbar degenerative disk disease. However, there is a paucity of studies comparing the risk of ASD after these procedures. METHODS: Patients who underwent 1- to 2-level LDA or ALIF between 2010 and 2022 were identified in the PearlDiver Mariner insurance all-claims database. Exclusion criteria included the history of prior lumbar spine surgery or surgery for tumors, trauma, or infection. 1:1 propensity matching was performed using demographic factors, medical comorbidities, and surgical factors, which were significantly associated with ASD. RESULTS: 1:1 propensity matching created two equal groups of 1625 patients without baseline differences who underwent LDA or ALIF. LDA was significantly associated with a lower risk of ASD (relative risk: 0.932, 95% CI, 0.899-0.967, P <0.001) and need for revision within 30 days (relative risk: 0.235, 95% CI, 0.079-0.698, P =0.007). There were no differences in all-cause surgical and medical complications between both groups. CONCLUSIONS: After risk adjustment for demographic and clinical characteristics, the results suggest that LDA is associated with a lower risk of ASD compared with ALIF. LDA was also associated with lower hospital cost and shorter length of stay.

Examining degenerative disease adjacent to lumbosacral transitional vertebrae: a retrospective cohort study.

OBJECTIVE: Bertolotti syndrome is a clinical diagnosis given to patients with low-back pain arising from a lumbosacral transitional vertebra (LSTV). While biomechanical studies have demonstrated abnormal torques and range of motion occurring at and above this type of LSTV, the long-term effects of these biomechanical changes on the LSTV adjacent segments are not well understood. This study examined degenerative changes at segments superjacent to the LSTV in patients with Bertolotti syndrome. METHODS: This study involved a retrospective comparison of patients between 2010 and 2020 with an LSTV and chronic back pain (Bertolotti syndrome) and control patients with chronic back pain with no LSTV. The presence of an LSTV was confirmed on imaging, and the caudal-most mobile segment above the LSTV was assessed for degenerative changes. Degenerative changes were assessed by grading the intervertebral disc, facets, degree of spinal stenosis, and spondylolisthesis using well documented grading systems. All computations were performed in R, version 4.1.0. All tests were two-sided, and p values < 0.05 was considered statistically significant. Separate logistic regression analyses were run with the associated dependent variables for each aim, with age at MRI and sex included as covariates. Odds ratios and 95% confidence intervals were computed. RESULTS: A total of 172 patients were included, 101 with Bertolotti syndrome and 71 controls. Control patients consisted of patients with low-back pain but no diagnosis of Bertolotti syndrome or an LSTV. Fifty-six Bertolotti (55.4%) and 27 control (38.0%) patients were female, (p = 0.03). After adjusting for age at MRI and sex, Bertolotti patients had pelvic incidence (PI) that was 9.83° greater than control patients (95% CI 5.15°-14.50°, p < 0.001). Sacral slope was not significantly different between the Bertolotti and control groups (beta estimate 3.10°, 95% CI -1.07° to 7.27°; p = 0.14). Bertolotti patients had 2.69 times higher odds of having a high disc grade at L4-5 (3-4 vs 0-2), compared with control patients (OR 2.69, 95% CI 1.28-5.90; p = 0.01). There were no significant differences between Bertolotti patients and controls for spondylolisthesis, facet grade, or spinal stenosis grade. CONCLUSIONS: Patients with Bertolotti syndrome had a significantly higher PI and were more likely to have adjacent-segment disease (ASD; L4-5) compared with control patients. However, after controlling for age and sex, PI and ASD did not appear to have a significant association within the cohort of Bertolotti patients. The altered biomechanics and kinematics in this condition may be a causative factor in this degeneration, although proof of causation is not possible in this study. This association may warrant closer follow-up protocols for patients being treated for Bertolotti syndrome, but further prospective studies are needed to establish if radiographic parameters can serve as an indicator for biomechanical alterations in vivo.

The Use of Shape-Memory Alloy Staples (Nitinol) in the Treatment of Pubic Symphyseal Disruptions: Clinical Results and Radiographic Outcomes.

Nitinol is a shape-memory alloy that has many diverse applications in the field of orthopedics. There have been no previous investigations reporting clinical or radiographic outcomes of the use of nitinol staples in the definitive stabilization of the pubic symphysis. A retrospective chart review was completed on 42 patients who underwent operative stabilization of pubic symphyseal disruption at an urban level-1 trauma center. Patients treated with pelvic staples alone, or in conjunction with traditional plates and screws, were compared with those treated without the use of a shape memory alloys. Thirty-four patients were included for final analysis (8 staples and 26 controls) in this investigation. Three of eight patients in the pelvic staple group had implant failures, with two having a loss of reduction (25%); this was not significantly different from the seven hardware failures (P = 0.61) seen in the control group without any loss of reduction (P = 0.17). Failures in the nitinol staple group occurred earlier at 17.3 days compared with the control group at 101.7 days (P = 0.003). There were no significant differences between groups with regards to any of the other pre- or postoperative variables investigated. The use of nitinol staples vs. traditional plate and screw constructs for stabilizing the pubic symphysis did not result in more clinical failures. The hardware failures identified in the nitinol staple group occurred significantly earlier in the postoperative period, and were associated with a loss of reduction of the pubic symphysis.

Cellular kinetics: A clinical and computational review of CAR-T cell pharmacology.

To the extent that pharmacokinetics influence the effectiveness of nonliving therapeutics, so too do cellular kinetics influence the efficacy of Chimeric Antigen Receptor (CAR) -T cell therapy. Like conventional therapeutics, CAR-T cell therapies undergo a distribution phase upon administration. Unlike other therapeutics, however, this distribution phase is followed by subsequent phases of expansion, contraction, and persistence. The magnitude and duration of these phases unequivocally influence clinical outcomes. Furthermore, the "pharmacodynamics" of CAR-T cells is truly dynamic, as cells can rapidly become exhausted and lose their therapeutic efficacy. Mathematical models are among the translational tools commonly applied to assess, characterize, and predict the complex cellular kinetics and dynamics of CAR-T cells. Here, we provide a focused review of the cellular kinetics of CAR-T cells, the mechanisms underpinning their complexity, and the mathematical modeling approaches used to interrogate them.

The trial effect in patients with glioblastoma: effect of clinical trial enrollment on overall survival.

PURPOSE: To determine whether participation in a clinical trial was associated with improved survival in patients with glioblastoma (GBM). METHODS: Following IRB approval, patients were identified using CPT and ICD codes. Data was collected using retrospective review of electronic medical records. When necessary, death data was obtained from online obituaries. Inverse propensity score matching was utilized to transform the two cohorts to comparable sets. Survival was compared using Kaplan-Meyer curves and Wilcoxon Rank Sum Test. RESULTS: In this cohort of 365 patients, 89 were enrolled in a clinical trial and 276 were not. Patients enrolled in clinical trials had a significantly higher mean baseline KPS score, higher proportion of surgical resections, and were more likely to receive temozolomide treatment than patients not enrolled in a clinical trial. After inverse propensity score matching, patients enrolled in a clinical trial lived significantly longer than those not enrolled (28.8 vs 22.2 months, p = 0.005). A potential confounder of this study is that patients not in a clinical trial had significantly fewer visits with neuro-oncologists than patients enrolled in a clinical trial (7 ± 8 vs 12 ± 9, p < 0. 0001). CONCLUSIONS: Clinical trials enroll patients with the most favorable prognostic features. Even when correcting for this bias, clinical trial enrollment is an independent predictor of increased survival regardless of treatment arm.

Degenerative Spine Disorders and Multiple Sclerosis.

Multiple sclerosis (MS) is an autoimmune inflammatory disease that results in demyelination of the central nervous system (CNS). MS affects as many as 350,000 individuals in the United States and commonly presents before the age of 45 years. Patients with MS, as the general population, are likely to encounter degenerative changes of the spine as they age, and this can pose a unique challenge to both patients with MS and physicians, as both conditions can have a great deal of symptomatic overlap despite stark differences in management. Currently there is no definitive approach that allows physicians to distinguish between the 2 conditions; however, specific clinical and radiologic findings have been identified as being useful in evaluating these patients.

Identifying the relationship between lumbar sacralization and adjacent ligamentous anatomy in patients with Bertolotti syndrome and healthy controls.

OBJECTIVE: Bertolotti syndrome is a diagnosis given to patients experiencing low-back pain due to a lumbosacral transitional vertebra (LSTV). LSTVs cause altered biomechanics at the lumbosacral junction, predisposing these patients to degenerative disease. It has been proposed that these patients have additional non-osseous variation such as ligamentous differences in the lumbar spine. The iliolumbar ligament, which attaches from the iliac crest to the transverse process of L4 and L5, plays a significant role in reducing lumbar motion in all six degrees of freedom; therefore, altered ligament anatomy can have a significant impact on stability. The purpose of this study was to examine the iliolumbar ligament complex in patients with Bertolotti syndrome and anatomically normal controls to determine if underdevelopment of the iliolumbar ligament complex is seen in Bertolotti syndrome. METHODS: This is a retrospective analysis of patients with Bertolotti syndrome and anatomically normal controls who received care at the authors' institution between 2010 and 2020. Axial thickness of the iliolumbar ligament at the L5 vertebral level was assessed via MRI. Results were compared between the defective and normal side within unilaterally affected (Castellvi types IIa and IIIa) Bertolotti syndrome patients, between defective sides in bilaterally affected Bertolotti syndrome patients (Castellvi types IIb, IIIb, and IV), and between the affected side in Bertolotti syndrome patients and the corresponding location in normal controls. RESULTS: A total of 173 patients were included in the study, 102 with Bertolotti syndrome and 71 controls. Among the Bertolotti patients, 49 had left LSTVs, 29 had right LSTVs, and 24 had bilateral LSTVs. For patients with unilateral defects, defective side ligaments were thinner than ligaments on the normal side (p < 0.05). For bilateral LSTVs, ligament thickness on each side was considered statistically equivalent (p < 0.05) and not significantly different from that in controls. CONCLUSIONS: Bertolotti syndrome correlates to significant underdevelopment of the iliolumbar ligament corresponding to the side of the LSTV as compared to the ligament on the contralateral side. In patients with bilateral LSTVs, no difference in the iliolumbar ligament compared to that in controls was seen. Developmental changes in the iliolumbar ligament may further exacerbate the altered lumbosacral biomechanics seen in patients with unilateral LSTV, whereas bilateral LSTVs may still allow normal development of the ligament complex. Further research should be done to examine the discrepancies seen in this study.

Quality-of-life and postoperative satisfaction following pseudoarthrectomy in patients with Bertolotti syndrome.

BACKGROUND CONTEXT: Bertolotti syndrome is a clinical diagnosis given to patients with back pain arising from a lumbosacral transitional vertebra (LSTV). A particular class of LSTV involves a pseudoarticulation between the fifth lumbar transverse process and the sacral ala, and surgical resection of the pseudoarticulation may be offered to patients failing conservative management. Bertolotti syndrome is still not well understood, particularly regarding how patients respond to surgical resection of the LSTV pseudoarticulation. PURPOSE: To examine change in quality-of-life (QOL) and patient satisfaction following surgical resection of the LSTV pseudoarticulation in patients with Bertolotti syndrome. DESIGN: Ambidirectional observational cohort study of patients seen at a single institution's tertiary spine center over a 10-year period. PATIENT SAMPLE: Cohort consisted of 31 patients with Bertolotti Syndrome who underwent surgical resection of the pseudoarticulation. OUTCOME MEASURES: Preoperative and postoperative Patient-Reported Outcomes Measurement Information System Global Health (PROMIS-GH) Mental and Physical Health T-scores, and a single-item postoperative satisfaction questionnaire. METHODS: Patients were identified through diagnostic and procedural codes. Immediate preoperative PROMIS-GH scores available in the chart were gathered retrospectively, and postoperative PROMIS-GH and satisfaction scores were gathered prospectively through a mail-in survey. RESULTS: Mean (SD) improvement of PROMIS-GH Physical Health T-score was 8.7 (10.5) (p<.001). Mean (SD) improvement of PROMIS-GH Mental Health T-scores was 5.9 (9.2) (p=.001). When stratifying PROMIS-GH T-scores by response to the patient satisfaction survey, there were significant group differences in mean change for Physical Health T-scores (p<.001), and Mental Health T-score (p=.009). Patients who stated, "The treatment met my expectations" had much greater mean improvement in the PROMIS-GH T-scores. CONCLUSIONS: Patients undergoing a pseudoarticulation resection procedure may experience a significant improvement in quality-of-life as measured by PROMIS-GH Mental and Physical Health.

Peritraumatic Plasma Omega-3 Fatty Acid Concentration Predicts Chronic Pain Severity Following Thermal Burn Injury.

Chronic pain is a significant comorbidity of burn injury affecting up to 60% of survivors. Currently, no treatments are available to prevent chronic pain after burn injury. Accumulating evidence suggests that omega-3 fatty acids (O3FAs) improve symptoms across a range of painful conditions. In this study, we evaluated whether low peritraumatic levels of O3FA predict greater pain severity during the year after burn injury. Burn survivors undergoing skin autograft were recruited from three participating burn centers. Plasma O3FA (n = 77) levels were assessed in the early aftermath of burn injury using liquid chromatography/mass spectrometry, and pain severity was assessed via the 0 to 10 numeric rating scale for 1 year following burn injury. Repeated-measures linear regression analyses were used to evaluate the association between peritraumatic O3FA concentrations and pain severity during the year following burn injury. Peritraumatic O3FA concentration and chronic pain severity were inversely related; lower levels of peritraumatic O3FAs predicted worse pain outcomes (ß = -0.002, P = .020). Future studies are needed to evaluate biological mechanisms mediating this association and to assess the ability of O3FAs to prevent chronic pain following burn injury.

Assessment of L5-S1 anterior lumbar interbody fusion stability in the setting of lengthening posterior instrumentation constructs: a cadaveric biomechanical study.

OBJECTIVE: Excessive stress and motion at the L5-S1 level can lead to degenerative changes, especially in patients with posterior instrumentation suprajacent to L5. Attention has turned to utilization of L5-S1 anterior lumbar interbody fusion (ALIF) to stabilize the lumbosacral junction. However, questions remain regarding the effectiveness of stand-alone ALIF in the setting of prior posterior instrumented fusions terminating at L5. The purpose of this study was to assess the biomechanical stability of an L5-S1 ALIF with increasing lengths of posterior thoracolumbar constructs. METHODS: Seven human cadaveric spines (T9-sacrum) were instrumented with pedicle screws from T10 to L5 and mounted to a 6 degrees-of-freedom robot. Posterior fusion construct lengths (T10-L5, T12-L5, L2-5, and L4-5) were instrumented to each specimen, and torque-fusion level relationships were determined for each construct in flexion-extension, axial rotation, and lateral bending. A stand-alone L5-S1 ALIF was then instrumented, and L5-S1 motion was measured as increasing pure moments (2 to 12 Nm) were applied. Motion reduction was calculated by comparing L5-S1 motion across the ALIF and non-ALIF states. RESULTS: The average motion at L5-S1 in axial rotation, flexion-extension, and lateral bending was assessed for each fusion construct with and without ALIF. After adding ALIF to a posterior fusion, L5-S1 motion was significantly reduced relative to the non-ALIF state in all but one fused surgical condition (p < 0.05). Longer fusions with ALIF produced larger L5-S1 motions, and in some cases resulted in motions higher than native state motion. CONCLUSIONS: Posterior fusion constructs up to L4-5 could be appropriately stabilized by a stand-alone L5-S1 ALIF when using a nominal threshold of 80% reduction in native motion as a potential positive indicator of fusion. The results of this study allow conclusions to be drawn from a biomechanical standpoint; however, the clinical implications of these data are not well defined. These findings, when taken in appropriate clinical context, can be used to better guide clinicians seeking to treat L5-S1 pathology in patients with prior posterior thoracolumbar constructs.

Expression of Tim-3 drives phenotypic and functional changes in Treg cells in secondary lymphoid organs and the tumor microenvironment.

Regulatory T cells (Treg cells) are critical mediators of self-tolerance, but they can also limit effective anti-tumor immunity. Although under homeostasis a small fraction of Treg cells in lymphoid organs express the putative checkpoint molecule Tim-3, this protein is expressed by a much larger proportion of tumor-infiltrating Treg cells. Using a mouse model that drives cell-type-specific inducible Tim-3 expression, we show that expression of Tim-3 by Treg cells is sufficient to drive Treg cells to a more effector-like phenotype, resulting in increases in suppressive activity, effector T cell exhaustion, and tumor growth. We also show that T-reg-cell-specific inducible deletion of Tim-3 enhances anti-tumor immunity. Enhancement of Treg cell function by Tim-3 is strongly correlated with increased expression of interleukin-10 (IL-10) and a shift to a more glycolytic metabolic phenotype. Our data demonstrate that Tim-3+ Treg cells may be a relevant therapeutic target cell type for the treatment of cancer.

Identifying treatment patterns in patients with Bertolotti syndrome: an elusive cause of chronic low back pain.

BACKGROUND CONTEXT: Bertolotti Syndrome is a diagnosis given to patients with lower back pain arising from a lumbosacral transitional vertebra (LSTV). These patients can experience symptomatology similar to common degenerative diseases of the spine, making Bertolotti Syndrome difficult to diagnose with clinical presentation alone. Castellvi classified the LSTV seen in this condition and specifically in types IIa and IIb, a "pseudoarticulation" is present between the fifth lumbar transverse process and the sacral ala, resulting in a semi-mobile joint with cartilaginous surfaces.Treatment outcomes for Bertolotti Syndrome are poorly understood but can involve diagnostic and therapeutic injections and ultimately surgical resection of the pseudoarticulation (pseudoarthrectomy) or fusion of surrounding segments. PURPOSE: To examine spine and regional injection patterns and clinical outcomes for patients with diagnosed and undiagnosed Bertolotti Syndrome. DESIGN: Retrospective observational cohort study of patients seen at a single institution's tertiary spine center over a 10-year period. PATIENT SAMPLE: Cohort consisted of 67 patients with an identified or unidentified LSTV who were provided injections or surgery for symptoms related to their chronic low back pain and radiculopathy. OUTCOME MEASURES: Self-reported clinical improvement following injections and pseudoarthrectomy. METHODS: Patient charts were reviewed. Identification of a type II LSTV was confirmed through provider notes and imaging. Variables collected included demographics, injection history and outcomes, and surgical history for those who underwent pseudoarthrectomy. RESULTS: A total of 22 out of 67 patients (33%) had an LSTV that was not identified by their provider. Diagnosed patients underwent fewer injections for their symptoms than those whose LSTV was never previously identified (p = 0.031). Only those diagnosed received an injection at the LSTV pseudoarticulation, which demonstrated significant symptomatic improvement at immediate follow up compared to all other injection types (p = 0.002). Patients who responded well to pseudoarticulation injections were offered a pseudoarthrectomy, which was more likely to result in symptom relief at most recent follow up than patients who underwent further injections without surgery (p < 0.001). CONCLUSIONS: Undiagnosed patients are subject to a higher quantity of injections at locations less likely to provide relief than pseudoarticulation injections. These patients in turn cannot be offered a pseudoarthrectomy which can result in significant relief compared to continued injections alone. Proper and timely identification of an LSTV dramatically alters the clinical course of these patients as they can only be offered treatment directed towards the LSTV once it is identified.

Clinical assessment and management of Bertolotti Syndrome: a review of the literature.

Bertolotti Syndrome is a diagnosis given to patients experiencing pain caused by the presence of a lumbosacral transitional vertebra (LSTV), which is characterized by enlargement of the L5 transverse process(es), with potential pseudoarticulation or fusion with the sacrum. The Castellvi classification system is commonly utilized to grade LSTVs based on the degree of contact between the L5 transverse process(es) and the sacrum. LSTVs present a diagnostic dilemma to the treating clinician, as they may remain unidentified on plain x-rays and even advanced imaging; additionally, even if the malformation is identified, patients with a LSTV may be asymptomatic or have nonspecific symptoms, such as low back pain with or without radicular symptoms. With low back pain being extremely prevalent in the general population; it can be difficult to implicate the LSTV as the source of this pain. Care should be taken however, to exclude Bertolotti Syndrome in patients under 30 years old presenting with persisting low back pain given its congenital origin. If a LSTV is identified, typically with acquisition of a MRI or CT scan of the lumbosacral spine, and there is an absence of a more compelling or obvious source for the patient's symptoms, a conservative, step-wise management plan is recommended. This may include assessing for improvement in symptoms with injections prior to proceeding with surgical intervention. Additional concerns arise from the biomechanical alterations that a LSTV induces in adjacent spinal levels, predisposing this patient population to a more rapid-onset of adjacent segment disease, raising the question as to the most appropriate surgery (resection of LSTV pseudoarticulation with or without fusion). Postoperative outcome data for patients undergoing surgical treatment is limited in the literature with promising, but variable, results. More large-scale, controlled studies must be performed to gain further insight into the ideal work-up and management of this pathology.

Peritraumatic Vitamin D Levels Predict Chronic Pain Severity and Contribute to Racial Differences in Pain Outcomes Following Major Thermal Burn Injury.

Major thermal burn injuries result in approximately 40,000 hospitalizations in the United States each year. Chronic pain affects up to 60% of burn survivors, and Black Americans have worse chronic pain outcomes than White Americans. Mechanisms of chronic pain pathogenesis after burn injury, and accounting for these racial differences, remain poorly understood. Due to socioeconomic disadvantage and differences in skin absorption, Black Americans have an increased prevalence of Vitamin D deficiency. We hypothesized that peritraumatic Vitamin D levels predict chronic pain outcomes after burn injury and contribute to racial differences in pain outcomes. Among burn survivors (n = 77, 52% White, 48% Black, 77% male), peritraumatic Vitamin D levels were more likely to be deficient in Blacks vs Whites (27/37 [73%] vs 14/40 [35%], P < .001). Peritraumatic Vitamin D levels were inversely associated with chronic post-burn pain outcomes across all burn injury survivors, including those who were and were not Vitamin D deficient, and accounted for approximately one-third of racial differences in post-burn pain outcome. Future studies are needed to evaluate potential mechanisms mediating the effect of Vitamin D on post-burn pain outcomes and the potential efficacy of Vitamin D in improving pain outcomes and reducing racial differences.