Elevated risk of recurrence and retreatment for silent pituitary adenomas.

PURPOSE: Pituitary adenomas are the most common tumor of the pituitary gland and comprise nearly 15% of all intracranial masses. These tumors are stratified into functional or silent categories based on their pattern of hormone expression and secretion. Preliminary evidence supports differential clinical outcomes between some functional pituitary adenoma (FPA) subtypes and silent pituitary adenoma (SPA) subtypes. METHODS: We collected and analyzed the medical records of all patients undergoing resection of SPAs or FPAs from a single high-volume neurosurgeon between 2007 and 2018 at Brigham and Women's Hospital. Descriptive statistics and the Mantel-Cox log-rank test were used to identify differences in outcomes between these cohorts, and multivariate logistic regression was used to identify predictors of radiographic recurrence for SPAs. RESULTS: Our cohort included 88 SPAs and 200 FPAs. The majority of patients in both cohorts were female (48.9% of SPAs and 63.5% of FPAs). SPAs were larger in median diameter than FPAs (2.1 cm vs. 1.2 cm, p < 0.001). The most frequent subtypes of SPA were gonadotrophs (55.7%) and corticotrophs (30.7%). Gross total resection (GTR) was achieved in 70.1% of SPA resections and 86.0% of FPA resections (p < 0.001). SPAs had a higher likelihood of recurring (hazard ratio [HR] 3.2, 95% confidence interval [95%CI] 1.6-7.2) and a higher likelihood of requiring retreatment for recurrence (HR 2.5; 95%CI 1.0-6.1). Subset analyses revealed that recurrence and retreatment were more both likely for subtotally resected SPAs than subtotally resected FPAs, but this pattern was not observed in SPAs and FPAs after GTR. Among SPAs, recurrence was associated with STR (odds ratio [OR] 9.3; 95%CI 1.4-64.0) and younger age (OR 0.92 per year; 95%CI 0.88-0.98) in multivariable analysis. Of SPAs that recurred, 12 of 19 (63.2%) were retreated with repeat surgery (n = 11) or radiosurgery (n = 1), while the remainder were observed (n = 7).There were similar rates of recurrence across different SPA subtypes. CONCLUSION: Patients undergoing resection of SPAs should be closely monitored for disease recurrence through more frequent clinical follow-up and diagnostic imaging than other adenomas, particularly among patients with STR and younger patients. Several patients can be observed after radiographic recurrence, and the decision to retreat should be individualized. Longitudinal clinical follow-up of SPAs, including an assessment of symptoms, endocrine function, and imaging remains critical.

Utilization of PROMIS Neuropathic Pain Quality for Detection and Monitoring Neuropathic Pain in Heel Pain Patients.

Background: Diagnosis and management of neuropathic pain (NP) in foot and ankle patients remain challenging. We investigated the plausibility of using Patient-Reported Outcomes Measurement Information System (PROMIS) Neuropathic Pain Quality (PQ-Neuro) as an initial screening tool to detect NP and track the treatment effects. Methods: Patients with heel pain were prospectively recruited and grouped to no-NP, mild-NP, and severe-NP based on the initial PROMIS PQ-Neuro t scores. Pain Interference (PI), Physical Function (PF), and Self-Efficacy (SE) scores were evaluated at baseline, 30-day, and 90-day follow-up. Other factors such as age, smoking, body mass index (BMI), low back/neck pain, anxiety/depression, and medications were analyzed. Linear mixed modeling was used to assess the main effects of time and NP on PROMIS t scores, comparing minimal clinically important difference (MCID). Results: Forty-eight patients with mean age of 52.4 years were recruited. Using the PROMIS PQ-Neuro as the assessment tool, 33 patients (69%) were detected to have NP at baseline-23 (48%) mild and 10 (21%) severe. BMI was the only independent factor associated with NP (P = .011). Higher baseline PQ-Neuro t score was significantly associated with higher follow-up PQ-Neuro (P < .001), PI (P = .005), and lower SE (P = .04) across time points. Patients with NP showed lower PF at baseline with significantly less improvement in PF (3 vs 9.9, P = .035) and did not meet MCID. Conclusion: Baseline PROMIS PQ-Neuro ≥46 was significantly associated with worse PI and SE across all time points, with less clinically significant improvements in PF. Prevalence of NP in heel pain patients was high. The PROMIS PQ-Neuro may serve as a valuable tool for detection of NP and guiding clinical treatment decision pathways for heel pain patients. Level of Evidence: Level III, prospective cohort study.

Price Transparency for Cervical Spinal Fusion Among High-Performing Spine Centers in the United States.

BACKGROUND AND OBJECTIVES: As of January 1, 2021, all US hospitals are required by the Hospital Price Transparency Final Rule (HPTFR) to publish standard charges for all items and services, yet the state of price transparency for cervical spinal fusion is unknown. Here, we assess the nationwide price transparency landscape for cervical spinal fusion among high-performing spine centers in the United States. METHODS: In this cross-sectional economic evaluation, we queried publicly available price transparency websites of 332 "high-performing" spine centers, as defined by the US News and World Report. We extracted variables including gross charges for cervical spinal fusion, payor options, price reporting methodology, and prices relevant to consumers including listed cash prices and minimum and maximum negotiated charges. RESULTS: While nearly all 332 high-performing spine surgery centers (99.4%) had an online cost estimation tool, the HPTFR compliance rate was only 8.4%. Gross charges for cervical spinal fusion were accessible for 68.1% of hospitals, discounted cash prices for 46.4% of hospitals, and minimum and maximum charges for 10.8% of hospitals. There were large IQRs for gross charges ($48 491.98-$99 293.37), discounted cash prices ($26 952.25-$66 806.63), minimum charges ($10 766.11-$21 248.36), and maximum charges ($39 280.49-$89 035.35). There was geographic variability in the gross charges of cervical spinal fusion among high-performing spine centers within and between states. There was a significant association between "excellent" discharge to home status and lower mean gross charges. CONCLUSION: Although online cost reporting has drastically increased since implementation of the HPTFR, data reported for cervical spinal fusion remain inadequate and difficult to interpret by both providers and patients.

Intertumoral lineage diversity and immunosuppressive transcriptional programs in well-differentiated gastroenteropancreatic neuroendocrine tumors.

Neuroendocrine tumors (NETs) are rare cancers that most often arise in the gastrointestinal tract and pancreas. The fundamental mechanisms driving gastroenteropancreatic (GEP)-NET growth remain incompletely elucidated; however, the heterogeneous clinical behavior of GEP-NETs suggests that both cellular lineage dynamics and tumor microenvironment influence tumor pathophysiology. Here, we investigated the single-cell transcriptomes of tumor and immune cells from patients with gastroenteropancreatic NETs. Malignant GEP-NET cells expressed genes and regulons associated with normal, gastrointestinal endocrine cell differentiation, and fate determination stages. Tumor and lymphoid compartments sparsely expressed immunosuppressive targets commonly investigated in clinical trials, such as the programmed cell death protein-1/programmed death ligand-1 axis. However, infiltrating myeloid cell types within both primary and metastatic GEP-NETs were enriched for genes encoding other immune checkpoints, including VSIR (VISTA), HAVCR2 (TIM3), LGALS9 (Gal-9), and SIGLEC10. Our findings highlight the transcriptomic heterogeneity that distinguishes the cellular landscapes of GEP-NET anatomic subtypes and reveal potential avenues for future precision medicine therapeutics.

Recent oncolytic virotherapy clinical trials outline a roadmap for the treatment of high-grade glioma.

Adult and pediatric high-grade gliomas (HGGs) are aggressive cancers of the central nervous system that confer dismal clinical prognoses. Standard radiation and chemotherapy have demonstrated only limited efficacy in HGGs, motivating the accelerated investigation of novel modalities such as oncolytic virus (OV) therapies. OV centered therapies work through a mixed mechanism centered on oncolysis and the stimulation of an antitumor immune response. Three recent clinical trials utilizing herpes simplex virus-1 and adenovirus-based oncolytic virotherapy demonstrated not only the safety and efficacy of OVs but also novel dosing strategies that augment OV response potential. Considering these recent trials, herein we present a roadmap for future clinical trials of oncolytic immunovirotherapy in both adult and pediatric HGG, as well as persistent roadblocks related to the assessment of OV efficacy within and between trials.

Endoscopic Versus Open Carpal Tunnel Surgery: Risk Factors and Rates of Revision Surgery.

PURPOSE: The purpose of our study was to compare the 1-year revision surgery rates and outcomes of open versus endoscopic carpal tunnel release. Our hypothesis was that, compared to open release, endoscopic carpal tunnel release was an independent risk factor for revision surgery within 1-year. METHODS: This was a retrospective cohort study of 4338 patients undergoing isolated endoscopic or open carpal tunnel release. Demographic data, medical comorbidities, surgical approach, need for revision surgery, hand dominance, history of prior injection, and Patient Reported Outcomes Measurement Information System upper extremity (UE), pain interference (PI) and physical function scores were analyzed. Multivariable analysis was used to identify the risk factors for revision surgery within one year of the index procedure. RESULTS: In total, 3280 patients (76%) underwent open and 1058 (24%) underwent endoscopic carpal tunnel release. Within one year of the index procedure, 45 patients required revision carpal tunnel release. The average time to revision was 143 days. The rate of revision carpal tunnel release in the open group was 0.71% compared to 2.08% in the endoscopic group. Multivariable analysis demonstrated that endoscopic surgery, male sex, cubital tunnel syndrome, tobacco use, and diabetes were associated independently with revision surgery. CONCLUSIONS: In this study, we found that endoscopic carpal tunnel release was associated independently with a 2.96 times greater likelihood of requiring revision carpal tunnel release within one year, compared to open carpal tunnel release. Male sex, concurrent cubital tunnel syndrome, tobacco use, and diabetes also were associated independently with greater risk of needing revision carpal tunnel release within one year. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Reduced time to imaging, length of stay, and hospital charges following implementation of a novel postoperative pathway for craniotomy.

OBJECTIVE: The authors created a postoperative postanesthesia care unit (PACU) pathway to bypass routine intensive care unit (ICU) admissions of patients undergoing routine craniotomies, to improve ICU resource utilization and reduce overall hospital costs and lengths of stay while maintaining quality of care and patient satisfaction. In the present study, the authors evaluated this novel PACU-to-floor clinical pathway for a subset of patients undergoing craniotomy with a case time under 5 hours and blood loss under 500 ml. METHODS: A single-institution retrospective cohort study was performed to compare 202 patients enrolled in the PACU-to-floor pathway and 193 historical controls who would have met pathway inclusion criteria. The pathway cohort consisted of all adult supratentorial brain tumor cases from the second half of January 2021 to the end of January 2022 that met the study inclusion criteria. Control cases were selected from the beginning of January 2020 to halfway through January 2021. The authors also discuss common themes of similar previously published pathways and the logistical and clinical barriers overcome for successful PACU pathway implementation. RESULTS: Pathway enrollees had a median age of 61 years (IQR 49-69 years) and 53% were female. Age, sex, pathology, and American Society of Anesthesiologists physical status distributions were similar between pathway and control patients (p > 0.05). Most of the pathway cases (96%) were performed on weekdays, and 31% had start times before noon. Nineteen percent of pathway patients had 30-day readmissions, most frequently for headache (16%) and syncope (10%), whereas 18% of control patients had 30-day readmissions (p = 0.897). The average time to MRI was 6 hours faster for pathway patients (p < 0.001) and the time to inpatient physical therapy and/or occupational therapy evaluation was 4.1 hours faster (p = 0.046). The average total length of stay was 0.7 days shorter for pathway patients (p = 0.02). A home discharge occurred in 86% of pathway cases compared to 81% of controls (p = 0.225). The average total hospitalization charges were $13,448 lower for pathway patients, representing a 7.4% decrease (p = 0.0012, adjusted model). Seven pathway cases were escalated to the ICU postoperatively because of attending physician preference (2 cases), agitation (1 case), and new postoperative neurological deficits (4 cases), resulting in a 96.5% rate of successful discharge from the pathway. In bypassing the ICU, critical care resource utilization was improved by releasing 0.95 ICU days per patient, or 185 ICU days across the cohort. CONCLUSIONS: The featured PACU-to-floor pathway reduces the stay of postoperative craniotomy patients and does not increase the risk of early hospital readmission.

Examining affective reactivity as a link between suicidality and social disconnection.

The link between suicidality and social disconnection is well-established. We explored possible mechanisms that may account for this link using a positive and negative valence systems framework in a clinical sample with and without suicidality (i.e., suicidal ideation and/or behaviors in the past month). Participants (N = 228) interacted with a trained confederate during a controlled conversation task designed to generate social affiliation. Participant-rated positive affect (PA) and negative affect (NA) were collected during the task (baseline, anticipation, post). Participant-rated desire for future interaction was collected after the task. We tested if (1) groups with (n = 82) and without (n = 146) suicidality differed in affect during the task and (2) whether affect accounted for the link between suicidality and desire for future interaction. Results revealed that groups differed in PA, but not NA, throughout the task. Participants with suicidality reported no significant changes in PA over the task (ps > .05); and, experienced less PA at post-task compared to those without (p = .003, d = 0.38) whereas participants without suicidality reported increased PA at post-task compared to baseline and anticipation of the task, ps < .001. Mediation analysis suggested blunted post-task PA accounted for the relationship between suicidality and less desire for future interaction, 95%CI [-2.59,-0.51]. Diminished PA reactivity during social affiliation opportunities may help explain the link between suicidality and social disconnection. Preliminary findings highlight PA as a potential mechanistic target for improving social connection for individuals at risk for suicide, though prospective and experimental research is needed.

Immunotherapy approaches for the treatment of diffuse midline gliomas.

Diffuse midline gliomas (DMG) are a highly aggressive and universally fatal subgroup of pediatric tumors responsible for the majority of childhood brain tumor deaths. Median overall survival is less than 12 months with a 90% mortality rate at 2 years from diagnosis. Research into the underlying tumor biology and numerous clinical trials have done little to change the invariably poor prognosis. Continued development of novel, efficacious therapeutic options for DMGs remains a critically important area of active investigation. Given that DMGs are not amenable to surgical resection, have only limited response to radiation, and are refractory to traditional chemotherapy, immunotherapy has emerged as a promising alternative treatment modality. This review summarizes the various immunotherapy-based treatments for DMG as well as their specific limitations. We explore the use of cell-based therapies, oncolytic virotherapy or immunovirotherapy, immune checkpoint inhibition, and immunomodulatory vaccination strategies, and highlight the recent clinical success of anti-GD2 CAR-T therapy in diffuse intrinsic pontine glioma (DIPG) patients. Finally, we address the challenges faced in translating preclinical and early phase clinical trial data into effective standardized treatment for DMG patients.

BAF Complex Maintains Glioma Stem Cells in Pediatric H3K27M Glioma.

Diffuse midline gliomas are uniformly fatal pediatric central nervous system cancers that are refractory to standard-of-care therapeutic modalities. The primary genetic drivers are a set of recurrent amino acid substitutions in genes encoding histone H3 (H3K27M), which are currently undruggable. These H3K27M oncohistones perturb normal chromatin architecture, resulting in an aberrant epigenetic landscape. To interrogate for epigenetic dependencies, we performed a CRISPR screen and show that patient-derived H3K27M-glioma neurospheres are dependent on core components of the mammalian BAF (SWI/SNF) chromatin remodeling complex. The BAF complex maintains glioma stem cells in a cycling, oligodendrocyte precursor cell-like state, in which genetic perturbation of the BAF catalytic subunit SMARCA4 (BRG1), as well as pharmacologic suppression, opposes proliferation, promotes progression of differentiation along the astrocytic lineage, and improves overall survival of patient-derived xenograft models. In summary, we demonstrate that therapeutic inhibition of the BAF complex has translational potential for children with H3K27M gliomas. SIGNIFICANCE: Epigenetic dysregulation is at the core of H3K27M-glioma tumorigenesis. Here, we identify the BRG1-BAF complex as a critical regulator of enhancer and transcription factor landscapes, which maintain H3K27M glioma in their progenitor state, precluding glial differentiation, and establish pharmacologic targeting of the BAF complex as a novel treatment strategy for pediatric H3K27M glioma. See related commentary by Beytagh and Weiss, p. 2730. See related article by Mo et al., p. 2906.

Activity of PD-1 blockade with nivolumab among patients with recurrent atypical/anaplastic meningioma: phase II trial results.

BACKGROUND: Programmed death ligand 1 (PD-L1) contributes to tumor immunosuppression and is upregulated in aggressive meningiomas. We performed a phase II study of nivolumab, a programmed death 1 (PD-1) blocking antibody among patients with grade ≥2 meningioma that recurred after surgery and radiation therapy. METHODS: Twenty-five patients received nivolumab (240 mg biweekly) until progression, voluntary withdrawal, unacceptable toxicity, or death. Tumor mutational burden (TMB) and quantification of tumor-infiltrating lymphocytes (TIL) were evaluated as potential immunocorrelative biomarkers. Change in neurologic function was prospectively assessed using the Neurologic Assessment in Neuro-Oncology (NANO) scale. RESULTS: Enrolled patients had multiple recurrences including ≥3 prior surgeries and ≥2 prior courses of radiation in 60% and 72%, respectively. Nivolumab was well tolerated with no unexpected adverse events. Six-month progression-free survival (PFS-6) rate was 42.4% (95% CI: 22.8, 60.7) and the median OS was 30.9 months (95% CI: 17.6, NA). One patient achieved radiographic response (ongoing at 4.5 years). TMB was >10/Mb in 2 of 15 profiled tumors (13.3%). Baseline TIL density was low but increased posttreatment in 3 patients including both patients with elevated TMB. Most patients who achieved PFS-6 maintained neurologic function prior to progression as assessed by NANO. CONCLUSION: Nivolumab was well tolerated but failed to improve PFS-6, although a subset of patients appeared to derive benefit. Low levels of TMB and TIL density were typically observed. NANO assessment of neurologic function contributed to outcome assessment. Future studies may consider rationally designed combinatorial regimens.

A molecularly integrated grade for meningioma.

BACKGROUND: Meningiomas are the most common primary intracranial tumor in adults. Clinical care is currently guided by the World Health Organization (WHO) grade assigned to meningiomas, a 3-tiered grading system based on histopathology features, as well as extent of surgical resection. Clinical behavior, however, often fails to conform to the WHO grade. Additional prognostic information is needed to optimize patient management. METHODS: We evaluated whether chromosomal copy-number data improved prediction of time-to-recurrence for patients with meningioma who were treated with surgery, relative to the WHO schema. The models were developed using Cox proportional hazards, random survival forest, and gradient boosting in a discovery cohort of 527 meningioma patients and validated in 2 independent cohorts of 172 meningioma patients characterized by orthogonal genomic platforms. RESULTS: We developed a 3-tiered grading scheme (Integrated Grades 1-3), which incorporated mitotic count and loss of chromosome 1p, 3p, 4, 6, 10, 14q, 18, 19, or CDKN2A. 32% of meningiomas reclassified to either a lower-risk or higher-risk Integrated Grade compared to their assigned WHO grade. The Integrated Grade more accurately identified meningioma patients at risk for recurrence, relative to the WHO grade, as determined by time-dependent area under the curve, average precision, and the Brier score. CONCLUSION: We propose a molecularly integrated grading scheme for meningiomas that significantly improves upon the current WHO grading system in prediction of progression-free survival. This framework can be broadly adopted by clinicians with relative ease using widely available genomic technologies and presents an advance in the care of meningioma patients.

The Current Landscape of Oncolytic Herpes Simplex Viruses as Novel Therapies for Brain Malignancies.

Despite advances in surgical resection and chemoradiation, high-grade brain tumors continue to be associated with significant morbidity/mortality. Novel therapeutic strategies and approaches are, therefore, desperately needed for patients and their families. Given the success experienced in treating multiple other forms of cancer, immunotherapy and, in particular, immunovirotherapy are at the forefront amongst novel therapeutic strategies that are currently under investigation for incurable brain tumors. Accordingly, herein, we provide a focused mini review of pertinent oncolytic herpes viruses (oHSV) that are being investigated in clinical trials.

Physical Function and Pain Interference Levels of Hallux Rigidus Patients Before and After Synthetic Cartilage Implant vs Arthrodesis Surgery.

BACKGROUND: Hallux rigidus is a common and painful degenerative condition of the great toe limiting a patient's physical function and quality of life. The purpose of this study was to investigate pre- and postoperative physical function (PF) and pain interference (PI) levels of patients undergoing synthetic cartilage implant hemiarthroplasty (SCI) vs arthrodesis (AD) for treatment of hallux rigidus using the Patient-Reported Outcomes Measurement Information System (PROMIS). METHODS: PROMIS PF and PI t scores were analyzed for patients who underwent either SCI or AD. Postoperative final PROMIS t scores were obtained via phone survey. Linear mixed model analysis was used to assess differences in PF and PI at each follow-up point. Final follow-up scores were analyzed using independent sample t tests. RESULTS: Total 181 (59 SCI, 122 AD) operatively managed patients were included for analysis of PROMIS scores. Final phone survey was performed at a minimum of 14 (mean 33, range, 14-59) months postoperatively, with 101 patients (40 SCI, 61 AD) successfully contacted. The mean final follow-up was significantly different for SCI and AD: 27 vs 38 months, respectively (P < .01). The mean age of the SCI cohort was lower than the AD cohort (57.5 vs 61.5 years old, P = .01). Average PF t scores were higher in the SCI cohort at baseline (47.1 and 43.9, respectively, P = .01) and at final follow-up (51.4 vs 45.9, respectively, P < .01). A main effect of superior improvement in PF was noted in the SCI group (+4.3) vs the AD group (+2) across time intervals (P < .01). PI t scores were similar between the 2 procedures across time points. CONCLUSION: The SCI cohort reported slightly superior PF t scores preoperatively and at most follow-up time points compared with the arthrodesis group. No differences were found for PI or complication rates between the 2 treatment groups during this study time frame. LEVEL OF EVIDENCE: Level IV, case series.

Intraoperative Site Vancomycin Powder Application in Infected Diabetic Heel Ulcers With Calcaneal Osteomyelitis.

BACKGROUND: Intraoperative site application of vancomycin powder has been found to be beneficial in foot and ankle surgery among diabetic patients undergoing elective procedures. However, there are concerns for risks such as selection of multidrug-resistant bacteria, local tissue irritation, and increased wound complications. The clinical utility of intraoperative site vancomycin powder application in infected diabetic foot ulcer surgery is unknown. We aimed to report the clinical outcomes of partial or total calcanectomy for diabetic heel ulcer (DHU) and determine if intraoperative site application of vancomycin powder placement at the time of wound closure leads to improved clinical outcomes. METHODS: A current procedural terminology query (CPT 28120: partial excision bone; talus or calcaneus) was run that identified 35 patients representing 38 calcanectomies performed secondary to infected DHU with calcaneal osteomyelitis. An initial group of 25 patients did not receive intraoperative site vancomycin powder, whereas the following 13 cases received intraoperative site vancomycin powder. Demographics, clinical characteristics, comorbidities, operative complications, unexpected return to the operating room (RTOR), and revision amputations were recorded for each patient. Average follow-up was 26.1 (6.5-51.6) months. RESULTS: There was a significantly higher rate of RTOR among the vancomycin powder cohort (VANC) relative to the no-vancomycin cohort (No-VANC) (84.6% vs 36.0%, P = .038). Of the 13 VANC patients, 3 healed the wound and did not require RTOR, 2 underwent below-knee amputation (BKA), 2 received irrigation and debridement (I&D), and 6 underwent revision or total calcanectomies. Of the 25 No-VANC patients, 17 healed the wound, 4 underwent BKAs, 1 received an I&D, and 2 required revision or total calcanectomy. There was a trend toward increased rates of revision calcanectomy and BKA among the VANC cohort, but this was not statistically significant (61.5% vs 28.0%, P = .079). CONCLUSION: Partial or total calcanectomies for the management of infected DHU resulted in an overall healing rate of 50.0%, unplanned RTOR and revision calcanectomy rate of 39.5%, and a limb salvage rate of 82.6%. We found no clinical benefit with the intraoperative site application of vancomycin powder. LEVEL OF EVIDENCE: Level III, retrospective case control study.

Adult sports-related traumatic spinal injuries: do different activities predispose to certain injuries?

OBJECTIVE: Sports injuries are known to present a high risk of spinal trauma. The authors hypothesized that different sports predispose participants to different injuries and injury severities. METHODS: The authors conducted a retrospective cohort analysis of adult patients who experienced a sports-related traumatic spinal injury (TSI), including spinal fractures and spinal cord injuries (SCIs), encoded within the National Trauma Data Bank from 2011 through 2014. Multiple imputation was used for missing data, and multivariable linear and logistic regression models were estimated. RESULTS: The authors included 12,031 cases of TSI, which represented 15% of all sports-related trauma. The majority of patients with TSI were male (82%), and the median age was 48 years (interquartile range 32-57 years). The most frequent mechanisms of injury in this database were cycling injuries (81%), skiing and snowboarding accidents (12%), aquatic sports injuries (3%), and contact sports (3%). Spinal surgery was required during initial hospitalization for 9.1% of patients with TSI. Compared to non-TSI sports-related trauma, TSIs were associated with an average 2.3-day increase in length of stay (95% CI 2.1-2.4; p < 0.001) and discharge to or with rehabilitative services (adjusted OR 2.6, 95% CI 2.4-2.7; p < 0.001). Among sports injuries, TSIs were the cause of discharge to or with rehabilitative services in 32% of cases. SCI was present in 15% of cases with TSI. Within sports-related TSIs, the rate of SCI was 13% for cycling injuries compared to 41% and 49% for contact sports and aquatic sports injuries, respectively. Patients experiencing SCI had a longer length of stay (7.0 days longer; 95% CI 6.7-7.3) and a higher likelihood of adverse discharge disposition (adjusted OR 9.69, 95% CI 8.72-10.77) compared to patients with TSI but without SCI. CONCLUSIONS: Of patients with sports-related trauma discharged to rehabilitation, one-third had TSIs. Cycling injuries were the most common cause, suggesting that policies to make cycling safer may reduce TSI.

Translational Windows in Chordoma: A Target Appraisal.

Chordomas are rare tumors that are notoriously refractory to chemotherapy and radiotherapy when radical surgical resection is not achieved or upon recurrence after maximally aggressive treatment. The study of chordomas has been complicated by small patient cohorts and few available model systems due to the rarity of these tumors. Emerging next-generation sequencing technologies have broadened understanding of this disease by implicating novel pathways for possible targeted therapy. Mutations in cell-cycle regulation and chromatin remodeling genes have been identified in chordomas, but their significance remains unknown. Investigation of the immune microenvironment of these tumors suggests that checkpoint protein expression may influence prognosis, and adjuvant immunotherapy may improve patient outcome. Finally, growing evidence supports aberrant growth factor signaling as potential pathogenic mechanisms in chordoma. In this review, we characterize the impact on treatment opportunities offered by the genomic and immunologic landscape of this tumor.

The diagnosis and management of primary and iatrogenic soft tissue sarcomas of the sella.

PURPOSE: Soft tissue sarcoma (STS) of the sella is exceptionally rare. We conducted a case series, literature review, and nationwide analysis of primary and iatrogenic (radiation-associated) STS of the sella to define the clinical course of this entity. METHODS: This study employed a multi-institutional retrospective case review, literature review, and nationwide analysis using the National Cancer Database (NCDB). RESULTS: We report five patients who were diagnosed at three institutions with malignant STS of the sella. All patients presented with symptoms related to mass effect in the sellar region. All tumors extended to the suprasellar space, with the majority displaying extension into the cavernous sinus. All patients underwent an operation via a transsphenoidal approach with a goal of maximal safe tumor resection in four patients and biopsy for 1 patient. Histopathologic evaluation demonstrated STS in all patients. Post-operative adjuvant radiotherapy and chemotherapy were given to 2 and 1 out of 4 patients with known post-operative clinical course, respectively. The 1-year and 5-year overall survival rates were 100% (5/5) and 25% (1/4). Twenty-two additional reports of primary, non-iatrogenic STS of the sella were identified in the literature. Including the three cases from our series, treatment included resection in all cases, and adjuvant radiotherapy and chemotherapy were utilized in 50% (12/24) and 17% (4/24) of cases, respectively. The national prevalence of malignant STS is estimated to be 0.01% among all pituitary and sellar tumors within the NCDB. CONCLUSIONS: We report the prevalence and survival rates of STS of the sella. Multimodal therapy, including maximal safe resection, chemotherapy, and radiotherapy are necessary to optimize outcomes for this uncommon pathology.

Molecular Advances in Central Nervous System Mesenchymal Tumors.

Mesenchymal tumors of the central nervous system (CNS) comprise an array of neoplasms that may arise from or secondarily affect the CNS and its immediate surroundings. This review focuses on meningiomas and solitary fibrous tumors, the most common primary CNS mesenchymal tumors, and discusses recent advances in unveiling the molecular landscapes of these neoplasms. An effort is made to underscore those molecular findings most relevant to tumor diagnostics and prognostication from a practical perspective. As molecular techniques become more readily used at the clinical level, such alterations may strengthen formal grading schemes and lend themselves to treatment with targeted therapies.