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Appropriate imaging modalities for screening, staging, and surveillance of patients with suspected and documented metastatic disease to bone include 99mTc bone scanning, MRI, CT, radiography, and 2-[18F]fluoro-2-deoxyglucose-PET. Clinical scenarios reviewed include asymptomatic stage 1 breast carcinoma, symptomatic stage 2 breast carcinoma, abnormal bone scan results with breast carcinoma, pathologic fracture with known metastatic breast carcinoma, asymptomatic well-differentiated and poorly differentiated prostate carcinoma, vertebral fracture with history of malignancy, non-small-cell lung carcinoma staging, symptomatic multiple myeloma, osteosarcoma staging and surveillance, and suspected bone metastasis in a pregnant patient. No single imaging modality is consistently best for the assessment of metastatic bone disease across all tumor types and clinical situations. In some cases, no imaging is indicated. The recommendations contained herein are the result of evidence-based consensus by the ACR Appropriateness Criteria® Expert Panel on Musculoskeletal Radiology. © 2010 American College of Radiology.

Purpose: Experimental and epidemiological evidence shows a beneficial role of vitamin D in cancer. In vitro evidence is consistent with a similar protective function in glioma; however, no study has yet examined the potential role of vitamin D in glioma.Methods: We evaluated the association between common genetic variants in the vitamin D pathway and glioma risk and patient outcome in 622 newly diagnosed glioma cases and 628 healthy controls enrolled in a clinic-based case-control study. Subjects were genotyped for 7 candidate and tagging single nucleotide polymorphisms in the vitamin D receptor and 8 additional variants in NADSYN1, GC, CYP24A1, CYP2R1, and C10ORF88 linked in genome-wide association studies to serum concentrations of vitamin D. Unconditional logistic regression was used to estimate age- and gender-adjusted odds ratios and 95 % confidence intervals for glioma risk according to vitamin D genotypes. Proportional hazards regression was used to estimate hazard ratios for glioma-related death among 320 patients diagnosed with high-grade tumors. P values were uncorrected for multiple comparisons.Results: Risk of astrocytic tumors was associated with variant alleles in rs3829251 (NADSYN1), rs10741657 (CYP2R1), rs2228570 (Fok1, VDR), and rs731236 (Taq1, VDR). No risk associations were found among oligodendroglial tumors. Survival associations were observed according to variant status for rs1544410 (Bsm1, VDR) and rs6013897 (CYP24A1).Conclusion: This exploratory analysis provides limited evidence of a role for genetic variation in vitamin D pathway genes with glioma risk and survival. [ABSTRACT FROM AUTHOR]

Questions and recommendations from the prior version of these guidelines without changeTarget populationAdult patients (older than 18 years of age) with newly diagnosed World Health Organization (WHO) Grade II gliomas (Oligodendroglioma, astrocytoma, mixed oligoastrocytoma).QuestionIs there a role for chemotherapy as adjuvant therapy of choice in treatment of patients with newly diagnosed low-grade gliomas?RecommendationLevel III: Chemotherapy is recommended as a treatment option to postpone the use of radiotherapy, to slow tumor growth and to improve progression free survival (PFS), overall survival (OS) and clinical symptoms in adult patients with newly diagnosed LGG.QuestionWho are the patients with newly diagnosed LGG that would benefit the most from chemotherapy?RecommendationLevel III: Chemotherapy is recommended as an optional component alone or in combination with radiation as the initial adjuvant therapy for all patients who cannot undergo gross total resection (GTR) of a newly diagnosed LGG. Patients with residual tumor >1 cm on post-operative MRI, presenting diameter of 4 cm or older than 40 years of age should be considered for adjuvant therapy as well.QuestionAre there tumor markers that can predict which patients can benefit the most from initial treatment with chemotherapy?RecommendationLevel III: The addition of chemotherapy to standard RT is recommended in LGG patients that carry IDH mutation. In addition, temozolomide (TMZ) is recommended as a treatment option to slow tumor growth in patients who harbor the 1p/19q co-deletion.QuestionHow soon should the chemotherapy be started once the diagnosis of LGG is confirmed?RecommendationThere is insufficient evidence to make a definitive recommendation on the timing of starting chemotherapy after surgical/pathological diagnosis of LGG has been made. However, using the 12 weeks mark as the latest timeframe to start adjuvant chemotherapy is suggested. It is recommended that patients be enrolled in properly designed clinical trials to assess the timing of chemotherapy initiation once diagnosis is confirmed for this target population.QuestionWhat chemotherapeutic agents should be used for treatment of newly diagnosed LGG?RecommendationThere is insufficient evidence to make a recommendation of one particular regimen. Enrollment of subjects in properly designed trials comparing the efficacy of these or other agents is recommended so as to determine which of these regimens is superior.QuestionWhat is the optimal duration and dosing of chemotherapy as initial treatment for LGG?RecommendationInsufficient evidence exists regarding the duration of any specific cytotoxic drug regimen for treatment of newly diagnosed LGG. Enrollment of subjects in properly designed clinical investigations assessing the optimal duration of this therapy is recommended.QuestionShould chemotherapy be given alone or in conjunction with RT as initial therapy for LGG?RecommendationInsufficient evidence exists to make recommendations in this regard. Hence, enrollment of patients in properly designed clinical trials assessing the difference between chemotherapy alone, RT alone or a combination of them is recommended.QuestionShould chemotherapy be given in addition to other type of adjuvant therapy to patients with newly diagnosed LGG?RecommendationLevel II: It is recommended that chemotherapy be added to the RT in patients with unfavorable LGG to improve their progression free survival.Updated Question and Recommendations from the Prior Version of These GuidelinesQuestionIn adult patients with pathologically confirmed WHO Grade II diffuse glioma does chemotherapy alone, combined with radiation therapy or after radiation therapy compared to radiotherapy alone result in better overall survival, progression free survival, local control, fewer complications, neurocognitive preservation, and quality of life?RecommendationLevel I: It is recommended that chemotherapy (PCV) be added to radiation therapy (RT) in all patients with newly diagnosed high-risk WHO Grade II diffuse glioma (Patients younger than 40 unable to get gross total resection and older than 40 regardless of the degree of resection) to improve their overall survival., Level Ii: It is recommended that chemotherapy be added to radiation therapy in all patients with newly diagnosed high-risk WHO Grade II diffuse glioma to improve overall survival without a decline in neurocognitive function., Level Iii: It is suggested that chemotherapy (temozolomide) be added to RT in all patients with newly diagnosed high-risk WHO Grade II diffuse glioma to improve progression free survival and overall survival., Level Iii: It is suggested that chemotherapy alone should be considered in patients with newly diagnosed WHO Grade II diffuse glioma in cases with 1p/19q co-deletion.New questions and recommendationsTarget populationThese recommendations apply to adult patients diagnosed with WHO Grade II diffuse glioma.QuestionIn adult patients with newly diagnosed WHO grade II diffuse glioma does administration of chemotherapy prior to surgical resection improve extent of resection, provide longer progression free survival and overall survival when compared to chemotherapy alone?RecommendationLevel III: Neo-adjuvant temozolomide may be used in patients with WHO Grade II diffuse gliomas deemed unsafe for resection due to infiltration of eloquent areas or with large contralateral extension as an initial step to improve the extent of resection.There is insufficient evidence to support a recommendation regarding the ability of chemotherapy provided prior to surgical resection to improve progression free survival (PFS) and overall survival (OS).QuestionIn adult patients with newly diagnosed WHO grade II diffuse glioma does the administration of temozolomide increase the rate of malignant transformation when compared to no chemotherapy or other chemotherapy regimens?RecommendationThere is insufficient evidence to support a recommendation against the use of temozolomide for WHO Grade II diffuse gliomas due to concern over increasing the rate of malignant transformation.QuestionIn adult patients with newly diagnosed WHO grade II diffuse glioma does administration of multi-agent chemotherapy improve progression free survival and overall survival when compared to administration of single-agent chemotherapy?RecommendationThere is insufficient evidence to support a recommendation for or against the use of multi-agent chemotherapy to improve progression free survival and overall survival when compared to administration of single-agent chemotherapy in patients with newly diagnosed WHO Grade II diffuse glioma., Competing Interests: Declarations. Conflict of interest: All Guideline Task Force members were required to disclose all potential COIs prior to beginning work on the guideline, using the COI disclosure form of the AANS/CNS Joint Guidelines Review Committee. The CNS Guidelines Committee and Guideline Task Force Chair reviewed the disclosures and either approved or disapproved the nomination and participation on the task force. The CNS Guidelines Committee and Guideline Task Force Chair may approve nominations of task force members with possible conflicts and restrict the writing, reviewing, and/or voting privileges of that person to topics that are unrelated to the possible COIs. The task force has not made any disclosures., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Radiation necrosis (RN) is a well-recognized late complication most commonly occurring within 2 years of stereotactic radiosurgery (SRS); however, late RN (LRN), RN occurring or recurring > 5 years after SRS, has been poorly described. This study analyzes the incidence of and risk factors for LRN occurring > 5 years after SRS., Methods: This retrospective analysis included patients treated with linear accelerator-based SRS for tumors or arteriovenous malformations with > 5 years of clinical and serial MRI follow-up. LRN was defined as new neurological symptoms with neuroanatomically correlated imaging findings without disease recurrence. Univariate and multivariate analyses for LRN were performed using the Cox proportional hazards model., Results: The authors identified a cumulative 297 lesions in 219 patients treated to a median dose of 17 Gy with a median follow-up of 7.4 years. In total, 290 (97.6%) lesions were treated in a single fraction, and 64 (21.5%) were treated after resection. The LRN occurred in 19 (8.7%) patients and in 23 (7.7%) lesions at a median of 6.1 years (range 5.1-13.9 years) after SRS. Fifteen of the 23 (65.2%) lesions were managed with steroids, bevacizumab, and/or antiepileptic drugs. The remaining 8 (34.8%) were resected; histopathology confirmed necrosis without disease recurrence in each. On multivariate analysis, only > 5-cm3 volume of the brain receiving 12 Gy (brain V12Gy) (HR 6.01, 95% CI 1.77-20.48; p = 0.004) and a history of early, previously resolved RN (HR 9.53, 95% CI 2.00-45.61; p = 0.005) remained significantly associated with LRN., Conclusions: RN risk persists well beyond 5 years after SRS, and recognizing LRN as an entity has important implications in managing these patients. LRN risk was highest in those with a brain V12Gy > 5 cm3 and a history of early RN after SRS, warranting close follow-up in perpetuity for select patients.

Enhancing the efficacy of immunotherapy in brain metastases (BrM) requires an improved understanding of the immune composition of BrM and how this is affected by radiation and dexamethasone. Our two-arm pilot study (NCT04895592) allocated 26 patients with BrM to either low (Arm A) or high (Arm B) dose peri-operative dexamethasone followed by pre-operative stereotactic radiosurgery (pSRS) and resection (n= 13 per arm). The primary endpoint, a safety analysis at 4 months, was met. The secondary clinical endpoints of overall survival, distant brain failure, leptomeningeal disease and local recurrence at 12-months were 66%, 37.3%, 6%, and 0% respectively and were not significantly different between arms (p= 0.7739, p= 0.3884, p= 0.3469). Immunological data from two large retrospective BrM datasets and confirmed by correlates from both arms of this pSRS prospective trial revealed that BrM CD8 T cells were composed of predominantly PD1+ TCF1+ stem-like and PD1+ TCF1-TIM3+ effector-like cells. Clustering of TCF1+ CD8 T cells with antigen presenting cells in immune niches was prognostic for local control, even without pSRS. Following pSRS, CD8 T cell and immune niche density were transiently reduced compared to untreated BrM, followed by a rebound 6+ days post pSRS with an increased frequency of TCF1- effector-like cells. In sum, pSRS is safe and therapeutically beneficial, and these data provide a framework for how pSRS may be leveraged to maximize intracranial CD8 T cell responses., (© 2024. The Author(s).)

Target population These recommendations apply to adult patients with recurrent WHO grade 2 infiltrative diffuse glioma (oligodendroglioma, astrocytoma).Questions and Recommendations:Imaging Q1: In adult patients with suspected recurrence of histologically proven WHO grade 2 diffuse glioma, do advanced imaging techniques using magnetic resonance spectroscopy, perfusion weighted imaging, diffusion weighted imaging or PET provide superior assessment of tumor recurrence and histologic progression compared to standard MRI neuroimaging?Recommendation Level III: In adult patients with suspected recurrence of histologically proven WHO grade 2 diffuse glioma, advanced imaging techniques using magnetic resonance spectroscopy, perfusion weighted imaging, diffusion weighted imaging or PET are suggested for identification of tumor recurrence or histologic progression.Pathology Q1: In adult patients with suspected recurrence of histologically proven WHO grade 2 diffuse glioma, is molecular testing for IDH-1, IDH-2, and TP53 Mutations and MGMT promotor methylation mutation warranted for predicting survival and formulating treatment recommendations?Recommendation Level III: It is suggested that IDH mutation status be determined for diagnostic purposes. TP53 mutations occur early in WHO grade 2 diffuse glioma pathogenesis, remain stable, and are not suggested as a marker of predisposition to malignant transformation at recurrence or other measures of prognosis. Assessment of MGMT status is suggested as an adjunct to assessing prognosis. Assessment of CDK2NA status is suggested since this is associated with malignant progression of WHO grade 2 diffuse gliomas.Q2: In adult patients with suspected recurrence of histologically proven WHO Grade 2 diffuse glioma, is testing of proliferation indices (MIB-1 and/or BUdR) warranted for predicting survival and formulating treatment recommendations?Recommendation Level III: It is suggested that proliferative indices (MIB-1 or BUdR) be measured in WHO grade 2 diffuse glioma as higher proliferation indices are associated with increased likelihood of recurrence and shorter progression free and overall survival.Chemotherapy Q1: In adult patients with suspected recurrence of histologically proven WHO grade 2 diffuse glioma, does addition of temozolomide (TMZ), other cytotoxic agents or targeted agents to their treatment regimen improve PFS and/or OS?Recommendation Level III: Temozolomide is suggested in the therapy of recurrent WHO grade 2 diffuse glioma as it may improve clinical symptoms. PCV is suggested in the therapy of WHO grade 2 diffuse glioma at recurrence as it may improve clinical symptoms with the strongest evidence being for oligodendrogliomas. TMZ is suggested as the initial choice for recurrent WHO grade 2 diffuse glioma. Carboplatin is not suggested as there is no significant benefit from carboplatin as single agent therapy for recurrent WHO grade 2 diffuse gliomas. There is insufficient evidence to make any recommendations regarding other agents in the management of recurrent WHO grade 2 diffuse glioma.Radiotherapy Q1: In adult patients with suspected recurrence of histologically proven WHO grade 2 diffuse glioma, does addition of radiotherapy to treatment regimen improve PFS and/or OS?Recommendation Level III: Radiation is suggested at recurrence if there was no previous radiation treatment. Q2: In adult patients with suspected recurrence of histologically proven WHO grade 2 diffuse glioma after previous radiotherapy, does addition of re-irradiation or proton therapy to the treatment regimen improve PFS and/or OS?Recommendation Level III: It is suggested that re-irradiation be considered in the setting of WHO grade 2 diffuse glioma recurrence as it may provide benefit in PFS and OS.Surgery Q1: In adult patients with suspected recurrence of histologically proven WHO grade 2 diffuse glioma, does surgical resection improve PFS and/or OS?. There is insufficient evidence to make any new specific recommendations regarding the value of surgery or extent of resection in relationship to survival for recurrent WHO grade 2 diffuse glioma., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Descriptions of glenoid deformities in glenohumeral osteoarthritis (GHOA) have focused on the axial plane. Less is known regarding arthritic glenoids with higher amounts of superior inclination and little evidence exists to guide management of inclination or combined version-inclination deformity when performing anatomic total shoulder arthroplasty (aTSA). We hypothesized that biplanar deformities (BD) would be present in a higher proportion of GHOA patients than previously appreciated, and these deformities would be difficult to adequately reconstruct with contemporary aTSA implants., Methods: A retrospective query was performed of GHOA patients indicated for TSA 2012-2017 with a computed tomography (CT) scan within three months of surgery. Images were uploaded to three-dimensional (3D) software for automated measurements. Glenoids with superior inclination ≥10°, and retroversion ≥20° were considered to have BD. Walch classification was determined, and C-type glenoids were excluded. Rotator-cuff muscle cross-sectional area (CSA) was measured and fatty infiltration was graded. Glenoids with BD were virtually planned for aTSA with correction to neutral inclination and version, then with 5° superior inclination and 10° retroversion., Results: Two-hundred and sixty-eight shoulders in 250 patients were included; average age was 65 years, 67% male. There were no differences in inclination between Walch types (P = .25). Twenty-nine shoulders with BD were identified (11%). These deformities were not associated with age (P = .47) or gender (P = .50) but were skewed towards Walch B-type, specifically B2 (P = .03). Acromial index and posterior humeral head subluxation were higher in BD patients (P = .04, P < .001, respectively). Biplanar deformities had similar cuff CSA compared to those without but were less frequently associated with fatty infiltration of the subscapularis (P = .05). When correcting to neutral version and inclination, 41% BD could not be reconstructed. Of those that could, 94% required augmented implants. When correcting to 5° superior inclination and 10° retroversion, 10% could not be reconstructed. Of those that could, 58% required augmented implants. With partial correction, augment use was predicted by retroversion >26° (P = .009). Inclination did not predict augment use (P = .90). Final implant position commonly involved unseating in the posterosuperior quadrant and cancellous exposure in the anteroinferior quadrant., Conclusions: This retrospective computed tomography (CT)-based study of 268 shoulders with GHOA found an 11% prevalence of BD. These deformities were commonly associated with Walch B2 wear patterns. Virtual aTSA planning showed a high failure rate (41%) when correcting to neutral version and inclination. Posteriorly augmented implants were frequently required, and often still involved unseating in the posterosuperior quadrant, increased cancellous exposure in the anteroinferior quadrant, and vault perforation., (Copyright © 2024 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: Optimal management of retroversion in anatomic total shoulder arthroplasty (aTSA) remains controversial, and limited attention has been directed to the impact of glenoid inclination. Prior biomechanical study suggests that residual glenoid inclination generates shear stresses that may lead to early glenoid loosening. Combined biplanar glenoid deformities may complicate anatomic glenoid reconstruction and affect outcomes. The goal of this matched-cohort analysis was to assess the relationship between biplanar deformities and midterm radiographic loosening in aTSA., Methods: The study cohort was identified via an institutional repository of 337 preoperative CT scans from 2010 to 2017. Glenoid retroversion, inclination, and humeral head subluxation were assessed via 3D-planning software. Patients with retroversion ≥20° and inclination ≥10° who underwent aTSA with eccentric reaming and nonaugmented components were matched by age, sex, retroversion, and Walch classification to patients with retroversion ≥20° only. Primary outcome was glenoid component Lazarus radiolucency score., Results: Twenty-eight study subjects were matched to 28 controls with retroversion only. No difference in age (61.3 vs. 63.6 years, P = .26), sex (19 [68%] vs. 19 [68%] male, P > .99), or follow-up (6.1 vs. 6.4 years, P = .59). Biplanar deformities had greater inclination (14.5° vs. 5.3°, P < .001), retroversion (30.0° vs. 25.6°, P = .01), and humeral subluxation (86.3% vs. 82.1%, P = .03). Biplanar patients had greater postoperative implant superior inclination (5.9° [4.6°] vs. 3.0° [3.6°], P = .01) but similar rate of complete seating 24 [86%] vs. 24 [86%] P > .99). At final follow-up, biplanar subjects had higher Lazarus radiolucent scores (2.4 [1.7] vs. 1.6 [1.1], P = .03) and a higher proportion of patients with glenoid radiolucency (19 [68%] vs. 11 [39%], P = .03). No difference in complete component seating (86% vs. 86%, P = .47) or initial radiolucency grade (0.21 vs. 0.29, P = .55) on immediate postop radiographs. Biplanar patients demonstrated a greater amount of posterior subluxation at immediate postoperative (3.5% [1.3%] vs. 1.8% [0.6%]; P = .03) and final follow-up (7.6% [2.8%] vs. 4.0% [1.8%]; P = .04). At final radiographic follow-up, biplanar subjects had higher Lazarus radiolucent scores (2.4 [1.7] vs. 1.6 [1.1], P = .03; ICC = 0.82). Bivariate regression analysis demonstrated that biplanar deformity was the only significant predictor (OR 3.3, P = .04) of glenoid radiolucency., Discussion: Biplanar glenoid deformity resulted in time-zero glenoid implant superior inclination and increased midterm radiographic loosening and posterior subluxation. Attention to glenoid inclination is important for successful anatomic glenoid reconstruction. Future research is warranted to understand the long-term implications of these findings and impact of using augmented implants or reverse shoulder arthroplasty to manage biplanar deformities., (Copyright © 2024 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: Numerous applications and strategies have been utilized to help assess the trends and patterns of readmissions after orthopaedic surgery in an attempt to extrapolate possible risk factors and causative agents. The aim of this work is to systematically summarize the available literature on the extent to which natural language processing, machine learning, and artificial intelligence (AI) can help improve the predictability of hospital readmissions after orthopaedic and spine surgeries., Methods: This is a systematic review and meta-analysis. PubMed, Embase and Google Scholar were searched, up until August 30, 2023, for studies that explore the use of AI, natural language processing, and machine learning tools for the prediction of readmission rates after orthopedic procedures. Data regarding surgery type, patient population, readmission outcomes, advanced models utilized, comparison methods, predictor sets, the inclusion of perioperative predictors, validation method, size of training and testing sample, accuracy, and receiver operating characteristics (C-statistic), among other factors, were extracted and assessed., Results: A total of 26 studies were included in our final dataset. The overall summary C-statistic showed a mean of 0.71 across all models, indicating a reasonable level of predictiveness. A total of 15 articles (57%) were attributed to the spine, making it the most commonly explored orthopaedic field in our study. When comparing accuracy of prediction models between different fields, models predicting readmissions after hip/knee arthroplasty procedures had a higher prediction accuracy (mean C-statistic = 0.79) than spine (mean C-statistic = 0.7) and shoulder (mean C-statistic = 0.67). In addition, models that used single institution data, and those that included intraoperative and/or postoperative outcomes, had a higher mean C-statistic than those utilizing other data sources, and that include only preoperative predictors. According to the Prediction model Risk of Bias Assessment Tool, the majority of the articles in our study had a high risk of bias., Conclusion: AI tools perform reasonably well in predicting readmissions after orthopaedic procedures. Future work should focus on standardizing study methodologies and designs, and improving the data analysis process, in an attempt to produce more reliable and tangible results., Level of Evidence: Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSREV/B118)., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: The natural history of rotator cuff tears often involves progressive pain development, tear enlargement, and advancing muscle fatty degeneration. Both surgery and conservative management have proven to be effective treatments. Our study purpose was to compare the short- to mid-term effects of rotator cuff repair on shoulder function, progression of tear size, and muscle degeneration compared to controls with asymptomatic tears that developed pain and were managed nonoperatively., Methods: This comparative study consists of 2 separate longitudinal study arms. The control group consisted of asymptomatic degenerative cuff tears followed until pain development and then managed nonoperatively with continued surveillance. The surgical group consisted of subjects with degenerative tears that failed nonoperative treatment and underwent surgical intervention with a minimum of 2 years follow-up. Outcomes included visual analog scale pain, American Shoulder and Elbow Surgeons, active range of motion, strength, and ultrasonography., Results: There were 83 controls and 65 surgical shoulders. The surgical group was younger at enrollment (58.9 ± 5.3 yr vs. 61.2 ± 7.8 yr, P = .04). The median follow-up for control subjects after pain development was 5.1 years (interquartile range [IQR] 3.6) and the median postoperative follow-up for the surgical group was 3.0 years (IQR 0.2). Baseline tear widths (median 14 mm, IQR 9 vs. 13 mm, IQR 8; P = .45) and tear lengths (median 14 mm, IQR 13 vs. median 11 mm, IQR 8; P = .06) were similar between the surgical group and controls. There were no differences in the baseline prevalence of fatty degeneration of the supraspinatus or infraspinatus muscles between groups (P = .43 and P = .58, respectively). At final follow-up, the surgical group demonstrated significantly lower visual analog scale pain (0 [IQR 2] vs. 3.5 [IQR 4], P = .0002), higher composite American Shoulder and Elbow Surgeons (95 [IQR 13] vs. 65.8 [IQR 32], P = .0002), and activities of daily living scores (29 [IQR 4] vs. 22 [IQR 8], P = .0002), greater abduction strength (69.6 N [standard deviation {SD} 29] vs. 35.9 N [SD 29], P = .0002), greater active forward elevation (155° [SD 8] vs. 142° [SD 28], P = .002), greater active external rotation in abduction (mean 98.5°, SD 12 vs. mean 78.2°, SD 20; P = .0002) compared to controls. Additionally, the prevalence of fatty muscle degeneration was lower in the surgical group for the supraspinatus and infraspinatus (25% vs. 41%, P = .05; 17% vs. 34%, P = .03; respectively)., Conclusion: This prospective longitudinal study comparing a surgical cohort undergoing rotator cuff repair with a control group treated nonoperatively supports the notion that surgical intervention has the potential to alter the early natural history of degenerative rotator cuff disease. Patients in the surgical group demonstrated clinically relevant differences in pain and functional outcomes. Surgical intervention was protective against progressive muscle degeneration compared to nonoperative treatment., (Copyright © 2024 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Clinical guidelines direct healthcare professionals toward evidence-based practices. Evaluating guideline impact can elucidate information penetration, relevance, effectiveness, and alignment with evolving medical knowledge and technological advancements. As the American Association of Neurological Surgeons/Congress of Neurological Surgeons Section on Tumors marks its 40th anniversary in 2024, this article reflects on the tumor guidelines established by the Section over the past decade and explores their impact on other publications, patents, and information dissemination. Six tumor guideline categories were reviewed: low-grade glioma, newly diagnosed glioblastoma, progressive glioblastoma, metastatic brain tumors, vestibular schwannoma, and pituitary adenomas. Citation data were collected from Google Scholar and PubMed. Further online statistics, such as social media reach, and features in policy, news, and patents were sourced from Altmetric. Online engagement was assessed through website and CNS+ mobile application visits. Data were normalized to time since publication. Metastatic Tumor guidelines (2019) had the highest PubMed citation rate at 26.1 per year and webpage visits (29 100 page views 1/1/2019-9/30/2023). Notably, this guideline had two endorsement publications by partner societies, the Society of Neuro-Oncology and American Society of Clinical Oncology, concerning antiepileptic prophylaxis and steroid use, and the greatest reach on X (19.7 mentions/y). Citation rates on Google Scholar were led by Vestibular Schwannoma (2018). Non-Functioning Pituitary Adenoma led Mendeley reads. News, patent, or policy publications were led by low-grade glioma at 1.5/year. Our study shows that the American Association of Neurological Surgeons/Congress of Neurological Surgeons Section on Tumors guidelines go beyond citations in peer-reviewed publications to include patents, online engagement, and information dissemination to the public., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Purpose: Gliomas are increasingly diagnosed in an aging population, with treatment outcomes influenced by factors like tumor genetics and patient frailty. This study focused on IDH-mutant gliomas and assessed how frailty affects 30-day readmission and overall survival (OS). We aimed to address a gap in understanding the impact of frailty on this specific glioma subtype., Methods: 136 patients with an IDH-mutant glioma between 2007 and 2021 were identified at our institution. High frailty was classified by scores ≥ 1 on the 5-factor modified frailty index (mFI-5) and ≥ 3 on the Charlson Comorbidity Index (CCI). Patient and tumor characteristics including age, sex, race, Karnofsky Performance Status (KPS), Body Mass Index (BMI), tumor type and location, type of operation, and therapy course were recorded. Outcomes measured included 30-day readmission and overall survival (OS). Analysis was conducted utilizing logistic regression and Kaplan-Meier curves., Results: Of the 136 patients, 52 (38%) had high frailty: 18 with CCI ≥ 3, 34 with mFI-5 ≥ 1. High frailty correlated with increased BMI (CCI: 30.2, mFI-5: 30.1 kg/m2), more neurological deficits (CCI: 61%, mFI-5: 56%), and older age at surgery (CCI: 63, mFI-5: 48 years). Hospital readmission within 30 days occurred in 8 (5.9%) patients. Logistic regression indicated no significant difference in 30-day readmission rates (CCI: p = 0.30, mFI-5: p = 0.62) or median OS between high and low frailty groups. However, patients treated at our institution with newly diagnosed tumors with high mFI-5 had a 6.79 times higher adjusted death hazard than those with low mFI-5 (p = .049)., Conclusion: Our analysis revealed that CCI and mFI-5 were not significantly associated with 30-day nor OS. However, in patients with non-recurrent tumors, there was a significant association of mFI-5 with OS. Further study of frailty with larger cohorts is warranted to enhance prognostication of outcome after neurosurgical treatment., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Progression of PCNSL remains a challenge with salvage therapies, including the risk of substantial morbidity and mortality. We report patterns of first tumor progression to inform opportunities for improvement., Methods: This is an institutional retrospective review from 2002 to 2021 of 95 consecutive patients with pathologically confirmed PCNSL, of whom 29 experienced progressive disease. Kaplan-Meier method, log-rank test, and Cox proportional hazard models are used to characterize associations of patient, tumor, and treatment variables with LC, PFS, and patterns of first failure., Results: Most patients were below 65 years old (62%) with KPS >70 (64%) and negative CSF cytology (70%). In 70 patients with MRIs, the median tumor volume was 12.6 mL (range: 0.5 to 67.8 mL). After a median follow-up of 11 months, 1-year PFS was 48% and 1-year LC was 80%. Of the 29 patients with progression, 24% were distant only, 17% were distant and local, and 59% were local only. On MVA, LC was associated with age (HR: 1.08/y, P =0.02), KPS (HR: 0.10, P =0.02), completion of >6 cycles of HD-MTX (HR: 0.10, P <0.01), and use of intrathecal chemotherapy (HR: 0.03, P <0.01). On UVA, local only first failure trended to be increased with >14 mL tumors (OR: 5.06, P =0.08) with 1-year LC 83% (<14 mL) versus 64% (>14mL). There were no significant associations with LC and WBRT ( P =0.37), Rituximab ( P =0.12), or attempted gross total resection ( P =0.72)., Conclusions: Our findings reaffirm the importance of systemic and intrathecal therapies for local control in PCNSL. However, bulky tumors trend to fail locally, warranting further investigation about the role of local therapies or systemic therapy intensification., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Total elbow arthroplasty (TEA) remains a valuable tool for treating inflammatory, degenerative, and traumatic elbow conditions. This study aimed to understand the incidence of and risk factors for reoperation following TEA at a high-volume center utilizing an implant with a convertible linkage and the potential for anatomic lateral column reconstruction., Methods: All patients undergoing primary TEA with the Latitude prosthesis (Stryker) from July 2001 to May 2020 were identified. Patient characteristics, the surgical indication, and implant characteristics were obtained. Additionally, the indications and timing were identified for reoperations. Postoperative radiographs were analyzed to assess cement quality, implant position, lateral column reconstruction, and distal humeral bone loss., Results: Two hundred and nineteen TEAs were performed in 206 patients; 162 (74.0%) were in female patients, the mean patient age was 61 years (range, 23 to 95 years), and the mean follow-up was 11.8 years (range, 2 to 21 years). The most common indication for surgery was sequelae of trauma (36%). Ninety elbows (41.1%) required 200 reoperations at a mean of 19.6 months. Forty TEAs (18.3%) required revision of nonmodular implants, with 14 (6.4%) undergoing definitive explantation. The 5 and 10-year survivorship was 86.1% and 79.7%, respectively. The most common of the reasons for revision was aseptic loosening (53.8%), and the most common cause for non-revision reoperation was infection (23%). Younger age and greater follow-up duration were associated with greater revision and reoperation risks. Aseptic ulnar loosening was associated with a short ulnar stem length and component linkage (30% of short linked ulnar stems loosened; p < 0.001). Aseptic humeral loosening was associated with less-than-adequate cement-mantle quality (p = 0.04)., Conclusions: Extended follow-up of the Latitude prosthesis at a high-volume center demonstrates that TEA continues to be hampered by a high reoperation rate, primarily due to infection and aseptic loosening. Technical factors such as good cement-mantle quality, longer stem length, and unlinked implants may play a role in preventing aseptic loosening. Further work is required to optimize long-term outcomes following TEA through improved understanding of appropriate surgical indications, techniques, and implant utilization., Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: No external funding was received for this work. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/I63 )., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: When arsenic trioxide (ATO) was combined with radiation for treatment of transplanted murine gliomas in the brain, tumor response improved with disrupted tumor blood flow and survival was significantly prolonged., Methods: Total of 31 patients with newly diagnosed glioblastoma were accrued to a multi-institutional, NCI-funded, phase I study to determine the maximum tolerated dose (MTD) of ATO administered with radiation. Secondary objectives were survival and pharmacodynamic changes in perfusion on magnetic resonance imaging (MRI). Patients (unknown MGMT and IDH status) received ATO either once or twice weekly during radiation without concurrent or adjuvant temozolomide., Results: Median age: 54.9 years, male: 68%, KPS ≥ 90: 77%, debulking surgery: 77%. Treatments were well-tolerated: 81% of patients received all the planned ATO doses. Dose-limiting toxicities included elevated liver function tests, hypokalemia, and edema. The MTD on the weekly schedule was 0.4 mg/kg and on the biweekly was 0.3 mg/kg. The median survival (mOS) for all patients was 17.7 months. Survival on the biweekly schedule (22.8 months) was longer than on the weekly schedule (12.1 months) ( P  = .039) as was progression-free survival ( P  = .004). Similarly, cerebral blood flow was significantly reduced in patients treated on the biweekly schedule ( P  = .007)., Conclusions: ATO with standard radiation is well tolerated in patients with newly diagnosed glioblastoma. Even without temozolomide or adjuvant therapy, the overall survival of all patients (17.7 months) and especially patients who received biweekly ATO (22.8 months) is surprising and accompanied by pharmacodynamic changes on MRI. Further studies of this regimen are warranted., Competing Interests: J.J.O. serves as an editorial consultant for American Cancer Society and receives NCI grant for targeting integrin pathways in medulloblastoma. B.N. receives consulting fees from Chimersx and AnHeart and serves data monitoring board for CNS Pharma. S.A.G. serves advisory board and consulting fee from PlusTherapeutics, and serves scientific advisory board with stock for Myosin. Others have no disclosure., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Primary effusion lymphoma (PEL) is an uncommon B-cell lymphoma associated with human herpesvirus 8 and comprises 3-4% of all HIV-related lymphomas. It traditionally presents as a pleural, pericardial, and/or peritoneal effusion, though it can occasionally manifest as an extracavitary or solid mass in the absence of an effusion. The extracavitary or solid variant of primary effusion lymphoma has been reported in the skin, gastrointestinal tract, lung, and lymph nodes. However, very few cases have been reported in the central nervous system. We describe a case of extracavitary or solid variant of primary effusion lymphoma presenting as a brain mass in an HIV-positive man, highlighting the clinicopathologic and immunophenotypic findings of a rare entity.

Background: The prevalence of failed reverse total shoulder arthroplasty (rTSA) is increasing. This can often present a challenging clinical situation with substantial bone loss and limited reconstruction options. This study reports a single tertiary referral center's experience with revision of failed rTSA managed with revision rTSA of bone-interfacing components., Methods: After institutional review board approval, all revision shoulder arthroplasty cases performed at a single institution between 2012 and 2020 were reviewed. Cases in which rTSA was revised to a new rTSA construct with revision of at least 1 bone-interfacing implant (humeral stem and/or baseplate) with a minimum 2-year follow-up were identified. Characteristics of revision cases-including indications, bony stock, revised components, and use of bone graft-were collected. All patients were contacted for patient-reported outcome measures at a minimum of 2 years after surgery. In addition, the incidence and indication for any reoperation after revision were determined., Results: Thirty-three patients with an average age of 66 years (range: 46-82 years), with 19 (58%) being female, met the inclusion criteria and had a mean follow-up of 4.2 years (range: 2-8 years). The most common indication for revision rTSA included humeral component loosening (33%; 11/33), baseplate loosening (27%; 9/33), and instability (21%; 7/33). Prerevision infectious workup demonstrated no cases of periprosthetic shoulder infection. Thirteen cases had massive bone loss-5 treated with humeral allograft prosthetic composite, 5 with glenoid bone grafting, and 3 with custom glenoid implant. In total, 10 of 33 cases (30%) required reoperation at a mean of 13 months (range: 1-44 months) for instability (4), humeral loosening (2), infection (1), baseplate loosening (1), or periprosthetic fracture (1). The reoperation rate for patients with revised baseplates only, humerus only, or combined was 23% (3/13), 28% (5/18), and 27% (3/11), respectively. Overall, the visual analog scale pain score improved from 6.5 preoperatively to 2.0 (P < .001), and the American Shoulder and Elbow Surgeons score improved from 30.7 to 67.5 (P < .001). However, the postoperative Single Assessment Numeric Evaluation score averaged only 51.2% (range: 2-100%)., Conclusion: This study demonstrates that failed rTSA can be salvaged with a revision rTSA. However, patient expectations for functional improvements should be tempered, and a high reoperation rate should be expected., (Copyright © 2023 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Spheno-orbital meningiomas arise from the arachnoid villi cap cells at the sphenoid ridge and have the ability to spread through soft tissue extension and cranial bone invasion. Owing to their orbital hyperostosis and intraorbital soft tissue extension, they commonly present with ophthalmologic manifestations. This study aims to investigate the correlation between tumor volume with the presenting symptoms and postoperative outcomes., Methods: This retrospective study analyzed patients who underwent surgical resection of spheno-orbital meningiomas. Tumor volumes in different compartments were measured using preoperative and postoperative imaging. Linear and logistic regression analyses were used to identify correlations between tumor volumes and presenting symptoms preoperatively and postoperative outcomes., Results: Sixty-six patients were included in this study, of whom 86.4% had proptosis, 80.3% had decreased visual acuity (VA), 30.3% had visual field defects, and 13.6% had periorbital edema. Preoperatively, proptosis linearly correlated with intraosseous tumor volume (coefficient = 0.6, P < .001), while the decrease in baseline VA correlated with the intraorbital tumor volume (coefficient = 0.3, P = .01). The odds of periorbital edema were found to increase with an increase in intraosseous tumor volume with an adjusted odds ratio of 1.4 (95% CI, 1.1-1.7, P = .003), while the odds of visual field defects were found to increase with an increase in intraorbital tumor volume with an adjusted odds ratio of 2.7 (95% CI, 1.3-5.6, P = .01). Postoperatively, the volume of intraosseous tumor resected linearly correlated with the improvement in proptosis (coefficient = 0.7, P < .001), while the volume of intraorbital tumor resected linearly correlated with improvement in VA (coefficient = 0.5, P < .001) and with a larger effect size in patients presenting with moderate-to-severe decrease in VA preoperatively (coefficient = 0.8)., Conclusion: Underscoring the importance of each tumor compartment relative to the patient's symptomatology serves as a valuable guide in implementing a compartmentalized resection approach tailored to the surgical objectives., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Current diagnostic and therapeutic approaches for gliomas have limitations hindering survival outcomes. We propose spectroscopic magnetic resonance imaging as an adjunct to standard MRI to bridge these gaps. Spectroscopic MRI is a volumetric MRI technique capable of identifying tumor infiltration based on its elevated choline (Cho) and decreased N-acetylaspartate (NAA). We present the clinical translatability of spectroscopic imaging with a Cho/NAA ≥ 5x threshold for delineating a biopsy target in a patient diagnosed with non-enhancing glioma. Then, we describe the relationship between the undertreated tumor detected with metabolite imaging and overall survival (OS) from a pilot study of newly diagnosed GBM patients treated with belinostat and chemoradiation. Each cohort (control and belinostat) were split into subgroups using the median difference between pre-radiotherapy Cho/NAA ≥ 2x and the treated T1-weighted contrast-enhanced (T1w-CE) volume. We used the Kaplan-Meier estimator to calculate median OS for each subgroup. The median OS was 14.4 months when the difference between Cho/NAA ≥ 2x and T1w-CE volumes was higher than the median compared with 34.3 months when this difference was lower than the median. The T1w-CE volumes were similar in both subgroups. We find that patients who had lower volumes of undertreated tumors detected via spectroscopy had better survival outcomes.

Background: Prior rotator cuff disease natural history studies have focused on tear-related factors that predict disease progression within a given shoulder. The purpose of this study was to examine both patient- and tear-related characteristics of a painful rotator cuff tear that predict future pain development and functional impairment in a shoulder with a contralateral asymptomatic cuff tear., Methods: This was a prospective longitudinal cohort study of patients aged ≤65 years who underwent surgery for a painful degenerative rotator cuff tear and possessed an asymptomatic contralateral tear. Patients were followed up prospectively by shoulder ultrasound, physical examination, and functional score assessment. The primary outcome was change in the American Shoulder and Elbow Surgeons (ASES) score at 2 years. Secondary outcomes included the Western Ontario Rotator Cuff Index (WORC) score, Patient-Reported Outcomes Measurement Information System (PROMIS) score, Hospital Anxiety Depression Scale (HADS) depression and anxiety scores, and Veterans RAND-12 (VR-12) mental component score (MCS)., Results: Sixty-five patients were included, with a mean follow-up period of 37 months (range, 24-42 months). In 17 patients (26%), contralateral shoulder pain developed at a median of 15.2 months (interquartile range [IQR], 10.5 months). No difference in age, sex, Charlson Comorbidity Index, or occupational demand was noted between patients in whom pain developed and those in whom pain did not develop. In the presenting painful shoulder, there was no difference in baseline tear size, muscle degeneration, or biceps pathology between groups. The mean baseline tear length (8.6 mm vs. 3.8 mm, P = .0008) and width (8.4 mm vs. 3.2 mm, P = .0004) were larger in asymptomatic shoulders in which pain subsequently developed compared with those in which pain did not develop. However, there was no difference in mean tear enlargement (P = .51 for length and P = .90 for width). There were no differences in baseline ASES, WORC, Patient-Reported Outcomes Measurement Information System (PROMIS), or HADS depression and anxiety scores between shoulders in which pain developed and those in which pain did not develop; however, patients in whom pain developed reported a lower baseline VR-12 MCS (53.3 vs. 57.6, P = .04). Shoulders in which pain developed had higher visual analog scale pain scores (2.9 [standard deviation (SD), 2.5] vs. 0.6 [SD, 1.0]; P = .016), lower ASES scores 75 [SD, 33] vs. 100 [SD, 11.6]; P = .001), and significant changes in all WORC scales with pain onset compared with those that remained asymptomatic. The study showed no significant difference in changes in the HADS anxiety and depression scores but found a significant increase in the VR-12 MCS in patients in whom pain developed (7.1 [interquartile range, 12.6] vs. -1.9 [interquartile range, 8.7]; P = .036)., Conclusion: In one-quarter of patients with painful cuff tears, pain developed in a contralateral asymptomatic cuff tear that resulted in a measurable decline in function within 3 years. Our analysis showed that only the baseline tear size of the asymptomatic shoulder was predictive of pain development. There were no tear-related features of the presenting painful rotator cuff tear or indices of mental health and physical function or occupational demand that were predictive of future pain development at short-term follow-up., (Copyright © 2023. Published by Elsevier Inc.)

Histological staining of tissue biopsies, especially hematoxylin and eosin (H&E) staining, serves as the benchmark for disease diagnosis and comprehensive clinical assessment of tissue. However, the typical formalin-fixation, paraffin-embedding (FFPE) process is laborious and time consuming, often limiting its usage in time-sensitive applications such as surgical margin assessment. To address these challenges, we combine an emerging 3D quantitative phase imaging technology, termed quantitative oblique back illumination microscopy (qOBM), with an unsupervised generative adversarial network pipeline to map qOBM phase images of unaltered thick tissues (i.e., label- and slide-free) to virtually stained H&E-like (vH&E) images. We demonstrate that the approach achieves high-fidelity conversions to H&E with subcellular detail using fresh tissue specimens from mouse liver, rat gliosarcoma, and human gliomas. We also show that the framework directly enables additional capabilities such as H&E-like contrast for volumetric imaging. The quality and fidelity of the vH&E images are validated using both a neural network classifier trained on real H&E images and tested on virtual H&E images, and a user study with neuropathologists. Given its simple and low-cost embodiment and ability to provide real-time feedback in vivo , this deep-learning-enabled qOBM approach could enable new workflows for histopathology with the potential to significantly save time, labor, and costs in cancer screening, detection, treatment guidance, and more., Competing Interests: Disclosures. R.L. is a co-founder of Histolix, Inc. T.M.A. is a paid employee of Stability AI. The other authors declare no competing financial interests.

Objective: The objective of the current study was to present the results of an international working group survey identifying perceived limitations of existing facial nerve grading scales to inform the development of a novel grading scale for assessing early postoperative facial paralysis that incorporates regional scoring and is anchored in recovery prognosis and risk of associated complications., Study Design: Survey., Setting: A working group of 48 multidisciplinary clinicians with expertise in skull base, cerebellopontine angle, temporal bone, or parotid gland surgery., Results: House-Brackmann grade is the most widely used system to assess facial nerve function among working group members (81%), although more than half (54%) agreed that the system they currently use does not adequately estimate the risk of associated complications, such as corneal injury, and confidence in interrater and intrarater reliability is generally low. Simplicity was ranked as the most important attribute of a novel postoperative facial nerve grading system to increase the likelihood of adoption, followed by reliability and accuracy. There was widespread consensus (91%) that the eye is the most critical facial region to focus on in the early postoperative setting., Conclusions: Members were invited to submit proposed grading systems in alignment with the objectives of the working group for subsequent validation. From these data, we plan to develop a simple, clinically anchored, and reproducible staging system with regional scoring for assessing early postoperative facial nerve function after surgery of the skull base, cerebellopontine angle, temporal bone, or parotid gland., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2023, Otology & Neurotology, Inc.)

Radiation is commonly used in the treatment of many cancers. However, its effects on anti-tumor immune responses are incompletely understood. Here, we present a detailed immunological analysis of two tumors from a patient with multiple non-small cell lung cancer metastases to the brain. One tumor was resected without treatment; the second was irradiated to a total dose of 30 Gy and resected following further progression. Comprehensive single-cell analysis reveals a substantially reduced immune cell fraction in the irradiated tumor, including the depletion of tissue-resident macrophages and infiltration of pro-inflammatory monocytes. Despite the presence of similar somatic mutations in both tumors, radiation is associated with the depletion of exhausted, tumor-resident T cell clones and their replacement by circulating clones unlikely to contribute to tumor-specific immunity. These results provide insight into the local effects of radiation on anti-tumor immunity and raise important considerations for the combination of radiation and immunotherapy., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: We studied 571 patients with intracranial meningioma for clinical characteristics and tumor location associated with high grade meningioma (WHO II/III)., Materials and Methods: Patients were participants in a multicentre epidemiologic study of risk factors for primary brain tumors including meningioma recruited from September 2005 to November 2019. We included patients 18 or older with a recent diagnosis of a primary intracranial meningioma of any subtype (ICD9/10: 9530-0, 9531-0, 9532-0, 9537-0, 9533-0, 9534-0, 9530-0, 9538-1, 9538-3) who were enrolled at neuro-oncology and neuro-surgery clinics in the southeastern U.S., Results: The median patient age was 58 years (IQR: 48-68) and the majority of patients were female ( n  = 415; 72.7%) and Caucasian ( n  = 516; 90.4%). Most patients were symptomatic ( n  = 460; 80.6%) and their tumours more commonly occurred in a non-skull base location ( n  = 298; 52.2%). A total of 86 patients (15.0%) had a WHO grade II/III meningioma. Compared to patients with WHO grade I tumours, patients with WHO II/III meningiomas were over 3-times more likely to be male (odds ratio (OR): 3.25; 95% confidence interval (CI): 1.98, 5.35) adjusting for age, race, symptomatic presentation, and skull-based location. Moreover, a WHO grade II/III meningioma was substantially less likely to be observed in asymptomatic patients (OR: 0.15, 95% CI: 0.04, 0.42), and in patients with a skull-based tumour (OR: 0.40, 95% CI: 0.24, 0.66), adjusting for other factors. Male gender, symptomatic tumour, and a non-skull base location were independently associated with WHO grade II/III meningioma., Conclusion: These findings may shed additional light on the underlying pathogenesis of meningioma.

Multidisciplinary tumor boards (TB) are an essential part of brain tumor care, but quantifying the impact of imaging on patient management is challenging due to treatment complexity and a lack of quantitative outcome measures. This work uses a structured reporting system for classifying brain tumor MRIs, the brain tumor reporting and data system (BT-RADS), in a TB setting to prospectively assess the impact of imaging review on patient management. Published criteria were used to prospectively assign three separate BT-RADS scores (an initial radiology report, secondary TB presenter review, and TB consensus) to brain MRIs reviewed at an adult brain TB. Clinical recommendations at TB were noted and management changes within 90 days after TB were determined by chart review. In total, 212 MRIs in 130 patients (median age = 57 years) were reviewed. Agreement was 82.2% between report and presenter, 79.0% between report and consensus, and 90.1% between presenter and consensus. Rates of management change increased with increasing BT-RADS scores (0-3.1%, 1a-0%, 1b-66.7%, 2-8.3%, 3a-38.5%, 3b-55.9, 3c-92.0%, and 4-95.6%). Of 184 (86.8%) cases with clinical follow-up within 90 days after the tumor board, 155 (84.2%) of the recommendations were implemented. Structured scoring of MRIs provides a quantitative way to assess rates of agreement interpretation alongside how often management changes are recommended and implemented in a TB setting.

Objective: To describe humerus shaft fractures after low-energy gunshot wound (GSW) and compare with blunt injuries. We hypothesized that nerve injury, infection, and fracture union would be similar., Design: Retrospective., Setting: Urban Level 1 trauma center., Patients/participants: Four hundred three patients were treated for a humeral shaft fracture over 18 years. Sixty-two patients sustained injury due to GSW., Intervention: Primary open reduction and internal fixation was pursued in 59%, including 32% after GSW., Main Outcome Measurements: Rates of nerve injury, infection, and fracture union., Results: Patients with GSW were younger with a mean age of 30 years, more likely male (90%), with isolated injuries (84%), and less likely to have simple fractures (84%). Both groups experienced high rates of union (98% of GSW fractures vs. 99% of closed high-energy fractures). Deep infection occurred in 1 patient (1.6%) after GSW. Rates of deep infection in the closed and open blunt trauma fracture groups were similarly low at 1% and 4.5%, respectively. Nerve injury on presentation after GSW was more common than after low-energy and high-energy closed fractures (47% vs. 13% and 27%), but similar to blunt open fracture (52%). Despite higher rates of nerve injury, nerve recovery occurred at similarly high rates after both GSW and blunt injuries (78% vs. 86%)., Conclusions: Nerve injuries are more common after GSW, but most recover without intervention. Infection is uncommon after GSW, and secondary unplanned operations are rare. Initial nonoperative care of most GSW humerus fractures, even with radial nerve injury at the time of presentation, seems appropriate., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Perioperative opioids are problematic following craniotomy as they can impede neurological examination because of excessive sedation and mask surgical complications. Multimodal anesthetic techniques including nerve blocks have been used successfully to deliver opioid-free anesthesia in other surgical populations; however, no clinical data evaluating opioid-free anesthesia for craniotomy exists within the current body of literature., Materials and Methods: Six prospectively identified patients underwent supratentorial craniotomy at Emory University Hospital using a multimodal opioid-free anesthetic (OFA) technique consisting of preoperative scalp block, dexmedetomidine and intravenous acetaminophen. These opioid-free patients were matched by age, sex, incision length, and incision location to 18 retrospectively identified control patients who underwent craniotomy using conventional, opioid-based anesthetic techniques. Postoperative opioid consumption and pain scores were compared and analyzed for noninferiority., Results: Noninferiority of the OFA technique was demonstrated for opioid consumption at all measured intervals from postanesthesia care unit arrival to 24 hours postoperatively. Noninferiority was also demonstrated with respect to average postoperative pain scores from 0 to 12 hours, 0 to 24 hours, as well as length of postanesthesia care unit stay. Noninferiority was not shown for time to first rescue opioid postoperatively, pain scores for the 12 to 24 hours postoperative period, or time to emergence from anesthesia., Conclusions: This pilot study demonstrates the feasibility of an OFA technique for patients undergoing supratentorial craniotomy and suggests that larger prospective randomized controlled trials are indicated to examine the role of multimodal anesthetic techniques for craniotomy., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Purpose: Standard of care for lower-grade glioma (LGG) is maximal safe resection and risk-adaptive adjuvant therapy. While patients who benefit the most from adjuvant chemotherapy have been elucidated in prospective randomized studies, comparable insights for adjuvant radiotherapy (RT) are lacking. We sought to identify and validate patterns of gene expression that are associated with differential outcomes among LGG patients treated by RT from two large genomics databases., Materials and Methods: Patients from The Cancer Genome Atlas (TCGA) with LGG (WHO grade II-III glioma) treated by surgery and adjuvant RT were randomized 1:1 to a discovery cohort or an internal validation cohort. Using the discovery cohort only, associations between tumor RNA-seq expression and progression-free survival (PFS) as well as overall survival (OS) were evaluated with adjustment for clinicopathologic covariates. A Genomic Risk Score (GRS) was then constructed from the expression levels of top genes also screened for involvement in glioma carcinogenesis. The prognostic value of GRS was further assessed in the internal validation cohort of TCGA and a second distinct database, compiled by the Chinese Glioma Genome Association (CGGA)., Results: From TCGA, 289 patients with LGG received adjuvant RT alone (38 grade II, 30 grade III) or chemoradiotherapy (CRT) (51 grade II, 170 grade III) between 2009 and 2015. From CGGA, 178 patients with LGG received adjuvant RT alone (40 grade II, 13 grade III) or CRT (41 grade II, 84 grade III) between 2004 and 2016. The genes comprising GRS are involved in MAP kinase activity, T cell chemotaxis, and cell cycle transition: MAP3K15, MAPK10, CCL3, CCL4, and ADAMTS1. High GRS, defined as having a GRS in the top third, was significantly associated with poorer outcomes independent of age, sex, glioma histology, WHO grade, IDH mutation, 1p/19q co-deletion, and chemotherapy status in the discovery cohort (PFS HR 1.61, 95% CI 1.10-2.36, P = 0.014; OS HR 2.74, 95% CI 1.68-4.47, P < 0.001). These findings were replicated in the internal validation cohort (PFS HR 1.58, 95% CI 1.05-2.37, P = 0.027; OS HR 1.84, 95% CI 1.13-3.00, P = 0.015) and the CGGA external validation cohort (OS HR 1.72, 95% CI 1.27-2.34, P < 0.001). Association between GRS and outcomes was observed only among patients who underwent RT, in both TCGA and CGGA., Conclusion: This study successfully identified an expression signature of five genes that stratified outcomes among LGG patients who received adjuvant RT, with two rounds of validation leveraging independent genomics databases. Expression levels of the highlighted genes were associated with PFS and OS only among patients whose treatment included RT, but not among those with omission of RT, suggesting that expression of these genes may be predictive of radiation treatment response. While additional prospective studies are warranted, interrogation of these genes may be considered in the multidisciplinary management of LGG., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Resection of posterior fossa tumors (PFTs) can result in hydrocephalus that requires permanent cerebrospinal fluid (CSF) diversion. Our goal was to prospectively validate a machine-learning model to predict postoperative hydrocephalus after PFT surgery requiring permanent CSF diversion., Methods: We collected preoperative and postoperative variables on 518 patients that underwent PFT surgery at our center in a retrospective fashion to train several statistical classifiers to predict the need for permanent CSF diversion as a binary class. A total of 62 classifiers relevant to our data structure were surveyed, including regression models, decision trees, Bayesian models, and multilayer perceptron artificial neural networks (ANN). Models were trained using the ( N = 518) retrospective data using 10-fold cross-validation to obtain accuracy metrics. Given the low incidence of our positive outcome (12%), we used the positive predictive value along with the area under the receiver operating characteristic curve (AUC) to compare models. The best performing model was then prospectively validated on a set of 90 patients., Results: Twelve percent of patients required permanent CSF diversion after PFT surgery. Of the trained models, 8 classifiers had an AUC greater than 0.5 on prospective testing. ANNs demonstrated the highest AUC of 0.902 with a positive predictive value of 83.3%. Despite comparable AUC, the remaining classifiers had a true positive rate below 35% (compared to ANN, P < .0001). The negative predictive value of the ANN model was 98.8%., Conclusions: ANN-based models can reliably predict the need for ventriculoperitoneal shunt after PFT surgery., (© The Author(s) 2022. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

The following questions and recommendations are pertinent to the following: TARGET POPULATION: These recommendations apply to adults with progressive GBM who have undergone standard primary treatment with surgery and/or chemoradiation. QUESTION 1: In adults with progressive glioblastoma is the use of bevacizumab as monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?, Recommendation: Level III: Treatment with bevacizumab is suggested in the treatment of progressive GBM, as it provides improved disease control compared to historical controls as measured by best imaging response and progression free survival at 6 months, while not providing evidence for improvement in overall survival. QUESTION 2: In adults with progressive glioblastoma is the use of bevacizumab as combination therapy with cytotoxic agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?, Recommendation: Level III: There is insufficient evidence to show benefit or harm of bevacizumab in combination with cytotoxic therapies in progressive glioblastoma due to a lack of evidence supporting a clearly defined benefit without significant toxicity. QUESTION 3: In adults with progressive glioblastoma is the use of bevacizumab as a combination therapy with targeted agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?, Recommendation: There is insufficient evidence to support a recommendation regarding this question. QUESTION 4: In adults with progressive glioblastoma is the use of targeted agents as monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?, Recommendation: There is insufficient evidence to support a recommendation regarding this question. QUESTION 5: In adults with progressive glioblastoma is the use of targeted agents in combination with cytotoxic therapies superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?, Recommendation: There is insufficient evidence to support a recommendation regarding this question. QUESTION 6: In adults with progressive glioblastoma is the use of immunotherapy monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?, Recommendation: There is insufficient evidence to support a recommendation regarding this question. QUESTION 7: In adults with progressive glioblastoma is the use of immunotherapy in combination with targeted agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?, Recommendation: There is insufficient evidence to support a recommendation regarding this question. QUESTION 8: In adults with progressive glioblastoma is the use of immunotherapy in combination with bevacizumab superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?, Recommendation: There is insufficient evidence to support a recommendation regarding this question., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Target Population: These recommendations apply to adult patients diagnosed with progressive glioblastoma (pGBM). QUESTION (Q1): In adult patients with pGBM does the use of temozolomide (TMZ) with alternative dosing or the use of TMZ in combination with other cytotoxic treatments result in increased overall survival compared to other chemotherapy?, Recommendation: Level III: Adult patients with pGBM might derive benefit in treatment with TMZ, especially those who progress after more than 5 months of TMZ-treatment free interval., Level Iii: Combination of TMZ with other cytotoxic agents such as nitrosourea, cisplatin, electrohyperthermia, or tamoxifen is not suggested in adult patients with pGBM as a stand-alone therapy. There is insufficient data to make a recommendation about which alternative TMZ dosing provides the best benefits. QUESTION (Q2): In adult patients with pGBM does the use of systemic or in situ nitrosourea result in increased overall survival compared to other chemotherapy?, Recommendation: Level III: In the setting of pGBM, fotemustine is suggested in elderly patients with methylated MGMT promoter status. There is insufficient evidence to compare fotemustine to other nitrosoureas. There is insufficient evidence to make a recommendation about the use of in situ nitrosourea in patients with pGBM who underwent the Stupp regimen. QUESTION (Q3): In adult patients with pGBM does the use of platinum compounds and topoisomerase result in increased survival compared to other chemotherapy?, Recommendation: Level III: Other chemotherapy including platinum compounds and topoisomerase inhibitors are not suggested to be used in adult patients with pGBM., Level Iii: Other cytotoxic therapies like perillyl acohol or ketogenic diet are not suggested for use in adult patients with pGBM as a stand-alone therapy. QUESTION (Q4): In adult patients with pGBM does the use of tumor treating field (TTF) result in increased overall survival compared to chemotherapy?, Recommendation: Level III: The use of TTF with other chemotherapy may be considered when treating adult patients with pGBM. There is insufficient evidence to recommend TTF to increase overall survival in adult patients with pGBM. QUESTION (Q5): In adult patients with pGBM does the use of oncolytic virotherapy result in increased survival compared to chemotherapy?, Recommendation: Level III: Oncolytic virotherapy is not suggested in patients with pGBM., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Target Population: These recommendations apply to adult patients (18 years of age and above) with progressive/recurrent glioblastoma multiforme (pGBM) after first line combined multimodality treatment., Question: Can re-irradiation (by using conventional radiotherapy, fractionated radiosurgery, or single fraction radiosurgery) be used in patients with pGBM after the first adjuvant combined multimodality treatment with radiation and chemotherapy?, Recommendation: Level III: When the target tumor is amenable for additional radiation, re-irradiation is recommended as it provides improved local tumor control, as measured by best imaging response. Such re-irradiation can take the form of conventional fractionation radiotherapy, fractionated radiosurgery, or single fraction radiosurgery., Level Iii: Re-Irradiation is recommended in order to maintain or improve a patient's neurological status and quality of life prior to any further tumor progression., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Target Population: These recommendations apply to adult patients with progressive or recurrent glioblastoma (GBM)., Question: For adult patients with progressive glioblastoma does testing for Isocitrate Dehydrogenase (IDH) 1 or 2 mutations provide new additional management or prognostic information beyond that derived from the tumor at initial presentation?, Recommendation: Level III: Repeat IDH mutation testing is not necessary if the tumor is histologically similar to the primary tumor and the patient's clinical course is as expected., Question: For adult patients with progressive glioblastoma does repeat testing for MGMT promoter methylation provide new or additional management or prognostic information beyond that derived from the tumor at initial presentation and what methods of detection are optimal?, Recommendation: Level III: Repeat MGMT promoter methylation is not recommended., Question: For adult patients with progressive glioblastoma does EGFR amplification or mutation testing provide management or prognostic information beyond that provided by histologic analysis and if performed on previous tissue samples, does it need to be repeated?, Recommendation: Level III: In cases that are difficult to classify as glioblastoma on histologic features EGFR amplification testing may help in classification. If a previous EGFR amplification was detected, repeat testing is not necessary. Repeat EGFR amplification or mutational testing may be recommended in patients in which target therapy is being considered., Question: For adult patients with progressive glioblastoma does large panel or whole genome sequencing provide management or prognostic information beyond that derived from histologic analysis?, Recommendation: Level III: Primary or repeat large panel or whole genome sequencing may be considered in patients who are eligible or interested in molecularly guided therapy or clinical trials., Question: For adult patients with progressive glioblastoma should immune checkpoint biomarker testing be performed to provide management and prognostic information beyond that obtained from histologic analysis?, Recommendation: Level III: The current evidence does not support making PD-L1 or mismatch repair (MMR) enzyme activity a component of standard testing., Question: For adult patients with progressive glioblastoma are there meaningful biomarkers for bevacizumab responsiveness and does their assessment provide additional information for tumor management and prognosis beyond that learned by standard histologic analysis?, Recommendation: Level III: No established Bevacizumab biomarkers are currently available based upon the inclusion criteria of this guideline., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Target Population: These recommendations apply to adults with glioblastoma who have been previously treated with first-line radiation or chemoradiotherapy and who are suspected of experiencing tumor progression., Question: In patients with previously treated glioblastoma, is standard contrast-enhanced magnetic resonance imaging including diffusion weighted imaging useful for diagnosing tumor progression and differentiating progression from treatment-related changes?, Level Ii: Magnetic resonance imaging with and without gadolinium enhancement including diffusion weighted imaging is recommended as the imaging surveillance method to detect the progression of previously diagnosed glioblastoma., Question: In patients with previously treated glioblastoma, does magnetic resonance spectroscopy add useful information for diagnosing tumor progression and differentiating progression from treatment-related changes beyond that derived from standard magnetic resonance imaging with and without gadolinium enhancement?, Level Ii: Magnetic resonance spectroscopy is recommended as a diagnostic method to differentiate true tumor progression from treatment-related imaging changes or pseudo-progression in patients with suspected progressive glioblastoma., Question: In patients with previously treated glioblastoma, does magnetic resonance perfusion add useful information for diagnosing tumor progression and differentiating progression from treatment-related changes beyond that derived from standard magnetic resonance imaging with and without gadolinium enhancement?, Level Iii: Magnetic resonance perfusion is suggested as a diagnostic method to differentiate true tumor progression from treatment-related imaging changes or pseudo-progression in patients with suspected progressive glioblastoma., Question: In patients with previously treated glioblastoma, does the addition of single-photon emission computed tomography (SPECT) provide additional useful information for diagnosing tumor progression and differentiating progression from treatment-related changes beyond that derived from standard magnetic resonance imaging with and without gadolinium enhancement?, Level Iii: Single-photon emission computed tomography imaging is suggested as a diagnostic method to differentiate true tumor progression from treatment-related imaging changes or pseudo-progression in patients with suspected progressive glioblastoma., Question: In patients with previously treated glioblastoma, does 18F-fluorodeoxyglucose positron emission tomography add useful information for diagnosing tumor progression and differentiating progression from treatment-related changes beyond that derived from standard magnetic resonance imaging with and without gadolinium enhancement?, Level Iii: The routine use of 18F-fluorodeoxyglucose positron emission tomography to identify progression of glioblastoma is not recommended., Question: In patients with previously treated glioblastoma, does positron emission tomography with amino acid agents add useful information for diagnosing tumor progression and differentiating progression from treatment-related changes beyond that derived from standard magnetic resonance imaging with and without gadolinium enhancement?, Level Iii: It is suggested that amino acid positron emission tomography be considered to assist in the differentiation of progressive glioblastoma from treatment related changes., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: The management of glioblastoma at the time of progression is an important facet of all physicians involved in neuro-oncology. This is an update of the evidence-based guidelines for management of progressive glioblastoma published by the Congress of Neurological Surgeons and American Association of Neurological Surgeons in 2014., Methods: The medical literature from July 1, 2012 through March 31, 2019 was searched in MEDLINE® and Embase® and the Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Registry, and Cochrane Database of Abstracts of Reviews of Effects to determine if information was available to update, modify or create new recommendations related to imaging, cytoreductive surgery, neuropathology, radiotherapy, cytotoxic chemotherapy, targeted therapy, and immunotherapy., Results: The writing group utilized the information from the updated literature search to formulate recommendations that were exclusively evidence based and not founded on potentially biased consensus or expert opinion., Conclusion: The series of guideline documents provides an update of the information and recommendations that could be derived in the 2014 version. It sets a benchmark as to what we really know about the management of this difficult disease. It also provides clues to key investigations that are necessary to move us toward truly effective disease control., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Question: In patients with previously diagnosed glioblastoma who are suspected of experiencing progression, does repeat cytoreductive surgery improve progression free survival or overall survival compared to alternative interventions?, Target Population: These recommendations apply to adults with previously diagnosed glioblastoma who are suspected of experiencing progression of the neoplastic process and are amenable to surgical resection., Recommendation: Level II: Repeat cytoreductive surgery is recommended in progressive glioblastoma patients to improve overall survival., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Neurologic injury is a rare and potentially devastating complication of shoulder arthroplasty. Patients typically present with a mixed plexopathy or mononeuropathy, most commonly affecting the axillary and radial nerves. Given the paucity of studies available on the topic, our goal was to elucidate the prevalence of nerve injury after shoulder arthroplasty and to describe the treatment course and outcomes of neurologic injuries., Methods: This is a retrospective case-control study performed at a single, urban, academic institution. Consecutive patients who underwent anatomic total shoulder arthroplasty (TSA) or reverse shoulder arthroplasty (RSA) by a single surgeon from 2014 to 2020 were reviewed, and patients with a documented nerve injury were identified. A control group of patients without nerve injury were selected in a 2:1 ratio controlling for age and procedure type (TSA vs. RSA; primary vs. revision). Data collected included demographics, comorbidities as per the Charlson Comorbidity Index, radiographic evaluations, surgical and implant details, patient-reported outcome measures, and perioperative complications., Results: Of 923 patients, 33 (3.6%) sustained an iatrogenic nerve injury: 10 (2.1%) after TSA, 23 (5.0%) after RSA, and 3 (7.8%) after revision arthroplasty. Axillary mononeuropathy was most common (42%), followed by brachial plexopathies (18%). There was no significant difference in age, sex, race, body mass index, and preoperative diagnoses between groups. Patients with nerve injury had fewer comorbidities (Charlson Comorbidity Index <3, 33 vs. 65%, P <.001). Patients with nerve injury had higher rates of cervical spine pathology (15 vs. 6%; P  = .15) and increased postoperative lateralization (8.9 mm [7.2] vs. 5.5 mm [7.3]; P <.06). The majority (91%) were managed with observation alone. Three (9%) underwent an additional procedure: carpal tunnel release (1, 3%), ulnar nerve decompression (1, 3%), and ulnar nerve transposition (1, 3%) for peripheral compressive neuropathies. At the final follow-up, 19 (57%) nerves fully recovered, and 14 (43%) showed mild residual sensorimotor dysfunction. The mean time to first sign of recovery and ultimate recovery were 11 (7.2) and 36 (23.5) weeks, respectively. At the final follow-up, patients with nerve injury performed worse on patient-reported outcomes, including visual analog score pain (2.2 vs. 1.0, P <.001), American Shoulder and Elbow Surgeons score (67.8 vs. 84.8, P <.001), and Single Assessment Numeric Evaluation scores (62 vs. 77, P  = .009)., Discussion: Nerve injury after shoulder arthroplasty is rare, occurring in 3.6% of our patient population. Axillary mononeuropathy and brachial plexopathies are the most common. Most patients can be managed expectantly with observation and will recover at least partial nerve function, although clinical outcomes remain inferior to those without nerve complication., (© 2022 Published by Elsevier Inc. on behalf of American Shoulder & Elbow Surgeons.)

Metastatic disease in the brain is difficult to control and predicts poor prognosis. Here, we analyze human brain metastases and demonstrate their robust infiltration by CD8 + T cell subsets with distinct antigen specificities, phenotypic states, and spatial localization within the tumor microenvironment. Brain metastases are densely infiltrated by T cells; the majority of infiltrating CD8 + T cells express PD-1. Single-cell RNA sequencing shows significant clonal overlap between proliferating and exhausted CD8 + T cells, but these subsets have minimal clonal overlap with circulating and other tumor-infiltrating CD8 + T cells, including bystander CD8 + T cells specific for microbial antigens. Using spatial transcriptomics and spatial T cell receptor (TCR) sequencing, we show these clonally unrelated, phenotypically distinct CD8 + T cell populations occupy discrete niches within the brain metastasis tumor microenvironment. Together, our work identifies signaling pathways within CD8 + T cells and in their surrounding environment that may be targeted for immunotherapy of brain metastases., Competing Interests: Declaration of interests R.A. holds patents related to the PD-1 pathway. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The Institute of Medicine best practice recommendation to review guidelines every 5 years is followed by the Congress of Neurological Surgeons Guidelines Committee. The aim of this work was to provide an updated literature review and evidence-based recommendations on the topic of diagnosis and treatment of patients with progressive glioblastoma (pGBM)., Objective: To review the literature published since the last guidelines on pGBM dated 2014, with literature search ending in June 2012., Methods: PubMed, Embase, and Cochrane were searched for the period July 1, 2012, to March 31, 2019, using search terms and search strategies to identify pertinent abstracts. These were then screened using published exclusion/inclusion criteria to identify full-text review articles. Evidence tables were constructed using data derived from full-text reviews and recommendations made from the evidence derived., Results: From the total 8786 abstracts identified by the search, 237 full-text articles met inclusion/exclusion criteria and were included in this update. Two new level II recommendations derived from this work. For the diagnosis of patients with GBM, the use of diffusion-weighted images is recommended to be included in the magnetic resonance images with and without contrast used for surveillance to detect pGBM. For the treatment of patients with pGBM, repeat cytoreductive surgery is recommended to improve overall survival. An additional 21 level III recommendations were provided., Conclusion: Recent published literature provides new recommendations for the diagnosis and treatment of pGBM. The Central Nervous System Guidelines Committee will continue to pursue timely updates to further improve the care of patients with diagnosis.https://www.cns.org/guidelines/browse-guidelines-detail/guidelines-management-of-progressive-glioblastoma., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)