Frailty in patients with IDH-mutant gliomas: experience from a high-volume tumor center.

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.

Three-dimensional analysis of biplanar glenoid deformities: what are they and can they be virtually reconstructed with anatomic total shoulder arthroplasty implants?

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.

Does Surgical Intervention Alter the Natural History of Degenerative Rotator Cuff Tears? Comparative Analysis from a Prospective Longitudinal Study.

INTRODUCTION: 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 two 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 VAS pain, ASES, AROM, 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=0.04). The median follow-up for control subjects after pain development was 5.1 years (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=0.45) and tear lengths (median 14 mm, IQR 13 vs. median 11 mm, IQR 8; p=0.06) 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=0.43 and p=0.58, respectively). At final follow-up, the surgical group demonstrated significantly lower VAS pain (0 [IQR 2] vs. 3.5 [IQR 4], p=0.0002), higher composite ASES (95 [IQR 13] vs. 65.8 [IQR 32], p=0.0002) and ADL scores (29 [IQR 4] vs. 22 [IQR 8], p=0.0002), greater abduction strength (69.6 N [SD 29] vs. 35.9 N [SD 29], p=0.0002), greater active forward elevation (155˚ [SD 8] vs. 142˚ [SD 28], p=0.002), greater active external rotation in abduction (mean 98.5˚, SD 12 vs. mean 78.2˚, SD 20; p=0.0002) 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=0.05; 17% vs. 34%, p=0.03; 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.

Phase I and pharmacodynamic study of arsenic trioxide plus radiotherapy in patients with newly diagnosed glioblastoma.

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.

American Association of Neurological Surgeons/Congress of the Neurological Surgeons Section on Tumors Guidelines: Assessing Their Impact on Brain Tumor Clinical Practice.

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.

Incidence of and Risk Factors for Reoperation and Revision Following Total Elbow Arthroplasty with an Anatomic Convertible Prosthesis.

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.

The Utility of Spectroscopic MRI in Stereotactic Biopsy and Radiotherapy Guidance in Newly Diagnosed Glioblastoma.

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.

Patterns of Treatment Failure in Primary Central Nervous System Lymphoma.

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.

Utility of Machine Learning, Natural Language Processing, and Artificial Intelligence in Predicting Hospital Readmissions After Orthopaedic Surgery: A Systematic Review and Meta-Analysis.

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.