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.

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.

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.

Bispecific VEGF-A and Angiopoietin-2 Antagonist RO-101 Preclinical Efficacy in Model of Neovascular Eye Disease.

Objective: To investigate preclinical data regarding the efficacy and biocompatibility of a bispecific protein, RO-101, with effects on VEGF-A and angiopoietin-2 (Ang-2) for use in retinal diseases. Design: Experimental study. Subjects: Brown Norway rats and New Zealand White Cross rabbits. Methods: Preclinical study data of RO-101 in terms of target-specific enzyme-linked immunosorbent assay binding affinity to VEGF-A and Ang-2, vitreous half-life, inhibition of target-receptor interaction, laser choroidal neovascular membrane animal model, human umbilical vein endothelial cell migration, and biocompatibility was obtained. Where applicable, study data were compared with other anti-VEGF agents. Main Outcome Measures: Binding affinity, half-life, biocompatibility, and efficacy of RO-101. Neovascularization prevention by RO-101. Results: RO-101 demonstrated a strong binding affinity for VEGF-A and Ang-2 and in vitro was able to inhibit binding to the receptor with higher affinity than faricimab. The half-life of RO-101 is comparable to or longer than current VEGF inhibitors used in retinal disease. RO-101 was found to be biocompatible with retinal tissue in Brown Norway rats. RO-101 was as effective or more effective than current anti-VEGF therapeutics in causing regression of neovascular growth in vivo. Conclusions: RO-101 is a promising candidate for use in retinal diseases. In preclinical models, RO-101 demonstrated similar or higher regression of neovascular growth to current anti-VEGF therapeutics with comparable or longer half-life. It also demonstrates a strong binding affinity for VEGF-A and Ang-2. It also was shown to be biocompatible with retinal tissue in animal studies, indicating potential compatibility for use in humans. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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.

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.

Intramedullary Spinal Cord Tumors: Whole-Genome Sequencing to Assist Management and Prognosis.

Intramedullary spinal cord tumors (IMSCTs) harbor unique genetic mutations which may play a role in prognostication and management. To this end, we present the largest cohort of IMSCTs with genetic characterization in the literature from our multi-site institutional registry. A total of 93 IMSCT patient records were reviewed from the years 1999 to 2020. Out of these, 61 complied with all inclusion criteria, 14 of these patients had undergone genetic studies with 8 undergoing whole-genomic sequencing. Univariate analyses were used to assess any factors associated with progression-free survival (PFS) using the Cox proportional hazards model. Firth's penalized likelihood approach was used to account for the low event rates. Fisher's exact test was performed to compare whole-genome analyses and specific gene mutations with progression. PFS (months) was given as a hazard ratio. Only the absence of copy neutral loss of heterozygosity (LOH) was shown to be significant (0.05, p = 0.008). Additionally, higher risk of recurrence/progression was associated with LOH (p = 0.0179). Our results suggest LOH as a genetic predictor of shorter progression-free survival, particularly within ependymoma and glioblastoma tumor types. Further genomic research with larger multi-institutional datasets should focus on these mutations as possible prognostic factors.

Revision of failed reverse total shoulder arthroplasty with reverse: short-term clinical outcomes.

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.

Volumetric Analysis of Spheno-Orbital Meningiomas: Prognostic Correlation and a Compartmentalized Approach.

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.

Predictors of pain development for contralateral asymptomatic degenerative rotator cuff tears based on features of an ipsilateral painful cuff tear: a prospective longitudinal cohort study.

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.

Rationale for the Development of a Novel Clinical Grading Scale for Postoperative Facial Nerve Function: Results of a Multidisciplinary International Working Group.

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.

Examining the Effect of ALK and EGFR Mutations on Survival Outcomes in Surgical Lung Brain Metastasis Patients.

In the context of the post-genomic era, where targeted oncological therapies like monoclonal antibodies (mAbs) and tyrosine-kinase inhibitors (TKIs) are gaining prominence, this study investigates whether these therapies can enhance survival for lung carcinoma patients with specific genetic mutations-EGFR-amplified and ALK-rearranged mutations. Prior to this study, no research series had explored how these mutations influence patient survival in cases of surgical lung brain metastases (BMs). Through a multi-site retrospective analysis, the study examined patients who underwent surgical resection for BM arising from primary lung cancer at Emory University Hospital from January 2012 to May 2022. The mutational statuses were determined from brain tissue biopsies, and survival analyses were conducted. Results from 95 patients (average age: 65.8 ± 10.6) showed that while 6.3% had anaplastic lymphoma kinase (ALK)-rearranged mutations and 20.0% had epidermal growth factor receptor (EGFR)-amplified mutations-with 9.5% receiving second-line therapies-these mutations did not significantly correlate with overall survival. Although the sample size of patients receiving targeted therapies was limited, the study highlighted improved overall survival and progression-free survival rates compared to earlier trials, suggesting advancements in systemic lung metastasis treatment. The study suggests that as more targeted therapies emerge, the prospects for increased overall survival and progression-free survival in lung brain metastasis patients will likely improve.

Label- and slide-free tissue histology using 3D epi-mode quantitative phase imaging and virtual H&E staining.

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 process is laborious and time-consuming, often limiting its usage in crucial 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.

Clinical and descriptive characteristics associated with high-grade meningioma in a large clinical series.

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.

Immune microenvironment remodeling after radiation of a progressing brain metastasis.

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.

Using Brain Tumor MRI Structured Reporting to Quantify the Impact of Imaging on Brain Tumor Boards.

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.

Prophylactic Colchicine After Radiofrequency Ablation of Atrial Fibrillation: The PAPERS Study.

BACKGROUND: Pericarditis is common after radiofrequency ablation for atrial fibrillation (AF). OBJECTIVES: Study investigators hypothesized an empirical post-AF ablation treatment protocol with colchicine may reduce the incidence and severity of pericarditis. PAPERS (Post-Ablation PEricarditis Reduction Study) aimed to quantify the risks and benefits associated with prophylactic use of colchicine to prevent pericarditis following AF ablation. METHODS: PAPERS is a multicenter, prospective, randomized controlled study. Patients were randomized on the day of the procedure to receive no postprocedure prophylaxis (group A; standard of care arm) or colchicine 0.6 mg orally twice daily for 7 days starting immediately post-procedure (group B; study arm). All participants underwent a follow-up survey at 14 days postoperatively. The primary endpoint was the development of clinical pericarditis within 2 weeks following ablation. Secondary outcomes included the incidence of pericarditis by ablation type and medical therapy. RESULTS: Among 139 patients enrolled, 66 were randomized to standard of care (group A), and 73 patients were randomized to the colchicine arm (group B). The primary outcome of clinical pericarditis was reached in 7 of 66 (10.6%) patients in group A and in 7 of 73 (9.6%) patients in group B (P = 0.84). The rate of gastrointestinal discomfort was 10 of 66 (15%) in group A and 34 of 73 (47%) in group B (P < 0.001). There was an increased incidence of pericarditis in patients who underwent cavotricuspid isthmus ablation (17 of 50; 34%) in addition to pulmonary vein isolation (6 of 69; 8.7%; P = 0.001). CONCLUSIONS: Prophylactic colchicine therapy initiated after the ablation procedure in patients with AF did not affect the incidence of post-ablation pericarditis and was associated with an increased incidence of gastrointestinal side effects.

Immune niches in brain metastases contain TCF1+ stem-like T cells, are associated with disease control and are modulated by preoperative SRS.

The CD8+ T-cell response is prognostic for survival outcomes in several tumor types. However, whether this extends to tumors in the brain, an organ with barriers to T cell entry, remains unclear. Here, we analyzed immune infiltration in 67 brain metastasis (BrM) and found high frequencies of PD1+ TCF1+ stem-like CD8+ T-cells and TCF1- effector-like cells. Importantly, the stem-like cells aggregate with antigen presenting cells in immune niches, and niches were prognostic for local disease control. Standard of care for BrM is resection followed by stereotactic radiosurgery (SRS), so to determine SRS's impact on the BrM immune response, we examined 76 BrM treated with pre-operative SRS (pSRS). pSRS acutely reduced CD8+ T cells at 3 days. However, CD8+ T cells rebounded by day 6, driven by increased frequency of effector-like cells. This suggests that the immune response in BrM can be regenerated rapidly, likely by the local TCF1+ stem-like population.

Complications and timing of soft tissue coverage after complete articular, open tibial plateau fractures.

PURPOSE: Complete articular tibial plateau fractures are typically high-energy injuries associated with significant soft tissue trauma. The primary aim of this study was to evaluate the incidence of wound complications and need for soft tissue coverage after open, complete articular tibial plateau fractures. The secondary aim was to study the effect of timing of fixation and timing of flap coverage on deep infection rates in these injuries. METHODS: This was a retrospective cohort study of consecutive patients > 18 years undergoing ORIF of a Bicondylar Tibial Plateau (BTP) fracture between 2001 and 2018. Surgical data were recorded for open fractures including number of debridements, timing of definitive ORIF and soft tissue coverage relative to injury. Primary outcomes included rates of deep infection and unplanned reoperation. RESULTS: 508 AO/OTA 41C BTP fractures were identified, with 51 open fractures included in 50 patients with a mean (SD) age 45.7 (12.3) years and a mean (SD) follow up of 4.3 (3.8) years. There were 20 cases of deep infection, unplanned reoperation occurred in 26 cases. The majority of cases (28 fractures) had initial external fixation placed, while 24 had ORIF at the initial debridement. Twelve patients had a planned flap for definitive closure on average of 6.4 days (SD 3.9) after injury, 14 required a flap for wound complications. Among patients with IIB and C injuries, rates of deep infection (5/6 vs 1/6, p = 0.02) and reoperation (5/7 vs 2/6, p = 0.08) were higher in patients treated with flap coverage >7 days from injury compared to early flap coverage. There were no differences in complication rates between early (<24hrs) and delayed fixation. CONCLUSIONS: Complete articular, open tibial plateau fractures are associated with high rates of complications. Time to flap coverage of seven days or more was a significant predictor of deep infection and unplanned reoperation in this cohort. Patients should be counseled about the high rate of unplanned reoperation and definitive soft tissue coverage should be accomplished within a week of injury whenever possible.