Citations

The AANS/CNS Section on Tumors was founded 40 years ago in 1984 to assist in the education of neurosurgeons interested in neuro-oncology, and serves as a resource for other national organizations regarding the clinical treatment of nervous system tumors. The Section on Tumors was the first national physicians’ professional organization dedicated to the study and treatment of patients with brain and spine tumors. Over the past 40 years, the Section on Tumors has built solid foundations, including establishing the tumor section satellite meetings, founding the Journal of Neuro-Oncology (the first medical journal dedicated to brain and spine surgical oncology), advancing surgical neuro-oncology education and research, promoting neurosurgical involvement in neuro-oncology clinical trials, and advocating for patients with brain and spine tumors. This review provides a synopsis of the Section on Tumors’ history, its challenges, and its opportunities, drawing on the section’s archives and input from the 17 section chairs who led it during its first 40 years.

Abstract Background Filgotinib (FIL), an oral, once-daily, Janus kinase 1 inhibitor, was approved for Ulcerative Colitis (UC) treatment after the phase 2b/3 SELECTION trial (NCT02914522). In SELECTION, a greater proportion of FIL200 mg (FIL200)-treated than placebo-treated patients achieved comprehensive disease control (CDC), a stringent multi-component endpoint. We examined the long-term outcomes of achieving CDC in patients continuing on FIL200 in the ongoing long-term extension (LTE) study SELECTIONLTE (NCT02914535). Methods This interim analysis included adult patients with UC who completed SELECTION and received ≤144 weeks of FIL200 in the LTE (up to data cut-off 24/02/22). CDC (biomarker remission, endoscopic improvement, IBDQ remission and partial Mayo Clinic Score [pMCS] remission achieved concurrently) was assessed at SELECTION week 58 (LTE baseline [BL]). Mean pMCS and IBDQ score, use of corticosteroids (CS) and incidence of TEAEs and serious TEAEs in the LTE were compared between SELECTION CDC achievers and non-achievers. A mixed model for repeated measures was fitted on pMCS and IBDQ score, with CDC achiever status, study visit and the interaction between CDC achiever status and study visit as fixed effects; p values were nominal. Results We analysed 148 patients (CDC achievers, n=41; CDC non-achievers, n=107). Mean pMCS was stable in CDC achievers (0.44, LTE BL; 0.50, LTE week 144) and decreased in CDC non-achievers (1.49, LTE BL; 0.77, LTE week 144; Figure). Mean IBDQ score was stable in CDC achievers (204.05, LTE BL; 197.21, LTE week 144) and increased in CDC non-achievers (181.55, LTE BL; 196.37, LTE week 144; Figure). There was a significant beneficial effect of achieving CDC on pMCS and IBDQ score overall (pMCS: fixed effect estimate: −0.5542, p=0.0025; IBDQ score: fixed effect estimate: 13.1585, p=0.0042). There was a significant interaction between achieving CDC and study visit for IBDQ score (p=0.0183), with the benefit of achieving CDC lessening by week 144. Generally, a lower proportion of CDC achievers used CS than non-achievers; 2.4–7.3% of CDC achievers used CS vs 1.9–15.9% of CDC non-achievers. Incidence of TEAEs and serious TEAEs were stable over time and similar between CDC achievers and non-achievers. Conclusion Follow-up for ~3 years showed high levels of long-term benefit with continued FIL200 treatment. Achieving comprehensive disease control at the end of the randomized trial with FIL200 was associated with long-term efficacy, improved HRQoL and low overall use of CS. This may demonstrate the value of filgotinib-induced achievement of CDC in UC disease course. The safety profile of FIL200 was consistent between CDC achievers and non-achievers, suggesting an acceptable long-term benefit–risk profile.

AbstractDespite its high prevalence among dementias, Lewy body dementia (LBD) remains poorly understood with a limited, albeit growing, evidence base. The public‐health burden that LBD imposes is worsened by overlapping pathologies, which contribute to misdiagnosis, and lack of treatments. For this report, we gathered and analyzed public‐domain information on advocacy, funding, research outputs, and the therapeutic pipeline to identify gaps in each of these key elements. To further understand the current gaps, we also conducted interviews with leading experts in regulatory/governmental agencies, LBD advocacy, academic research, and biopharmaceutical research, as well as with funding sources. We identified wide gaps across the entire landscape, the most critical being in research. Many of the experts participated in a workshop to discuss the prioritization of research areas with a view to accelerating therapeutic development and improving patient care. This white paper outlines the opportunities for bridging the major LBD gaps and creates the framework for collaboration in that endeavor.Highlights A group representing academia, government, industry, and consulting expertise was convened to discuss current progress in Dementia with Lewy Body care and research. Consideration of expert opinion,natural language processing of the literature as well as publicly available data bases, and Delphi inspired discussion led to a proposed consensus document of priorities for the field.

Background Nephritis is a common manifestation of IgA vasculitis and is morphologically indistinguishable from IgA nephropathy. While MEST-C scores are predictive of kidney outcomes in IgA nephropathy, their value in IgA vasculitis nephritis has not been investigated in large multiethnic cohorts. Methods Biopsies from 262 children and 99 adults with IgA vasculitis nephritis ( N =361) from 23 centers in North America, Europe, and Asia were independently scored by three pathologists. MEST-C scores were assessed for correlation with eGFR/proteinuria at biopsy. Because most patients ( N =309, 86%) received immunosuppression, risk factors for outcomes were evaluated in this group using latent class mixed models to identify classes of eGFR trajectories over a median follow-up of 2.7 years (interquartile range, 1.2–5.1). Clinical and histologic parameters associated with each class were determined using logistic regression. Results M, E, T, and C scores were correlated with either eGFR or proteinuria at biopsy. Two classes were identified by latent class mixed model, one with initial improvement in eGFR followed by a late decline (class 1, N =91) and another with stable eGFR (class 2, N =218). Class 1 was associated with a higher risk of an established kidney outcome (time to ≥30% decline in eGFR or kidney failure; hazard ratio, 5.84; 95% confidence interval, 2.37 to 14.4). Among MEST-C scores, only E1 was associated with class 1 by multivariable analysis. Other factors associated with class 1 were age 18 years and younger, male sex, lower eGFR at biopsy, and extrarenal noncutaneous disease. Fibrous crescents without active changes were associated with class 2. Conclusions Kidney outcome in patients with biopsied IgA vasculitis nephritis treated with immunosuppression was determined by clinical risk factors and endocapillary hypercellularity (E1) and fibrous crescents, which are features that are not part of the International Study of Diseases of Children classification.

Context.— The Nottingham Grading System (NGS) developed by Elston and Ellis is used to grade invasive breast cancer (IBC). Glandular (acinar)/tubule formation is a component of NGS. Objective.— To investigate the ability of pathologists to identify individual structures that should be classified as glandular (acinar)/tubule formation. Design.— A total of 58 hematoxylin-eosin photographic images of IBC with 1 structure circled were classified as tubules (41 cases) or nontubules (17 cases) by Professor Ellis. Images were sent as a PowerPoint (Microsoft) file to breast pathologists, who were provided with the World Health Organization definition of a tubule and asked to determine if a circled structure represented a tubule. Results.— Among 35 pathologists, the κ statistic for assessing agreement in evaluating the 58 images was 0.324 (95% CI, 0.314–0.335). The median concordance rate between a participating pathologist and Professor Ellis was 94.1% for evaluating 17 nontubule cases and 53.7% for 41 tubule cases. A total of 41% of the tubule cases were classified correctly by less than 50% of pathologists. Structures classified as tubules by Professor Ellis but often not recognized as tubules by pathologists included glands with complex architecture, mucinous carcinoma, and the “inverted tubule” pattern of micropapillary carcinoma. A total of 80% of participants reported that they did not have clarity on what represented a tubule. Conclusions.— We identified structures that should be included as tubules but that were not readily identified by pathologists. Greater concordance for identification of tubules might be obtained by providing more detailed images and descriptions of the types of structures included as tubules.

Importance Oncocytic (Hürthle cell) thyroid carcinoma is a follicular cell-derived neoplasm that accounts for approximately 5% of all thyroid cancers. Until recently, it was categorized as a follicular thyroid carcinoma, and its management was standardized with that of other differentiated thyroid carcinomas. In 2022, given an improved understanding of the unique molecular profile and clinical behavior of oncocytic thyroid carcinoma, the World Health Organization reclassified oncocytic thyroid carcinoma as distinct from follicular thyroid carcinoma. The International Thyroid Oncology Group and the American Head and Neck Society then collaborated to review the existing evidence on oncocytic thyroid carcinoma, from diagnosis through clinical management and follow-up surveillance. Observations Given that oncocytic thyroid carcinoma was previously classified as a subtype of follicular thyroid carcinoma, it was clinically studied in that context. However, due to its low prevalence and previous classification schema, there are few studies that have specifically evaluated oncocytic thyroid carcinoma. Recent data indicate that oncocytic thyroid carcinoma is a distinct class of malignant thyroid tumor with a group of distinct genetic alterations and clinicopathologic features. Oncocytic thyroid carcinoma displays higher rates of somatic gene variants and genomic chromosomal loss of heterozygosity than do other thyroid cancers, and it harbors unique mitochondrial DNA variations. Clinically, oncocytic thyroid carcinoma is more likely to have locoregional (lymph node) metastases than is follicular thyroid carcinoma—with which it was formerly classified—and it develops distant metastases more frequently than papillary thyroid carcinoma. In addition, oncocytic thyroid carcinoma rarely absorbs radioiodine. Conclusions and Relevance The findings of this review suggest that the distinct clinical presentation of oncocytic thyroid carcinoma, including its metastatic behavior and its reduced avidity to radioiodine therapy, warrants a tailored disease management approach. The reclassification of oncocytic thyroid carcinoma by the World Health Organization is an important milestone toward developing a specific and comprehensive clinical management for oncocytic thyroid carcinoma that considers its distinct characteristics.

BACKGROUND AND OBJECTIVES: Degenerative spine disease is a leading cause of disability, with increasing prevalence in the older patients. While age has been identified as an independent predictor of outcomes, its predictive value is limited for similar older patients. Here, we aimed to determine the most predictive frailty score of adverse events in patients aged 80 and older undergoing instrumented lumbar fusion. METHODS: We proceeded with a multisite (3 tertiary academic centers) retrospective review including patients undergoing instrumented fusion aged 80 and older from January 2010 to present. A composite end point encompassing 30-day return to operating room, readmission, and mortality was created. We estimated the area under the receiver operating characteristic curve for frailty scores (Modified Frailty Index-5 [MFI-5], Modified Frailty Index-11 [MFI-11], and Charlson Comorbidity Index [CCI]) in relation to that composite score. In addition, we estimated the association between each score and the composite end point by means of logistic regression. RESULTS: A total of 153 patients with an average age of 85 years at the time of surgery were included. We observed a 30-day readmission rate of 11.1%, reoperation of 3.9%, and mortality of 0.6%. The overall rate of the composite end point at 30 days was 25 (15.1%). The AUC for MFI-5 was 0.597 (0.501-0.693), for MFI-11 was 0.620 (0.518-0.723), and for CCI was 0.564 (0.453-0.675). The association between the scores and composite end point did not reach statistical significance for MFI-5 (odds ratio [OR] = 1.45 [0.98-2.15], P = .061) and CCI (OR = 1.13 [0.97-1.31], P = .113) but was statistically significant for MFI-11 (OR = 1.46 [1.07-2.00], P = .018). CONCLUSION: This is the largest study comparing frailty index scores in octogenarians undergoing instrumented lumbar fusion. Our findings suggest that while MFI-11 score correlated with adverse events, the predictive ability of existing scores remains limited, highlighting the need for better approaches to identify select patients at age extremes.

Septal Myectomy (SM) and Alcohol Septal Ablation (ASA) improve symptoms in patients with Hypertrophic Cardiomyopathy with outflow tract obstruction (oHCM). However, outcomes data in this population is predominantly from specialized centers. The National Inpatient Database was queried from 2011 to 2019 for relevant international classification of diseases (ICD)-9 and -10 diagnostic and procedural codes. We compared baseline characteristics and in-hospital outcomes of patients with oHCM who underwent SM vs ASA. A p-value < 0.001 was considered statistically significant. We identified 15,119 patients with oHCM who underwent septal reduction therapies, of whom 57.4% underwent SM, and 42.6% underwent ASA. Patients who underwent SM had higher all-cause mortality (OR: 1.8 (1.3–2.5)), post-procedure ischemic stroke (OR: 2.3 (1.7–3.2)), acute kidney injury (OR: 1.4 (1.2–1.7)), vascular complications (OR: 3.6 (2.3–5.3)), ventricular septal defect (OR: 4.4 (3.2–6.1)), cardiogenic shock (OR: 1.7 (1.3–2.3)), sepsis (OR: 3.2 (1.9–5.4)), and left bundle branch block (OR: 3.5 (3–4)), compared to ASA. Patients who underwent ASA had higher post-procedure complete heart block (OR: 1.3 (1.1–1.4)), right bundle branch block (OR: 6.3 (5–7.7)), ventricular tachycardia (OR: 2.2 (1.9–2.6)), supraventricular tachycardia (OR: 1.6 (1.4–2)), and more commonly required pacemaker insertion (OR: 1.4 (1.3–1.7)) (p < 0.001 for all) compared to SM. This nationwide analysis evidenced that patients undergoing SM had higher in-hospital mortality and periprocedural complications than ASA; however, those undergoing ASA had more post-procedure conduction abnormalities and pacemaker implantation. The implications of these findings warrant further investigation regarding patient selection strategies for these therapies.