Gross Motor Function in Pediatric Onset TUBB4A-Related Leukodystrophy: GMFM-88 Performance and Validation of GMFC-MLD in TUBB4A.

TUBB4A pathogenic variants are associated with a spectrum of neurologic impairments including movement disorders and leukodystrophy. With the development of targeted therapies, there is an urgent unmet need for validated tools to measure mobility impairment. Our aim is to explore gross motor function in a pediatric-onset TUBB4A-related leukodystrophy cohort with existing gross motor outcome tools. Gross Motor Function Measure-88 (GMFM-88), Gross Motor Function Classification System (GMFCS-ER), and Gross Motor Function Classification-Metachromatic Leukodystrophy (GMFC-MLD) were selected through face validity. Subjects with a confirmed clinical and molecular diagnosis of TUBB4A-related leukodystrophy were enrolled. Participants' sex, age, genotype, and age at disease onset were collected, together with GMFM-88 and concurrent GMFCS-ER and GMFC-MLD. Performances on each measure were compared. GMFM-88 floor effect was defined as total score below 20%. A total of 35 subjects participated. Median performance by GMFM-88 was 16.24% (range 0-97.31), with 42.9% (n = 15) of individuals performing above the floor. GMFM-88 Dimension A (Lying and Rolling) was the best-performing dimension in the GMFM-88 (n = 29 above the floor). All levels of the Classification Scales were represented, with the exception of the GMFC-MLD level 0. Evaluation by GMFM-88 was strongly correlated with the Classification Scales (Spearman correlations: GMFCS-ER:GMFM-88 r = 0.90; GMFC-MLD:GMFM-88 r = 0.88; GMFCS-ER:GMFC-MLD: r = 0.92). Despite overall observation of a floor effect, the GMFM-88 is able to accurately capture the performance of individuals with attenuated phenotypes. GMFM-88 Dimension A shows no floor effect. GMFC-MLD shows a strong correlation with GMFCS-ER and GMFM-88, supporting its use as an age-independent functional score in TUBB4A-related leukodystrophy.

The Effect of the New Eighth Edition Breast Cancer Staging System on 100 Consecutive Patients.

BACKGROUND: In October 2016 the American Joint Committee on Cancer published the early eighth edition breast cancer prognostic staging system, incorporating biomarkers into previously accepted staging. The updated and current eighth edition became effective nationwide in January 2018 after a large update to its staging guidelines. This study's aim was to compare patients' anatomic seventh edition (anatomic), early eighth (pre-update, prognostic), and current eighth (post-update, prognostic) pathological stages and to assess the utility of recent inclusions to staging criteria. Additionally, we observed how the aforementioned stage changes aligned with breast cancer histologic subtypes. METHODS: An Institutional Review Board (IRB)-approved retrospective chart review was performed. Inclusion criteria included female patients between the ages of 35 to 95 years with a diagnosis of invasive ductal or lobular carcinoma of the breast (n = 100) at three Hackensack Meridian Health hospitals. The study evaluated any trends in patients' stage changes between the seventh edition, early eighth edition, and current eighth edition breast cancer staging guidelines. Breast cancer restaging was performed using a novel staging tool on Microsoft Excel. RESULTS: Only 26% of patients' stages changed when comparing the seventh edition stage vs. current eighth edition prognostic staging, most of which were downstaged. When comparing the seventh with early eighth edition prognostic staging, 38% of the patients' stages changed, with a majority of them being upstaged. Lastly, 95% of total stage changes were downstages between the early eighth and current eighth edition staging guidelines. CONCLUSIONS: When comparing the seventh edition vs. current eighth edition staging, few patients (especially those with early stage cancer) underwent a stage change. However, there were significant changes in stage when comparing early eighth vs. current eighth stages. Considering these changes were mostly downstages and many patients reverted to their original seventh edition stage, the current eighth edition is based on a personalized, less radical staging approach, one that is more synonymous with original seventh edition staging.