Citations

PURPOSE The Response Assessment in Neuro-Oncology (RANO) criteria for high-grade gliomas (RANO-HGG) and low-grade gliomas (RANO-LGG) were developed to improve reliability of response assessment in glioma trials. Over time, some limitations of these criteria were identified, and challenges emerged regarding integrating features of the modified RANO (mRANO) or the immunotherapy RANO (iRANO) criteria. METHODS Informed by data from studies evaluating the different criteria, updates to the RANO criteria are proposed (RANO 2.0). RESULTS We recommend a standard set of criteria for both high- and low-grade gliomas, to be used for all trials regardless of the treatment modalities being evaluated. In the newly diagnosed setting, the postradiotherapy magnetic resonance imaging (MRI), rather than the postsurgical MRI, will be used as the baseline for comparison with subsequent scans. Since the incidence of pseudoprogression is high in the 12 weeks after radiotherapy, continuation of treatment and confirmation of progression during this period with a repeat MRI, or histopathologic evidence of unequivocal recurrent tumor, are required to define tumor progression. However, confirmation scans are not mandatory after this period nor for the evaluation of treatment for recurrent tumors. For treatments with a high likelihood of pseudoprogression, mandatory confirmation of progression with a repeat MRI is highly recommended. The primary measurement remains the maximum cross-sectional area of tumor (two-dimensional) but volumetric measurements are an option. For IDH wild-type glioblastoma, the nonenhancing disease will no longer be evaluated except when assessing response to antiangiogenic agents. In IDH-mutated tumors with a significant nonenhancing component, clinical trials may require evaluating both the enhancing and nonenhancing tumor components for response assessment. CONCLUSION The revised RANO 2.0 criteria refine response assessment in gliomas.

Background: Acute kidney injury (AKI) increases the risk of hospital readmission, chronic kidney disease, and death. Therefore, effective communication in discharge summaries is essential for safe transitions of care. Objective: The objectives of this study were to determine the quality of discharge summaries in AKI survivors and identify predictors of higher quality discharge summaries. Design: Retrospective chart review. Setting: Tertiary care academic center in Ontario, Canada. Patients: We examined the discharge summary quality of 300 randomly selected adult patients who survived a hospitalization with AKI at our tertiary care hospital, stratified by AKI severity. We included 150 patients each from 2015 to 2016 and 2018 to 2019, before and after introduction of a post-AKI clinic in 2017. Measurements: We reviewed charts for 9 elements of AKI care to create a composite score summarizing discharge summary quality. Methods: We used multivariable logistic regression to identify predictors of discharge summary quality. Results: The median discharge summary composite score was 4/9 (interquartile range, 2-6). The least frequently mentioned elements were baseline creatinine (n = 55, 18%), AKI-specific follow-up labs (n = 66, 22%), and medication recommendations (n = 80, 27%). The odds of having a higher quality discharge summary (composite score ≥4/9) was greater for every increase in baseline creatinine of 25 μmol/L (adjusted odds ratio [aOR]: 1.27; 95% confidence interval [CI]: 1.03, 1.56), intrarenal etiology (aOR: 2.32; 95% CI: 1.26, 4.27), and increased AKI severity (stage 2 aOR: 2.57; 95% CI: 1.35, 4.91 and stage 3 aOR: 3.36; 95% CI: 1.56, 7.22). There was no association between discharge summary quality and the years before and after introduction of a post-AKI clinic (aOR: 0.77; 95% CI: 0.46, 1.29). Limitations: The single-center study design limits generalizability. Conclusions: Most discharge summaries are missing key AKI elements, even in patients with severe AKI. These gaps suggest several opportunities exist to improve discharge summary communication following AKI.

AbstractINTRODUCTIONStudies suggest distinct differences in the development, presentation, progression, and response to treatment of Alzheimer's disease (AD) between females and males. We investigated sex differences in cognition, neuroimaging, and fluid biomarkers in dominantly inherited AD (DIAD).METHODSThree hundred twenty‐five mutation carriers (55% female) and one hundred eighty‐six non‐carriers (58% female) of the Dominantly Inherited Alzheimer Network Observational Study were analyzed. Linear mixed models and Spearman's correlation explored cross‐sectional sex differences in cognition, cerebrospinal fluid (CSF) biomarkers, Pittsburgh compound B positron emission tomography (11C‐PiB PET) and structural magnetic resonance imaging (MRI).RESULTSFemale carriers performed better than males on delayed recall and processing speed despite similar hippocampal volumes. As the disease progressed, symptomatic females revealed higher increases in MRI markers of neurodegeneration and memory impairment. PiB PET and established CSF AD markers revealed no sex differences.DISCUSSIONOur findings suggest an initial cognitive reserve in female carriers followed by a pronounced increase in neurodegeneration coupled with worse performance on delayed recall at later stages of DIAD.

Abstract AIMS High-grade glioma continues to have dismal survival with current standard-of-care treatment, owing in part to its intra- and inter-patient heterogeneity. Typical diagnostic biopsies are taken from the dense tumor core to determine the presence of abnormal cells and the status of a few key genes (e.g. IDH1, MGMT). However, the tumor core is typically resected, leaving behind possibly genetically, transcriptomically and/or phenotypically distinct invasive margins that repopulate the disease. As these remaining populations are the ones ultimately being treated, it is important to know their compositional differences from the tumor core. We aim to identify the phenotypic niches defined by the relative composition of key cellular populations and understand their variation amongst patients. METHOD We have established an image-localized research biopsy study, that samples from both the invasive margin and tumor core. From this protocol, we currently have 202 samples from 58 patients with available bulk RNA-Seq, collected between Mayo Clinic and Barrow Neurological Institute. Using a single-cell reference dataset from our collaborators at Columbia University, we used CIBERSORTx, a deconvolution method, to predict relative abundances of 7 normal, 6 glioma, and 5 immune cell states for each sample. RESULTS We find that these cell state abundances connect to patient survival and show regional differences. For example, proneural glioma states were higher in invasive regions, whereas proliferative and mesenchymal states were higher in the tumor core. CONCLUSIONS Our analysis demonstrates a need to characterize the residual tissue following glioma resection to better understand the recurrent disease.

Abstract BACKGROUND The Response Assessment in Neuro-Oncology (RANO) criteria for high-grade gliomas (RANO-HGG) and low-grade gliomas (RANO-LGG) were developed to improve reliability of response assessment in glioma trials. Over time some limitations of these criteria were identified, and uncertainty emerged regarding integrating features of the modified RANO (mRANO) or the immunotherapy RANO (iRANO) criteria. MATERIAL AND METHODS Informed by data from a cohort of glioblastoma patients and other evaluations of RANO criteria that allowed evaluation of features of the different criteria, the RANO working group developed updates to the RANO criteria (RANO 2.0). RESULTS Based on the 2021 WHO classification of gliomas, we recommend a standard set of criteria for both high and low-grade gliomas, to be used for all trials regardless of the treatment modalities being evaluated. In the newly diagnosed setting, the post-radiotherapy MRI, rather than the post-surgical MRI, will be used as the baseline for future comparison. Since the incidence of pseudoprogression is high in the 12 weeks following radiotherapy, continuation of treatment and confirmation of progression during this period with a repeat MRI, or histopathologic evidence of unequivocal recurrent tumor, is required to define tumor progression. However, confirmation scans are not mandatory after this period nor for recurrent tumors. For treatments with a high likelihood of pseudoprogression, mandatory confirmation of progression with a repeat MRI is highly recommended. The primary measurement remains the maximum cross-sectional area of tumor (2-dimensional) but volumetric measurements are an option. For IDH-wildtype glioblastoma, the non-enhancing disease will no longer be evaluated. In IDH-mutated tumors with a significant non-enhancing component, clinical trials may require evaluating both the enhancing and non-enhancing tumor components for response assessment. CONCLUSION These criteria represent a work in progress that will hopefully improve the assessment of response in glioma trials. Future updates will incorporate novel developments, advanced imaging techniques, and endpoints as they become validated.

AbstractBackgroundVarious injection algorithms have been proposed in the past which are in line with the three aesthetic principles: upper face first, lateral face first, and deep regions first. However, increasing evidence is provided that the upper midface can be targeted with superficial soft tissue filler injections alone too.ObjectiveTo investigate in a prospective split‐face study design whether superficial or deep upper midfacial injections provide superior aesthetic outcomes.MethodsA total of n = 20 study participants (100% females; age 43.95 (11.7) years; BMI 22.92 (2.6) kg/m2) were treated with superficial soft tissue filler injections on side of their face and deep injections on the contralateral side with a mean volume of 0.78 cc. Outcome was evaluated at 7 weeks follow‐up for midfacial, and lower facial volume, for medial and lateral facial skin vector displacement, and for improvement of nasolabial, crow's feet, and upper cheek fullness severity scores.ResultsNo adverse events related to safety or product tolerability were observed during the entire study period. All semiquantitative scores improved statistically significantly after the observational period (p < 0.001) but displayed no difference between the two applied injection techniques (p > 0.05).ConclusionThe results of this split‐face study revealed that both the superficial and the deep cannula injection technique for midface volumization statistically significantly improve the midfacial volume, reduce nasolabial fold and crow's feet severity. No statistically significant difference was observed between the two injection techniques when compared via semiquantitative and objective outcome evaluation after 7 weeks follow‐up.

AbstractCD19‐directed CAR T‐cell therapy with brexucabtagene autoleucel (brexu‐cel) has substantially improved treatment outcomes for patients with relapsed/refractory mantle cell lymphoma (r/r MCL). Prolonged cytopenias and infections represent common and clinically relevant side effects. In this multicenter observational study, we describe cytopenias and infections in 103 r/r MCL patients receiving brexu‐cel. Furthermore, we report associations between the baseline CAR‐HEMATOTOX (HT) score and toxicity events, non‐relapse mortality (NRM), and progression‐free/overall survival (PFS/OS). At lymphodepletion, 56 patients were HTlow (score 0–1) while 47 patients were HThigh (score ≥2). The HThigh cohort exhibited prolonged neutropenia (median 14 vs. 6 days, p < .001) and an increased rate of severe infections (30% vs. 5%, p = .001). Overall, 1‐year NRM was 10.4%, primarily attributed to infections, and differed by baseline HT score (high vs. low: 17% vs. 4.6%, p = .04). HThigh patients experienced inferior 90‐day complete response rate (68% vs. 93%, p = .002), PFS (median 9 months vs. not‐reached, p < .0001), and OS (median 26 months vs. not‐reached, p < .0001). Multivariable analyses showed that high HT scores were independently associated with severe hematotoxicity, infections, and poor PFS/OS. In conclusion, infections and hematotoxicity are common after brexu‐cel and contribute to NRM. The baseline HT score identified patients at increased risk of poor treatment outcomes.