Citations

AbstractExtramedullary multiple myeloma is seen in advanced and aggressive disease and occurs due to plasma cell infiltration of sites other than the bone marrow. Myelomatous ascites or pleural effusion is seen in less than 1% of cases and can be differentiated from infectious etiologies based on fluid cytology.

Abstract Background: Somatic EGFR mutations define a subset of non–small cell lung cancers (NSCLC) that have clinical impact on NSCLC risk and outcome. However, EGFR-mutation-status is often missing in epidemiologic datasets. We developed and tested pragmatic approaches to account for EGFR-mutation-status based on variables commonly included in epidemiologic datasets and evaluated the clinical utility of these approaches. Methods: Through analysis of the International Lung Cancer Consortium (ILCCO) epidemiologic datasets, we developed a regression model for EGFR-status; we then applied a clinical-restriction approach using the optimal cut-point, and a second epidemiologic, multiple imputation approach to ILCCO survival analyses that did and did not account for EGFR-status. Results: Of 35,356 ILCCO patients with NSCLC, EGFR-mutation-status was available in 4,231 patients. A model regressing known EGFR-mutation-status on clinical and demographic variables achieved a concordance index of 0.75 (95% CI, 0.74–0.77) in the training and 0.77 (95% CI, 0.74–0.79) in the testing dataset. At an optimal cut-point of probability-score = 0.335, sensitivity = 69% and specificity = 72.5% for determining EGFR-wildtype status. In both restriction-based and imputation-based regression analyses of the individual roles of BMI on overall survival of patients with NSCLC, similar results were observed between overall and EGFR-mutation-negative cohort analyses of patients of all ancestries. However, our approach identified some differences: EGFR-mutated Asian patients did not incur a survival benefit from being obese, as observed in EGFR-wildtype Asian patients. Conclusions: We introduce a pragmatic method to evaluate the potential impact of EGFR-status on epidemiological analyses of NSCLC. Impact: The proposed method is generalizable in the common occurrence in which EGFR-status data are missing.

AbstractBackgroundPrior evidence has suggested associations between hearing loss and smaller brain volumes particularly in the temporal lobe where the primary auditory cortex is located, probably due to changes in cortical organization associated with reduced auditory stimulation. Evidence regarding associations of central auditory processing with brain volumes is relatively limited. The study aims to investigate cross‐sectional associations of central auditory processing with brain volumes in older adults.MethodWe studied 587 cognitively normal (Mini‐Mental State Exam ≥23 if high school degree or less and ≥25 if above high school degree) older adults (mean age: 77±4 years, 56% female, 17% black), including 426 with hearing loss from the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) baseline (2018‐19), which is an ancillary randomized controlled trial of the Atherosclerosis Risk in Communities (ARIC) Study and 161 with normal hearing, comparable age and cognitive status from the ARIC Visit 6/7 (2016‐17/2018‐19). Brain volumes were measured by magnetic resonance imaging (MRI) scans and were transformed to z‐scores. Central auditory processing was measured by the Quick Speech‐in‐Noise (QuickSIN) test. Total scores range from 0 to 30 with lower scores indicating worse speech‐in‐noise performance. Multivariable‐adjusted linear regression was used to estimate cross‐sectional differences in standardized brain volumes associated with differences in QuickSIN score. Models adjusted for age, sex, race, education, cohort, body mass index, smoking, hypertension, diabetes, stroke, intracranial volume, and pure‐tone average.ResultEvery 5‐point decrease in QuickSIN score (worse performance) was associated with smaller volumes of the temporal lobe (‐0.07SD, 95% CI: ‐0.13, ‐0.01). QuickSIN score was also associated with subregions of the temporal lobe related to auditory processing, memory and emotion, including amygdala (‐0.13SD, 95% CI: ‐0.21, ‐0.04), middle (‐0.08SD, 95% CI: ‐0.15, ‐0.00) and superior temporal gyri (‐0.08SD, 95% CI: ‐0.15, ‐0.01).ConclusionPoorer central auditory processing was associated with smaller temporal lobe volumes, including but not limited to subregions important for auditory processing. The ongoing collection of ACHIEVE data with longitudinal MRI data will facilitate understanding of association between hearing loss and brain atrophy as well as the potential promising effects of hearing treatment in mitigating brain aging.

Objectives Quantitative magnetization transfer (qMT) is useful for measurement of murine renal fibrosis at high and ultrahigh field strengths. However, its utility at clinical field strengths and in human-like kidneys remains unknown. We tested the hypothesis that qMT would successfully detect fibrosis in swine kidneys with unilateral renal artery stenosis (RAS) at 3.0 T. Methods The qMT protocol is composed of MT scans with variable flip angles and offset frequencies, and of B0 , B1 , and T1 mapping. Pigs were scanned 10 weeks after RAS or control. A 2-pool model was used to fit the bound pool fraction f of the renal cortex (CO) and outer medulla (OM). Then qMT-derived f in 5 normal and 10 RAS pigs was compared with histological fibrosis determined using Masson's trichrome staining and to renal perfusion assessed with computed tomography. Results The qMT 2-pool model provided accurate fittings of data collected on swine kidneys. Stenotic kidneys showed significantly elevated f in both the CO (9.8% ± 2.7% vs 6.4% ± 0.9%, P = 0.002) and OM (7.6% ± 2.2% vs 4.7% ± 1.1%, P = 0.002), as compared with normal kidneys. Histology-measured renal fibrosis and qMT-derived f correlated directly in both the cortex (Pearson correlation coefficient r = 0.93, P < 0.001) and OM (r = 0.84, P = 0.002), and inversely with stenotic kidney perfusion (r = 0.85, P = 0.002). Conclusions This study demonstrates the feasibility of qMT for measuring fibrosis in human-like swine kidneys, and the association between tissue macromolecule content and renal perfusion. Therefore, qMT may be useful as a tool for noninvasive assessment of renal fibrosis in subjects with RAS at clinical field strengths.

Abstract We investigated the cross-sectional associations of speech-in-noise performance with magnetic resonance imaging brain volumes among 588 cognitively normal participants (77±4 years, 56% female) from the Aging and Cognitive Health Evaluation in Elders Study (randomized trial embedded in the Atherosclerosis Risk in Communities (ARIC) Study) baseline in 2018-19 (N=427, with hearing loss) and ARIC (N=161, normal hearing) Visit 6/7 in 2016-17/2018-19. Central auditory processing was measured by Quick Speech-in-Noise (QuickSIN) test; range: 0 to 30, lower scores=worse performance. In models adjusted for demographic and disease covariates, every 5-point decrease in QuickSIN score was associated with smaller volumes of the temporal lobe overall (-0.07SD, 95% CI:-0.13,-0.01) as well as subregions including but not limited to those important for auditory processing (amygdala:-0.13SD, 95% CI:-0.21,-0.04; middle temporal gyrus:-0.08SD, 95% CI:-0.15,-0.00; superior temporal gyrus:-0.08SD, 95% CI:-0.15,-0.01). Further research is needed to understand the mechanisms underlying these observed associations.

AbstractWaldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is often differentiated from myeloma based on the presence of lytic bone lesions (LBL). However, WM/LPL can present with LBL, and management is poorly understood. We describe a case of an 81‐year‐old woman with LPL who presented with LBL and was successfully treated with chemoimmunotherapy.

R47H- TREM2 mutation enhances AKT signaling in human AD microglia and mediates proinflammatory and synaptic toxicity in a tauopathy mouse model.