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207. Automated scoring of total inflammation in renal allograft biopsies.

Author

Smith, Byron, Grande, Joseph, Ryan, Maggie, Smith, Maxwell, Denic, Aleksandar, Hermsen, Meyke, Park, Walter, Kremers, Walter, and Stegall, Mark

Subjects
RENAL biopsy, CONVOLUTIONAL neural networks, IMAGE analysis, INFLAMMATION, KIDNEY transplantation
Abstract

Background: Computer‐assisted scoring is gaining prominence in the evaluation of renal histology; however, much of the focus has been on identifying larger objects such as glomeruli. Total inflammation impacts graft outcome, and its quantification requires tools to identify objects at the cellular level or smaller. The goal of the current study was to use CD45 stained slides coupled with image analysis tools to quantify the amount of non‐glomerular inflammation within the cortex. Methods: Sixty renal transplant whole slide images were used for digital image analysis. Multiple thresholding methods using pixel intensity and object size were used to identify inflammation in the cortex. Additionally, convolutional neural networks were used to separate glomeruli from other objects in the cortex. This combined measure of inflammation was then correlated with rescored Banff total inflammation classification and outcomes. Results: Identification of glomeruli on biopsies had high fidelity (mean pixelwise dice coefficient of.858). Continuous total inflammation scores correlated well with Banff rescoring (maximum Pearson correlation.824). A separate set of thresholds resulted in a significant correlation with alloimmune graft loss. Conclusions: Automated scoring of inflammation showed a high correlation with Banff scoring. Digital image analysis provides a powerful tool for analysis of renal pathology, not only because it is reproducible and can be automated, but also because it provides much more granular data for studies. [ABSTRACT FROM AUTHOR]

Published
2023
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215. Abstract 10133: Cerebrovascular Imaging Biomarkers, Neuropsychiatric Symptoms, and Mild Cognitive Impairment

Author

Vassilaki, Maria, primary, Syrjanen, Jeremy, additional, Scharf, Eugene, additional, Krell-Roesch, Janina, additional, Vemuri, Prashanthi, additional, Graff-radford, Jonathan, additional, Mielke, Michelle, additional, Machulda, Mary M., additional, Kremers, Walter, additional, Lowe, Val, additional, Jack, Clifford, additional, Knopman, David, additional, Petersen, Ronald, additional, and Geda, Yonas E., additional

Published
2021
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216. Progressive decline of function in renal allografts with normal 1‐year biopsies: Gene expression studies fail to identify a classifier

Author

Park, Walter D., primary, Kim, Dean Y., additional, Mai, Martin L., additional, Reddy, Kunam S., additional, Gonwa, Thomas, additional, Ryan, Margaret S., additional, Herrera Hernandez, Loren P., additional, Smith, Maxwell L., additional, Geiger, Xochiquetzal J., additional, Turkevi‐Nagy, Sandor, additional, Cornell, Lynn D., additional, Smith, Byron H., additional, Kremers, Walter K., additional, and Stegall, Mark D., additional

Published
2021
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218. A Comparison of Cross-Sectional and Longitudinal Methods of Defining Objective Subtle Cognitive Decline in Preclinical Alzheimer’s Disease Based on Cogstate One Card Learning Accuracy Performance

Author

Pudumjee, Shehroo B., primary, Lundt, Emily S., additional, Albertson, Sabrina M., additional, Machulda, Mary M., additional, Kremers, Walter K., additional, Jack, Clifford R., additional, Knopman, David S., additional, Petersen, Ronald C., additional, Mielke, Michelle M., additional, and Stricker, Nikki H., additional

Published
2021
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219. Durability analysis of the highly effective BNT162b2 vaccine against COVID-19

Author

Puranik, Arjun, primary, Lenehan, Patrick J., additional, O’Horo, John C., additional, Niesen, Michiel J.M., additional, Virk, Abinash, additional, Swift, Melanie D., additional, Kremers, Walter, additional, Venkatakrishnan, A.J., additional, Gordon, Joel E., additional, Geyer, Holly L., additional, Speicher, Leigh Lewis, additional, Soundararajan, Venky, additional, and Badley, Andrew D., additional

Published
2021
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227. Mayo‐PACC: Optimizing a parsimonious Preclinical Alzheimer's disease cognitive composite comprised of public‐domain measures.

Author

Karstens, Aimee J., Twohy, Erin L, Albertson, Sabrina M., Kremers, Walter K., Machulda, Mary M., Jack, Clifford R., Knopman, David S., Mielke, Michelle M., Petersen, Ronald C., and Stricker, Nikki H.

Abstract

Background: Preclinical Alzheimer's cognitive composites (PACC) are designed to detect subtle cognitive changes in clinical trials. PACCs often include measures of memory, attention, and semantic fluency, with variations based on available measures. We created a Mayo Clinic PACC (Mayo‐PACC) to address limitations of existing PACCs by prioritizing parsimony, non‐proprietary measures, clinical applicability, and psychometric properties. We developed a Mayo‐PACC and examined sensitivity to detecting longitudinal cognitive change in amyloid positive (A+) older adults relative to the Preclinical Alzheimer's Cognitive Composite‐Revised (PACC‐R). Exploratory analyses included comparison to other composites. Method: Participants included 614 individuals in the Mayo Clinic Study of Aging (428 A‐ and 186 A+) age 65‐85 who were cognitively unimpaired at baseline with 7 years mean follow‐up. A+ was defined as PiB‐PET meta‐ROI SUVR ≥ 1.48 (centiloid 22). The Mayo‐PACC included the AVLT sum of trials (trials 1‐5, short delay, long delay), Trails B and Animal fluency. Measures included in the PACC‐R and other comparison composites are listed in Table 1. We calculated study‐specific z‐scores and examined psychometric properties of component measures including test‐retest reliability, practice effects, and distributional properties (ceiling/floor effects, skew, kurtosis). We examined sensitivity to preclinical cognitive change using slope estimates (difference in annualized change across A+ and A‐ groups) from linear mixed models (LMMs) for each composite. A jackknife procedure was used to calculate the standard error and subsequent confidence intervals of differences in rates of change (A+>A‐ indicating more significant decline in A+). Significance was determined based on whether the 95% Confidence Interval (CI) contained 0 (alpha =.05). Result: All composites showed sensitivity to amyloid‐related longitudinal cognitive decline (A+>A‐ annualized change p<.05; see Table 2). Jack‐knife comparisons revealed comparable utility of Mayo‐PACC and PACC‐R (CI contained 0, see Table 3). Exploratory analyses revealed Mayo‐PACC performed similarly to an adaptation of the ADCS‐PACC, Global‐z, Memory‐z and Attention‐z. The Mayo‐PACC performed better than a 2‐measure Mayo‐PACC‐remote and a single memory measure. Conclusion: The Mayo‐PACC provides a parsimonious composite score that has comparable utility for detecting A+>A‐ cognitive decline compared to the PACC‐R and other composites and can be widely used in both research and clinical settings. [ABSTRACT FROM AUTHOR]

Published
2023
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232. A longitudinal investigation of Aβ, anxiety, depression, and mild cognitive impairment.

Author

Pink, Anna, Krell‐Roesch, Janina, Syrjanen, Jeremy A., Vassilaki, Maria, Lowe, Val J., Vemuri, Prashanthi, Stokin, Gorazd B., Christianson, Teresa J., Kremers, Walter K., Jack, Clifford R., Knopman, David S., Petersen, Ronald C., and Geda, Yonas E.

Abstract

Introduction: We investigated the longitudinal relationship between cortical amyloid deposition, anxiety, and depression and the risk of incident mild cognitive impairment (MCI). Methods: We followed 1440 community‐dwelling, cognitively unimpaired individuals aged ≥ 50 years for a median of 5.5 years. Clinical anxiety and depression were assessed using Beck Anxiety and Depression Inventories (BAI, BDI‐II). Cortical amyloid beta (Aβ) was measured by Pittsburgh compound B positron emission tomography (PiB‐PET) and elevated deposition (PiB+) was defined as standardized uptake value ratio ≥ 1.48. We calculated Cox proportional hazards models with age as the time scale, adjusted for sex, education, and medical comorbidity. Results: Cortical Aβ deposition (PiB+) independent of anxiety (BAI ≥ 10) or depression (BDI‐II ≥ 13) increased the risk of MCI. There was a significant additive interaction between PiB+ and anxiety (joint effect hazard ratio 6.77; 95% confidence interval 3.58–12.79; P =.031) that is, being PiB+ and having anxiety further amplified the risk of MCI. Discussion: Anxiety modified the association between PiB+ and incident MCI. [ABSTRACT FROM AUTHOR]

Published
2022
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235. Detection of Alzheimer's disease amyloid beta 1‐42, p‐tau, and t‐tau assays

Author

Harten, Argonde C., primary, Wiste, Heather J., additional, Weigand, Stephen D., additional, Mielke, Michelle M., additional, Kremers, Walter K., additional, Eichenlaub, Udo, additional, Dyer, Roy B., additional, Algeciras‐Schimnich, Alicia, additional, Knopman, David S., additional, Jack, Clifford R., additional, and Petersen, Ronald C., additional

Published
2021
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236. Cerebral Microbleeds

Author

Graff-Radford, Jonathan, primary, Lesnick, Timothy, additional, Rabinstein, Alejandro A., additional, Gunter, Jeffrey L., additional, Przybelski, Scott A., additional, Noseworthy, Peter A., additional, Preboske, Gregory M., additional, Mielke, Michelle M., additional, Lowe, Val J., additional, Knopman, David S., additional, Petersen, Ronald C., additional, Kremers, Walter K., additional, Jack, Clifford R., additional, Vemuri, Prashanthi, additional, and Kantarci, Kejal, additional

Published
2021
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237. Dementia with Lewy bodies: association of Alzheimer pathology with functional connectivity networks

Author

Schumacher, Julia, primary, Gunter, Jeffrey L, additional, Przybelski, Scott A, additional, Jones, David T, additional, Graff-Radford, Jonathan, additional, Savica, Rodolfo, additional, Schwarz, Christopher G, additional, Senjem, Matthew L, additional, Jack, Clifford R, additional, Lowe, Val J, additional, Knopman, David S, additional, Fields, Julie A, additional, Kremers, Walter K, additional, Petersen, Ronald C, additional, Graff-Radford, Neill R, additional, Ferman, Tanis J, additional, Boeve, Bradley F, additional, Thomas, Alan J, additional, Taylor, John-Paul, additional, and Kantarci, Kejal, additional

Published
2021
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238. 95-OR: Safety and Feasibility Evaluation of Closed-Loop Glycemic Management in Pregnant Women with Type 1 Diabetes

Author

OZASLAN, BASAK, primary, LEVY, CAROL J., additional, PINSKER, JORDAN E., additional, O'MALLEY, GRENYE, additional, KAUR, RAVINDER JEET, additional, CASTORINO, KRISTIN N., additional, LEVISTER, CAMILLA, additional, TRINIDAD, MARI CHARISSE, additional, DESJARDINS, DONNA, additional, CHURCH, MEI MEI, additional, PLESSER, MITCHELL, additional, MCCRADY-SPITZER, SHELLY K., additional, BAKUS, CLARA, additional, OGYAADU, SELASSIE J., additional, NELSON, KRISTEN, additional, REID, COREY, additional, DESHPANDE, SUNIL, additional, KREMERS, WALTER K., additional, DOYLE, FRANCIS J., additional, ROSENN, BARAK, additional, KUDVA, YOGISH C., additional, and DASSAU, EYAL, additional

Published
2021
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240. Public health impact of delaying second dose of BNT162b2 or mRNA-1273 covid-19 vaccine: simulation agent based modeling study

Author

Massachusetts Institute of Technology. Media Laboratory, Romero-Brufau, Santiago, Chopra, Ayush, Ryu, Alex J, Gel, Esma, Raskar, Ramesh, Kremers, Walter, Anderson, Karen S, Subramanian, Jayakumar, Krishnamurthy, Balaji, Singh, Abhishek, Pasupathy, Kalyan, Dong, Yue, O’Horo, John C, Wilson, Walter R, Mitchell, Oscar, Kingsley, Thomas C, Massachusetts Institute of Technology. Media Laboratory, Romero-Brufau, Santiago, Chopra, Ayush, Ryu, Alex J, Gel, Esma, Raskar, Ramesh, Kremers, Walter, Anderson, Karen S, Subramanian, Jayakumar, Krishnamurthy, Balaji, Singh, Abhishek, Pasupathy, Kalyan, Dong, Yue, O’Horo, John C, Wilson, Walter R, Mitchell, Oscar, and Kingsley, Thomas C

Abstract

Objective: To estimate population health outcomes with delayed second dose versus standard schedule of SARS-CoV-2 mRNA vaccination. Design: Simulation agent based modeling study. Setting: Simulated population based on real world US county. Participants: The simulation included 100 000 agents, with a representative distribution of demographics and occupations. Networks of contacts were established to simulate potentially infectious interactions though occupation, household, and random interactions. Interventions: Simulation of standard covid-19 vaccination versus delayed second dose vaccination prioritizing the first dose. The simulation runs were replicated 10 times. Sensitivity analyses included first dose vaccine efficacy of 50%, 60%, 70%, 80%, and 90% after day 12 post-vaccination; vaccination rate of 0.1%, 0.3%, and 1% of population per day; assuming the vaccine prevents only symptoms but not asymptomatic spread (that is, non-sterilizing vaccine); and an alternative vaccination strategy that implements delayed second dose for people under 65 years of age, but not until all those above this age have been vaccinated. Main outcome measures: Cumulative covid-19 mortality, cumulative SARS-CoV-2 infections, and cumulative hospital admissions due to covid-19 over 180 days. Results: Over all simulation replications, the median cumulative mortality per 100 000 for standard dosing versus delayed second dose was 226 v179, 233 v207, and 235 v236 for 90%, 80%, and 70% first dose efficacy, respectively. The delayed second dose strategy was optimal for vaccine efficacies at or above 80% and vaccination rates at or below 0.3% of the population per day, under both sterilizing and non-sterilizing vaccine assumptions, resulting in absolute cumulative mortality reductions between 26 and 47 per 100 000. The delayed second dose strategy for people under 65 performed consistently well under all vaccination rates tested. Conclusions: A delayed second dose vaccination strategy, at least

Published
2021

244. Plasma inflammation for predicting phenotypic conversion and clinical progression of autosomal dominant frontotemporal lobar degeneration

Author

Asken, Breton M, Ljubenkov, Peter A, Staffaroni, Adam M, Casaletto, Kaitlin B, Vandevrede, Lawren, Cobigo, Yann, Rojas-Rodriguez, Julio C, Rankin, Katherine P, Kornak, John, Heuer, Hilary, Shigenaga, Judy, Appleby, Brian S, Bozoki, Andrea C, Domoto-Reilly, Kimiko, Ghoshal, Nupur, Huey, Edward, Litvan, Irene, Masdeu, Joseph C, Mendez, Mario F, Pascual, Belen, Pressman, Peter, Tartaglia, Maria Carmela, Kremers, Walter, Forsberg, Leah K, Boeve, Brad F, Boxer, Adam L, Rosen, Howie J, and Kramer, Joel H

Abstract

BackgroundMeasuring systemic inflammatory markers may improve clinical prognosis and help identify targetable pathways for treatment in patients with autosomal dominant forms of frontotemporal lobar degeneration (FTLD).MethodsWe measured plasma concentrations of IL-6, TNFα and YKL-40 in pathogenic variant carriers (MAPT, C9orf72, GRN) and non-carrier family members enrolled in the ARTFL-LEFFTDS Longitudinal Frontotemporal Lobar Degeneration consortium. We evaluated associations between baseline plasma inflammation and rate of clinical and neuroimaging changes (linear mixed effects models with standardised (z) outcomes). We compared inflammation between asymptomatic carriers who remained clinically normal (‘asymptomatic non-converters’) and those who became symptomatic (‘asymptomatic converters’) using area under the curve analyses. Discrimination accuracy was compared with that of plasma neurofilament light chain (NfL).ResultsWe studied 394 participants (non-carriers=143, C9orf72=117, GRN=62, MAPT=72). In MAPT, higher TNFα was associated with faster functional decline (B=0.12 (0.02, 0.22), p=0.02) and temporal lobe atrophy. In C9orf72,higher TNFα was associated with faster functional decline (B=0.09 (0.03, 0.16), p=0.006) and cognitive decline (B=−0.16 (−0.22, −0.10), p<0.001), while higher IL-6 was associated with faster functional decline (B=0.12 (0.03, 0.21), p=0.01). TNFα was higher in asymptomatic converters than non-converters (β=0.29 (0.09, 0.48), p=0.004) and improved discriminability compared with plasma NfL alone (ΔR2=0.16, p=0.007; NfL: OR=1.4 (1.03, 1.9), p=0.03; TNFα: OR=7.7 (1.7, 31.7), p=0.007).ConclusionsSystemic proinflammatory protein measurement, particularly TNFα, may improve clinical prognosis in autosomal dominant FTLD pathogenic variant carriers who are not yet exhibiting severe impairment. Integrating TNFα with markers of neuronal dysfunction like NfL could optimise detection of impending symptom conversion in asymptomatic pathogenic variant carriers and may help personalise therapeutic approaches.

Published
2023
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245. MRI quantitative susceptibility mapping of the substantia nigra as an early biomarker for Lewy body disease

Author

Chen, Qin, primary, Boeve, Bradley F., additional, Forghanian‐Arani, Arvin, additional, Senjem, Matthew L., additional, Jack, Clifford R., additional, Przybelski, Scott A., additional, Lesnick, Timothy G., additional, Kremers, Walter K., additional, Fields, Julie A., additional, Schwarz, Christopher G., additional, Gunter, Jeffrey L., additional, Trzasko, Joshua D., additional, Graff‐Radford, Jonathan, additional, Savica, Rodolfo, additional, Knopman, David S., additional, Dickson, Dennis W., additional, Ferman, Tanis J., additional, Graff‐Radford, Neill, additional, Petersen, Ronald C., additional, and Kantarci, Kejal, additional

Published
2021
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246. Public health impact of delaying second dose of BNT162b2 or mRNA-1273 covid-19 vaccine: simulation agent based modeling study

Author

Romero-Brufau, Santiago, primary, Chopra, Ayush, additional, Ryu, Alex J, additional, Gel, Esma, additional, Raskar, Ramesh, additional, Kremers, Walter, additional, Anderson, Karen S, additional, Subramanian, Jayakumar, additional, Krishnamurthy, Balaji, additional, Singh, Abhishek, additional, Pasupathy, Kalyan, additional, Dong, Yue, additional, O’Horo, John C, additional, Wilson, Walter R, additional, Mitchell, Oscar, additional, and Kingsley, Thomas C, additional

Published
2021
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247. Association of Aspirin Treatment With Cardiac Allograft Vasculopathy Progression and Adverse Outcomes After Heart Transplantation

Author

Asleh, Rabea, primary, Briasoulis, Alexandros, additional, Smith, Byron, additional, Lopez, Camden, additional, Alnsasra, Hilmi, additional, Pereira, Naveen L., additional, Edwards, Brooks S., additional, Clavell, Alfredo L., additional, Stulak, John M., additional, Locker, Chaim, additional, Kremers, Walter K., additional, Daly, Richard C., additional, Lerman, Amir, additional, and Kushwaha, Sudhir S., additional

Published
2021
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248. Changing the face of neuroimaging research: Comparing a new MRI de-facing technique with popular alternatives

Author

Schwarz, Christopher G., primary, Kremers, Walter K., additional, Wiste, Heather J., additional, Gunter, Jeffrey L., additional, Vemuri, Prashanthi, additional, Spychalla, Anthony J., additional, Kantarci, Kejal, additional, Schultz, Aaron P., additional, Sperling, Reisa A., additional, Knopman, David S., additional, Petersen, Ronald C., additional, and Jack, Clifford R., additional

Published
2021
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