Faculty Scholarship

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Faculty Scholarship

The Faculty Scholarship webpage is designed to share the news of faculty accomplishments in medical education including publications, conference presentations, and grants. The webpage may also serve as a resource for faculty looking to identify collaborators with shared research interests. Entries are accepted throughout the academic year, and the page is updated monthly.

November 2021 features:

Publications

  1. Boothe, E., West, B., Hendon, L. G., Kaplan, J. D., & Kirmse, B. (2021). Asynchronous telemedicine for clinical genetics consultations in the NICU: a single center’s solution. Journal of Perinatology. Online ahead of print. doi:10.1038/s41372-021-01070-1.

    Many infants in the neonatal intensive care unit (NICU) have genetic disorders or birth defects. The demand for genetic services is often complicated by a shortage of genetic providers. Our hospital experienced a significant reduction in genetic workforce, leading to insufficient genetic services to meet demand. The Plan-Do-Study-Act method of quality improvement was used to assess available resources, select an intervention plan, and collect patient outcome and provider satisfaction data. An asynchronous telehealth model was deployed for clinical genetics consultations in our NICU utilizing a remote clinical geneticist. The pilot study included 111 asynchronous telehealth consultations; 21% received a genetic diagnosis before discharge. Diagnoses were primarily chromosomal and single gene disorders. Referring NICU providers reported high satisfaction. Asynchronous telehealth for clinical genetics is a feasible and successful alternative to an on-site clinical geneticist and should be considered in areas with a genetic workforce shortage.

  2. Gonzalez-Fernandez,E., Liu, Y., Auchus, A.P., Fan, F., Roman, R.J. Vascular contributions to cognitive impairment and dementia: the emerging role of 20-HETE. Clinical Science (Lond). 2021 Aug 13;135(15):1929-1944. doi: 10.1042/CS20201033. PMID: 34374423.

    The accumulation of extracellular amyloid-β (Aβ) and intracellular hyperphosphorylated τ proteins in the brain are the hallmarks of Alzheimer's disease (AD). Much of the research into the pathogenesis of AD has focused on the amyloid or τ hypothesis. These hypotheses propose that Aβ or τ aggregation is the inciting event in AD that leads to downstream neurodegeneration, inflammation, brain atrophy and cognitive impairment. Multiple drugs have been developed and are effective in preventing the accumulation and/or clearing of Aβ or τ proteins. However, clinical trials examining these therapeutic agents have failed to show efficacy in preventing or slowing the progression of the disease. Thus, there is a need for fresh perspectives and the evaluation of alternative therapeutic targets in this field. Epidemiology studies have revealed significant overlap between cardiovascular and cerebrovascular risk factors such as hypertension, diabetes, atherosclerosis and stroke to the development of cognitive impairment. This strong correlation has given birth to a renewed focus on vascular contributions to AD and related dementias. However, few genes and mechanisms have been identified. 20-Hydroxyeicosatetraenoic acid (20-HETE) is a potent vasoconstrictor that plays a complex role in hypertension, autoregulation of cerebral blood flow and blood-brain barrier (BBB) integrity. Multiple human genome-wide association studies have linked mutations in the cytochrome P450 (CYP) 4A (CYP4A) genes that produce 20-HETE to hypertension and stroke. Most recently, genetic variants in the enzymes that produce 20-HETE have also been linked to AD in human population studies. This review examines the emerging role of 20-HETE in AD and related dementias.

  3. Görürgöz, C., Orhan, K., Bayrakdar, I.S., Çelik, Ö., Bilgir, E., Odabaş, A., Aslan, A.F., Jagtap, R. Performance of a convolutional neural network algorithm for tooth detection and numbering on periapical radiographs. Dentomaxillofacial Radiology. 2021 Oct;50:20210246.

    The present study aimed to evaluate the performance of a Faster Region-based Convolutional Neural Network (R-CNN) algorithm for tooth detection and numbering on periapical images. Methods: The data sets of 1686 randomly selected periapical radiographs of patients were collected retrospectively. A pre-trained model (GoogLeNet Inception v3 CNN) was employed for pre-processing, and transfer learning techniques were applied for data set training. The algorithm consisted of: (1) the Jaw classification model, (2) Region detection models, and (3) the Final algorithm using all models. Finally, an analysis of the latest model has been integrated alongside the others. The sensitivity, precision, true-positive rate, and false-positive/ negative rate were computed to analyze the performance of the algorithm using a confusion matrix. Results: An artificial intelligence algorithm (CranioCatch, Eskisehir-Turkey) was designed based on R-CNN inception architecture to automatically detect and number the teeth on periapical images. Of 864 teeth in 156 periapical radiographs, 668 were correctly numbered in the test data set. The F1 score, precision, and sensitivity were 0.8720, 0.7812, and 0.9867, respectively. Conclusion: The study demonstrated the potential accuracy and efficiency of the CNN algorithm for detecting and numbering teeth. The deep learning-based methods can help clinicians reduce workloads, improve dental records, and reduce turnaround time for urgent cases. This architecture might also contribute to forensic science. Dentomaxillofacial Radiology (2021) 50, 20210246. doi: 10.1259/dmfr.20210246

  4. Huang, J., Cohen, M., Safar, J., Auchus, A.P. Variably Protease-sensitive Prionopathy in a Middle-aged Man With Rapidly Progressive Dementia. Cognitive and Behavioral Neurology. 2021 Sep 2;34(3):220-225. doi: 10.1097/WNN.0000000000000276. PMID: 34473674.

    Variably protease-sensitive prionopathy (VPSPr) is a recently described sporadic prion disease with distinctive clinical and histopathological features. We report the clinical, imaging, and neuropathological features of VPSPr in a 46-year-old right-handed man who presented with progressive cognitive decline, behavior disturbances, and a 50-pound weight loss over 6 months. The initial evaluation revealed severe cognitive impairment with no focal neurologic deficits. His cognitive, psychiatric, and behavior symptoms progressed rapidly, and he died 12 months after the initial visit. Throughout his disease course, workup for rapid progressive dementia was unremarkable except that brain MRI diffusion-weighted imaging showed persistent diffuse cortical and thalamic signal abnormalities. Sporadic Creutzfeldt-Jakob disease was highly suspected; however, two EEGs (8 months apart) demonstrated only nonspecific cerebral dysfunction. The patient's CSF 14-3-3 protein was negative at the initial visit and again 8 months later. His CSF real-time quaking-induced conversion and total tau level were normal. An autopsy of his brain was performed, and the neuropathological findings confirmed VPSPr. Our case underlines the importance of considering VPSPr in the spectrum of prion disease phenotypes when evaluating individuals with rapidly progressive dementia.

  5. Nasrallah, I.M., Gaussoin, S.A., Pomponio, R., Dolui, S., Erus, G., Wright, C.B., Launer, L.J., Detre, J.A., Wolk, D.A., Davatzikos, C., Williamson, J.D., Pajewski, N.M., Bryan, R.N.; SPRINT Research Group. Association of Intensive vs Standard Blood Pressure Control With Magnetic Resonance Imaging Biomarkers of Alzheimer Disease: Secondary Analysis of the SPRINT MIND Randomized Trial. JAMA Neurology. 2021 May 1;78(5):568-577. doi: 10.1001/jamaneurol.2021.0178. PMID: 33683313; PMCID: PMC7941253.

    Meta-analyses of randomized clinical trials have indicated that improved hypertension control reduces the risk for cognitive impairment and dementia. However, it is unclear to what extent pathways reflective of Alzheimer disease (AD) pathology are affected by hypertension control. This is a substudy of the Systolic Blood Pressure Intervention Trial (SPRINT MIND), a multicenter randomized clinical trial that compared the efficacy of 2 different blood pressure-lowering strategies. Potential participants (n = 1267) 50 years or older with hypertension and without a history of diabetes or stroke were approached for a brain magnetic resonance imaging (MRI) study. Of these, 205 participants were deemed ineligible and 269 did not agree to participate; 673 and 454 participants completed brain MRI at baseline and at 4-year follow-up, respectively; the final follow-up date was July 1, 2016. Analysis began September 2019 and ended November 2020. Participants were randomized to either a systolic blood pressure goal of less than 120 mm Hg (intensive treatment: n = 356) or less than 140 mm Hg (standard treatment: n = 317). Intensive treatment was associated with a small but statistically significant greater decrease in hippocampal volume compared with standard treatment, consistent with the observation that intensive treatment is associated with greater decreases in total brain volume. However, intensive treatment was not associated with changes in any of the other MRI biomarkers of AD compared with standard treatment.

  6. SPRINT Research Group, Lewis, C.E., Fine, L.J., Beddhu, S., Cheung, A.K., Cushman, W.C., Cutler, J.A., Evans, G.W., Johnson, K.C., Kitzman, D.W., Oparil, S., Rahman, M., Reboussin, D.M., Rocco, M.V., Sink, K.M., Snyder, J.K., Whelton, P.K., Williamson, J.D., Wright, J.T. Jr, Ambrosius, W.T. Final Report of a Trial of Intensive versus Standard Blood-Pressure Control. New England Journal of Medicine. 2021 May 20;384(20):1921-1930. doi: 10.1056/NEJMoa1901281. PMID: 34010531.

    In a previously reported randomized trial of standard and intensive systolic blood-pressure control, data on some outcome events had yet to be adjudicated and post-trial follow-up data had not yet been collected. We randomly assigned 9361 participants who were at increased risk for cardiovascular disease but did not have diabetes or previous stroke to adhere to an intensive treatment target (systolic blood pressure, <120 mm Hg) or a standard treatment target (systolic blood pressure, <140 mm Hg). The primary outcome was a composite of myocardial infarction, other acute coronary syndromes, stroke, acute decompensated heart failure, or death from cardiovascular causes. Additional primary outcome events occurring through the end of the intervention period (August 20, 2015) were adjudicated after data lock for the primary analysis. We also analyzed post-trial observational follow-up data through July 29, 2016. Among patients who were at increased cardiovascular risk, targeting a systolic blood pressure of less than 120 mm Hg resulted in lower rates of major adverse cardiovascular events and lower all-cause mortality than targeting a systolic blood pressure of less than 140 mm Hg, both during receipt of the randomly assigned therapy and after the trial. Rates of some adverse events were higher in the intensive-treatment group. (Funded by the National Institutes of Health; SPRINT ClinicalTrials.gov number, NCT01206062.).

  7. Tamura, M.K., Gaussoin, S., Pajewski, N.M., Zaharchuk, G., Freedman, B.I., Rapp, S.R., Auchus, A.P., Haley, W.E., Oparil, S., Kendrick, J., Roumie, C.L., Beddhu, S., Cheung, A.K., Williamson, J.D., Detre, J.A., Dolui, S., Bryan, R.N., Nasrallah, I.M. SPRINT Research Group. Kidney Disease, Hypertension Treatment, and Cerebral Perfusion and Structure. American Journal of Kidney Diseases. 2021 Sep 17:S0272-6386(21)00877-5. doi: 10.1053/j.ajkd.2021.07.024. Epub ahead of print. PMID: 34543687.

    The safety of intensive blood pressure (BP) targets is controversial for persons with chronic kidney disease (CKD). We studied the effects of hypertension treatment on cerebral perfusion and structure in those with and without CKD. A subset of participants in the Systolic Blood Pressure Intervention Trial who underwent brain MRI studies. Presence of baseline CKD was assessed by estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR). Participants were randomly assigned to intensive (systolic BP <120 mm Hg) versus standard (systolic BP <140 mm Hg) BP lowering. The magnetic resonance imaging outcome measures were the four-year change in global cerebral blood flow, white matter lesion (WML) volume, and total brain volume. Among hypertensive adults with primarily early kidney disease, intensive versus standard blood pressure treatment did not appear to have a detrimental effect on brain perfusion or structure. The findings support the safety of intensive blood pressure treatment targets on brain health in persons with early kidney disease.

Grants

  1. CACNA1C Genotype: Correlation with Brain and Blood Levels of CACNA1C and Treatment Responsiveness, Harry Pantazopoulos, PhD, PI. Baszucki Brain Research Foundation, $200,000.

    These studies will test the role of CACNA1C genetic polymorphisms in the neuropathology and treatment responsiveness of people with Bipolar Disorder. Specifically, these studies will test the hypothesis that genetic polymorphisms in the CACNA1C gene can be used to identify a subgroup of people with bipolar disorder who will benefit from calcium channel blockers. These studies aim to link CACNA1C genotype with blood and brain levels of CACNA1C and with responsiveness to treatments such as lithium, with the goal of establishing a foundation for use of calcium channel blockers for people with bipolar disorder based on CACNA1C genotype and blood levels of CACNA1C.