Igor Feinstein

All Publications

• Plasma Aβ42/Aβ40 is sensitive to early cerebral amyloid accumulation and predicts risk of cognitive decline across the Alzheimer's disease spectrum. Alzheimer's & dementia : the journal of the Alzheimer's Association Trelle, A. N., Young, C. B., Vossler, H., Ramos Benitez, J., Cody, K. A., Mendiola, J. H., Swarovski, M. S., Guen, Y. L., Feinstein, I., Butler, R. R., Channappa, D., Romero, A., Park, J., Shahid-Besanti, M., Corso, N. K., Chau, K., Smith, A. N., Skylar-Scott, I., Yutsis, M. V., Fredericks, C. A., Tian, L., Younes, K., Kerchner, G. A., Deutsch, G. K., Davidzon, G. A., Sha, S. J., Henderson, V. W., Longo, F. M., Greicius, M. D., Wyss-Coray, T., Andreasson, K. I., Poston, K. L., Wagner, A. D., Mormino, E. C., Wilson, E. N. 2024

  Abstract

  The availability of amyloid beta (Aβ) targeting therapies for Alzheimer's disease (AD) is increasing the demand for scalable biomarkers that are sensitive to early cerebral Aβ accumulation.We evaluated fully-automated Lumipulse plasma Aβ42/Aβ40 immunoassays for detecting cerebral Aβ in 457 clinically unimpaired (CU) and clinically impaired (CI) Stanford Alzheimer's Disease Research Center (Stanford ADRC) participants and 186 CU in the Stanford Aging and Memory Study (SAMS). Longitudinal change in ADRC plasma Aβ42/Aβ40 and cognition and cross-sectional associations with SAMS memory and tau positron emission tomography (PET) were examined.Plasma Aβ42/Aβ40 exhibited high performance in detecting amyloid positivity defined by PET (area under the curve [AUC]: 0.885, 95% confidence interval [CI]: 0.816-0.955). Once abnomal, plasma Aβ42/Aβ40 remained low and predicted cognitive decline in both CU and CI individuals. Among SAMS CU, plasma Aβ42/Aβ40 was associated with poorer hippocampal-dependent memory and elevated tau accumulation.Lumipulse plasma Aβ42/Aβ40 is a scalable assay for detection of cerebral Aβ and prediction of risk for cognitive decline across the AD continuum.Lumipulse plasma amyloid beta (Aβ)42/Aβ40 exhibited high accuracy in detecting amyloid positivity. Plasma amyloid-positive (Aβ+) individuals exhibited stability of Aβ42/Aβ40 over time. Plasma Aβ42/Aβ40 predicted future cognitive decline across the Alzheimer's disease (AD) spectrum. Plasma Aβ42/Aβ40 was sensitive to memory and tau burden in clinically unimpaired older adults.

  View details for DOI 10.1002/alz.14442

  View details for PubMedID 39713875

• Variability and relative contribution of surgeon and anesthesia specific time components to total procedural time in cardiac surgery. The Journal of thoracic and cardiovascular surgery Vanneman, M. W., Thuraiappah, M., Feinstein, I., Fielding-Singh, V., Peterson, A., Kronenberg, S., Angst, M. S., Aghaeepour, N. 2023

  Abstract

  OBJECTIVES: Decreasing variability in time intensive tasks during cardiac surgery may reduce total procedural time, lower costs, reduce clinician burnout, and improve patient access. The relative contribution and variability of surgeon and anesthesia control times to total procedural time is unknown.METHODS: 669 patients undergoing coronary artery bypass graft surgery were enrolled. Using linear regression, we estimated adjusted surgeon and anesthesia control times controlling for patient and procedural covariates. The primary end point compared overall surgeon and anesthesia control times. The secondary end point compared the variability in adjusted surgeon and anesthesiologist control times. Sensitivity analyses quantified the relative importance of the specific surgeon and anesthesiologist in the adjusted linear models.RESULTS: The median surgeon control time was 4.1 hours (interquartile range: 3.4 to 4.9 hours) compared to a median anesthesia control time of 1.0 hours (interquartile range: 0.8 to 1.2 hours, p < 0.001). Using linear regression, the variability in adjusted surgeon control time amongst surgeons (range: 1.8 hours) was 3.5-fold greater than the variability in adjusted anesthesia control time amongst anesthesiologists (range: 0.5 hours, p < 0.001). The specific surgeon and anesthesiologist accounted for 50% of the explanatory power of the predictive model (p < 0.001).CONCLUSIONS: Surgeon control time variability is significantly greater than anesthesia control time variability and strongly associated with the surgeon performing the procedure. While these results suggest surgeon control time variability is an attractive operational target, further studies are needed to determine practitioner specific and modifiable attributes to reduce variability and improve efficiency.

  View details for DOI 10.1016/j.jtcvs.2023.08.011

  View details for PubMedID 37574007

• Performance of a fully-automated Lumipulse plasma phospho-tau181 assay for Alzheimer's disease. Alzheimer's research & therapy Wilson, E. N., Young, C. B., Ramos Benitez, J., Swarovski, M. S., Feinstein, I., Vandijck, M., Le Guen, Y., Kasireddy, N. M., Shahid, M., Corso, N. K., Wang, Q., Kennedy, G., Trelle, A. N., Lind, B., Channappa, D., Belnap, M., Ramirez, V., Skylar-Scott, I., Younes, K., Yutsis, M. V., Le Bastard, N., Quinn, J. F., van Dyck, C. H., Nairn, A., Fredericks, C. A., Tian, L., Kerchner, G. A., Montine, T. J., Sha, S. J., Davidzon, G., Henderson, V. W., Longo, F. M., Greicius, M. D., Wagner, A. D., Wyss-Coray, T., Poston, K. L., Mormino, E. C., Andreasson, K. I. 2022; 14 (1): 172

  Abstract

  BACKGROUND: The recent promise of disease-modifying therapies for Alzheimer's disease (AD) has reinforced the need for accurate biomarkers for early disease detection, diagnosis and treatment monitoring. Advances in the development of novel blood-based biomarkers for AD have revealed that plasma levels of tau phosphorylated at various residues are specific and sensitive to AD dementia. However, the currently available tests have shortcomings in access, throughput, and scalability that limit widespread implementation.METHODS: We evaluated the diagnostic and prognostic performance of a high-throughput and fully-automated Lumipulse plasma p-tau181 assay for the detection of AD. Plasma from older clinically unimpaired individuals (CU, n = 463) and patients with mild cognitive impairment (MCI, n = 107) or AD dementia (n = 78) were obtained from the longitudinal Stanford University Alzheimer's Disease Research Center (ADRC) and the Stanford Aging and Memory Study (SAMS) cohorts. We evaluated the discriminative accuracy of plasma p-tau181 for clinical AD diagnosis, association with amyloid beta peptides and p-tau181 concentrations in CSF, association with amyloid positron emission tomography (PET), and ability to predict longitudinal cognitive and functional change.RESULTS: The assay showed robust performance in differentiating AD from control participants (AUC 0.959, CI: 0.912 to 0.990), and was strongly associated with CSF p-tau181, CSF Abeta42/Abeta40 ratio, and amyloid-PET global SUVRs. Associations between plasma p-tau181 with CSF biomarkers were significant when examined separately in Abeta+ and Abeta- groups. Plasma p-tau181 significantly increased over time in CU and AD diagnostic groups. After controlling for clinical diagnosis, age, sex, and education, baseline plasma p-tau181 predicted change in MoCA overall and change in CDR Sum of Boxes in the AD group over follow-up of up to 5 years.CONCLUSIONS: This fully-automated and available blood-based biomarker assay therefore may be useful for early detection, diagnosis, prognosis, and treatment monitoring of AD.

  View details for DOI 10.1186/s13195-022-01116-2

  View details for PubMedID 36371232

• A case report of an open aortic valve replacement followed by open adrenalectomy in a patient with symptomatic pheochromocytoma and critical aortic stenosis. Journal of cardiothoracic surgery Feinstein, I., Lee, T., Khan, S., Raleigh, L., Mihm, F. 2021; 16 (1): 282

  Abstract

  BACKGROUND: Pheochromocytoma is a rare medical condition caused by catecholamine-secreting tumor cells. Operative resection can be associated with significant hemodynamic fluctuations due to the nature of the tumor, as well as associated post-resection vasoplegia. To allow for cardiovascular recovery before surgery, patients require pre-operative alpha-adrenergic blockade, which would be limited in the setting of co-existent severe aortic stenosis. In this report, we describe a patient with severe aortic stenosis and symptomatic pheochromocytoma.CASE PRESENTATION: A 51-year-old man with severe aortic stenosis (valve area 0.8 cm2) was found to have a highly active 4*4cm left adrenal pheochromocytoma. Alpha-adrenergic blockade for his pheochromocytoma was limited by syncope in the setting of his aortic stenosis. Open aortic valve replacement (AVR) was performed, followed by adrenalectomy the next day. The perioperative course for each surgical procedure was hemodynamically volatile, exacerbated by severe alcohol withdrawal. During the adrenalectomy, cardiogenic and vasoplegic shock developed immediately after securing the vascular supply to his tumor. This shock was refractory to vasopressin and methylene blue, but responded well to angiotensin II and epinephrine. After both surgeries were completed, his course was further complicated by severe ICU psychosis, ileus, fungal bacteremia, pneumonia/hypoxic respiratory failure and atrial fibrillation. He ultimately recovered and was discharged from the hospital after 38days.CONCLUSION: To our knowledge, this is the first report of surgical AVR and pheochromocytoma resection in a patient with critical aortic stenosis. The appropriate order and timing of surgeries when both these conditions co-exist remains controversial.

  View details for DOI 10.1186/s13019-021-01665-x

  View details for PubMedID 34583724

• Plasma Biomarkers of Tau and Neurodegeneration During Major Cardiac and Noncardiac Surgery. JAMA neurology Feinstein, I., Wilson, E. N., Swarovski, M. S., Andreasson, K. I., Angst, M. S., Greicius, M. D. 2021

  View details for DOI 10.1001/jamaneurol.2021.2823

  View details for PubMedID 34542578

• First lung and kidney multi-organ transplant following COVID-19 Infection. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Guenthart, B. A., Krishnan, A., Alassar, A., Madhok, J., Kakol, M., Miller, S., Cole, S. P., Rao, V. K., Acero, N. M., Hill, C. C., Cheung, C., Jackson, E. C., Feinstein, I., Tsai, A. H., Mooney, J. J., Pham, T., Elliott, I. A., Liou, D. Z., La Francesca, S., Shudo, Y., Hiesinger, W., MacArthur, J. W., Brar, N., Berry, G. J., McCarra, M. B., Desai, T. J., Dhillon, G. S., Woo, Y. J. 2021

  Abstract

  As the world responds to the global crisis of the COVID-19 pandemic an increasing number of patients are experiencing increased morbidity as a result of multi-organ involvement. Of these, a small proportion will progress to end-stage lung disease, become dialysis dependent, or both. Herein, we describe the first reported case of a successful combined lung and kidney transplantation in a patient with COVID-19. Lung transplantation, isolated or combined with other organs, is feasible and should be considered for select patients impacted by this deadly disease.

  View details for DOI 10.1016/j.healun.2021.02.015

  View details for PubMedID 34059432

• Acute N-methyl-D-aspartate receptor hypofunction induced by MK801 evokes sex-specific changes in behaviors observed in open-field testing in adult male and proestrus female rats. Neuroscience Feinstein, I., Kritzer, M. F. 2013; 228: 200-14

  Abstract

  Schizophrenia is a complex constellation of positive, negative and cognitive symptoms. Acute administration of the non-competitive antagonist of the N-methyl-d-aspartate receptor (NMDAR) dizocilpine (MK801) in rats is one of few preclinical animal models of this disorder that has both face and/or construct validity for these multiple at-risk behavioral domains and predictive power for the efficacy of therapeutic drugs in treating them. This study asked whether and to what extent the rat NMDAR hypofunction model also embodies the sex differences that distinguish the symptoms of schizophrenia and their treatment. Thus, we compared the effects of acute MK801, with and without pretreatment with haloperidol or clozapine, on seven discrete spontaneous open-field activities in adult male and female rats. These analyses revealed that MK801 was more effective in stimulating ataxia and locomotion and inhibiting stationary behavior in females while more potently stimulating stereotypy and thigmotaxis and inhibiting rearing and grooming in males. Haloperidol and clozapine pretreatments had markedly different efficacies in terms of behaviors but strong similarities in their effectiveness in male and female subjects. These results bear intriguing relationships with the complex male/female differences that characterize the symptoms of schizophrenia and suggest possible applications for acute NMDAR hypofunction as a preclinical model for investigating the neurobiology that underlies them.

  View details for DOI 10.1016/j.neuroscience.2012.10.026

  View details for PubMedID 23085219

  View details for PubMedCentralID PMC3525798

• Diagnosis and treatment of glossopharyngeal and vagal neuropathies in a patient with laryngopharyngeal reflux. Anesthesiology Lokshina, I., Feinstein, I., Agin, C., Katz, R. 2008; 109 (4): 741-3

  View details for DOI 10.1097/ALN.0b013e31818631e7

  View details for PubMedID 18813053

  View details for PubMedCentralID PMC4345407

• Anatomical and functional phenotyping of mice models of Alzheimer's disease by MR microscopy. Annals of the New York Academy of Sciences Benveniste, H., Ma, Y., Dhawan, J., Gifford, A., Smith, S. D., Feinstein, I., Du, C., Grant, S. C., Hof, P. R. 2007; 1097: 12-29

  Abstract

  The wide variety of transgenic mouse models of Alzheimer's disease (AD) reflects the search for specific genes that influence AD pathology and the drive to create a clinically relevant animal model. An ideal AD mouse model must display hallmark AD pathology such as amyloid plaques, neurofibrillary tangles, reactive gliosis, dystrophic neurites, neuron and synapse loss, and brain atrophy and in parallel behaviorally mimic the cognitive decline observed in humans. Magnetic resonance (MR) microscopy (MRM) can detect amyloid plaque load, development of brain atrophy, and acute neurodegeneration. MRM examples of AD pathology will be presented and discussed. What has lagged behind in preclinical research using transgenic AD mouse models is functional phenotyping of the brain; in other words, the ability to correlate a specific genotype with potential aberrant brain activation patterns. This lack of information is caused by the technical challenges involved in performing functional MRI (fMRI) in mice including the effects of anesthetic agents and the lack of relevant "cognitive" paradigms. An alternative approach to classical fMRI using external stimuli as triggers of brain activation in rodents is to electrically or pharmacologically stimulate regions directly while simultaneously locally tracking the activated interconnected regions of rodents using, for example, the manganese-enhanced MRI (MEMRI) technique. Finally, transgenic mouse models, MRM, and future AD research would be strengthened by the ability to screen for AD-like pathology in other non-AD transgenic mouse models. For example, molecular biologists may focus on cardiac or pulmonary pathologies in transgenic mice models and as an incidental finding discover behavioral AD phenotypes. We will present MRM data of brain and cardiac phenotyping in transgenic mouse models with behavioral deficits.

  View details for DOI 10.1196/annals.1379.006

  View details for PubMedID 17413006