Shriram Nallamshetty, MD

All Publications

• Generation of induced pluripotent stem cell lines from South Asian ethnicity. Stem cell research Khokhar, Y., Bhowmik, A., Rui Zhao, S., Cook, Z., Nallamshetty, S., Wu, J. C. 2023; 74: 103272

  Abstract

  South Asians, which represent around 25% of the world's population, have a disproportionately high risk of cardiometabolic disease, two-fold higher risk of myocardial infarction, and 4- to 6-fold higher risk for diabetes compared to Caucasians. We generated two induced pluripotent stem cell (iPSC) lines from healthy South Asian donors and validated the pluripotency and ability of these cell lines to differentiate into three germ layers. These iPSC lines can be applied to generate many cardiovascular cell types such as cardiomyocytes, endothelial cells, and mural cells to investigate different cardiovascular disease mechanisms triggered by environmental risk factors or drugs in vitro.

  View details for DOI 10.1016/j.scr.2023.103272

  View details for PubMedID 38100915

• Clinical predictors of improvement in left ventricular ejection fraction in U.S. veterans with heart failure. American heart journal plus : cardiology research and practice Nallamshetty, S., Castillo, A., Nguyen, A., Haddad, F., Heidenreich, P. 2022; 19: 100183

  Abstract

  Our understanding of the factors associated with improvement of LVEF and a heart failure with improved EF (HFimpEF) phenotype remains incomplete.We conducted a retrospective study using a national database of patients followed in the Veterans Affairs (VA) health system with serial assessment of left ventricular ejection fraction (LVEF) by echocardiography. We identified US veterans with a new diagnosis of heart failure with: (i) LVEF of <40 % in the 12 months prior to diagnosis, and (ii) follow-up LVEF assessment at least 6 months after their diagnosis. We defined HFimpEF as a final LVEF of ≥40 %.Among the 106,414 US veterans with an initial LVEF of <40 % in this analysis, 39,994 (37.6 %) had a final EF of >40 % after a median follow up of 5 years. Multivariate regression analysis identified several factors that were independently associated with LVEF improvement including female sex, younger age, higher BMI, and a history of specific comorbid conditions such as hypertension, valve disease, atrial fibrillation, connective tissue disease, liver disease, and malignancy (p < 0.001). Conversely, a history of ischemic heart disease and peripheral arterial disease, as well as specific racial backgrounds (Black and Hispanic) were associated with lower rates of LVEF improvement. The model c-statistic for predicting LVEF improvement was 0.70.This large, detailed dataset facilitated an analysis of a large number of variables that significantly associated with HFimpEF; however, their combined discriminatory value for LVEF improvement remained modest, underscoring the complexity of the gene-environment-treatment interactions that govern LV function.

  View details for DOI 10.1016/j.ahjo.2022.100183

  View details for PubMedID 38558863

  View details for PubMedCentralID PMC10978352

• A Retrospective Analysis of Medical Student Performance Evaluations, 2014-2020: Recommend with Reservations. Journal of general internal medicine Tisdale, R. L., Filsoof, A. R., Singhal, S., Caceres, W., Nallamshetty, S., Rogers, A. J., Verghese, A. C., Harrington, R. A., Witteles, R. M. 2022

  Abstract

  BACKGROUND: The Medical Student Performance Evaluations (MSPE) is a cornerstone of residency applications. Little is known regarding adherence to Association of American Medical Colleges (AAMC) MSPE recommendations and longitudinal changes in MSPE content.OBJECTIVES: Evaluate current MSPE quality and longitudinal changes in MSPE and grading practices.DESIGN: Retrospective analysis.PARTICIPANTS: Students from all Liaison Committee on Medical Education (LCME)-accredited medical schools from which the Stanford University Internal Medicine residency program received applications between 2014-2015 and 2019-2020.MAIN MEASURES: Inclusion of key words to describe applicant performance and metrics thereof, including distribution among students and key word assignment explanation; inclusion of clerkship grades, grade distributions, and grade composition; and evidence of grade inflation over time.KEY RESULTS: MSPE comprehensiveness varied substantially among the 149 schools analyzed. In total, 25% of schools provided complete information consistent with AAMC recommendations regarding key word/categorization of medical students and clerkship grades in 2019-2020. Seventy-seven distinct key word terms appeared across the 139 schools examined in 2019-2020. Grading practices markedly varied, with 2-83% of students receiving the top internal medicine clerkship grade depending on the year and school. Individual schools frequently changed key word and grading practices, with 33% and 18% of schools starting and/or stopping use of key words and grades, respectively. Significant grade inflation occurred over the 6-year study period, with an average 14% relative increase in the proportion of students receiving top clerkship grades.CONCLUSIONS: A minority of schools complies with AAMC MSPE guidelines, and MSPEs are inconsistent across time and schools. These practices may impair evaluation of students within and between schools.

  View details for DOI 10.1007/s11606-022-07502-8

  View details for PubMedID 35710660

• Nontargeted mass spectrometry of dried blood spots for interrogation of the human circulating metabolome (vol 56, e4772, 2021) JOURNAL OF MASS SPECTROMETRY Ward, C., Nallamshetty, S., Watrous, J. D., Acres, E., Long, T., Mathews, I. T., Sharma, S., Cheng, S., Imam, F., Jain, M. 2022; 57 (2)

  View details for DOI 10.1002/jms.4780

  View details for Web of Science ID 000750803300007

• Effective Access to Care in a Crisis Period: Hypertension Control during the COVID-19 Pandemic via Telemedicine. Mayo Clinic proceedings. Innovations, quality & outcomes Taylor, P., Berg, C., Thompson, J., Dean, K., Yuan, T., Nallamshetty, S., Tong, I. 2021

  Abstract

  Objectives: To assess the effectiveness of telemedicine video visits in the management of hypertensive patients at home during the first year of the COVID-19 pandemic. We also evaluated associated measures of patient satisfaction with these holistic visits.Patients and Methods: A quantitative analysis was performed of all home video visits coded with a diagnosis of Essential Hypertension during the first 12 months of the COVID-19 pandemic (March, 2020 through February, 2021). A total of 10,634 patients with 16,194 hypertension visits were present in our national telemedicine practice database during this time period. Among this population, a total of 569 patients who had 1,785 hypertension visits met the criteria of having two or more blood pressure readings, with the last blood pressure reading occurring in the report period. We analyzed baseline characteristics and blood pressure trends of these 569 patients over the study period. Voluntarily submitted patient satisfaction ratings, which were systematically requested at the end of each visit, were also analyzed.Results: The mean age of the patients in this study cohort of 569 patients was 43.9 years, and 48.3% were women. Over 62% of the patients had an initial systolic BP over140 mm Hg, and 25% had an initial SBP of greater than 160 mm Hg. The average number of visits over the study period was 3.1 visits per patient. An average of 6.4 BP measurements per patient were available over the study period. Over the study period, 77% of the patients experienced an improvement in either systolic or diastolic blood pressure, with mean reductions of -9.7 mm Hg and -6.8 mm Hg in systolic and diastolic blood pressures, respectively. A total of 416 patients in the cohort started with a blood pressure above 140/90 mm Hg. For this subset of patients, 55.7% achieved a BP of <=140/90 by the end of the study period, and the average reductions in systolic and diastolic blood pressures were -17.9 mm Hg and -12.8 mm Hg respectively, which corresponded to improvements of 11.2% and 12.4% respectively. These improvements did not vary significantly when patients were stratified by age, sex, or geographic region of residence (rural versus urban/suburban). Voluntarily submitted patient surveys indicated a high degree of patient satisfaction, with a mean satisfaction score of 4.94 (5 point scale).Conclusion: Clinician-patient relationships established in a video-first telemedicine model were broadly effective for addressing sub-optimally controlled hypertension. Patient satisfaction with these visits was very high.

  View details for DOI 10.1016/j.mayocpiqo.2021.11.006

  View details for PubMedID 34805763

• Nontargeted mass spectrometry of dried blood spots for interrogation of the human circulating metabolome. Journal of mass spectrometry : JMS Ward, C., Nallamshetty, S., Watrous, J. D., Acres, E., Long, T., Mathews, I. T., Sharma, S., Cheng, S., Imam, F., Jain, M. 2021; 56 (8): e4772

  Abstract

  Advances in high-resolution, nontargeted mass spectrometry allow for the simultaneous measure of thousands of metabolites in a single biosample. Application of these analytical approaches to population-scale human studies has been limited by the need for resource-intensive blood sample collection, preparation, and storage. Dried blood spotting, a technique developed decades ago for newborn screening, may offer a simple approach to overcome barriers in human blood acquisition and storage. In this study, we find that over 4,400 spectral features across diverse chemical classes may be efficiently and reproducibly extracted and relatively quantified from human dried blood spots using nontargeted metabolomic analysis employing HILIC and reversed-phase liquid chromatography coupled to Orbitrap mass spectrometry. Moreover, over 80% of metabolites were found to be chemically stable in dried blood spots stored at room temperature for up to a week. In direct relation to plasma samples, dried blood spots exhibited comparable representation of the human circulating metabolome, capturing both known and previously uncharacterized metabolites. Dried blood spot approaches provide an opportunity for rapid and facile human biosampling and storage and will enable widespread metabolomics study of populations, particularly in resource-limited areas.

  View details for DOI 10.1002/jms.4772

  View details for PubMedID 34240506

• Adiponectin Receptor 3 is Associated With Endothelial Nitric Oxide Synthase Dysfunction and Predicts Insulin Resistance in South Asians Chandy, M., Sayed, N., Lau, E., Liu, C., Wei Tzu-Tang, Chen, I. Y., Thomas, D., Rhee, J., Oh, B., Pepic, L., Husain, M., Quertermous, T., Nallamshetty, S., Wu, J. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000511467800216

• CardioClick an Innovative Telehealth Approach to Lifestyle Intervention in High Risk South Asians Parameswaran, V., Josan, K., Winterbottom, J., Shearer, J., Khandelwal, A., Nallamshetty, S., Dash, R., Rodriguez, F. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for DOI 10.1161/circ.139.suppl_1.P337

  View details for Web of Science ID 000478079000280

• A resident-created hospitalist curriculum for internal medicine housestaff. Journal of hospital medicine Kumar, A., Smeraglio, A., Witteles, R., Harman, S., Nallamshetty, S., Rogers, A., Harrington, R., Ahuja, N. 2016; 11 (9): 646-649

  Abstract

  The growth of hospital medicine has led to new challenges, and recent graduates may feel unprepared to meet the expanding clinical duties expected of hospitalists. At our institution, we created a resident-inspired hospitalist curriculum to address the training needs for the next generation of hospitalists. Our program provided 3 tiers of training: (1) clinical excellence through improved training in underemphasized areas of hospital medicine, (2) academic development through required research, quality improvement, and medical student teaching, and (3) career mentorship. In this article, we describe the genesis of our program, our final product, and the challenges of creating a curriculum while being internal medicine residents. Journal of Hospital Medicine 2016. © 2016 Society of Hospital Medicine.

  View details for DOI 10.1002/jhm.2590

  View details for PubMedID 27079160

• Increased Risk of Progression of Coronary Artery Calcification in Male Subjects with High Baseline Waist-to-Height Ratio: The Kangbuk Samsung Health Study. Diabetes & metabolism journal Oh, H. G., Nallamshetty, S., Rhee, E. J. 2016; 40 (1): 54-61

  Abstract

  The waist-to-height ratio (WHtR) is an easy and inexpensive adiposity index that reflects central obesity. In this study, we examined the association of baseline WHtR and progression of coronary artery calcification (CAC) over 4 years of follow-up in apparently healthy Korean men.A total of 1,048 male participants (mean age, 40.9 years) in a health-screening program in Kangbuk Samsung Hospital, Seoul, Korea who repeated a medical check-up in 2010 and 2014 were recruited. Baseline WHtR was calculated using the value for the waist in 2010 divided by the value for height in 2010. The CAC score (CACS) of each subject was measured by multi-detector computed tomography in both 2010 and 2014. Progression of CAC was defined as a CACS change over 4 years greater than 0.During the follow-up period, progression of CAC occurred in 278 subjects (26.5%). The subjects with CAC progression had slightly higher but significant baseline WHtR compared to those who did not show CAC progression (0.51±0.04 vs. 0.50±0.04, P<0.01). The proportion of subjects with CAC progression significantly increased as the baseline WHtR increased from the 1st quartile to 4th quartile groups (18.3%, 18.7%, 28.8%, and 34.2%; P<0.01). The risk for CAC progression was elevated with an odds ratio of 1.602 in the 4th quartile group of baseline WHtR even after adjustment for confounding variables (95% confidence interval, 1.040 to 2.466).Increased baseline WHtR was associated with increased risk for CAC progression. WHtR might be a useful screening tool to identify individuals at high risk for subclinical atherosclerosis.

  View details for DOI 10.4093/dmj.2016.40.1.54

  View details for PubMedID 26912156

  View details for PubMedCentralID PMC4768051

• Transcriptional profiling of in vitro smooth muscle cell differentiation identifies specific patterns of gene and pathway activation PHYSIOLOGICAL GENOMICS Spin, J. M., Nallamshetty, S., Tabibiazar, R., Ashley, E. A., King, J. Y., Chen, M., Tsao, P. S., Quertermous, T. 2004; 19 (3): 292-302

  Abstract

  Mesodermal and epidermal precursor cells undergo phenotypic changes during differentiation to the smooth muscle cell (SMC) lineage that are relevant to pathophysiological processes in the adult. Molecular mechanisms that underlie lineage determination and terminal differentiation of this cell type have received much attention, but the genetic program that regulates these processes has not been fully defined. Study of SMC differentiation has been facilitated by development of the P19-derived A404 embryonal cell line, which differentiates toward this lineage in the presence of retinoic acid and allows selection for cells adopting a SMC fate through a differentiation-specific drug marker. We sought to define global alterations in gene expression by studying A404 cells during SMC differentiation with oligonucleotide microarray transcriptional profiling. Using an in situ 60-mer array platform with more than 20,000 mouse genes derived from the National Institute on Aging clone set, we identified 2,739 genes that were significantly upregulated after differentiation was completed (false-detection ratio <1). These genes encode numerous markers known to characterize differentiated SMC, as well as many unknown factors. We further characterized the sequential patterns of gene expression during the differentiation time course, particularly for known transcription factor families, providing new insights into the regulation of the differentiation process. Changes in genes associated with specific biological ontology-based pathways were evaluated, and temporal trends were identified for functional pathways. In addition to confirming the utility of the A404 model, our data provide a large-scale perspective of gene regulation during SMC differentiation.

  View details for DOI 10.1152/physiolgenomics.00148.2004

  View details for PubMedID 15340120

• A growth factor-dependent nuclear kinase phosphorylates p27(Kip1) and regulates cell cycle progression EMBO JOURNAL Boehm, M., Yoshimoto, T., Crook, M. F., Nallamshetty, S., True, A., Nabel, G. J., Nabel, E. G. 2002; 21 (13): 3390-3401

  Abstract

  The cyclin-dependent kinase inhibitor, p27(Kip1), which regulates cell cycle progression, is controlled by its subcellular localization and subsequent degradation. p27(Kip1) is phosphorylated on serine 10 (S10) and threonine 187 (T187). Although the role of T187 and its phosphorylation by Cdks is well-known, the kinase that phosphorylates S10 and its effect on cell proliferation has not been defined. Here, we identify the kinase responsible for S10 phosphorylation as human kinase interacting stathmin (hKIS) and show that it regulates cell cycle progression. hKIS is a nuclear protein that binds the C-terminal domain of p27(Kip1) and phosphorylates it on S10 in vitro and in vivo, promoting its nuclear export to the cytoplasm. hKIS is activated by mitogens during G(0)/G(1), and expression of hKIS overcomes growth arrest induced by p27(Kip1). Depletion of KIS using small interfering RNA (siRNA) inhibits S10 phosphorylation and enhances growth arrest. p27(-/-) cells treated with KIS siRNA grow and progress to S/G(2 )similar to control treated cells, implicating p27(Kip1) as the critical target for KIS. Through phosphorylation of p27(Kip1) on S10, hKIS regulates cell cycle progression in response to mitogens.

  View details for Web of Science ID 000176784100018

  View details for PubMedID 12093740

• Coexpression of guanylate kinase with thymidine kinase enhances prodrug cell killing in vitro and suppresses vascular smooth muscle cell proliferation in vivo MOLECULAR THERAPY Akyurek, L. M., Nallamshetty, S., Aoki, K., San, H., Yang, Z. Y., Nabel, G. J., Nabel, E. G. 2001; 3 (5): 779-786

  Abstract

  Herpes simplex virus-thymidine kinase (HSV-TK) phosphorylates the prodrugs ganciclovir (GCV) and acyclovir (ACV), leading to disruption of DNA synthesis and inhibition of cell proliferation. HSV-TK vectors have been successfully employed in cardiovascular and cancer gene therapy. Activation of GCV and ACV, after an initial phosphorylation step by the viral thymidine kinase, is carried out by guanylate kinase. We reasoned that coexpression of guanylate kinase (GK) with HSV-TK would augment phosphorylation of GCV or ACV, leading to increased cell killing. To test this hypothesis, a vector expressing TK with GK (TKciteGK) was developed and tested on vascular smooth muscle cells (vsmcs) in vitro and in vivo. Compared to HSV-TK vectors, killing of vascular cells transduced with TKciteGK and exposed to GCV was significantly increased (P = 0.03). The TKciteGK construct was evaluated with three promoters: CMV, EF1alpha, and SM22alpha. TKciteGK expression driven by a CMV promoter induced cell killing more effectively than SM22alpha or EF1alpha promoters in primary vsmcs. Based upon these in vitro findings, TKciteGK vectors with a CMV promoter were tested in two animal models of cardiovascular disease: balloon angioplasty and stent deployment in pig arteries. Following vascular injury, expression of CMV-TKciteGK with GCV significantly reduced vsmc proliferation and intimal lesion formation compared to control vectors with GCV. In the angioplasty model, there was an 80% reduction in intima-to-media area ratio (P = 0.0002). These findings were paralleled in a stent model with 66% reduction in intimal lesions (P = 0.006). Coexpression of GK with TK increases cell killing and permits administration of GCV at lower doses. These modifications in TKciteGK vectors and GCV showed enhanced efficacy at lower prodrug doses, leading to improved safety for cardiovascular gene therapy.

  View details for Web of Science ID 000168924400016

  View details for PubMedID 11356082