Master of Health and Science, Yale University (2015)
Doctor of Medicine, Yale University (2015)
Bachelor of Arts, Johns Hopkins University (2010)
- Is it time for a consumerized or home-based 12-lead electrocardiogram? Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 2021
Deep learning evaluation of biomarkers from echocardiogram videos.
2021; 73: 103613
BACKGROUND: Laboratory testing is routinely used to assay blood biomarkers to provide information on physiologic state beyond what clinicians can evaluate from interpreting medical imaging. We hypothesized that deep learning interpretation of echocardiogram videos can provide additional value in understanding disease states and can evaluate common biomarkers results.METHODS: We developed EchoNet-Labs, a video-based deep learning algorithm to detect evidence of anemia, elevated B-type natriuretic peptide (BNP), troponin I, and blood urea nitrogen (BUN), as well as values of ten additional lab tests directly from echocardiograms. We included patients (n=39,460) aged 18 years or older with one or more apical-4-chamber echocardiogram videos (n=70,066) from Stanford Healthcare for training and internal testing of EchoNet-Lab's performance in estimating the most proximal biomarker result. Without fine-tuning, the performance of EchoNet-Labs was further evaluated on an additional external test dataset (n=1,301) from Cedars-Sinai Medical Center. We calculated the area under the curve (AUC) of the receiver operating characteristic curve for the internal and external test datasets.FINDINGS: On the held-out test set of Stanford patients not previously seen during model training, EchoNet-Labs achieved an AUC of 0.80 (0.79-0.81) in detecting anemia (low hemoglobin), 0.86 (0.85-0.88) in detecting elevated BNP, 0.75 (0.73-0.78) in detecting elevated troponin I, and 0.74 (0.72-0.76) in detecting elevated BUN. On the external test dataset from Cedars-Sinai, EchoNet-Labs achieved an AUC of 0.80 (0.77-0.82) in detecting anemia, of 0.82 (0.79-0.84) in detecting elevated BNP, of 0.75 (0.72-0.78) in detecting elevated troponin I, and of 0.69 (0.66-0.71) in detecting elevated BUN. We further demonstrate the utility of the model in detecting abnormalities in 10 additional lab tests. We investigate the features necessary for EchoNet-Labs to make successful detection and identify potential mechanisms for each biomarker using well-known and novel explainability techniques.INTERPRETATION: These results show that deep learning applied to diagnostic imaging can provide additional clinical value and identify phenotypic information beyond current imaging interpretation methods.FUNDING: J.W.H. and B.H. are supported by the NSF Graduate Research Fellowship. D.O. is supported by NIH K99 HL157421-01. J.Y.Z. is supported by NSF CAREER 1942926, NIH R21 MD012867-01, NIH P30AG059307 and by a Chan-Zuckerberg Biohub Fellowship.
View details for DOI 10.1016/j.ebiom.2021.103613
View details for PubMedID 34656880
Role of digital health in detection and management of atrial fibrillation.
Heart (British Cardiac Society)
Atrial fibrillation is a common arrhythmia associated with significant morbidity, mortality and decreased quality of life. Mobile health devices marketed directly to consumers capable of detecting atrial fibrillation through methods including photoplethysmography, single-lead ECG as well as contactless methods are becoming ubiquitous. Large-scale screening for atrial fibrillation is feasible and has been shown to detect more cases than usual care-however, controversy still exists surrounding screening even in older higher risk populations. Given widespread use of mobile health devices, consumer-driven screening is happening on a large scale in both low-risk and high-risk populations. Given that young people make up a large portion of early adopters of mobile health devices, there is the potential that many more patients with early onset atrial fibrillation will come to clinical attention requiring possible referral to genetic arrythmia clinic. Physicians need to be familiar with these technologies, and understand their risks, and limitations. In the current review, we discuss current mobile health devices used to detect atrial fibrillation, recent and upcoming trials using them for diagnosis of atrial fibrillation, practical recommendations for patients with atrial fibrillation diagnosed by a mobile health device and special consideration in young patients.
View details for DOI 10.1136/heartjnl-2020-318262
View details for PubMedID 34344729
- Comparison of QT Interval Measurement Methods and Correction Formulas in Atrial Fibrillation AMERICAN JOURNAL OF CARDIOLOGY 2019; 123 (11): 1822–27
Frequency and timing of short-term complications following abdominoperineal resection.
The Journal of surgical research
2018; 231: 69–76
Abdominoperineal resection (APR) is primarily used for rectal cancer and is associated with a high rate of complications. Though the majority of APRs are performed as open procedures, laparoscopic APRs have become more popular. The differences in short-term complications between open and laparoscopic APR are poorly characterized.We conducted a retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program database to determine the frequency and timing of onset of 30-d postoperative complications after APR and identify differences between open and laparoscopic APR.A total of 7681 patients undergoing laparoscopic or open APR between 2011 and 2015 were identified. The total complication rate for APR was high (45.4%). APRs were commonly complicated by blood transfusion (20.1%), surgical site infection (19.3%), and readmission (12.3%). Laparoscopic APR was associated with a 14% lower total complication rate compared to open APR (36.0% versus 50.1%, P < 0.001). This was primarily driven by a decreased rate of transfusion (10.7% versus 24.9%, P < 0.001) and surgical site infection (15.5% versus 21.2%, P < 0.001). Laparoscopic APR had shorter length of stay and decreased reoperation rate but similar rates of readmission and death. Cardiopulmonary complications occurred earlier in the postoperative period after APR, whereas infectious complications occurred later.Short-term complications following APR are common and occur more frequently in patients who undergo open APR. This, along with factors such as risk of positive pathologic margins, surgeon skill set, and patient characteristics, should contribute to the decision-making process when planning rectal cancer surgery.
View details for PubMedID 30278971
Perioperative outcomes of coronary artery bypass graft in renal transplant recipients in the United States: results from the Nationwide Inpatient Sample.
2016; 30 (10): 1258-1263
Cardiovascular disease is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). In fact, death from cardiovascular disease is the number one cause of graft loss in kidney transplant (KTx) patients. Compared to patients on dialysis, CKD patients with KTx have increased quality and length of life. It is not known, however, whether outcomes of coronary artery bypass graft (CABG) surgery differ between CKD patients with KTx or on dialysis.This was a retrospective cohort study comparing CKD patients with KTx or on dialysis undergoing CABG surgery included in the Nationwide Inpatient Sample from 2002 to 2011. Logistic and linear regression models were used to estimate the adjusted associations of KTx on all-cause in-hospital mortality, length of stay, cost of hospitalization, and rate of complications in CABG surgery.CKD patients with KTx had decreased all-cause in-hospital mortality (2.68% vs 5.86%, odds ratio (OR)=0.56, 95% confidence interval (CI)=0.32 to 0.99, P=.046), length of stay (β=-2.96, 95% CI=-3.67 to -2.46, P<.001), and total hospital charges (difference=-$38 884, 95% CI=-$48 173 to -29 596, P<.001). They also had decreased rate of a number of perioperative complications.CKD patient with KTx have better perioperative outcomes in CABG surgery compared to patients on dialysis.
View details for DOI 10.1111/ctr.12816
View details for PubMedID 27440000
Partners in Crime: Kidney Transplantation and Seizure Disorder.
2016; 48 (8): 2700-2708
Seizure disorder is a common neurologic complication of kidney transplantation and often presents as a complex management challenge. Little is known about the risks mutually conferred by the 2 clinical entities and the effects of such risks on clinical outcomes. Using the National Inpatient Sample, our goal was to examine the effects of kidney transplantation and seizure disorder on mortality, hospitalization statistics, clinical complications, and cost of care. A history of kidney transplantation was shown to negatively affect the care of seizure disorder, and a history of seizure disorder also negatively affected the clinical outcomes of kidney transplantation. Our findings are important for initiating discussions and prompting future studies to further examine disease-specific risks of kidney transplantation.
View details for DOI 10.1016/j.transproceed.2016.06.041
View details for PubMedID 27788804
Changes in T-cell subsets identify responders to FcR-nonbinding anti-CD3 mAb (teplizumab) in patients with type 1 diabetes
EUROPEAN JOURNAL OF IMMUNOLOGY
2016; 46 (1): 230-241
The mechanisms whereby immune therapies affect progression of type 1 diabetes (T1D) are not well understood. Teplizumab, an FcR nonbinding anti-CD3 mAb, has shown efficacy in multiple randomized clinical trials. We previously reported an increase in the frequency of circulating CD8(+) central memory (CD8CM) T cells in clinical responders, but the generalizability of this finding and the molecular effects of teplizumab on these T cells have not been evaluated. We analyzed data from two randomized clinical studies of teplizumab in patients with new- and recent-onset T1D. At the conclusion of therapy, clinical responders showed a significant reduction in circulating CD4(+) effector memory T cells. Afterward, there was an increase in the frequency and absolute number of CD8CM T cells. In vitro, teplizumab expanded CD8CM T cells by proliferation and conversion of non-CM T cells. Nanostring analysis of gene expression of CD8CM T cells from responders and nonresponders versus placebo-treated control subjects identified decreases in expression of genes associated with immune activation and increases in expression of genes associated with T-cell differentiation and regulation. We conclude that CD8CM T cells with decreased activation and regulatory gene expression are associated with clinical responses to teplizumab in patients with T1D.
View details for DOI 10.1002/eji.201545708
View details for Web of Science ID 000368234800026
View details for PubMedID 26518356
View details for PubMedCentralID PMC4882099
Biomarkers in type 1 diabetes: application to the clinical trial setting
CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY
2014; 21 (4): 287-292
Biomarkers of type 1 diabetes (T1D) are important for assessing risk of developing disease, monitoring disease progression, and determining responses to clinical treatments. Here we review recent advances in the development of biomarkers of T1D with a focus on their utility in clinical trials.Measurements of autoantibodies and metabolic outcomes have been the foundation of monitoring T1D for the past 20 years. Recent advancements have led to improvements in T-cell-specific assays that have been used in large-scale clinical trials to measure antigen-specific T cell responses. Additionally, new tools are being developed for the measurement of β cell mass and death that will allow for more direct measurement of disease activity. Lastly, recent studies have used both immunologic and nonimmunologic biomarkers to identify responders to treatments in clinical trials.Use of biomarkers in the study of T1D has largely not changed over the past 20 years; however, recent advancements in the field are establishing new techniques that allow for more precise monitoring of disease progression. These new tools will ultimately lead to an improvement in understanding of disease and will be utilized in clinical trials.
View details for DOI 10.1097/MED.0000000000000076
View details for Web of Science ID 000338130600006
View details for PubMedID 24937037
New and future immunomodulatory therapy in type 1 diabetes
TRENDS IN MOLECULAR MEDICINE
2012; 18 (3): 173-181
Type 1 diabetes is a common autoimmune disease that affects millions of people worldwide and has an incidence that is increasing at a striking rate, especially in young children. It results from the targeted self-destruction of the insulin-secreting β cells of the pancreas and requires lifelong insulin treatment. The effects of chronic hyperglycemia - the result of insulin deficiency - include secondary endorgan complications. Over the past two decades our increased understanding of the pathogenesis of this disease has led to the development of new immunomodulatory treatments. None have yet received regulatory approval, but this report highlights recent progress in this area.
View details for DOI 10.1016/j.molmed.2012.01.001
View details for Web of Science ID 000302455400006
View details for PubMedID 22342807
Teplizumab Induces Human Gut-Tropic Regulatory Cells in Humanized Mice and Patients
SCIENCE TRANSLATIONAL MEDICINE
2012; 4 (118)
The development and optimization of immune therapies in patients has been hampered by the lack of preclinical models in which their effects on human immune cells can be studied. As a result, observations that have been made in preclinical studies have suggested mechanisms of drug action in murine models that have not been confirmed in clinical studies. Here, we used a humanized mouse reconstituted with human hematopoietic stem cells to study the mechanism of action of teplizumab, an Fc receptor nonbinding humanized monoclonal antibody to CD3 being tested in clinical trials for the treatment of patients with type 1 diabetes mellitus. In this model, human gut-tropic CCR6(+) T cells exited the circulation and secondary lymph organs and migrated to the small intestine. These cells then produced interleukin-10 (IL-10), a regulatory cytokine, in quantities that could be detected in the peripheral circulation. Blocking T cell migration to the small intestine with natalizumab, which prevents cellular adhesion by inhibiting α(4) integrin binding, abolished the treatment effects of teplizumab. Moreover, IL-10 expression by CD4(+)CD25(high)CCR6(+)FoxP3 cells returning to the peripheral circulation was increased in patients with type 1 diabetes treated with teplizumab. These findings demonstrate that humanized mice may be used to identify novel immunologic mechanisms that occur in patients treated with immunomodulators.
View details for Web of Science ID 000299539500008
View details for PubMedID 22277969
The 1.75 angstrom resolution structure of fission protein Fis1 from Saccharomyces cerevisiae reveals elusive interactions of the autoinhibitory domain
ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION COMMUNICATIONS
2011; 67: 1310-1315
Fis1 mediates mitochondrial and peroxisomal fission. It is tail-anchored to these organelles by a transmembrane domain, exposing a soluble cytoplasmic domain. Previous studies suggested that Fis1 is autoinhibited by its N-terminal region. Here, a 1.75 Å resolution crystal structure of the Fis1 cytoplasmic domain from Saccharomyces cerevisiae is reported which adopts a tetratricopeptide-repeat fold. It is observed that this fold creates a concave surface important for fission, but is sterically occluded by its N-terminal region. Thus, this structure provides a physical basis for autoinhibition and allows a detailed examination of the interactions that stabilize the inhibited state of this molecule.
View details for DOI 10.1107/S1744309111029368
View details for Web of Science ID 000296793300001
View details for PubMedID 22102223
View details for PubMedCentralID PMC3212442
Epidermal growth factor inhibits intestinal NHE8 expression via reducing its basal transcription
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
2010; 299 (1): C51-C57
Sodium/hydrogen exchangers (NHEs) play a major role in Na(+) absorption, cell volume regulation, and intracellular pH regulation. Of the nine identified mammalian NHEs, three (NHE2, NHE3, and NHE8) are localized on the apical membrane of epithelial cells in the small intestine and the kidney. Although the regulation of NHE2 and NHE3 expression has been extensively studied in the past decade, little is known about the regulation of NHE8 gene expression under physiological conditions. The current studies were performed to explore the role of epidermal growth factor (EGF) on NHE8 expression during intestinal maturation. Brush-border membrane vesicles (BBMV) were isolated from intestinal epithelia, and Western blot analysis was performed to determine NHE8 protein expression of sucking male rats treated with EGF. Real-time PCR was used to quantitate NHE8 mRNA expression in rats and Caco-2 cells. Human NHE8 promoter activity was characterized through transfection of Caco-2 cells. Gel mobility shift assays (GMSAs) were used to identify the promoter sequences and the transcriptional factors involved in EGF-mediated regulation. Our results showed that intestinal NHE8 mRNA expression was decreased in EGF-treated rats and Caco-2 cells, and NHE8 protein abundance was also decreased in EGF-treated rats. The activity of the human NHE8 gene promoter transfected in Caco-2 cells was also reduced by EGF treatment. This could be explained by reduced binding of transcription factor Sp3 on the NHE8 basal promoter region in the presence of EGF. Pretreatment with MEK1/2 inhibitor UO-126 could prevent EGF-mediated inhibition of NHE8 gene expression. In conclusion, this study showed that EGF inhibits NHE8 gene expression through reducing its basal transcription, suggesting an important role of EGF in regulating NHE expression during intestinal maturation.
View details for DOI 10.1152/ajpcell.00081.2010
View details for Web of Science ID 000278887800008
View details for PubMedID 20375273