Jonathan Michael Chen
VerifiedUniversity of Pennsylvania · Rehabilitation Medicine
Active 2004–2026
About
Jonathan Michael Chen, M.D., is a Professor of Surgery at the Children's Hospital of Philadelphia. He is affiliated with the Department of Surgery at the University of Pennsylvania. His educational background includes a B.S. in Molecular Biophysics and Biochemistry from Yale University in 1990 and an M.D. from Columbia University College of Physicians & Surgeons in 1994. Dr. Chen's professional focus involves pediatric cardiac surgery, with a particular emphasis on pediatric heart transplantation, ventricular assist devices, and related surgical innovations. His contributions include research and publications on topics such as pediatric heart transplantation, ECMO, and graft loss prediction, reflecting a commitment to advancing surgical techniques and patient outcomes in pediatric cardiothoracic care.
Research topics
- Medicine
- Internal medicine
- Statistics
- Oncology
- Computer science
Selected publications
Advanced Science · 2026-04-02
articleOpen accessCalcium Oxalate (CaOx) kidney stones with high recurrence are a major clinical and economic health burden. Randall's Plaques (RP) serve as a nidus for CaOx stones, but it remains poorly understood how renal interstitial hydroxyapatite (HAP) deposition erodes through the papillary urothelium to create sites for urinary CaOx crystal adherence. Here, it is observed loss of urothelium above interstitial HAP deposition, and revealed that Fas Ligand (FASLG) derived from renal interstitial fibroblasts (RIFs) in HAP-rich microenvironment induced anoikis of urothelium to trigger RP exposure to urine. Mechanistically, HAP interacted with membrane protein THY1 of RIFs, which increased the affinity of THY1 to SFRP1 but suppressed its affinity to NDP, leading to activation of GSK3α/β-β-catenin pathway and thus upregulating FASLG. Moreover, the upregulated FASLG is identified as the predictor for recurrence in patients with CaOx stones following lithotripsy. Furthermore, Benarthin, a small compound binding to THY1, is found to inhibit HAP-induced FASLG and thus attenuate the anoikis of urothelium in RP mice. It is anticipated that investigations of urothelial anoikis caused by FASLG from HAP-induced fibroblasts will offer novel insights into RP exposure, enabling preventive strategies for CaOx stone formation.
Journal of the American College of Cardiology · 2026-03-27
articleRacial Differences in Screening Eligibility by Breast Density After State-Level Insurance Expansion
JAMA Network Open · 2025-08-05 · 1 citations
articleOpen accessImportance: Women with dense breasts have elevated risk of false-negative mammograms and may benefit from supplemental screening. Objective: To assess potential outcomes of Pennsylvania's law mandating insurance coverage for supplemental breast cancer screening among Black and White women. Design, Setting, and Participants: This cross-sectional study included Black and White women, aged 40 to 74 years, without prior breast cancer or known BRCA1/2 variants who underwent mammography screening at a large urban academic health system from January 2015 to December 2021, with cancer outcomes ascertained through December 2022. Data analysis was conducted from June 2023 to April 2025. Exposures: Dense breasts; the law mandates insurance coverage for women with extremely dense breasts or those with heterogeneously dense breasts plus a greater than 20% lifetime breast cancer risk by risk models. Main Outcomes and Measures: The main outcomes were odds of eligibility for supplemental coverage and of a false-negative mammogram. Results: A total of 68 478 women (38 397 Black women [median (IQR) age, 57 (49-64) years] and 30 081 White women [median (IQR) age, 58 (49-65) years]) were used for the analysis. Fewer Black women had extremely dense breasts (561 [2.1%] vs 1464 [5.8%]; P = .02) and greater than 20% lifetime risk of breast cancer identified (257 [0.7%] vs 1905 [6.4%]; P = .04) compared with White women. Consequently, Black women were less likely to meet the eligibility criteria for supplemental screening (523 [1.6%] vs 2081 [8.4%]; P = .02). The criteria showed lower sensitivity but higher specificity for detecting false-negative mammograms in Black compared with White women in one round of screening. Using heterogeneously or extremely dense breasts alone would detect more false negatives but with significantly more women recommended for magnetic resonance imaging. Conclusions and Relevance: In this study of 68 478 screening mammograms among Black and White women from 2015 to 2021, retrospectively applying criteria for supplemental screening based on heterogeneously or extremely dense breast density and lifetime risk had limited ability to identify women at risk for a false-negative mammogram. Given lower density and lifetime risk estimates, few Black women met criteria for insurance coverage in Pennsylvania, and the criteria had poor sensitivity for identifying Black women with false-negative mammograms. Additionally, using the current breast density criteria for magnetic resonance imaging may not accurately reflect breast cancer risk in Black women.
Hypertension in Pregnancy · 2025-09-30
articleOpen accessIMPORTANCE: Hypertensive disorders of pregnancy (HDP) increase cardiovascular disease risk. Postpartum interventions can motivate lifestyle changes but are not universally effective. OBJECTIVE: Our objective was to determine how behavioral phenotypes are associated with response to a digital health intervention designed to increase physical activity among 122 postpartum individuals with HDP. DESIGN AND METHODS: We conducted a secondary analysis of the STEP UP Mom trial, comparing a wearable step tracker with team-based gamification to a wearable step tracker alone over 12 weeks. Baseline behavioral characteristics were obtained using validated surveys. We applied the k-means clustering method to identify clusters. MAIN OUTCOME AND MEASURE: Linear mixed-effects models were used to estimate mean step count difference between arms from baseline across follow-up within each cluster. RESULTS: We identified two distinct, non-overlapping clusters. Cluster 1 had higher baseline steps and greater psychosocial distress, without significant difference in change in step count in the intervention arm compared to the control arm. Cluster 2 had lower baseline steps and less psychosocial distress and walked 1,335 significantly more steps per day in the intervention arm compared to the control arm. Sustained engagement with the study intervention did not differ between clusters. CONCLUSIONS AND RELEVANCE: Behavioral phenotypes may help identify postpartum individuals who may benefit from tailored interventions in future studies to improve lifestyle changes.
Circulation · 2025-11-03
articleIntroduction: The development of chronic hypertension (HTN) in the postpartum period increases cardiovascular disease risk later in life. Area Deprivation Index (ADI) is a validated measure that integrates neighborhood-based socioeconomic factors at the census block level and is associated with cardiovascular outcomes. The association between ADI, race, and postpartum HTN has not been well studied. Research Questions: Is there an association between ADI and the development of incident HTN in the postpartum period, and does ADI mitigate the association between race and postpartum HTN? Methods: This retrospective analysis examined electronic health record data of patients without a history of pre-pregnancy HTN who delivered between 2012-2020 within a large US-based healthcare system. ADI was grouped into quintiles, with the highest quintile representing the most socioeconomically disadvantaged group. High ADI (quintiles 4 and 5) was compared to lower ADI (quintiles 1-3). The outcome of incident HTN was assessed between 6 and 24 months postpartum based on diagnosis codes, blood pressure values, and medications. Logistic regression was used to model the association between covariates of interest and postpartum HTN. Results: The cohort consisted of 23,787 patients with mean age of 30.3 (SD 5.7) years and 37.4% identified as non-Hispanic Black. The incidence of chronic HTN varied across ADI quintiles (quintile 1 to 5): 1.6%, 2.4%, 3.0%, 4.1%, and 3.8%, respectively. Compared to the lowest ADI quintile, each ADI quintile was associated with incident HTN. After adjusting for demographic and clinical characteristics, Black patients had higher odds of postpartum HTN compared to White patients (Table 1). When ADI was added to the model, the effect estimate associated with Black race was slightly attenuated, however ADI was no longer significant (Table 2). Conclusions: Residing in a deprived neighborhood at the time of delivery is associated with incident chronic HTN in the postpartum period, however, this association does not persist after adjusting for race and other clinical characteristics. Furthermore, neighborhood deprivation does not entirely mitigate the impact of race on postpartum HTN. Additional factors that are not directly incorporated into the ADI framework, such as maternal stress and social support, racial segregation, and healthcare accessibility, may play a greater role in the association between race and incident chronic HTN in the postpartum period.
Variant‐Specific Mendelian Risk Prediction Model
Statistics in Medicine · 2025-12-01
articleOpen accessMany pathogenic sequence variants (PSVs) have been associated with increased risk of cancers. Mendelian risk prediction models use Mendelian laws of inheritance, as well as specified PSV frequency and penetrance (age-specific probability of developing cancer given genotype), to predict the probability of having a PSV based on family history. Most existing models assume that the penetrance is the same for all PSVs in a certain gene. However, for some genes (e.g., BRCA1/2), cancer risk has been shown to vary by PSV. We propose an extension of Mendelian risk prediction models that relaxes the assumption of homogeneous gene-level risk by incorporating PSV-specific penetrances and illustrate this extension on an existing Mendelian risk prediction model, Fam3PRO. We illustrate our proposed Fam3PRO-variant model by incorporating variant-specific BRCA1/2 PSVs through region classifications. Based on prior literature, we defined three cancer-specific risk regions: The breast cancer clustering region (BCCR), the ovarian cancer clustering region (OCCR), and the "other" region. We conducted simulations to evaluate the performance of the proposed illustrative Fam3PRO-variant model compared to the existing Fam3PRO model. Simulation results showed that the Fam3PRO-variant model was well calibrated to predict region-specific BRCA1/2 carrier status with high discrimination and accuracy. Importantly, our simulations also highlighted the impact of underreporting in family history data on model performance: While underreporting slightly reduced absolute calibration, the Fam3PRO-variant model remained robust in discrimination and provided more accurate region-specific PSV risk predictions than gene-level models. We further evaluated Fam3PRO-variant on two cohorts: 1897 families from the Cancer Genetics Network (CGN) and 25 671 families from the Clinical Cancer Genomics Community Research Network (CCGCRN). Results showed that our proposed model provides region-specific PSV carrier probabilities with high accuracy, while the calibration, discrimination, and accuracy of gene-specific PSV carrier probabilities were comparable to the existing gene-specific model. Moreover, we assessed the clinical utility of Fam3PRO-variant by evaluating positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity at clinically relevant thresholds (2.5%, 5%, and 10%), as recommended by NCCN guidelines. Fam3PRO-variant performed comparably to Fam3PRO at the gene level across all metrics, with notably high specificity and NPV at the region-specific level. These results suggest that, even in the presence of underreporting, Mendelian risk prediction models can be effectively extended to incorporate variant-specific penetrances, providing more precise region-specific PSV carrier probabilities and improving cancer prevention and risk prediction.
Algorithm-Based Palliative Care in Patients With Cancer
JAMA Network Open · 2025-02-21 · 11 citations
articleOpen accessImportance: Among patients with advanced solid malignant tumors, early specialty palliative care (PC) is guideline recommended, but strategies to increase PC access and effectiveness in community oncology are lacking. Objective: To test whether algorithm-based defaults with opting out and accountable justification embedded in the electronic health record (EHR) increase completed PC visits. Design, Setting, and Participants: This 2-arm cluster randomized clinical trial was conducted from November 1, 2022, to December 31, 2023. Eligible patients from 15 urban or rural clinics within a large community oncology network in Tennessee had advanced lung or noncolorectal gastrointestinal cancer and were identified by an automated EHR algorithm adapted from national guidelines. Data were analyzed between November 1, 2023, and March 4, 2024. Intervention: At sites randomized to control, clinicians received weekly reports detailing PC referral rates compared with peer clinicians (peer comparison) and referred patients to PC at their discretion. At sites randomized to intervention, clinicians also received default PC orders using the EHR. Clinicians who opted out of PC consultation were asked to provide justification (accountable justification). If clinicians did not opt out, a study coordinator contacted patients to introduce and schedule PC visits using a standardized, predefined script. Main Outcomes and Measures: The primary outcome was a completed PC consultation within 12 weeks of enrollment. Exploratory outcomes included quality of life, feeling heard and understood, and intensive end-of-life care. Outcomes were analyzed using clustered generalized linear and logistic regression models. Results: The trial enrolled 562 patients (mean [SD] age, 68.5 [10.1] years; 288 male [51.2%]), of whom 433 (77.0%) had lung cancer. There were 130 of 296 patients (43.9%) randomized to the intervention group and 22 of 266 (8.3%) randomized to the control group who completed PC visits (adjusted odds ratio, 8.9 [95% CI, 5.5-14.6]; P < .001). Among 179 patients who died at the 24-week follow-up, 6 of 92 (6.5%) in the intervention group compared with 14 of 87 (16.1%) in the control group received systemic therapy within 14 days of death (adjusted odds ratio, 0.3 [95% CI, 0.1-0.7]; P = .05). There were no differences in quality of life, feeling heard and understood, or late hospice referral. Conclusions and Relevance: In this randomized clinical trial of algorithm-based EHR defaults, the intervention increased PC consultations and decreased end-of-life systemic therapy. The intervention provides a scalable implementation strategy to increase specialty PC referrals in the community oncology setting. Trial Registration: ClinicalTrials.gov Identifier: NCT05590962.
BMC Medicine · 2025-07-18 · 9 citations
articleOpen accessBACKGROUND: Early identification of high-risk women is critical for preventing gestational diabetes mellitus (GDM). We aimed to improve early prediction of GDM using multiple panels of cardiometabolic biomarkers assessed in early and mid-pregnancy, considering clinical accessibility. METHODS: In a US study of 2802 pregnant individuals, we assessed 91 cardiometabolic biomarkers at 10-14 (random blood) and 15-26 (fasting) gestational weeks (GW) in 107 GDM cases and 214 controls. Candidate biomarkers were categorized by clinical accessibility from high to low: group I (clinically accessible tests like HbA1c, lipids), group II (clinically accessible biomarkers upon request like insulin-like growth factor (IGF) axis markers, adipokines), and group III (specialty lab-required targeted metabolomics: amino acids (AAs) and phospholipid fatty acids (FAs)). At each visit, we constructed a full model incorporating all candidate biomarkers and conventional predictors. We built alternative models utilizing different groups of biomarkers considering clinical accessibility. Variable selection was performed to retain variables with a p value < 0.10 for a parsimonious model. Model performance was evaluated by area under receiver operating characteristics curve (AUC), proportion of cases followed (PCF, %) and proportion needed to follow (PNF, %), and decision curve analysis. RESULTS: A full model comprising conventional predictors, clinical and non-clinical cardiometabolic biomarkers, and metabolomic markers achieved the highest discriminative accuracy (AUC: 0.842 at 10-14 GW, 0.829 at 15-26 GW). The addition of novel biomarkers increased PCF and decreased PNF, suggesting increased clinical utility. For example, at 10-14 GW, 69.5% of GDM cases are expected to be detected from women whose risk is above the 80% percentile estimated by the full model vs. 49.1% by the conventional model. Additionally, 46.1% of women identified as being at the highest risk by the full model are expected to account for 90.0% of GDM cases vs. 71.1% by the conventional model. Decision curve analysis showed that models incorporating novel biomarkers performed better than the conventional model including glucose, and the full model at 10-14 GW had the highest net benefit, overall. CONCLUSIONS: This study suggested that a selected panel of cardiometabolic biomarkers using early-pregnancy random plasma samples predicted GDM comparably to those using mid-pregnancy fasting samples.
Advances in Radiation Oncology · 2025-04-16
articleOpen accessPurpose: Our objective was to characterize the early changes in cardiac function after thoracic radiation therapy (RT) using 3D echocardiography. Methods and Materials: In a prospective longitudinal cohort study of 69 patients with breast cancer, lung cancer, or mediastinal lymphoma treated with chemotherapy and RT, clinical and 3D echocardiographic data were assessed before, immediately after, and 5 to 9 months after RT completion. 3D left ventricular ejection fraction, global circumferential strain, global longitudinal strain (GLS), average 3D strain, twist, and torsion were quantified. Associations among mean heart dose (MHD), V5, and V30 and early changes in echocardiography-derived measures of cardiac function were assessed with generalized estimating equations. Results: > .05). Conclusions: Early abnormalities in cardiac function as measured by 3D echocardiography can be detected following RT. Additional work is needed to define the determinants of changes in cardiac function with RT and long-term impact of early changes on clinical outcomes.
JAMA Health Forum · 2025-08-15 · 3 citations
articleOpen accessImportance: Clinical risk algorithms inform clinical decision support and system-level quality metrics. However, algorithm performance can drift over time and possibly promote misinformed decision-making and resource allocation. The Veterans Health Administration (VA) Care Assessment Needs (CAN) algorithm is a nationally deployed population risk algorithm used to predict risk of 90-day hospitalization and/or mortality and to allocate resources for more than 5 million veterans annually. However, drift affecting the VA CAN has not been assessed. Objective: To evaluate the impact of drift in the VA CAN algorithm and the extent, mechanisms, and clinical consequences of performance changes. Design, Setting, and Participants: This was a retrospective cohort study using electronic health records (EHRs) and administrative data from the VA Corporate Data Warehouse, which contains observations from more than 5 million veterans per study year. The data comprised 27 787 152 observations among 7 215 711 unique veterans receiving VA primary care from 2016 to 2021. Data analysis was performed from January 2023 and December 2024. Main Outcomes and Measures: Two primary outcomes were change in model performance (true positive rate [TPR], false positive rate [FPR], positive predictive value [PPV], negative predictive value [NPV], F1 score, and accuracy); and a national quality metric (% of veterans with CAN ≥90th percentile with a palliative care visit). Results: The study population included 7 215 711 eligible veterans, with a mean (SD) age of 62.1 (16.5); 91.2% were male and 18.2% were Black, 6.6% Hispanic, and 76.2% White individuals. From 2016 to 2021, PPV decreased by 4.0% (95% CI, -2.8% to -5.1%); F1 score decreased by 4.6% (95% CI, -6.1% to 3.0%); NPV increased by 0.43% (95% CI, 0.30% to 0.57%); and FPR increased by 0.34% (95% CI, 0.10% to 0.58%), which corresponds with 18 288 increased false positive results. TPR and accuracy remained stable. The 90-day hospitalization and/or death rates decreased from 3.8% in 2017 to 3.0% in 2021. Covariate shifts were observed in 19 covariates, with demographic characteristics, health care utilization, and laboratory covariates exhibiting the largest shifts. The palliative care quality metric was 2.9% (95% CI, 2.8% to 2.9%) in 2018, 2.6% (95% CI, 2.6% to 2.7%) in 2019, and 2.8% (95% CI, 2.7% to 2.8%) in 2020, with FPRs among metric-eligible veterans increasing from 81.6% (95% CI, 81.5% to 81.7%) in 2018 to 85.7% (95% CI, 85.6% to 85.8%) in 2020. Conclusions and Relevance: This cohort study found that CAN algorithm performance declined from 2016 to 2021 due to shifts in outcome prevalence and distributions of health care utilization and demographic covariates. Close surveillance of clinical risk algorithms and quality metrics derived from algorithm-generated risk scores could mitigate suboptimal resource allocation or decision-making.
Recent grants
Precision Assessment and Delivery of Cancer Risks in BRCA 1/2 Mutation Cancers
NIH · $3.6M · 2017–2023
Data and Information Integration for Risk Prediction in the Era of Big Data
NIH · $2.2M · 2019–2025
NIH · $41.5M · 2016–2027
Statistical Methods for Analyzing Electronic Health Record Data
NIH · $397k · 2018–2023
NIH · $1.4M · 2019
Frequent coauthors
- 127 shared
Jacques Bénichou
Université de Rouen Normandie
- 119 shared
Barry I. Graubard
National Cancer Institute
- 110 shared
Mitchell H. Gail
National Cancer Institute
- 109 shared
Rajeev Ayyagari
Analysis Group (United States)
- 109 shared
David Pee
Information Management Services
- 109 shared
Celia Byrne
Uniformed Services University of the Health Sciences
- 109 shared
Catherine Schairer
- 45 shared
Ravi B. Parikh
Penn Center for AIDS Research
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