Sharon F. Chen

All Publications

• A Multi-Institution Collaboration to Define Core Content and Design Flexible Curricular Components for a Foundational Medical School Course: Implications for National Curriculum Reform. Academic medicine : journal of the Association of American Medical Colleges Chen, S. F., Deitz, J., Batten, J. N., DeCoste-Lopez, J., Adam, M., Alspaugh, J. A., Amieva, M. R., Becker, P., Boslett, B., Carline, J., Chin-Hong, P., Engle, D. L., Hayward, K. N., Nevins, A., Porwal, A., Pottinger, P. S., Schwartz, B. S., Smith, S., Sow, M., Teherani, A., Prober, C. G. 2019

  Abstract

  Medical educators have not reached widespread agreement on core content for a U.S. medical school curriculum. As a first step toward addressing this, five U.S. medical schools formed the Robert Wood Johnson Foundation Reimagining Medical Education collaborative to define, create, implement, and freely share core content for a foundational medical school course on microbiology and immunology. This proof-of-concept project involved delivery of core content to preclinical medical students through online videos and class time interactions between students and facilitators. A flexible, modular design allowed four of the medical schools to successfully implement the content modules in diverse curricular settings. Compared to the prior year, student satisfaction ratings after implementation were comparable or showed a statistically significant improvement. Students who took this course at a time point in their training similar to when the USMLE Step 1 reference group took Step 1 earned equivalent scores on National Board of Medical Examiners-Customized Assessment Services microbiology exam items. Exam scores for three schools ranged from 0.82 to 0.84, compared to 0.81 for the national reference group; exam scores were 0.70 at the fourth school, where students took the exam in their first quarter, two years earlier than the reference group. This project demonstrates that core content for a foundational medical school course can be defined, created, and used by multiple medical schools without compromising student satisfaction or knowledge. This project offers one approach to collaboratively defining core content and designing curricular resources for preclinical medical school education that can be shared.

  View details for PubMedID 30801270

• The Use of Short, Animated, Patient-Centered Springboard Videos to Underscore the Clinical Relevance of Preclinical Medical Student Education. Academic medicine Adam, M., Chen, S. F., Amieva, M., Deitz, J., Jang, H., Porwal, A., Prober, C. 2017

  Abstract

  Medical students often struggle to appreciate the clinical relevance of material taught in the preclinical years. The authors believe videos could be effectively used to interweave a patient's illness script with foundational basic science concepts.In collaboration with four other U.S. medical schools, educators at the Stanford University School of Medicine created 36 short, animated, patient-centered springboard videos (third-person, narrated accounts of authentic patient cases conveying foundational pathophysiology) in 2014. The videos were used to introduce students to 36 content modules, created as part of a microbiology, immunology, and infectious diseases curriculum. The videos were created with input from faculty content experts and in some cases medical students, and were piloted using a flipped classroom pedagogical approach in January 2015-June 2016.Student feedback from course evaluations and focus groups was analyzed using a mixed-methods approach. On the course evaluations, the majority of students rated the patient-centered videos positively, and the majority of comments on the videos were positive, highlighting both enhanced engagement and enhanced learning and retention. Comments from focus groups mirrored the course evaluation comments and highlighted different usage patterns for the videos.The authors will continue to gather and analyze data from schools using the videos as part of their core preclinical curriculum, and will produce similar videos for use in other areas of undergraduate medical education. These videos could support students' review of content taught previously and be repurposed for use in continuing and graduate medical education, as well as patient education.

  View details for DOI 10.1097/ACM.0000000000001574

  View details for PubMedID 28121656

• Limited Variation in BK Virus T-Cell Epitopes Revealed by Next-Generation Sequencing. Journal of clinical microbiology Sahoo, M. K., Tan, S. K., Chen, S. F., Kapusinszky, B., Concepcion, K. R., Kjelson, L., Mallempati, K., Farina, H. M., Fernández-Viña, M., Tyan, D., Grimm, P. C., Anderson, M. W., Concepcion, W., Pinsky, B. A. 2015; 53 (10): 3226-3233

  Abstract

  BK virus (BKV) infection and end-organ disease remains a formidable challenge to the hematopoietic cell transplant (HCT) and kidney transplant fields. As BKV-specific treatments are limited, immunologic-based therapies may be a promising and novel therapeutic option for transplant recipients with persistent BKV infection. Here, we describe a whole-genome, deep sequencing methodology and bioinformatics pipeline that identifies BKV variants across the genome and at BKV-specific HLA-A2, HLA-B0702, and HLA-B08 restricted CD8 T-cell epitopes. BKV whole genomes were amplified using long-range PCR with four inverse primer sets and fragmentation libraries were sequenced on the Ion Torrent PGM. An error model and variant calling algorithm were developed to accurately identify rare variants. 65 samples from 18 pediatric HCT and kidney recipients with quantifiable BKV DNAemia underwent whole-genome sequencing. Limited genetic variation was observed. The median number of amino acid variants identified per sample was 8 (range 2-37, interquartile range 10), with the majority of variants (77%) detected at a frequency of less than 5%. When normalized for length, there was no statistical difference in the median number of variants across all genes. Similarly, the predominant virus population within samples harbored T-cell epitopes similar to the reference BKV strain that was matched for BKV genotype. Despite the conservation of epitopes, low-level variants in T-cell epitopes were detected in 77.7% (14/18) of patients. Understanding epitope variation across the whole genome provides insight into the virus-immune interface and may help guide the development of protocols for novel immunologic-based therapies.

  View details for DOI 10.1128/JCM.01385-15

  View details for PubMedID 26202116

• Novel protocol including liver biopsy to identify and treat CD8+ T-cell predominant acute hepatitis and liver failure. Pediatric transplantation McKenzie, R. B., Berquist, W. E., Nadeau, K. C., Louie, C. Y., Chen, S. F., Sibley, R. K., Glader, B. E., Wong, W. B., Hofmann, L. V., Esquivel, C. O., Cox, K. L. 2014; 18 (5): 503-509

  Abstract

  In the majority of children with ALF, the etiology is unknown and liver transplantation is often needed for survival. A patient case prompted us to consider that immune dysregulation may be the cause of indeterminate acute hepatitis and liver failure in children. Our study includes nine pediatric patients treated under a multidisciplinary clinical protocol to identify and treat immune-mediated acute liver injury. Patients with evidence of inflammation and no active infection on biopsy received treatment with intravenous immune globulin and methylprednisolone. Seven patients had at least one positive immune marker before or after treatment. All patients had a CD8+ T-cell predominant liver injury that completely or partially responded to immune therapy. Five of the nine patients recovered liver function and did not require liver transplantation. Three of these patients subsequently developed bone marrow failure and were treated with either immunosuppression or stem cell transplant. This series highlights the importance of this tissue-based approach to diagnosis and treatment that may improve transplant-free survival. Further research is necessary to better characterize the immune injury and to predict the subset of patients at risk for bone marrow failure who may benefit from earlier and stronger immunosuppressive therapy.

  View details for DOI 10.1111/petr.12296

  View details for PubMedID 24930635

• Longitudinal Kinetics of Cytomegalovirus-specific T-cell Immunity and Viral Replication in Infants with Congenital Cytomegalovirus Infection Journal of the Pediatric Infectious Diseases Society Chen, S. F., Holmes, T. H., Slifer, T., Ramachandran, V., Mackey, S., Hebson, C., Arvin, A. M., Lewis, D. B., Dekker, C. L. 2014

  View details for DOI 10.1093/jpids/piu089

• Antiviral CD8 T cells in the control of primary human cytomegalovirus infection in early childhood 40th Annual Meeting of the Infectious-Diseases-Society-of-America Chen, S. F., Tu, W. W., Sharp, M. A., Tongson, E. C., He, X. S., Greenberg, H. B., Holmes, T. H., Wang, Z. T., Kemble, G., Manganello, A. M., Adler, S. P., Dekker, C. L., Levvis, D. B., Arvin, A. M. UNIV CHICAGO PRESS. 2004: 1619–27

  Abstract

  Human cytomegalovirus (CMV) establishes persistent infection, with control of replication thought to be mediated by CMV-specific CD8 T cells. Primary CMV infection commonly affects young children and causes prolonged viral shedding in saliva and urine. We investigated whether this virus-host interaction pattern reflects a developmental deficiency of antiviral CD8 T cell-mediated immunity during childhood. CMV-specific CD8 T cell responses in asymptomatic children with active infection were not different from adults with recent or long-term infection in frequency and functional analyses. High urine CMV concentrations were detected, despite these CMV-specific CD8 T cell responses. We conclude that delayed resolution of primary CMV infection in young children is not caused by a deficient CMV-specific CD8 T cell response. Because these healthy children continue to have local CMV replication, we suggest that CD8 T cells may function primarily to prevent symptomatic, disseminated disease.

  View details for PubMedID 15116298

• Persistent and selective deficiency of CD4(+) T cell immunity to cytomegalovirus in immunocompetent young children JOURNAL OF IMMUNOLOGY Tu, W. W., Chen, S., Sharp, M., Dekker, C., Manganello, A. M., Tongson, E. C., Maecker, H. T., Holmes, T. H., Wang, Z. T., Kemble, G., Adler, S., Arvin, A., Lewis, D. B. 2004; 172 (5): 3260-3267

  Abstract

  Healthy young children who acquire CMV have prolonged viral shedding into the urine and saliva, but whether this is attributable to limitations in viral-specific immune responses has not been explored. In this study, we found that otherwise immunocompetent young children after recent primary CMV infection accumulated markedly fewer CMV-specific CD4(+) T cells that produced IFN-gamma than did adults. These differences in CD4(+) T cell function persisted for more than 1 year after viral acquisition, and did not apply to CMV-specific IFN-gamma production by CD8(+) T cells. The IFN-gamma-producing CD4(+) T cells of children or adults that were reactive with CMV Ags were mainly the CCR7(low) cell subset of memory (CD45R0(high)CD45RA(low)) cells. The decreased IFN-gamma response to CMV in children was selective, because their CCR7(low) memory CD4(+) T cells and those of adults produced similar levels of this cytokine after stimulation with staphylococcal enterotoxin B superantigen. CD4(+) T cells from children also had reduced CMV-specific IL-2 and CD154 (CD40 ligand) expression, suggesting an early blockade in the differentiation of viral-specific CD4(+) T cells. Following CMV acquisition, children, but not adults, persistently shed virus in urine, and this was observable for at least 29 mo postinfection. Thus, CD4(+) T cell-mediated immunity to CMV in humans is generated in an age-dependent manner, and may have a substantial role in controlling renal viral replication and urinary shedding.

  View details for PubMedID 14978134

• Clinical characteristics and outcomes of pediatric patients with CMV DNA detection in bronchoalveolar lavage fluid. Pediatric pulmonology Burgener, E. B., Waggoner, J., Pinsky, B. A., Chen, S. F. 2017; 52 (1): 112-118

  Abstract

  Cytomegalovirus (CMV) infection can cause severe pulmonary disease in immunocompromised patients. There are no standard diagnostic criteria for CMV pulmonary disease beyond histopathology findings on lung tissue, which is challenging to obtain in pediatric patients. Bronchoalveolar lavage (BAL) fluid is easier to obtain. Since CMV remains latent after primary infection and can potentially reactivate due to any inflammatory response, CMV detection in BAL specimen may not indicate acute CMV pulmonary disease. Thus, we describe the clinical manifestations and outcomes of pediatric patients with CMV detection in BAL fluid.We reviewed the clinical, radiologic, and laboratory data of patients <19 years old with a BAL specimen positive for CMV during a 5-year period.Thirty-four encounters in 29 patients were found with CMV detected in their BAL specimen. Half (17/34) of the encounters were in immunocompromised patients. CMV, polymerase chain reaction (PCR) was the most common positive test. Forty-seven percent of the patients had other infections detected in BAL specimens. The majority of patients were never treated for CMV and resolved their acute respiratory illness. Only one patient had probable CMV pulmonary disease.CMV is frequently recovered from BAL specimens but does not usually indicate acute CMV pulmonary disease. We would suggest that other diagnoses be considered first, even if CMV is recovered. Pediatr Pulmonol. 2016; 9999:XX-XX. © 2016 Wiley Periodicals, Inc.

  View details for DOI 10.1002/ppul.23494

  View details for PubMedID 27280337

• Molecular and Culture-Based Bronchoalveolar Lavage Fluid Testing for the Diagnosis of Cytomegalovirus Pneumonitis. Open forum infectious diseases Tan, S. K., Burgener, E. B., Waggoner, J. J., Gajurel, K., Gonzalez, S., Chen, S. F., Pinsky, B. A. 2016; 3 (1): ofv212-?

  Abstract

  Background.  Cytomegalovirus (CMV) is a major cause of morbidity and mortality in immunocompromised patients, with CMV pneumonitis among the most severe manifestations of infection. Although bronchoalveolar lavage (BAL) samples are frequently tested for CMV, the clinical utility of such testing remains uncertain. Methods.  Retrospective analysis of adult patients undergoing BAL testing via CMV polymerase chain reaction (PCR), shell vial culture, and conventional viral culture between August 2008 and May 2011 was performed. Cytomegalovirus diagnostic methods were compared with a comprehensive definition of CMV pneumonitis that takes into account signs and symptoms, underlying host immunodeficiency, radiographic findings, and laboratory results. Results.  Seven hundred five patients underwent 1077 bronchoscopy episodes with 1090 BAL specimens sent for CMV testing. Cytomegalovirus-positive patients were more likely to be hematopoietic cell transplant recipients (26% vs 8%, P < .0001) and less likely to have an underlying condition not typically associated with lung disease (3% vs 20%, P < .0001). Histopathology was performed in only 17.3% of CMV-positive bronchoscopy episodes. When CMV diagnostic methods were evaluated against the comprehensive definition, the sensitivity and specificity of PCR, shell vial culture, and conventional culture were 91.3% and 94.6%, 54.4% and 97.4%, and 28.3% and 96.5%, respectively. Compared with culture, PCR provided significantly higher sensitivity and negative predictive value (P ≤ .001), without significantly lower positive predictive value. Cytomegalovirus quantitation did not improve test performance, resulting in a receiver operating characteristic curve with an area under the curve of 0.53. Conclusions.  Cytomegalovirus PCR combined with a comprehensive clinical definition provides a pragmatic approach for the diagnosis of CMV pneumonitis.

  View details for DOI 10.1093/ofid/ofv212

  View details for PubMedID 26885542

• Pleural Effusion and Fever in an Immunocompromised Patient. Journal of the Pediatric Infectious Diseases Society Kay, A. W., Itoh, M., Valdez, J., Chen, S. F., Mathew, R., Gans, H. A. 2015; 4 (1): e6-9

  View details for DOI 10.1093/jpids/piu018

  View details for PubMedID 26407371

• BK Polyomavirus Subtype III in a Pediatric Renal Transplant Patient with Nephropathy. Journal of clinical microbiology Kapusinszky, B., Chen, S. F., Sahoo, M. K., Lefterova, M. I., Kjelson, L., Grimm, P. C., Kambham, N., Concepcion, W., Pinsky, B. A. 2013; 51 (12): 4255-4258

  Abstract

  BK polyomavirus (BKV) is an emerging pathogen in immunocompromised individuals. BKV subtype III is rarely identified and has not previously been associated with disease. Here we provide the whole-genome sequence of a subtype III BKV from a pediatric kidney transplant patient with polyomavirus-associated nephropathy.

  View details for DOI 10.1128/JCM.01801-13

  View details for PubMedID 24048534

  View details for PubMedCentralID PMC3838085

• Human Parvovirus B19 in Solid Organ Transplantation AMERICAN JOURNAL OF TRANSPLANTATION Eid, A. J., Chen, S. F. 2013; 13: 201-205

  View details for DOI 10.1111/ajt.12111

  View details for Web of Science ID 000315907900021

  View details for PubMedID 23465012

• Conversion From Tacrolimus/Mycophenolic Acid to Tacrolimus/Leflunomide to Treat Cutaneous Warts in a Series of Four Pediatric Renal Allograft Recipients TRANSPLANTATION Lieuko Nguyen, L., McClellan, R. B., Chaudhuri, A., Alexander, S. R., Chen, S. F., Concepcion, W., Grimm, P. 2012; 94 (5): 450-455

  Abstract

  The challenge of immunosuppression in pediatric renal transplantation is to balance preventing rejection while avoiding infectious complications. A dermatological complication of immunosuppression is viral warts, which cause significant disfigurement and increase the risk of skin malignancy.We present three pediatric and adolescent renal allograft recipients with multiple, recalcitrant verrucae vulgares lesions and one patient with molluscum contagiosum who were switched from mycophenolate mofetil to leflunomide. Teriflunomide metabolite levels were carefully maintained between 50,000 and 100,000 ng/mL to balance its immunosuppressive and antiviral properties. No adverse events requiring discontinuation of leflunomide were encountered.Switching from mycophenolate mofetil to leflunomide successfully cleared verrucae vulgares and molluscum lesions in all four renal transplant patients.The ability to minimize and even resolve warts can improve quality of life by reducing risk of skin malignancies and emotional distress in solid organ transplant patients. Leflunomide is a potential therapeutic option for posttransplantation patients with skin warts because it serves both as an adjunct to the immunosuppressive regimen and an antiviral agent.

  View details for DOI 10.1097/TP.0b013e318264351e

  View details for Web of Science ID 000308668000012

  View details for PubMedID 22960763

• Mycobacterium bovis disease in a pediatric renal transplant patient PEDIATRIC INFECTIOUS DISEASE JOURNAL Chen, S. F., Gutierrez, K. 2006; 25 (6): 564-566

  Abstract

  We describe a pediatric renal transplant patient with Mycobacterium bovis disease who was successfully treated using an antituberculosis regimen that included rifampin. We discuss the history of M. bovis and the diagnosis and management of M. bovis infection in renal transplant patients.

  View details for DOI 10.1097/01.inf.0000219482.75490.d5

  View details for Web of Science ID 000238432300020

  View details for PubMedID 16732161

• Staphylococcus aureus decolonization PEDIATRIC INFECTIOUS DISEASE JOURNAL Chen, S. F. 2005; 24 (1): 79-80

  View details for DOI 10.1097/01.0000152261.65169.e6

  View details for Web of Science ID 000226467100012

  View details for PubMedID 15665714

• Acute retinal necrosis syndrome in a child PEDIATRIC INFECTIOUS DISEASE JOURNAL Chen, S., Weinberg, G. A. 2002; 21 (1): 78-80

  Abstract

  We recently cared for an 11-year-old child with acute retinal necrosis syndrome, an ophthalmologic condition characterized by the triad of anterior uveitis, occlusive retinal vasculitis and progressive peripheral retinal necrosis. Acute retinal necrosis syndrome occurs primarily in nonimmunocompromised adults as a result of reactivated herpes simplex or varicella-zoster virus infection. Antiviral and antiinflammatory therapy appears to reduce the incidence of vision-threatening retinal necrosis and involvement of the contralateral eye.

  View details for Web of Science ID 000173306400020

  View details for PubMedID 11791109