Bio

Clinical Focus


  • Pulmonary & Critical Care
  • Pulmonary Disease

Academic Appointments


Honors & Awards


  • Parker B. Francis Fellow 2014, Parker B. Francis Foundation (2014-2017)

Professional Education


  • Medical Education:Tufts University (2002) MA
  • Residency:Stanford University Medical Center (2005) CA
  • Fellowship:Stanford University - CAPS (2009) CA
  • Board Certification: Critical Care Medicine, American Board of Internal Medicine (2009)
  • Board Certification: Pulmonary Disease, American Board of Internal Medicine (2008)
  • Board Certification: Internal Medicine, American Board of Internal Medicine (2005)
  • Internship:Stanford University Medical Center (2003) CA
  • Residency, Stanford University, Internal Medicine (2005)
  • MPH, Boston University, Epidemiology (1996)

Research & Scholarship

Current Research and Scholarly Interests


I am interested in translational research. I am currently working to develop a novel devices to detect infections in immunocompromised patients and in gas samples. If successful this research may extend to the development of a point of care device that could detect fungal, bacterial and viral infections rapidly and accurately

Publications

Journal Articles


  • Application of a non-amplification-based technology to detect invasive fungal pathogens DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE Hsu, J. L., Binkley, J., Clemons, K. V., Stevens, D. A., Nicolls, M. R., Holodniy, M. 2014; 78 (2): 137-140

    Abstract

    Current diagnostic techniques for fungal diseases could be improved with respect to sensitivity, specificity, and timeliness. To address this clinical need, we adapted a non-amplification-based nucleic acid detection technology to identify fungal pathogens. We demonstrate a high-specificity, detection sensitivity, reproducibility, and multiplex capacity for detecting fungal strains.

    View details for DOI 10.1016/j.diagmicrobio.2013.11.013

    View details for Web of Science ID 000330149700007

    View details for PubMedID 24359934

  • Promotion of airway anastomotic microvascular regeneration and alleviation of airway ischemia by deferoxamine nanoparticles. Biomaterials Jiang, X., Malkovskiy, A. V., Tian, W., Sung, Y. K., Sun, W., Hsu, J. L., Manickam, S., Wagh, D., Joubert, L., Semenza, G. L., Rajadas, J., Nicolls, M. R. 2014; 35 (2): 803-813

    Abstract

    Airway tissue ischemia and hypoxia in human lung transplantation is a consequence of the sacrifice of the bronchial circulation during the surgical procedure and is a major risk factor for the development of airway anastomotic complications. Augmented expression of hypoxia-inducible factor (HIF)-1α promotes microvascular repair and alleviates allograft ischemia and hypoxia. Deferoxamine mesylate (DFO) is an FDA-approved iron chelator which has been shown to upregulate cellular HIF-1α. Here, we developed a nanoparticle formulation of DFO that can be topically applied to airway transplants at the time of surgery. In a mouse orthotopic tracheal transplant (OTT) model, the DFO nanoparticle was highly effective in enhancing airway microvascular perfusion following transplantation through the production of the angiogenic factors, placental growth factor (PLGF) and stromal cell-derived factor (SDF)-1. The endothelial cells in DFO treated airways displayed higher levels of p-eNOS and Ki67, less apoptosis, and decreased production of perivascular reactive oxygen species (ROS) compared to vehicle-treated airways. In summary, a DFO formulation topically-applied at the time of surgery successfully augmented airway anastomotic microvascular regeneration and the repair of alloimmune-injured microvasculature. This approach may be an effective topical transplant-conditioning therapy for preventing airway complications following clinical lung transplantation.

    View details for DOI 10.1016/j.biomaterials.2013.09.092

    View details for PubMedID 24161166

  • Aspergillus fumigatus Invasion Increases with Progressive Airway Ischemia PLOS ONE Hsu, J. L., Khan, M. A., Sobel, R. A., Jiang, X., Clemons, K. V., Nguyen, T. T., Stevens, D. A., Martinez, M., Nicolls, M. R. 2013; 8 (10)

    Abstract

    Despite the prevalence of Aspergillus-related disease in immune suppressed lung transplant patients, little is known of the host-pathogen interaction. Because of the mould's angiotropic nature and because of its capacity to thrive in hypoxic conditions, we hypothesized that the degree of Aspergillus invasion would increase with progressive rejection-mediated ischemia of the allograft. To study this relationship, we utilized a novel orthotopic tracheal transplant model of Aspergillus infection, in which it was possible to assess the effects of tissue hypoxia and ischemia on airway infectivity. Laser Doppler flowmetry and FITC-lectin were used to determine blood perfusion, and a fiber optic microsensor was used to measure airway tissue oxygen tension. Fungal burden and depth of invasion were graded using histopathology. We demonstrated a high efficacy (80%) for producing a localized fungal tracheal infection with the majority of infection occurring at the donor-recipient anastomosis; Aspergillus was more invasive in allogeneic compared to syngeneic groups. During the study period, the overall kinetics of both non-infected and infected allografts was similar, demonstrating a progressive loss of perfusion and oxygenation, which reached a nadir by days 10-12 post-transplantation. The extent of Aspergillus invasion directly correlated with the degree of graft hypoxia and ischemia. Compared to the midtrachea, the donor-recipient anastomotic site exhibited lower perfusion and more invasive disease; a finding consistent with clinical experience. For the first time, we identify ischemia as a putative risk factor for Aspergillus invasion. Therapeutic approaches focused on preserving vascular health may play an important role in limiting Aspergillus infections.

    View details for DOI 10.1371/journal.pone.0077136

    View details for Web of Science ID 000325887300058

    View details for PubMedID 24155924

  • Tie2-dependent VHL knockdown promotes airway microvascular regeneration and attenuates invasive growth of Aspergillus fumigatus JOURNAL OF MOLECULAR MEDICINE-JMM Jiang, X., Hsu, J. L., Tian, W., Yuan, K., Olcholski, M., Perez, V. D., Semenza, G. L., Nicolls, M. R. 2013; 91 (9): 1081-1093
  • Vasopressin Compared with Norepinephrine Augments the Decline of Plasma Cytokine Levels in Septic Shock AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Russell, J. A., Fjell, C., Hsu, J. L., Lee, T., Boyd, J., Thair, S., Singer, J., Patterson, A. J., Walley, K. R. 2013; 188 (3): 356-364

    Abstract

    Changes in plasma cytokine levels may predict mortality and therapies (vasopressin versus norepinephrine) could change plasma cytokine levels in early septic shock.Our hypotheses were that changes in plasma cytokine levels over 24 hours differ between survivors and non-survivors and there are different effects of vasopressin vs. norepinephrine on plasma cytokine levels in septic shock.We studied 394 patients in a randomized, controlled trial of vasopressin vs. norepinephrine in septic shock. We used hierarchical clustering and principal components analysis (PCA) of the baseline cytokine concentrations to subgroup cytokines; we then compared survivors to non-survivors (28-day) and compared vasopressin- vs. norepinephrine-induced changes in cytokine levels over 24 hours.Thirty-nine plasma cytokines were measured at baseline and 24 hours. Hierarchical clustering and PCA grouped cytokines similarly. Survivors (vs. non-survivors) had greater decreases of overall cytokine levels (p < 0.001). Vasopressin decreased overall 24-hour cytokine concentration compared to norepinephrine (p = 0.037). In less severe septic shock, the difference in plasma cytokine reduction over 24 hours between survivors and non-survivors was less pronounced than seen in more severe septic shock. Furthermore, vasopressin decreased IP-10 and GCSF more than did norepinephrine in less severe septic shock, whereas vasopressin decreased GMCSF in patients who had more severe shock.Survivors of septic shock had greater decreases of cytokines, chemokines and growth factors in early septic shock. Vasopressin decreased 24-hour plasma cytokine levels more than did norepinephrine. The vasopressin-associated decrease of cytokines differed according to severity of shock.

    View details for DOI 10.1164/rccm.201302-0355OC

    View details for Web of Science ID 000322617800017

    View details for PubMedID 23796235

  • Propofol infusion syndrome resuscitation with extracorporeal life support: a case report and review of the literature. Annals of intensive care Mayette, M., Gonda, J., Hsu, J. L., Mihm, F. G. 2013; 3 (1): 32-?

    Abstract

    We report a case of propofol infusion syndrome (PRIS) in a young female treated for status epilepticus. In this case, PRIS rapidly evolved to full cardiovascular collapse despite aggressive supportive care in the intensive care unit, as well as prompt discontinuation of the offending agent. She progressed to refractory cardiac arrest requiring emergent initiation of venoarterial extracorporeal membrane oxygenation (ECMO) during cardiopulmonary resuscitation (CPR). She regained a perfusing rhythm after prolonged (>8 hours) asystole, was weaned off ECMO and eventually all life support, and was discharged to home. We also present a review of the available literature on the use of ECMO for PRIS.

    View details for DOI 10.1186/2110-5820-3-32

    View details for PubMedID 24059786

  • The diagnostic yield of CT-guided percutaneous lung biopsy in solid organ transplant recipients CLINICAL TRANSPLANTATION Hsu, J. L., Kuschner, W. G., Paik, J., Bower, N., Guillamet, M. C., Kothary, N. 2012; 26 (4): 615-621

    Abstract

    Despite the widespread use of computed tomography(CT)-guided percutaneous lung biopsy (PLB) in immunocompetent patients, the diagnostic yield and safety in solid organ transplant (SOT)recipients is unknown. The purpose of this investigation was to determine the test performance of CT-PLB in SOT recipients.We performed a 10-yr single-center, retrospective analysis among heart, lung, kidney, and liver transplant recipients. We included all adult patients who underwent a PLB of a parenchymal lung nodule following their transplantation.Within the study period, 1754 SOTs were performed, of which 45 biopsies met study criteria. Overall, the incidence of PLB in SOT was 3%.PLB established a diagnosis in 24 of 45 cases. The yield of PLB was better for combined biopsy technique (fine-needle aspiration biopsy [FNAB]) and core biopsy than for FNAB alone (odds ratio [OR]: 4.2, 95% confidence interval [CI]: 1.2, 15.6), and for lesions that were malignant (OR: 10.0, 95%CI: 1.8, 75.4) or caused by an invasive fungal infection (OR: 5.0, 95% CI:1.1, 27.9). Complications occurred in 13% (6/45) of patients.CT-guided PLB is a safe modality that provides a moderate yield for diagnosing pulmonary nodules of malignant or fungal etiology in SOT recipients.

    View details for DOI 10.1111/j.1399-0012.2011.01582.x

    View details for Web of Science ID 000307344400032

    View details for PubMedID 23050274

  • Potential for overuse of corticosteroids and vasopressin in septic shock. Critical care (London, England) Hsu, J. L., Liu, V., Patterson, A. J., Martin, G. S., Nicolls, M. R., Russell, J. A. 2012; 16 (5): 447

    View details for PubMedID 23102413

  • Diagnosing invasive fungal disease in critically ill patients CRITICAL REVIEWS IN MICROBIOLOGY Hsu, J. L., Ruoss, S. J., Bower, N. D., Lin, M., Holodniy, M., Stevens, D. A. 2011; 37 (4): 277-312

    Abstract

    Fungal infections are increasing, with a changing landscape of pathogens and emergence of new groups at risk for invasive disease. We review current diagnostic techniques, focusing on studies in critically ill patients. Microbiological cultures, the current "gold standard", demonstrate poor sensitivity, thus diagnosis of invasive disease in the critically ill is difficult. This diagnostic dilemma results in under- or over-treatment of patients, potentially contributing to poor outcomes and antifungal resistance. While other current diagnostic tests perform moderately well, many lack timeliness, efficacy, and are negatively affected by treatments common to critically ill patients. New nucleic acid-based research is promising.

    View details for DOI 10.3109/1040841X.2011.581223

    View details for Web of Science ID 000295616800001

    View details for PubMedID 21749278

  • One-year outcomes of community-acquired and healthcare-associated pneumonia in the Veterans Affairs Healthcare System INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES Hsu, J. L., Siroka, A. M., Smith, M. W., Holodniy, M., Meduri, G. U. 2011; 15 (6): E382-E387

    Abstract

    While studies have demonstrated higher medium-term mortality for community-acquired pneumonia (CAP), mortality and costs have not been characterized for healthcare-associated pneumonia (HCAP) over a 1-year period.We conducted a retrospective cohort study to evaluate mortality rates and health system costs for patients with CAP or HCAP during initial hospitalization and for 1 year after hospital discharge. We selected 50 758 patients admitted to the Veterans Affairs (VA) healthcare system between October 2003 and May 2007. Main outcome measures included hospital, post-discharge, and cumulative mortality rates and cost during initial hospitalization and at 12 months following discharge.Hospital and 1-year HCAP mortality were nearly twice that of CAP. HCAP was an independent predictor for hospital mortality (odds ratio (OR) 1.62, 95% confidence interval (CI) 1.49-1.76) and 1-year mortality (OR 1.99, 95% CI 1.87-2.11) when controlling for demographics, comorbidities, pneumonia severity, and factors associated with multidrug-resistant infection, including immune suppression, previous antibiotic treatment, and aspiration pneumonia. HCAP patients consistently had higher mortality in each stratum of the Charlson-Deyo-Quan comorbidity index. HCAP patients incurred significantly greater cost during the initial hospital stay and in the following 12 months. Demographics and comorbid conditions, particularly aspiration pneumonia, accounted for 19-33% of this difference.HCAP represents a distinct category of pneumonia with particularly poor survival up to 1 year after hospital discharge. While comorbidities, pneumonia severity, and risk factors for multidrug-resistant infection may interact to produce even higher mortality compared to CAP, they alone do not explain the observed differences.

    View details for DOI 10.1016/j.ijid.2011.02.002

    View details for Web of Science ID 000290588800003

    View details for PubMedID 21393043

  • Understanding and Identifying Bias and Confounding in the Medical Literature SOUTHERN MEDICAL JOURNAL Hsu, J. L., Banerjee, D., Kuschner, W. G. 2008; 101 (12): 1240-1245

    Abstract

    Bias and confounding are types of error that may be encountered in the collection, analysis, or interpretation of research data. Bias and confounding may result in erroneous research conclusions with adverse consequences for patients and health care providers. In this article, we provide clinician-friendly descriptions and examples of bias (including surveillance, information, selection, lead, length, and publication) and confounding. The purpose of the article is to help clinicians to recognize two important sources of error in research and in turn to help clinicians to assess the validity and generalizability of a research report.

    View details for Web of Science ID 000261778000015

    View details for PubMedID 19005435

  • Epstein-Barr virus and breast cancer: State of the evidence for viral carcinogenesis CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Glaser, S. L., Hsu, J. L., Gulley, M. L. 2004; 13 (5): 688-697

    Abstract

    As the etiology and progression of breast cancer remain incompletely understood, novel routes of disease pathogenesis are important to consider. Viral pathogens have not been much explored, but recent interest has focused on Epstein-Barr virus (EBV). Studies of an association of this ubiquitous herpesvirus with breast cancer have had notably inconsistent results, marked by varying EBV presence (from 0% to 50% of tumors) and the absence of certain viral characteristics found in other EBV-related malignancies. The research has been plagued by the technical challenges of localizing EBV to tumor cells and by a tendency to overlook epidemiological cofactors, shown in all other EBV-related cancers to impact the EBV association. Breast cancer studies to date have used several viral detection methods of varying or uncertain sensitivity and specificity; most have involved small and/or poorly characterized case series and paid insufficient attention to epidemiological cofactors relevant to breast cancer and to EBV-related malignancies. Given these limitations and the established complexity of the connection of EBV with other cancers, a definitive judgment regarding the presence of this virus in breast cancer cannot yet be rendered. Recent advances in laboratory methodologies should help overcome the challenges of EBV detection in breast cancers. Further research is warranted, given the potential for an EBV association to inform not only breast cancer etiology but also early detection, treatment, and prevention.

    View details for Web of Science ID 000221573300001

    View details for PubMedID 15159298

  • Hodgkin's disease in Asians: incidence patterns and risk factors in population-based data LEUKEMIA RESEARCH Glaser, S. L., Hsu, J. L. 2002; 26 (3): 261-269

    Abstract

    Hodgkin's disease (HD) has been reported to be rare in Asians. Data sparseness has hindered studies exploring the relative contributions of environment and heredity to HD etiology, and individual risk factors have never been studied in an Asian population. With the most recent, uniformly collected population-based data from the US and Asia, we compared HD incidence rates in Chinese, Japanese, Filipinos, and Asian Indians in the US and in Asia. HD incidence rates were quite low in all Asian subgroups, but approximately double in US Asians as in native Asians. In both, rates were lower for Japanese and Chinese than for Filipinos and Asian Indians. A modest young-adult rate peak occurred for most US Asian groups, but not for any population in Asia. In data from a population-based case-control study of HD in San Francisco area women, young-adult Asian cases, like young-adult cases of other racial/ethnic groups, had childhood social environments indicative of less early contact with children. Given environmental and lifestyle differences between the US and Asia, the consistently low rates of HD in Asians suggest genetic resistance to disease development, possibly associated with HLA type. International and inter-ethnic differences, and risk factor patterns in case-control data, implicate environmental influences in the etiology of HD.

    View details for Web of Science ID 000174697000007

    View details for PubMedID 11792415

  • Epstein-Barr virus-associated malignancies: epidemiologic patterns and etiologic implications CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY Hsu, J. L., Glaser, S. L. 2000; 34 (1): 27-53

    Abstract

    Epstein-Barr virus (EBV), a ubiquitous B-lymphotrophic herpesvirus, has been found in the tumor cells of a heterogeneous group of malignancies (Burkitt's lymphoma, lymphomas associated with immunosuppression, other non-Hodgkin's lymphomas, Hodgkin's disease, nasopharyngeal carcinoma, gastric adenocarcinoma, lymphoepithelioma-like carcinomas, and immunodeficiency-related leiomyosarcoma). As the epidemiologic characteristics of these cancers have not been considered together, this review seeks to relate their incidence patterns and risk factors to EBV biology and virus-host interaction in an attempt to help elucidate factors involved in EBV-related carcinogenesis. We include a brief review of EBV virology and primary infection to provide a biologic context for considering the epidemiology, summarize the most salient epidemiologic features of each malignancy, synthesize epidemiologic data by risk factor to uncover commonalities and informative contrasts across the diseases, and propose hypotheses regarding etiologic mechanisms, based on the possible effect of the risk factors at various stages in the viral life cycle.

    View details for Web of Science ID 000087010800002

    View details for PubMedID 10781747

  • Absence of Epstein-Barr virus EBER-1 transcripts in an epidemiologically diverse group of breast cancers INTERNATIONAL JOURNAL OF CANCER Glaser, S. L., Ambinder, R. F., DiGiuseppe, J. A., Horn-Ross, P. L., Hsu, J. L. 1998; 75 (4): 555-558

    Abstract

    Epstein-Barr virus (EBV), a ubiquitous herpesvirus associated with certain lymphomas and carcinomas, has been identified within the malignant cells of a small proportion of breast tumors. As breast cancer is a very common malignancy in women, a pathogenetic role of EBV for even a subgroup of patients could have important implications for etiology and prevention. Therefore, we attempted to confirm the EBV-breast cancer association by exploring it in a representative case series stratified by characteristics that modify breast cancer risk. We studied a sample of 97 female and 28 male patients identified from a US population-based cancer registry. Patients were selected randomly within age, sex, ethnicity and tumor estrogen-receptor status groups. With their archived tumor tissues, we examined EBV presence using in situ hybridization for the EBER-1 transcript. In the 107 technically adequate specimens, we did not detect this viral transcript in any tumors, including one from a woman who also had an EBER-positive nasopharyngeal carcinoma. Our uniformly negative findings are extremely unlikely to have occurred by chance and cannot be attributed to selective sampling, as our study group included persons at diverse risk for breast cancer. We conclude that the EBV EBER-1 transcript is not commonly expressed in breast cancer, based on a broadly representative case series, though we cannot exclude an association of EBV within a particular population subgroup.

    View details for Web of Science ID 000071797400010

    View details for PubMedID 9466655

  • Racial/ethnic differences in breast cancer survival among San Francisco Bay Area women JOURNAL OF THE NATIONAL CANCER INSTITUTE Hsu, J. L., Glaser, S. L., West, D. W. 1997; 89 (17): 1311-1312

    View details for Web of Science ID A1997XU08000014

    View details for PubMedID 9293922

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