William James Collins

All Publications

• Adapted large language models can outperform medical experts in clinical text summarization. Nature medicine Van Veen, D., Van Uden, C., Blankemeier, L., Delbrouck, J. B., Aali, A., Bluethgen, C., Pareek, A., Polacin, M., Reis, E. P., Seehofnerová, A., Rohatgi, N., Hosamani, P., Collins, W., Ahuja, N., Langlotz, C. P., Hom, J., Gatidis, S., Pauly, J., Chaudhari, A. S. 2024

  Abstract

  Analyzing vast textual data and summarizing key information from electronic health records imposes a substantial burden on how clinicians allocate their time. Although large language models (LLMs) have shown promise in natural language processing (NLP) tasks, their effectiveness on a diverse range of clinical summarization tasks remains unproven. Here we applied adaptation methods to eight LLMs, spanning four distinct clinical summarization tasks: radiology reports, patient questions, progress notes and doctor-patient dialogue. Quantitative assessments with syntactic, semantic and conceptual NLP metrics reveal trade-offs between models and adaptation methods. A clinical reader study with 10 physicians evaluated summary completeness, correctness and conciseness; in most cases, summaries from our best-adapted LLMs were deemed either equivalent (45%) or superior (36%) compared with summaries from medical experts. The ensuing safety analysis highlights challenges faced by both LLMs and medical experts, as we connect errors to potential medical harm and categorize types of fabricated information. Our research provides evidence of LLMs outperforming medical experts in clinical text summarization across multiple tasks. This suggests that integrating LLMs into clinical workflows could alleviate documentation burden, allowing clinicians to focus more on patient care.

  View details for DOI 10.1038/s41591-024-02855-5

  View details for PubMedID 38413730

  View details for PubMedCentralID 5593724

• Clinical Text Summarization: Adapting Large Language Models Can Outperform Human Experts. Research square Veen, D. V., Uden, C. V., Blankemeier, L., Delbrouck, J. B., Aali, A., Bluethgen, C., Pareek, A., Polacin, M., Reis, E. P., Seehofnerova, A., Rohatgi, N., Hosamani, P., Collins, W., Ahuja, N., Langlotz, C., Hom, J., Gatidis, S., Pauly, J., Chaudhari, A. 2023

  Abstract

  Sifting through vast textual data and summarizing key information from electronic health records (EHR) imposes a substantial burden on how clinicians allocate their time. Although large language models (LLMs) have shown immense promise in natural language processing (NLP) tasks, their efficacy on a diverse range of clinical summarization tasks has not yet been rigorously demonstrated. In this work, we apply domain adaptation methods to eight LLMs, spanning six datasets and four distinct clinical summarization tasks: radiology reports, patient questions, progress notes, and doctor-patient dialogue. Our thorough quantitative assessment reveals trade-offs between models and adaptation methods in addition to instances where recent advances in LLMs may not improve results. Further, in a clinical reader study with ten physicians, we show that summaries from our best-adapted LLMs are preferable to human summaries in terms of completeness and correctness. Our ensuing qualitative analysis highlights challenges faced by both LLMs and human experts. Lastly, we correlate traditional quantitative NLP metrics with reader study scores to enhance our understanding of how these metrics align with physician preferences. Our research marks the first evidence of LLMs outperforming human experts in clinical text summarization across multiple tasks. This implies that integrating LLMs into clinical workflows could alleviate documentation burden, empowering clinicians to focus more on personalized patient care and the inherently human aspects of medicine.

  View details for DOI 10.21203/rs.3.rs-3483777/v1

  View details for PubMedID 37961377

  View details for PubMedCentralID PMC10635391

• Right Ventricular Dysfunction Patterns Among Patients with COVID-19 in the Intensive Care Unit - a Retrospective Cohort Analysis. Annals of the American Thoracic Society Sanchez, P. A., O'Donnell, C. T., Francisco, N., Santana, E. J., Moore, A. R., Pacheco-Navarro, A., Roque, J., Lebold, K. M., Parmer, C. M., Pienkos, S. M., Celestin, B. E., Levitt, J. E., Collins, W. J., Lanspa, M. J., Ashley, E. A., Wilson, J. G., Haddad, F., Rogers, A. J. 2023

  Abstract

  Right ventricular (RV) dysfunction is common among patients hospitalized with COVID-19; however, its epidemiology may depend on the echocardiographic parameters used to define it.To evaluate the prevalence of abnormalities in three common echocardiographic parameters of RV function among COVID-19 patients admitted to the intensive care unit, as well as the effect of RV dilatation on differential parameter abnormality and the association of RV dysfunction with 60-day mortality.Retrospective cohort study of COVID-19 ICU patients between March 4th,2020 to March 4th, 2021, who received a transthoracic echocardiogram within 48 hours before to at most 7 days after ICU admission. RV dysfunction and dilatation respectively defined by guideline thresholds for tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RVFAC), RV free wall longitudinal strain (RVFWS), and RV basal dimension or RV end-diastolic area. Association of RV dysfunction with 60-day mortality assessed through logistic regression adjusting for age, prior history of congestive heart failure, invasive ventilation at time of TTE and APACHE II score.116 patients were included, of which 69% had RV dysfunction by > 1 parameter and 36.3% of these had RV dilatation. The three most common patterns of RV dysfunction included: Presence of 3 abnormalities, the combination of abnormal RVFWS and TAPSE, and isolated TAPSE abnormality. Patients with RV dilatation had worse RVFAC (24% vs 36%, p = 0.001), worse RVFWS (16.3% vs 19.1%, p = 0.005), higher RVSP (45mmHg vs 31mmHg, p = 0.001) but similar TAPSE (13mm vs 13mm, p = 0.30) compared to those with normal RV size. After multivariable adjustment, 60-day mortality was significantly associated with RV dysfunction (OR 2.91, 95% CI 1.01 - 9.44), as was the presence of at least 2 parameter abnormalities.ICU patients with COVID-19 had significant heterogeneity in RV function abnormalities present with different patterns associated with RV dilatation. RV dysfunction by any parameter was associated with increased mortality. Therefore, a multiparameter evaluation may be critical in recognizing RV dysfunction in COVID-19.

  View details for DOI 10.1513/AnnalsATS.202303-235OC

  View details for PubMedID 37478340

• Transitioning from epicutaneous to oral peanut immunotherapy. Frontiers in allergy Wong, L., Kost, L., Anderson, B., Long, A., Sindher, S. B., Chinthrajah, R. S., Collins, W. J. 2023; 4: 1089308

  Abstract

  Epicutaneous immunotherapy (EPIT) has been tested in clinical trials for children with peanut allergy (PA) for its safety and efficacy in inducing desensitization. Aside from peanut avoidance and symptom management, oral immunotherapy (OIT) is another option for PA patients. However, OIT can be associated with adverse events and pose safety concerns to children and their caregivers.This study assessed 27 children who successfully completed a peanut EPIT trial. 18 of them transitioned to peanut OIT with starting doses ranging from 10-600 mg of peanut protein. Our aim was to learn more about the EPIT to OIT experience through descriptive survey responses and to gather information that may support the sequential use of the two immunotherapies for safe and positive outcomes that may not be achieved by either alone.Overall, children and their caregivers had less anxiety about starting OIT after having had peanut exposure through EPIT. Most children who transitioned from EPIT to OIT had no or minor symptoms initially, with symptoms lessening later in OIT. Most were also able to maintain or increase their peanut dose over time, achieving maintenance doses of 60-2,000 mg.In comparison with current literature on OIT for PA in children, the reported symptoms appeared less severe and less prevalent in the EPIT to OIT group. However, there were 3 participants who withdrew from OIT due to the development of intolerable symptoms. This study provides initial data in support of EPIT to OIT, and larger randomized controlled trials assessing effectiveness of the two therapies together are warranted.

  View details for DOI 10.3389/falgy.2023.1089308

  View details for PubMedID 36814725

  View details for PubMedCentralID PMC9939758

• The Effects of Long-term Food Oral Immunotherapy on Compliance, Quality of Life, and Perceived Burden of Care Tirumalasetty, J., Sullivan, L., Martinez, K., Collins, W., Albarran, M., Gajare, P., Kost, L., Chinthrajah, S., Sindher, S., Cao, S. MOSBY-ELSEVIER. 2023: AB29

  View details for Web of Science ID 000991651900084

• Association between Obesity and Length of COVID-19 Hospitalization: Unexpected Insights from the American Heart Association National COVID-19 Registry. Journal of obesity & metabolic syndrome Collins, W. J., Chang, A. Y., Weng, Y., Dahlen, A., O'Brien, C. G., Hom, J., Ahuja, N., Rodriguez, F., Rohatgi, N. 2022

  Abstract

  Background: Observational analyses have noted an association between obesity and poor clinical outcome from Coronavirus Disease 2019 (COVID-19). The mechanism for this finding remains unclear.Methods: We analyzed data from 22,915 COVID-19 patients hospitalized in non-intensive care units using the American Heart Association National COVID Registry of adult COVID-19 admissions from March 2020 to April 2021. A multivariable Poisson model adjusted for age, sex, medical history, admission respiratory status, hospitalization characteristics, and select laboratory findings was used to calculate length of stay (LOS) as a function of body mass index (BMI) category. Additionally, 5,327 patients admitted to intensive care units were similarly analyzed for comparison.Results: Relative to normal BMI subjects, overweight, class I obese, and class II obese patients had approximately half-day reductions in LOS (-0.469 days, P<0.01; -0.480 days, P<0.01; -0.578 days, P<0.01, respectively).Conclusion: The model identified a dose-dependent, inverse relationship between BMI category and LOS for COVID-19, which was not seen when the model was applied to critically ill patients.

  View details for DOI 10.7570/jomes22042

  View details for PubMedID 36058896

• Anti-nucleocapsid antibody levels and pulmonary comorbid conditions are linked to post-COVID-19 syndrome. JCI insight Jia, X., Cao, S., Lee, A. S., Manohar, M., Sindher, S. B., Ahuja, N., Artandi, M., Blish, C. A., Blomkalns, A. L., Chang, I., Collins, W. J., Desai, M., Din, H. N., Do, E., Fernandes, A., Geng, L. N., Rosenberg-Hasson, Y., Mahoney, M. R., Glascock, A. L., Chan, L. Y., Fong, S. Y., Phelps, M., Raeber, O., Purington, N., Röltgen, K., Rogers, A. J., Snow, T., Wang, T. T., Solis, D., Vaughan, L., Verghese, M., Maecker, H., Wittman, R., Puri, R., Kistler, A., Yang, S., Boyd, S. D., Pinsky, B. A., Chinthrajah, S., Nadeau, K. C. 2022; 7 (13)

  Abstract

  BACKGROUNDProlonged symptoms after SARS-CoV-2 infection are well documented. However, which factors influence development of long-term symptoms, how symptoms vary across ethnic groups, and whether long-term symptoms correlate with biomarkers are points that remain elusive.METHODSAdult SARS-CoV-2 reverse transcription PCR-positive (RT-PCR-positive) patients were recruited at Stanford from March 2020 to February 2021. Study participants were seen for in-person visits at diagnosis and every 1-3 months for up to 1 year after diagnosis; they completed symptom surveys and underwent blood draws and nasal swab collections at each visit.RESULTSOur cohort (n = 617) ranged from asymptomatic to critical COVID-19 infections. In total, 40% of participants reported at least 1 symptom associated with COVID-19 six months after diagnosis. Median time from diagnosis to first resolution of all symptoms was 44 days; median time from diagnosis to sustained symptom resolution with no recurring symptoms for 1 month or longer was 214 days. Anti-nucleocapsid IgG level in the first week after positive RT-PCR test and history of lung disease were associated with time to sustained symptom resolution. COVID-19 disease severity, ethnicity, age, sex, and remdesivir use did not affect time to sustained symptom resolution.CONCLUSIONWe found that all disease severities had a similar risk of developing post-COVID-19 syndrome in an ethnically diverse population. Comorbid lung disease and lower levels of initial IgG response to SARS-CoV-2 nucleocapsid antigen were associated with longer symptom duration.TRIAL REGISTRATIONClinicalTrials.gov, NCT04373148.FUNDINGNIH UL1TR003142 CTSA grant, NIH U54CA260517 grant, NIEHS R21 ES03304901, Sean N Parker Center for Allergy and Asthma Research at Stanford University, Chan Zuckerberg Biohub, Chan Zuckerberg Initiative, Sunshine Foundation, Crown Foundation, and Parker Foundation.

  View details for DOI 10.1172/jci.insight.156713

  View details for PubMedID 35801588

• Detailed characterization of hospitalized patients infected with the Omicron variant of SARS-CoV-2. Journal of internal medicine Ozdalga, E., Ahuja, N., Sehgal, N., Hom, J., Weng, Y., Pinsky, B., Schulman, K. A., Collins, W. 2022

  View details for DOI 10.1111/joim.13501

  View details for PubMedID 35417053

• Constrictive Pericarditis Revealing Rare Case of ALH Amyloidosis With Underlying Lymphoplasmacytic Lymphoma (Waldenstrom Macroglobulinemia). JACC. Case reports Ho, V. V., O'Sullivan, J. W., Collins, W. J., Ozdalga, E., Bell, C. F., Shah, N. D., Krishnam, M. S., Ozawa, M. G., Witteles, R. M. 2022; 4 (5): 271-275

  Abstract

  We present a case of pericardial amyloidosis with associated lymphoplasmacytic lymphoma in a patient with chronic worsening shortness of breath and cough. This case highlights the wide variation in the presentation of cardiac amyloidosis, and the rare occurrence of clinically significant light-chain and heavy-chain amyloidosis in the pericardium.(Level of Difficulty: Advanced.).

  View details for DOI 10.1016/j.jaccas.2022.01.007

  View details for PubMedID 35257101

• SARS-CoV-2 and Perceived Physical, Mental and Social Health in Northern California Fast, K., Lee, A., Hampton, Q., Chinthrajah, S., Sindher, S., Jia, X., Collins, W., Nadeau, K., Cao, S. MOSBY-ELSEVIER. 2022: AB46

  View details for Web of Science ID 000778999300137

• Feasibility of Virtual Reality Technology to Improve Experience During Pediatric Oral Food Challenge Collins, W., Adlou, B., Rodriguez, A., Albarran, M., O'Neal, E., Weiss, T., Hsu, K., Sindher, S., Bailenson, J., Caruso, T., Chinthrajah, S. MOSBY-ELSEVIER. 2022: AB108

  View details for Web of Science ID 000778999300326

• Self-reported food allergy-associated anxiety during oral immunotherapy declines with time Jiang, S., Cao, S., Collins, W., Fast, K., Hampton, Q., Landes, G., Martinez, K., Tang, H., Sindher, S., Chinthrajah, S. MOSBY-ELSEVIER. 2022: AB140

  View details for Web of Science ID 000778999300423

• Climate Change and Global Health: A Call to more Research and more Action. Allergy Agache, I., Sampath, V., Aguilera, J., Akdis, C., Akdis, M., Barry, M., Bouagnon, A., Chinthrajah, S., Collins, W., Dulitzki, C., Erny, B., Gomez, J., Goshua, A., Jutel, M., Kizer, K. W., Kline, O., LaBeaud, A. D., Pali-Scholl, I., Perrett, K. P., Peters, R. L., Plaza, M. P., Prunicki, M., Sack, T., Salas, R. N., Sindher, S. B., Sokolow, S. H., Thiel, C., Veidis, E., Wray, B. D., Traidl-Hoffmann, C., Witt, C., Nadeau, K. C. 1800

  Abstract

  There is increasing understanding, globally, that climate change and increased pollution will have a profound and mostly harmful effect on human health. This review brings together international experts to describe both the direct (such as heat waves) and indirect (such as vector-borne disease incidence) health impacts of climate change. These impacts vary depending on vulnerability (i.e., existing diseases) and the international, economic, political and environmental context. This unique review also expands on these issues to address a third category of potential longer-term impacts on global health: famine, population dislocation, and environmental justice and education. This scholarly resource explores these issues fully, linking them to global health in urban and rural settings in developed and developing countries. The review finishes with a practical discussion of action that health professionals around the world in our field can yet take.

  View details for DOI 10.1111/all.15229

  View details for PubMedID 35073410

• Building a Learning Health System: Creating an Analytical Workflow for Evidence Generation to Inform Institutional Clinical Care Guidelines. Applied clinical informatics Dash, D., Gokhale, A., Patel, B. S., Callahan, A., Posada, J., Krishnan, G., Collins, W., Li, R., Schulman, K., Ren, L., Shah, N. H. 2022; 13 (1): 315-321

  Abstract

  BACKGROUND: One key aspect of a learning health system (LHS) is utilizing data generated during care delivery to inform clinical care. However, institutional guidelines that utilize observational data are rare and require months to create, making current processes impractical for more urgent scenarios such as those posed by the COVID-19 pandemic. There exists a need to rapidly analyze institutional data to drive guideline creation where evidence from randomized control trials are unavailable.OBJECTIVES: This article provides a background on the current state of observational data generation in institutional guideline creation and details our institution's experience in creating a novel workflow to (1) demonstrate the value of such a workflow, (2) demonstrate a real-world example, and (3) discuss difficulties encountered and future directions.METHODS: Utilizing a multidisciplinary team of database specialists, clinicians, and informaticists, we created a workflow for identifying and translating a clinical need into a queryable format in our clinical data warehouse, creating data summaries and feeding this information back into clinical guideline creation.RESULTS: Clinical questions posed by the hospital medicine division were answered in a rapid time frame and informed creation of institutional guidelines for the care of patients with COVID-19. The cost of setting up a workflow, answering the questions, and producing data summaries required around 300hours of effort and $300,000 USD.CONCLUSION: A key component of an LHS is the ability to learn from data generated during care delivery. There are rare examples in the literature and we demonstrate one such example along with proposed thoughts of ideal multidisciplinary team formation and deployment.

  View details for DOI 10.1055/s-0042-1743241

  View details for PubMedID 35235994

• Asthma phenotypes, associated comorbidities, and long-term symptoms in COVID-19. Allergy Eggert, L. E., He, Z., Collins, W., Lee, A. S., Dhondalay, G., Jiang, S. Y., Fitzpatrick, J., Snow, T. T., Pinsky, B. A., Artandi, M., Barman, L., Puri, R., Wittman, R., Ahuja, N., Blomkalns, A., O'Hara, R., Cao, S., Desai, M., Sindher, S. B., Nadeau, K., Chinthrajah, R. S. 2021

  Abstract

  BACKGROUND: It is unclear if asthma and its allergic phenotype are risk factors for hospitalization or severe disease from SARS-CoV-2.METHODS: All patients over 28 days oldtesting positive for SARS-CoV-2 between March 1 and September 30, 2020, were retrospectively identified and characterized through electronic analysis at Stanford. A sub-cohort was followed prospectively to evaluate long-term COVID-19 symptoms.RESULTS: 168,190 patients underwent SARS-CoV-2 testing, and 6,976 (4.15%) tested positive. In a multivariate analysis, asthma was not an independent risk factor for hospitalization (OR 1.12 [95% CI 0.86, 1.45], p=0.40). Among SARS-CoV-2 positive asthmatics, allergic asthma lowered the risk of hospitalization and had a protective effect compared to non-allergic asthma (OR 0.52 (0.28, 0.91), p=0.026); there was no association between baseline medication use as characterized by GINA and hospitalization risk. Patients with severe COVID-19 disease had lower eosinophil levels during hospitalization compared to patients with mild or asymptomatic disease, independent of asthma status (p=0.0014). In a patient sub-cohort followed longitudinally, asthmatics and non-asthmatics had similar time to resolution of COVID-19 symptoms, particularly lower respiratory symptoms.CONCLUSIONS: Asthma is not a risk factor for more severe COVID-19 disease. Allergic asthmatics were half as likely to be hospitalized with COVID-19 compared to non-allergic asthmatics. Lower levels of eosinophil counts (allergic biomarkers) were associated with a more severe COVID-19 disease trajectory. Recovery was similar among asthmatics and non-asthmatics with over 50% of patients reporting ongoing lower respiratory symptoms three months post-infection.

  View details for DOI 10.1111/all.14972

  View details for PubMedID 34080210

• Vaccines and Allergic reactions: the past, the current COVID-19 pandemic, and future perspectives. Allergy Sampath, V., Rabinowitz, G., Shah, M., Jain, S., Diamant, Z., Jesenak, M., Rabin, R., Vieths, S., Agache, I., Akdis, M., Barber, D., Breiteneder, H., Chinthrajah, S., Chivato, T., Collins, W., Eiwegger, T., Fast, K., Fokkens, W., O'Hehir, R. E., Ollert, M., O'Mahony, L., Palomares, O., Pfaar, O., Riggioni, C., Shamji, M. H., Sokolowska, M., Torres, M. J., Traidl-Hoffmann, C., van Zelm, M., Wang, D. Y., Zhang, L., Akdis, C., Nadeau, K. C. 2021

  Abstract

  Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of individuals are vaccinated. The COVID-19 vaccines are expected to have similar positive impacts on health across the globe. While serious allergic reactions to vaccines are rare, their underlying mechanisms and implications for clinical management should be considered to provide individuals with the safest care possible. In this review, we provide an overview of different types of allergic adverse reactions that can potentially occur aftervaccination and individual vaccine components capable of causing the allergic adverse reactions. We present the incidence of allergic adverse reactions during clinical studies and through post-authorization and post-marketing surveillance and provide plausible causes of these reactions based on potential allergenic components present in several common vaccines. Additionally, we review implications for individual diagnosis and management and vaccine manufacturing overall. Finally, we suggest areas for future research.

  View details for DOI 10.1111/all.14840

  View details for PubMedID 33811364

• Asthma as a predictor of more severe outcomes in COVID-19 infection Eggert, L., Cao, S., He, Z., Dhondalay, G., Jiang, S., Collins, W., Sindher, S., Nadeau, K., Sharon Chinthrajah, R. MOSBY-ELSEVIER. 2021: AB44

  View details for Web of Science ID 000629158000139

• Virtual Reality Reduces Pediatric Anxiety During Food Allergy Clinical Trials: A Pilot Randomized, Pragmatic Study. Frontiers in allergy Alonzi, S., Caruso, T. J., Sindher, S. B., Cao, S., Varadharajulu, S., Collins, W. J., Chinthrajah, R. S. 2021; 2: 779804

  Abstract

  Phlebotomy procedures required in food allergy (FA) diagnosis and clinical trials often induce fear and anxiety for pediatric patients. The primary aim of this study was to determine whether virtual reality (VR) applications were effective in reducing anxiety for pediatric FA patients undergoing phlebotomy during FA clinical trials. Secondary aims assessed fear, pain, procedural compliance, and adverse events. Participants undergoing phlebotomy were enrolled and randomized to a VR group or standard of care (SOC) group for this prospective pilot randomized, pragmatic study. Participants in the VR group played interactive applications on a customized Samsung Gear VR headset and those in the SOC group received the standard of care. Participants' anxiety, fear, and pain were assessed with the Children's Anxiety Meter, Children's Fear Scale, and FACES pain scale pre, during, and post phlebotomy procedure. Compliance was assessed using the modified Induction Compliance Checklist during the procedure and compared between two groups. Forty-nine participants were randomized to VR (n = 26) and SOC (n = 23) groups. Although both the VR and SOC groups experienced a decrease in anxiety and fear from pre- to post-procedure, those in the VR group experienced less anxiety and fear during the procedure than SOC participants. Similarly, both groups experienced an increase in pain from pre- to post-procedure; however, the VR group reported less pain during the procedure than SOC. Fewer symptoms of procedural non-compliance were reported in the VR group. Interactive VR applications may be an effective tool for reducing fear, anxiety, and pain during phlebotomy for FA clinical trials.

  View details for DOI 10.3389/falgy.2021.779804

  View details for PubMedID 35387040

  View details for PubMedCentralID PMC8974765

• Asthma phenotypes, associated comorbidities, and long-term symptoms in COVID-19 European Journal of Allergy and Clinical Immunology Eggert, L. E., He, Z., Collins, W., Lee, A. S., Nadeau, K., Chinthrajah, R. 2021

  View details for DOI 10.1111/all.14972

• COVID-19 coagulopathy and thrombosis: Analysis of hospital protocols in response to the rapidly evolving pandemic THROMBOSIS RESEARCH Parks, A. L., Auerbach, A. D., Schnipper, J. L., Anstey, J. E., Sterken, D. G., Hecht, T. H., Fang, M. C., Vaughn, V. M., Dunn, A. S., Linker, A. S., Hunt, D. P., Choi, J. J., Brotman, D. J., Streiff, M. B., Mattison, M. P., Pappas, M. A., Greysen, S., Hemsey, D. F., Dapaah-Afriyie, K., Ahuja, N., Collins, W. J., Herzig, S. J., Bhandari, S., Schumacher, E. R., Duggirala, V. S., O'Leary, K. J., Menard, G. E., Lin, M. Y., Hosp Med Reengn Network HOMERuN 2020; 196: 355–58

  Abstract

  As the Coronavirus disease 2019 (COVID-19) pandemic spread to the US, so too did descriptions of an associated coagulopathy and thrombotic complications. Hospitals created institutional protocols for inpatient management of COVID-19 coagulopathy and thrombosis in response to this developing data. We collected and analyzed protocols from 21 US academic medical centers developed between January and May 2020. We found greatest consensus on recommendations for heparin-based pharmacologic venous thromboembolism (VTE) prophylaxis in COVID-19 patients without contraindications. Protocols differed regarding incorporation of D-dimer tests, dosing of VTE prophylaxis, indications for post-discharge pharmacologic VTE prophylaxis, how to evaluate for VTE, and the use of empiric therapeutic anticoagulation. These findings support ongoing efforts to establish international, evidence-based guidelines.

  View details for DOI 10.1016/j.thromres.2020.09.018

  View details for Web of Science ID 000592174300032

  View details for PubMedID 32977136

  View details for PubMedCentralID PMC7492800

• Perceived Burden of Treatment and Quality of Life in Long-Term Follow Up after Oral Immunotherapy in Food Allergic Patients Collins, W., Raeber, O., Tupa, D., Cao, S., Nadeau, K., Sindher, S., Chinthrajah, S. MOSBY-ELSEVIER. 2020: AB147

  View details for Web of Science ID 000517092700470

• NOTCH1 regulates matrix gla protein and calcification gene networks in human valve endothelium JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY White, M. P., Theodoris, C. V., Liu, L., Collins, W. J., Blue, K. W., Lee, J., Meng, X., Robbins, R. C., Ivey, K. N., Srivastava, D. 2015; 84: 13–23

  Abstract

  Valvular and vascular calcification are common causes of cardiovascular morbidity and mortality. Developing effective treatments requires understanding the molecular underpinnings of these processes. Shear stress is thought to play a role in inhibiting calcification. Furthermore, NOTCH1 regulates vascular and valvular endothelium, and human mutations in NOTCH1 can cause calcific aortic valve disease. Here, we determined the genome-wide impact of altering shear stress and NOTCH signaling on human aortic valve endothelium. mRNA-sequencing of primary human aortic valve endothelial cells (HAVECs) with or without knockdown of NOTCH1, in the presence or absence of shear stress, revealed NOTCH1-dependency of the atherosclerosis-related gene connexin 40 (GJA5), and numerous repressors of endochondral ossification. Among these, matrix gla protein (MGP) is highly expressed in aortic valve and vasculature, and inhibits soft tissue calcification by sequestering bone morphogenetic proteins (BMPs). Altering NOTCH1 levels affected MGP mRNA and protein in HAVECs. Furthermore, shear stress activated NOTCH signaling and MGP in a NOTCH1-dependent manner. NOTCH1 positively regulated endothelial MGP in vivo through specific binding motifs upstream of MGP. Our studies suggest that shear stress activates NOTCH1 in primary human aortic valve endothelial cells leading to downregulation of osteoblast-like gene networks that play a role in tissue calcification.

  View details for PubMedID 25871831

  View details for PubMedCentralID PMC4468000