Andra Leah Blomkalns

All Publications

• Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection. JAMA Thaweethai, T., Jolley, S. E., Karlson, E. W., Levitan, E. B., Levy, B., McComsey, G. A., McCorkell, L., Nadkarni, G. N., Parthasarathy, S., Singh, U., Walker, T. A., Selvaggi, C. A., Shinnick, D. J., Schulte, C. C., Atchley-Challenner, R., Horwitz, L. I., Foulkes, A. S., RECOVER Consortium, Alba, G. A., Alicic, R., Altman, N., Anglin, K., Argueta, U., Ashktorab, H., Baslet, G., Bassett, I. V., Bateman, L., Bedi, B., Bhattacharyya, S., Bind, M., Blomkalns, A. L., Bonilla, H., Bush, P. A., Castro, M., Chan, J., Charney, A. W., Chen, P., Chibnik, L. B., Chu, H. Y., Clifton, R. G., Costantine, M. M., Cribbs, S. K., Davila Nieves, S. I., Deeks, S. G., Duven, A., Emery, I. F., Erdmann, N., Erlandson, K. M., Ernst, K. C., Farah-Abraham, R., Farner, C. E., Feuerriegel, E. M., Fleurimont, J., Fonseca, V., Franko, N., Gainer, V., Gander, J. C., Gardner, E. M., Geng, L. N., Gibson, K. S., Go, M., Goldman, J. D., Grebe, H., Greenway, F. L., Habli, M., Hafner, J., Han, J. E., Hanson, K. A., Heath, J., Hernandez, C., Hess, R., Hodder, S. L., Hoffman, M. K., Hoover, S. E., Huang, B., Hughes, B. L., Jagannathan, P., John, J., Jordan, M. R., Katz, S. D., Kaufman, E. S., Kelly, J. D., Kelly, S. W., Kemp, M. M., Kirwan, J. P., Klein, J. D., Knox, K. S., Krishnan, J. A., Kumar, A., Laiyemo, A. O., Lambert, A. A., Lanca, M., Lee-Iannotti, J. K., Logarbo, B. P., Longo, M. T., Luciano, C. A., Lutrick, K., Maley, J. H., Marathe, J. G., Marconi, V., Marshall, G. D., Martin, C. F., Matusov, Y., Mehari, A., Mendez-Figueroa, H., Mermelstein, R., Metz, T. D., Morse, R., Mosier, J., Mouchati, C., Mullington, J., Murphy, S. N., Neuman, R. B., Nikolich, J. Z., Ofotokun, I., Ojemakinde, E., Palatnik, A., Palomares, K., Parimon, T., Parry, S., Patterson, J. E., Patterson, T. F., Patzer, R. E., Peluso, M. J., Pemu, P., Pettker, C. M., Plunkett, B. A., Pogreba-Brown, K., Poppas, A., Quigley, J. G., Reddy, U., Reece, R., Reeder, H., Reeves, W. B., Reiman, E. M., Rischard, F., Rosand, J., Rouse, D. J., Ruff, A., Saade, G., Sandoval, G. J., Schlater, S. M., Shepherd, F., Sherif, Z. A., Simhan, H., Singer, N. G., Skupski, D. W., Sowles, A., Sparks, J. A., Sukhera, F. I., Taylor, B. S., Teunis, L., Thomas, R. J., Thorp, J. M., Thuluvath, P., Ticotsky, A., Tita, A. T., Tuttle, K. R., Urdaneta, A. E., Valdivieso, D., VanWagoner, T. M., Vasey, A., Verduzco-Gutierrez, M., Wallace, Z. S., Ward, H. D., Warren, D. E., Weiner, S. J., Welch, S., Whiteheart, S. W., Wiley, Z., Wisnivesky, J. P., Yee, L. M., Zisis, S. 2023

  Abstract

  Importance: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals.Objective: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections.Design, Setting, and Participants: Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling.Exposure: SARS-CoV-2 infection.Main Outcomes and Measures: PASC and 44 participant-reported symptoms (with severity thresholds).Results: A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months.Conclusions and Relevance: A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.

  View details for DOI 10.1001/jama.2023.8823

  View details for PubMedID 37278994

• Deconvoluting complex correlates of COVID-19 severity with a multi-omic pandemic tracking strategy. Nature communications Parikh, V. N., Ioannidis, A. G., Jimenez-Morales, D., Gorzynski, J. E., De Jong, H. N., Liu, X., Roque, J., Cepeda-Espinoza, V. P., Osoegawa, K., Hughes, C., Sutton, S. C., Youlton, N., Joshi, R., Amar, D., Tanigawa, Y., Russo, D., Wong, J., Lauzon, J. T., Edelson, J., Mas Montserrat, D., Kwon, Y., Rubinacci, S., Delaneau, O., Cappello, L., Kim, J., Shoura, M. J., Raja, A. N., Watson, N., Hammond, N., Spiteri, E., Mallempati, K. C., Montero-Martín, G., Christle, J., Kim, J., Kirillova, A., Seo, K., Huang, Y., Zhao, C., Moreno-Grau, S., Hershman, S. G., Dalton, K. P., Zhen, J., Kamm, J., Bhatt, K. D., Isakova, A., Morri, M., Ranganath, T., Blish, C. A., Rogers, A. J., Nadeau, K., Yang, S., Blomkalns, A., O'Hara, R., Neff, N. F., DeBoever, C., Szalma, S., Wheeler, M. T., Gates, C. M., Farh, K., Schroth, G. P., Febbo, P., deSouza, F., Cornejo, O. E., Fernandez-Vina, M., Kistler, A., Palacios, J. A., Pinsky, B. A., Bustamante, C. D., Rivas, M. A., Ashley, E. A. 2022; 13 (1): 5107

  Abstract

  The SARS-CoV-2 pandemic has differentially impacted populations across race and ethnicity. A multi-omic approach represents a powerful tool to examine risk across multi-ancestry genomes. We leverage a pandemic tracking strategy in which we sequence viral and host genomes and transcriptomes from nasopharyngeal swabs of 1049 individuals (736 SARS-CoV-2 positive and 313 SARS-CoV-2 negative) and integrate them with digital phenotypes from electronic health records from a diverse catchment area in Northern California. Genome-wide association disaggregated by admixture mapping reveals novel COVID-19-severity-associated regions containing previously reported markers of neurologic, pulmonary and viral disease susceptibility. Phylodynamic tracking of consensus viral genomes reveals no association with disease severity or inferred ancestry. Summary data from multiomic investigation reveals metagenomic and HLA associations with severe COVID-19. The wealth of data available from residual nasopharyngeal swabs in combination with clinical data abstracted automatically at scale highlights a powerful strategy for pandemic tracking, and reveals distinct epidemiologic, genetic, and biological associations for those at the highest risk.

  View details for DOI 10.1038/s41467-022-32397-8

  View details for PubMedID 36042219

• 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

• Factors driving burnout and professional fulfillment among emergency medicine residents: A national wellness survey by the Society for Academic Emergency Medicine. AEM education and training Sakamoto, J. T., Lee, J., Lu, D. W., Sundaram, V., Bird, S. B., Blomkalns, A. L., Alvarez, A. 2022; 6 (Suppl 1): S5-S12

  Abstract

  This study aimed to identify rates of and contributors to burnout and professional fulfillment among emergency medicine (EM) resident physicians.This was a cross-sectional, national survey of resident members of the Society for Academic Emergency Medicine (SAEM). Primary outcomes were burnout and professional fulfillment measured using a previously validated instrument with additional domains pertaining to the academic environment. The survey included question domains examining organizational factors (e.g., academic work environment, satisfaction with training, electronic health records, values alignment, and control over schedule) and individual factors (e.g., self-compassion, meaningfulness of clinical work, impact of work on health and personal relationships, perceived appreciation, thoughts of attrition, and expectations of the field of EM). Logistic regression was performed to determine the relationships between the primary outcomes and each domain.The survey was sent electronically to 2641 SAEM resident members. A total of 275 residents completed the survey with a response rate of 10.4%. A total of 151 (55%) respondents were male, and 210 (76%) were White. A total of 132 (48%) residents reported burnout, and 75 (28%) reported professional fulfillment. All organizational and individual factors were significantly associated with both primary outcomes. EM residents reported that meaningfulness of clinical work had the most significant positive association with professional fulfillment (adjusted odds ratio [OR] 2.2 [95% confidence interval {CI} 1.8-2.7]) and negative association with burnout (adjusted OR 0.46 [95% CI 0.37-0.56]). Thoughts of attrition from academics and accurate expectations of EM were also associated with both primary outcomes, with adjusted ORs (95% CIs) of 0.40 (0.21-0.72) and 5.6 (1.9-23.8) for professional fulfillment and 4.1 (2.5-7.1) and 0.19 (0.08-0.40) for burnout, respectively.This study found a high prevalence of burnout and a low prevalence of professional fulfillment among EM residents. Multiple factors were significantly associated with each occupational phenomenon, with meaningfulness of clinical work demonstrating the strongest relationships with burnout and professional fulfillment.

  View details for DOI 10.1002/aet2.10746

  View details for PubMedID 35783080

  View details for PubMedCentralID PMC9222870

• Factors driving burnout and professional fulfillment among emergency medicine residents: A national wellness survey by the Society for Academic Emergency Medicine AEM EDUCATION AND TRAINING Sakamoto, J. T., Lee, J., Lu, D. W., Sundaram, V., Bird, S. B., Blomkalns, A. L., Alvarez, A. 2022; 6: S5-S12

  View details for DOI 10.1002/aet2.10746

  View details for Web of Science ID 000814784200001

• Taking Aim at the Injury Prevention Curriculum: Educating Residents on Talking to Patients About Firearm Injury. Academic medicine : journal of the Association of American Medical Colleges Mueller, K. L., Blomkalns, A. L., Ranney, M. L. 2022

  Abstract

  The medical community recognizes that firearm injury is a public health problem. Yet we lack both the tools for and the implementation of evidence-based firearm injury screening and counseling techniques. One reason for these deficits is the lack of clinical training related to engaging patients in firearm injury risk reduction. In this issue, Rickert et al describe a pre-post evaluation of a 2-part firearm injury prevention training curriculum for first-year medical residents at a single academic medical center. Their manuscript serves an important, but still preliminary, step forward for the field of postgraduate medical education on firearm injury and its prevention. Important elements of this project and paper consist of the inclusion of multiple medical disciplines and the use of standardized patients to evaluate participants' learning. This project also points to the need for further growth. We must commit to consistently and conscientiously framing injuries from guns not as "gun violence" but rather as "firearm injuries" to ensure that they are considered squarely in both the public health space and the clinical space. An ideal curriculum would also highlight the importance of trauma-informed care, cultural competency, and antiracist medical practice while countering implicit biases (e.g., towards gun owners, victims of firearm violence, perpetrators of violence). It should address barriers, as well as facilitators, to change. And most importantly, future educational work must evaluate the effect of these trainings on actual clinical practice-and, even better, the efficacy of education in changing behavior and patient-level outcomes.

  View details for DOI 10.1097/ACM.0000000000004707

  View details for PubMedID 35442908

• Drivers of Professional Fulfillment and Burnout Among Emergency Medicine Faculty: A National Wellness Survey by the Society for Academic Emergency Medicine. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine Lu, D. W., Lee, J., Alvarez, A., Sakamoto, J. T., Bird, S. B., Sundaram, V., Lall, M. D., Nordenholz, K. E., Manfredi, R. A., Blomkalns, A. L. 2022

  Abstract

  BACKGROUND: Professional fulfillment and the mitigation of burnout can enhance clinician well-being and the resiliency of the healthcare organization. This study examined the extent to which specific individual and workplace factors are associated with professional fulfillment and burnout among a national sample of academic emergency physicians.METHODS: This was a cross-sectional survey of faculty members of the Society for Academic Emergency Medicine. Primary outcomes were professional fulfillment and burnout. The survey also examined individual and workplace factors, as well as faculty's thoughts of attrition from academic and clinical medicine. Logistic regression was performed to determine the relationships between each outcome and each factor, respectively.RESULTS: 771 out of 3130 faculty completed the survey (response rate 24.6%). 38.7% reported professional fulfillment and 39.1% reported burnout. Meaningfulness of work (OR 2.2, 95% CI 1.9-2.5), perceived appreciation (OR 1.9, 95% CI 1.7-2.1), and the academic work environment (OR 1.7, 95% CI 1.5-1.9) had the highest odds of being associated with professional fulfillment. In contrast, low score responses for meaningfulness of work (OR 0.6, 95% CI 0.5-0.6), self-compassion (0.6, 95% CI 0.5-0.6), and control over schedule (OR 0.6, 95% CI 0.6-0.7) were most associated with burnout. Faculty with professional fulfillment were less likely to report plans for attrition from academics (OR 0.1, 95% CI 0.1-0.2) and from clinical medicine (OR 0.2, 95% CI 0.1-0.4). Faculty with burnout were more likely to report plans for attrition from academics (OR 7, 95% CI 4.8-10.4) and clinical medicine (OR 5.7, 95% CI 3.9-8.6).CONCLUSIONS: Individual and workplace factors that contributed to professional fulfillment and burnout were identified, with meaningfulness of clinical work demonstrating the strongest association with both occupational phenomena. Knowledge of which factors are most impactful in promoting professional fulfillment and mitigating burnout may be useful in guiding efforts to enhance clinician well-being.

  View details for DOI 10.1111/acem.14487

  View details for PubMedID 35304931

• Role of prostaglandin D2 receptors in the pathogenesis of abdominal aortic aneurysm formation. Clinical science (London, England : 1979) Weintraub, N. L., Blomkalns, A. L., Ogbi, M., Horimatsu, T., Benson, T. W., Huo, Y., Fulton, D., Agarwal, G., Lee, R., Winkler, M. A., Young, L., Fujise, K., Guha, A., Fukai, T., Ushio-Fukai, M., Long, X., Annex, B., Kim, H. W. 2022

  Abstract

  PGD2 released from immune cells or other cell types activates its receptors, DP1 and DP2, to promote inflammatory responses in allergic and lung diseases. Prostaglandin-mediated inflammation may also contribute to vascular diseases such as abdominal aortic aneurysms (AAA). However, the role of DP receptors in the pathogenesis of AAA has not been systematically investigated. In this study, DP1 deficient mice and pharmacological inhibitors of either DP1 or DP2 were tested in two distinct mouse models of AAA formation: angiotensin II (AngII) infusion and calcium chloride (CaCl2) application. DP1 deficient mice [both heterozygous (DP1+/-) and homozygous (DP1-/-)] were protected against CaCl2-induced AAA formation, in conjunction with decreased MMP activity and adventitial inflammatory cell infiltration. In the AngII infusion model, DP1+/- mice, but not DP1-/- mice, exhibited reduced AAA formation. Interestingly, compensatory upregulation of the DP2 receptor was detected in DP1-/- mice in response to AngII infusion, suggesting a potential role for DP2 receptors in AAA. Treatment with selective antagonists of DP1 (laropiprant) or DP2 (fevipiprant) protected against AAA formation, in conjunction with reduced elastin degradation and aortic inflammatory responses. In conclusion, PGD2 signaling contributes to AAA formation in mice, suggesting that antagonists of DP receptors, which have been extensively tested in allergic and lung diseases, may be promising candidates to ameliorate AAA.

  View details for DOI 10.1042/CS20220031

  View details for PubMedID 35132998

• Institutional Solutions Addressing Disparities in Compensation and Advancement of Emergency Medicine Physicians: A Critical Appraisal of Gaps and Associated Recommendations. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine Madsen, T. E., Heron, S., Lall, M. D., Blomkalns, A., Arbelaez, C., Lopez, B., Lin, M., Rounds, K., Sethuraman, K. N., Safdar, B. 1800

  Abstract

  BACKGROUND: Disparities in salary and advancement of emergency medicine (EM) faculty by race and gender have been consistently demonstrated for over three decades. Prior studies have largely focused on individual-level solutions. To identify systems-based interventions, the Society of Academic Emergency Medicine (SAEM) formed the Research Equity Task Force in 2018 with members from multiple academies (the Academy of Academic Chairs in Emergency Medicine (AACEM), the Academy of Academic Administrators in Emergency Medicine (AAAEM), the Academy for Women in Academic Emergency Medicine (AWAEM), and the Academy for Diversity and Inclusion in Emergency Medicine (ADIEM), and sought recommendations from EM departmental leaders.METHODS: The taskforce conducted interviews containing both open-ended narrative and closed-ended questions in multiple phases. Phase 1 included a convenience sample of chairs of EM departments across the U.S., and phase 2 included vice-chairs and other faculty who lead promotion and advancement. The taskforce identified common themes from the interviews and then developed three-tiered sets of recommendations (minimal, target, and aspirational) based on participant responses. In phase 3, iterative feedback was collected and implemented on these recommendations from study participants and chairs participating in a national AACEM webinar.RESULTS: In findings from 53 interviews of chairs, vice-chairs, and faculty leaders from across the U.S., we noted heterogeneity in the faculty development and promotion processes across institutions. Four main themes were identified from the interviews: the need for a directed, structured promotion process, provision of structured mentorship, clarity on requirements for promotion within tracks, and transparency in salary structure. Recommendations were developed to address gaps in structured mentorship and equitable promotion and compensation.CONCLUSIONS: These recommendations for AEM departments have the potential to increase structured mentorship programs, improve equity in promotion and advancement, and reduce disparities in the AEM workforce. These recommendations have been endorsed by SAEM, AACEM, AWAEM, and ADIEM.

  View details for DOI 10.1111/acem.14452

  View details for PubMedID 35064998

• Association Between SARS-CoV-2 RNAemia and Postacute Sequelae of COVID-19. Open forum infectious diseases Ram-Mohan, N., Kim, D., Rogers, A. J., Blish, C. A., Nadeau, K. C., Blomkalns, A. L., Yang, S. 2022; 9 (2): ofab646

  Abstract

  Determinants of Post-Acute Sequelae of COVID-19 are not known. Here we show that 83.3% of patients with viral RNA in blood (RNAemia) at presentation were symptomatic in the post-acute phase. RNAemia at presentation successfully predicted PASC, independent of patient demographics, worst disease severity, and length of symptoms.

  View details for DOI 10.1093/ofid/ofab646

  View details for PubMedID 35111870

  View details for PubMedCentralID PMC8802799

• Feasibility of Specimen Self-collection in Young Children Undergoing SARS-CoV-2 Surveillance for In-Person Learning. JAMA network open Altamirano, J., Lopez, M., Robinson, I. G., Chun, L. X., Tam, G. K., Shaikh, N. J., Hoyte, E. G., Carrington, Y. J., Jani, S. G., Toomarian, E. Y., Hsing, J. C., Ma, J., Pulendran, U., Govindarajan, P., Blomkalns, A. L., Pinsky, B. A., Wang, C. J., Maldonado, Y. 2022; 5 (2): e2148988

  Abstract

  There is an urgent need to assess the feasibility of COVID-19 surveillance measures in educational settings.To assess whether young children can feasibly self-collect SARS-CoV-2 samples for surveillance testing over the course of an academic year.This prospective pilot cohort study was conducted from September 10, 2020, to June 10, 2021, at a K-8 school in San Mateo County, California. The research consisted of quantitative data collection efforts: (1) demographic data collected, (2) student sample self-collection error rates, and (3) student sample self-collection time durations. Students were enrolled in a hybrid learning model, a teaching model in which students were taught in person and online, with students having the option to attend virtually as needed. Data were collected under waiver of consent from students participating in weekly SARS-CoV-2 testing.Errors over time for self-collection of nasal swabs such as contaminated swabs and inadequate or shallow swabbing; time taken for sample collection.Of 296 participants, 148 (50.0%) were boys and 148 (50.0%) were girls. A total of 87 participants (29.2%) identified as Asian; 2 (0.6%), Black or African American; 13 (4.4%), Hispanic/Latinx; 103 (34.6%), non-Hispanic White; 87 (29.2%), multiracial; and 6 (2.0%), other. The median school grade was fourth grade. From September 2020 to March 2021, a total of 4203 samples were obtained from 221 students on a weekly basis, while data on error rates were collected. Errors occurred in 2.7% (n = 107; 95% CI, 2.2%-3.2%) of student encounters, with the highest rate occurring on the first day of testing (20 [10.2%]). There was an overall decrease in error rates over time. From April to June 2021, a total of 2021 samples were obtained from 296 students on a weekly basis while data on encounter lengths were collected. Between April and June 2021, 193 encounters were timed. The mean duration of each encounter was 70 seconds (95% CI, 66.4-73.7 seconds).Mastery of self-collected lower nasal swabs is possible for children 5 years and older. Testing duration can be condensed once students gain proficiency in testing procedures. Scalability for larger schools is possible if consideration is given to the resource-intensive nature of the testing and the setting's weather patterns.

  View details for DOI 10.1001/jamanetworkopen.2021.48988

  View details for PubMedID 35175340

• Assessment of Allergic and Anaphylactic Reactions to mRNA COVID-19 Vaccines With Confirmatory Testing in a US Regional Health System. JAMA network open Warren, C. M., Snow, T. T., Lee, A. S., Shah, M. M., Heider, A., Blomkalns, A., Betts, B., Buzzanco, A. S., Gonzalez, J., Chinthrajah, R. S., Do, E., Chang, I., Dunham, D., Lee, G., O'Hara, R., Park, H., Shamji, M. H., Schilling, L., Sindher, S. B., Sisodiya, D., Smith, E., Tsai, M., Galli, S. J., Akdis, C., Nadeau, K. C. 2021; 4 (9): e2125524

  Abstract

  Importance: As of May 2021, more than 32 million cases of COVID-19 have been confirmed in the United States, resulting in more than 615 000 deaths. Anaphylactic reactions associated with the Food and Drug Administration (FDA)-authorized mRNA COVID-19 vaccines have been reported.Objective: To characterize the immunologic mechanisms underlying allergic reactions to these vaccines.Design, Setting, and Participants: This case series included 22 patients with suspected allergic reactions to mRNA COVID-19 vaccines between December 18, 2020, and January 27, 2021, at a large regional health care network. Participants were individuals who received at least 1 of the following International Statistical Classification of Diseases and Related Health Problems, Tenth Revision anaphylaxis codes: T78.2XXA, T80.52XA, T78.2XXD, or E949.9, with documentation of COVID-19 vaccination. Suspected allergy cases were identified and invited for follow-up allergy testing.Exposures: FDA-authorized mRNA COVID-19 vaccines.Main Outcomes and Measures: Allergic reactions were graded using standard definitions, including Brighton criteria. Skin prick testing was conducted to polyethylene glycol (PEG) and polysorbate 80 (P80). Histamine (1 mg/mL) and filtered saline (negative control) were used for internal validation. Basophil activation testing after stimulation for 30 minutes at 37 °C was also conducted. Concentrations of immunoglobulin (Ig) G and IgE antibodies to PEG were obtained to determine possible mechanisms.Results: Of 22 patients (20 [91%] women; mean [SD] age, 40.9 [10.3] years; 15 [68%] with clinical allergy history), 17 (77%) met Brighton anaphylaxis criteria. All reactions fully resolved. Of patients who underwent skin prick tests, 0 of 11 tested positive to PEG, 0 of 11 tested positive to P80, and 1 of 10 (10%) tested positive to the same brand of mRNA vaccine used to vaccinate that individual. Among these same participants, 10 of 11 (91%) had positive basophil activation test results to PEG and 11 of 11 (100%) had positive basophil activation test results to their administered mRNA vaccine. No PEG IgE was detected; instead, PEG IgG was found in tested individuals who had an allergy to the vaccine.Conclusions and Relevance: Based on this case series, women and those with a history of allergic reactions appear at have an elevated risk of mRNA vaccine allergy. Immunological testing suggests non-IgE-mediated immune responses to PEG may be responsible in most individuals.

  View details for DOI 10.1001/jamanetworkopen.2021.25524

  View details for PubMedID 34533570

• Empowering patients: simplifying discharge instructions. BMJ open quality DeSai, C., Janowiak, K., Secheli, B., Phelps, E., McDonald, S., Reed, G., Blomkalns, A. 2021; 10 (3)

  Abstract

  Patients who do not have enough information about their discharge plans have decreased treatment compliance, decreased patient safety, increased emergency department (ED) recidivism, and poor satisfaction. This project aimed to develop and implement a method to assess and improve patient understanding of treatment and discharge plan in the ED. The authors developed a questionnaire to assess patient knowledge using Centers for Medicare and Medicaid Services and Joint Commission recommendations, areas of communication deficits reported in other manuscripts, and ED staff and provider input. Responses from patient interviews were then scored against the medical record. Three trained scorers graded all responses, and inter-rater reliability was calculated using the kappa statistic.Baseline observations found that written discharge instructions were long and tedious, and important information was difficult to find. Based on initial patient scores, stakeholder interviews, and fishbone diagrams, the team developed a one-page simplified information page (SIP) targeted to inform patients their most relevant discharge instructions. Next, the SIP was tested on 118 patients to measure its effect on patient understanding. At the baseline study, no patients had complete understanding of their discharge instructions. The areas of lowest scores were medication instructions and indications to return to the ED. Implementation of the SIP resulted in statistically significant changes in score distribution across all questions assessed with the Wilcoxon signed-rank test. Interrater reliability between scorers was high (kappa=0.84). We incorporated the concept of the SIP to the cover page of our standard discharge instructions.Healthcare providers often spend valuable time educating their patients, and it is important to assess the effectiveness of this teaching to identify areas in which we may improve health literacy and patient understanding. This project has shown that a simple, easy-to-read, concise page developed with patient input significantly improved ED discharge instruction knowledge.

  View details for DOI 10.1136/bmjoq-2021-001419

  View details for PubMedID 34521621

• Multi-omic profiling reveals widespread dysregulation of innate immunity and hematopoiesis in COVID-19. The Journal of experimental medicine Wilk, A. J., Lee, M. J., Wei, B., Parks, B., Pi, R., Martinez-Colon, G. J., Ranganath, T., Zhao, N. Q., Taylor, S., Becker, W., Stanford COVID-19 Biobank, Jimenez-Morales, D., Blomkalns, A. L., O'Hara, R., Ashley, E. A., Nadeau, K. C., Yang, S., Holmes, S., Rabinovitch, M., Rogers, A. J., Greenleaf, W. J., Blish, C. A. 2021; 218 (8)

  Abstract

  Our understanding of protective versus pathological immune responses to SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is limited by inadequate profiling of patients at the extremes of the disease severity spectrum. Here, we performed multi-omic single-cell immune profiling of 64 COVID-19 patients across the full range of disease severity, from outpatients with mild disease to fatal cases. Our transcriptomic, epigenomic, and proteomic analyses revealed widespread dysfunction of peripheral innate immunity in severe and fatal COVID-19, including prominent hyperactivation signatures in neutrophils and NK cells. We also identified chromatin accessibility changes at NF-kappaB binding sites within cytokine gene loci as a potential mechanism for the striking lack of pro-inflammatory cytokine production observed in monocytes in severe and fatal COVID-19. We further demonstrated that emergency myelopoiesis is a prominent feature of fatal COVID-19. Collectively, our results reveal disease severity-associated immune phenotypes in COVID-19 and identify pathogenesis-associated pathways that are potential targets for therapeutic intervention.

  View details for DOI 10.1084/jem.20210582

  View details for PubMedID 34128959

• 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

• SARS-CoV-2 IgG Seropositivity and Acute Asymptomatic Infection Rate Among Firefighter First Responders in an Early Outbreak County in California. Prehospital emergency care : official journal of the National Association of EMS Physicians and the National Association of State EMS Directors Newberry, J. A., Gautreau, M., Staats, K., Carrillo, E., Mulkerin, W., Yang, S., Kohn, M. A., Matheson, L., Boyd, S. D., Pinsky, B. A., Blomkalns, A. L., Strehlow, M. C., D'Souza, P. A. 2021: 1–10

  Abstract

  Objective: Firefighter first responders and other emergency medical services (EMS) personnel have been among the highest risk healthcare workers for illness during the SARS-CoV-2 pandemic. We sought to determine the rate of seropositivity for SARS-CoV-2 IgG antibodies and of acute asymptomatic infection among firefighter first responders in a single county with early exposure in the pandemic.Methods: We conducted a cross-sectional study of clinically active firefighters cross-trained as paramedics or EMTs in the fire departments of Santa Clara County, California. Firefighters without current symptoms were tested between June and August 2020. Our primary outcomes were rates of SARS-CoV-2 IgG antibody seropositivity and SARS-CoV-2 RT-PCR swab positivity for acute infection. We report cumulative incidence, participant characteristics with frequencies and proportions, and proportion positive and associated relative risk (with 95% confidence intervals).Results: We enrolled 983 out of 1339 eligible participants (response rate: 73.4%). Twenty-five participants (2.54%, 95% CI 1.65-3.73) tested positive for IgG antibodies and 9 (0.92%, 95% CI 0.42-1.73) tested positive for SARS-CoV-2 by RT-PCR. Our cumulative incidence, inclusive of self-reported prior positive PCR tests, was 34 (3.46%, 95% CI 2.41-4.80).Conclusion: In a county with one of the earliest outbreaks in the United States, the seroprevalence among firefighter first responders was lower than that reported by other studies of frontline health care workers, while the cumulative incidence remained higher than that seen in the surrounding community.

  View details for DOI 10.1080/10903127.2021.1912227

  View details for PubMedID 33819128

• Establishing a Data Science Unit in an Academic Medical Center: An Illustrative Model. Academic medicine : journal of the Association of American Medical Colleges Desai, M., Boulos, M., Pomann, G. M., Steinberg, G. K., Longo, F. M., Leonard, M., Montine, T., Blomkalns, A. L., Harrington, R. A. 2021

  Abstract

  The field of data science has great potential to address critical questions relevant for academic medical centers. Data science initiatives are consequently being established within academic medicine. At the cornerstone of such initiatives are scientists who practice data science. These scientists include biostatisticians, clinical informaticians, database and software developers, computational scientists, and computational biologists. Too often, however, those involved in the practice of data science are viewed by academic leadership as providing a noncomplex service to facilitate research and further the careers of other academic faculty. The authors contend that the success of data science initiatives relies heavily on the understanding that the practice of data science is a critical intellectual contribution to the overall science conducted at an academic medical center. Further, careful thought by academic leadership is needed for allocation of resources devoted to the practice of data science. At the Stanford University School of Medicine, the authors have developed an innovative model for a data science collaboratory based on 4 fundamental elements: an emphasis on collaboration over consultation; a subscription-based funding mechanism that reflects commitment by key partners; an investment in the career development of faculty who practice data science; and a strong educational component for data science members in team science and for clinical and translational investigators in data science. As data science becomes increasingly essential to learning health systems, centers that specialize in the practice of data science are a critical component of the research infrastructure and intellectual environment of academic medical centers.

  View details for DOI 10.1097/ACM.0000000000004079

  View details for PubMedID 33769342

• SARS-CoV-2 RNAemia predicts clinical deterioration and extrapulmonary complications from COVID-19. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Ram-Mohan, N. n., Kim, D. n., Zudock, E. J., Hashemi, M. M., Tjandra, K. C., Rogers, A. J., Blish, C. A., Nadeau, K. C., Newberry, J. A., Quinn, J. V., O'Hara, R. n., Ashley, E. n., Nguyen, H. n., Jiang, L. n., Hung, P. n., Blomkalns, A. L., Yang, S. n. 2021

  Abstract

  The determinants of COVID-19 disease severity and extrapulmonary complications (EPCs) are poorly understood. We characterized relationships between SARS-CoV-2 RNAemia and disease severity, clinical deterioration, and specific EPCs.We used quantitative (qPCR) and digital (dPCR) PCR to quantify SARS-CoV-2 RNA from plasma in 191 patients presenting to the Emergency Department (ED) with COVID-19. We recorded patient symptoms, laboratory markers, and clinical outcomes, with a focus on oxygen requirements over time. We collected longitudinal plasma samples from a subset of patients. We characterized the role of RNAemia in predicting clinical severity and EPCs using elastic net regression.23.0% (44/191) of SARS-CoV-2 positive patients had viral RNA detected in plasma by dPCR, compared to 1.4% (2/147) by qPCR. Most patients with serial measurements had undetectable RNAemia within 10 days of symptom onset, reached maximum clinical severity within 16 days, and symptom resolution within 33 days. Initially RNAaemic patients were more likely to manifest severe disease (OR 6.72 [95% CI, 2.45 - 19.79]), worsening of disease severity (OR 2.43 [95% CI, 1.07 - 5.38]), and EPCs (OR 2.81 [95% CI, 1.26 - 6.36]). RNA load correlated with maximum severity (r = 0.47 [95% CI, 0.20 - 0.67]).dPCR is more sensitive than qPCR for the detection of SARS-CoV-2 RNAemia, which is a robust predictor of eventual COVID-19 severity and oxygen requirements, as well as EPCs. Since many COVID-19 therapies are initiated on the basis of oxygen requirements, RNAemia on presentation might serve to direct early initiation of appropriate therapies for the patients most likely to deteriorate.

  View details for DOI 10.1093/cid/ciab394

  View details for PubMedID 33949665

• Emergency Medicine Research: 2030 Strategic Goals. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine Neumar, R. W., Blomkalns, A. L., Cairns, C. B., D'Onofrio, G., Kuppermann, N., Lewis, R. J., Newgard, C. D., O'Neil, B. J., Rathlev, N. K., Rothman, R. E., Wright, D. W. 2021

  Abstract

  All academic medical specialties have the obligation to continuously create new knowledge that will improve patient care and outcomes. Emergency medicine (EM) is no exception. Since its origins over 50 year ago, EM has struggled to fulfill its research mission. EM ranks last among clinical specialties in the percent of medical school faculty who are NIH-funded principal investigators (PIs) (1.7%) and percent of medical school departments with NIH-funded PIs (33%). Although there has been a steady increase in the number of NIH-funded projects and total NIH dollars, the slowing growth in the number of NIH-funded PIs and lack of growth in the number of EM departments with NIH-funded PIs is cause for concern. In response, the AACEM Research Task Force proposes a set of 2030 strategic goals for the EM research enterprise that are based on sustaining historic growth rates in NIH-funding. These goals have been endorsed by the AACEM Executive committee and the Boards of SAEM, ACEP, and AAEM. The 2030 strategic goals include 200 NIH-funded projects led by 150 EM PIs in at least 50 EM Depts with over $100M in annual funding resulting in over 3% of EM faculty being NIH-funded PIs. Achieving these goals will require a targeted series of focused strategies to increase the number of EM faculty who are competitive for NIH funding. This requires a coordinated, intentional effort with investments at the national, departmental, and individual levels. These efforts are ideally led by medical school department chairs, who can create the culture and provide the resources needed to be successful. The specialty of EM has the obligation to improve the health of the public and to fulfill its research mission.

  View details for DOI 10.1111/acem.14367

  View details for PubMedID 34363718

• A randomized, placebo-controlled clinical trial of bamlanivimab and etesevimab together in high-risk ambulatory patients with COVID-19 and validation of the prognostic value of persistently high viral load. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Dougan, M., Azizad, M., Mocherla, B., Gottlieb, R. L., Chen, P., Hebert, C., Perry, R., Boscia, J., Heller, B., Morris, J., Crystal, C., Igbinadolor, A., Huhn, G., Cardona, J., Shawa, I., Kumar, P., Blomkalns, A., Adams, A. C., Van Naarden, J., Custer, K. L., Knorr, J., Oakley, G., Schade, A. E., Holzer, T. R., Ebert, P. J., Higgs, R. E., Sabo, J., Patel, D. R., Dabora, M. C., Williams, M., Klekotka, P., Shen, L., Skovronsky, D. M., Nirula, A. 2021

  Abstract

  Based on interim analyses and modelling data, lower doses of bamlanivimab and etesevimab together (700mg/1400mg) were investigated to determine optimal dose and expand availability of treatment.This Phase 3 portion of the BLAZE-1 trial characterized the effect of bamlanivimab with etesevimab on overall patient clinical status and virologic outcomes in ambulatory patients ≥12 years old, with mild-to-moderate COVID-19, and ≥1 risk factor for progressing to severe COVID-19 and/or hospitalization. Bamlanivimab and etesevimab together (700mg/1400mg) or placebo were infused intravenously within 3 days of patients' first positive COVID-19 test.769 patients were infused (median age [range]; 56.0 years [12, 93], 30.3% of patients ≥65 years of age and median duration of symptoms; 4 days). By day 29, 4/511 patients (0.8%) in the antibody treatment group had a COVID-19-related hospitalization or any-cause death, as compared with 15/258 patients (5.8%) in the placebo group (Δ[95% CI]=-5.0 [-8.0, -2.1], p<0.001). No deaths occurred in the bamlanivimab and etesevimab group compared with 4 deaths (all COVID-19-related) in the placebo group. Patients receiving antibody treatment had a greater mean reduction in viral load from baseline to Day 7 (Δ[95% CI]=-0.99 [-1.33, -0.66], p<0.0001) compared with those receiving placebo. Persistently high viral load at Day 7 correlated with COVID-19-related hospitalization or any-cause death by Day 29 in all BLAZE-1 cohorts investigated.These data support the use of bamlanivimab and etesevimab (700mg/1400mg) for ambulatory patients at high risk for severe COVID-19. Evolution of SARS-CoV-2 variants will require continued monitoring to determine the applicability of this treatment.

  View details for DOI 10.1093/cid/ciab912

  View details for PubMedID 34718468

• 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

• SARS-CoV-2 Seroprevalence in Healthcare Personnel in Northern California Early in the COVID-19 Pandemic. Infection control and hospital epidemiology Rosser, J. I., Roltgen, K., Dymock, M., Shepard, J., Martin, A., Hogan, C. A., Blomkalns, A., Mathew, R., Parsonnet, J., Pinsky, B. A., Maldonado, Y. A., Boyd, S. D., Chang, S., Holubar, M., Stanford Healthcare COVID-19 Workforce Response Group 2020: 1–27

  Abstract

  OBJECTIVE: We aimed to assess the magnitude of unidentified SARS-CoV-2 infections in our healthcare personnel (HCP) early in the COVID-19 pandemic and evaluate risk factors for infection in order to identify areas for infection control practice improvement in a northern California academic medical center.METHODS: We reviewed the anti-SARS-CoV-2 receptor binding domain (RBD) IgG serologic test results and self-reported risk factors for seropositivity among 10,449 asymptomatic HCP who underwent voluntary serology testing between April 20 and May 20, 2020.RESULTS: In total, 136 employees (1.3%) tested positive for SARS-CoV-2 IgG. This included 41 (30.1%) individuals who had previously tested positive for SARS-CoV-2 by nasopharyngeal reverse transcription polymerase chain reaction (RT-PCR) between March 13 and April 16, 2020. In multivariable analysis, employees of Hispanic ethnicity (OR = 2.01; 95% CI = 1.22-3.46) and those working in environmental services/food services/patient transport (OR = 4.81; 95% CI = 2.08-10.30) were at increased risk for seropositivity compared to other groups. Employees reporting a household contact with COVID-19 were also at higher risk for seropositivity (OR = 3.25; 95% CI = 1.47-6.44), but those with a work exposure were not (OR = 1.27; 95% CI = 0.58-2.47). Importantly, one-third of seropositive individuals reported no prior symptoms, no suspected exposures, and no prior positive RT-PCR test.CONCLUSION: In this study, SARS-CoV-2 seropositivity among HCP early in the northern California epidemic appeared to be quite low and was more likely attributable to community rather than occupational exposure.

  View details for DOI 10.1017/ice.2020.1358

  View details for PubMedID 33292895

• Niacin protects against abdominal aortic aneurysm formation via GPR109A independent mechanisms: role of NAD(+)/nicotinamide CARDIOVASCULAR RESEARCH Horimatsu, T., Blomkalns, A. L., Ogbi, M., Moses, M., Kim, D., Patel, S., Gilreath, N., Reid, L., Benson, T. W., Pye, J., Ahmadieh, S., Thompson, A., Robbins, N., Mann, A., Edgell, A., Benjamin, S., Stansfield, B. K., Huo, Y., Fulton, D. J., Agarwal, G., Singh, N., Offermanns, S., Weintraub, N. L., Kim, H. 2020; 116 (14): 2226–38

  Abstract

  Chronic adventitial and medial infiltration of immune cells play an important role in the pathogenesis of abdominal aortic aneurysms (AAAs). Nicotinic acid (niacin) was shown to inhibit atherosclerosis by activating the anti-inflammatory G protein-coupled receptor GPR109A [also known as hydroxycarboxylic acid receptor 2 (HCA2)] expressed on immune cells, blunting immune activation and adventitial inflammatory cell infiltration. Here, we investigated the role of niacin and GPR109A in regulating AAA formation.Mice were supplemented with niacin or nicotinamide, and AAA was induced by angiotensin II (AngII) infusion or calcium chloride (CaCl2) application. Niacin markedly reduced AAA formation in both AngII and CaCl2 models, diminishing adventitial immune cell infiltration, concomitant inflammatory responses, and matrix degradation. Unexpectedly, GPR109A gene deletion did not abrogate the protective effects of niacin against AAA formation, suggesting GPR109A-independent mechanisms. Interestingly, nicotinamide, which does not activate GPR109A, also inhibited AAA formation and phenocopied the effects of niacin. Mechanistically, both niacin and nicotinamide supplementation increased nicotinamide adenine dinucleotide (NAD+) levels and NAD+-dependent Sirt1 activity, which were reduced in AAA tissues. Furthermore, pharmacological inhibition of Sirt1 abrogated the protective effect of nicotinamide against AAA formation.Niacin protects against AAA formation independent of GPR109A, most likely by serving as an NAD+ precursor. Supplementation of NAD+ using nicotinamide-related biomolecules may represent an effective and well-tolerated approach to preventing or treating AAA.

  View details for DOI 10.1093/cvr/cvz303

  View details for Web of Science ID 000606530600017

  View details for PubMedID 31710686

  View details for PubMedCentralID PMC7695356

• Echocardiographic assessment of insulin-like growth factor binding protein-7 and early identification of acute heart failure. ESC heart failure Kalayci, A., Peacock, W. F., Nagurney, J. T., Hollander, J. E., Levy, P. D., Singer, A. J., Shapiro, N. I., Cheng, R. K., Cannon, C. M., Blomkalns, A. L., Walters, E. L., Christenson, R. H., Chen-Tournoux, A., Nowak, R. M., Lurie, M. D., Pang, P. S., Kastner, P., Masson, S., Gibson, C. M., Gaggin, H. K., Januzzi, J. L. 2020

  Abstract

  AIMS: Concentrations of insulin-like growth factor binding protein-7 (IGFBP7) have been linked to abnormal cardiac structure and function in patients with chronic heart failure (HF), but cardiovascular correlates of the biomarker in patients with more acute presentations are lacking. We aimed to determine the relationship between IGFBP7 concentrations and cardiac structure and to evaluate the impact of IGFBP7 on the diagnosis of acute HF among patients with acute dyspnoea.METHODS AND RESULTS: In this pre-specified subgroup analysis of the International Collaborative of N-terminal pro-B-type Natriuretic Peptide Re-evaluation of Acute Diagnostic Cut-Offs in the Emergency Department (ICON-RELOADED) study, we included 271 patients with and without acute HF. All patients presented to an emergency department with acute dyspnoea, had blood samples for IGFBP7 measurement, and detailed echocardiographic evaluation. Higher IGFBP7 concentrations were associated with numerous cardiac abnormalities, including increased left atrial volume index (LAVi; r=0.49, P<0.001), lower left ventricular ejection fraction (r=-0.27, P<0.001), lower right ventricular fractional area change (r=-0.31, P<0.001), and higher tissue Doppler E/e' ratio (r=0.44, P<0.001). In multivariable linear regression analyses, increased LAVi (P=0.01), lower estimated glomerular filtration rate (P=0.008), higher body mass index (P=0.001), diabetes (P=0.009), and higher concentrations of amino-terminal pro-B-type natriuretic peptide (NT-proBNP, P=0.02) were independently associated with higher IGFBP7 concentrations regardless of other variables. Furthermore, IGFBP7 (odds ratio=12.08, 95% confidence interval 2.42-60.15, P=0.02) was found to be independently associated with the diagnosis of acute HF in the multivariable logistic regression analysis.CONCLUSIONS: Among acute dyspnoeic patients with and without acute HF, increased IGFBP7 concentrations are associated with a range of cardiac structure and function abnormalities. Independent association with increased LAVi suggests elevated left ventricular filling pressure is an important trigger for IGFBP7 expression and release. IGFBP7 may enhance the diagnosis of acute HF.

  View details for DOI 10.1002/ehf2.12722

  View details for PubMedID 32406612

• Assessment of Sensitivity and Specificity of Patient-Collected Lower Nasal Specimens for Sudden Acute Respiratory Syndrome Coronavirus 2 Testing. JAMA network open Altamirano, J. n., Govindarajan, P. n., Blomkalns, A. L., Kushner, L. E., Stevens, B. A., Pinsky, B. A., Maldonado, Y. n. 2020; 3 (6): e2012005

  View details for DOI 10.1001/jamanetworkopen.2020.12005

  View details for PubMedID 32530469

• Characteristics of Emergency Department Patients With COVID-19 at a Single Site in Northern California: Clinical Observations and Public Health Implications. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine Duanmu, Y. n., Brown, I. P., Gibb, W. R., Singh, J. n., Matheson, L. W., Blomkalns, A. L., Govindarajan, P. n. 2020

  Abstract

  In December 2019, a novel coronavirus disease (COVID-19) emerged in Wuhan, China and spread globally, resulting in the first World Health Organization (WHO) classified pandemic in over a decade.1 As of April 2020, the United States (US) has the most confirmed COVID-19 cases worldwide, but public health interventions and testing availability have varied across the country. 2.

  View details for DOI 10.1111/acem.14003

  View details for PubMedID 32344458

• The AAMC Standardized Video Interview: Lessons Learned From the Residency Selection Process. Academic medicine : journal of the Association of American Medical Colleges Gallahue, F. E., Deiorio, N. M., Blomkalns, A. n., Bird, S. B., Dunleavy, D. n., Fraser, R. n., Overton, B. R. 2020; 95 (11): 1639–42

  Abstract

  Calls to change the residency selection process have increased in recent years, with many focusing on the need for holistic review and alternatives to academic metrics. One aspect of applicant performance to consider in holistic review is proficiency in behavioral competencies. The Association of American Medical Colleges (AAMC) developed the AAMC Standardized Video Interview (SVI), an online, asynchronous video interview that assesses applicants' knowledge of professionalism and their interpersonal and communication skills. The AAMC worked with the emergency medicine community to pilot the SVI. Data from 4 years of research (Electronic Residency Application Service [ERAS] 2017-2020 cycles) show the SVI is a reliable, valid assessment of these behavioral competencies. It provides information not available in the ERAS application packet, and it does not disadvantage individuals or groups. Yet despite the SVI's psychometric properties, the AAMC elected not to renew or expand the pilot in residency selection.In this Invited Commentary, the authors share lessons learned from the AAMC SVI project about introducing a new tool for use in residency selection. They recommend that future projects endeavoring to find ways to support holistic review engage all stakeholders from the start; communicate the value of the new tool early and often; make direct comparisons with existing tools; give new tools time and space to succeed; strike a balance between early adopters and broad participation; help stakeholders understand the limitations of what a tool can do; and set clear expectations about both stakeholder input and pricing. They encourage the medical education community to learn from the SVI project and to consider future partnerships with the AAMC or other specialty organizations to develop new tools and approaches that prioritize the community's needs. Finding solutions to the challenges facing residency selection should be a priority for all stakeholders.

  View details for DOI 10.1097/ACM.0000000000003573

  View details for PubMedID 33112586

• The Role of An Academic Emergency Department in Advancing Equity and Justice. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine Landry, A. M., Brown, I. n., Blomkalns, A. L., Wolfe, R. E. 2020

  Abstract

  In the midst of the coronavirus pandemic, the chronic issue of police brutality directed toward Black Americans reached a tipping in late May with the brutal murder of George Floyd. The social response raised equity and justice awareness, kickstarting one of the largest movements in U.S. history. A national dialogue on systemic racism as a public health concern has reemerged. Though traditionally viewed as taboo within academic medicine, the dialogue surrounding racial inequality is unavoidable.

  View details for DOI 10.1111/acem.14164

  View details for PubMedID 33125762

• SARS-CoV-2 RNAaemia predicts clinical deterioration and extrapulmonary complications from COVID-19. medRxiv : the preprint server for health sciences Ram-Mohan, N. n., Kim, D. n., Zudock, E. J., Hashemi, M. M., Tjandra, K. C., Rogers, A. J., Blish, C. A., Nadeau, K. C., Newberry, J. A., Quinn, J. V., O'Hara, R. n., Ashley, E. n., Nguyen, H. n., Jiang, L. n., Hung, P. n., Blomkalns, A. L., Yang, S. n. 2020

  Abstract

  The determinants of COVID-19 disease severity and extrapulmonary complications (EPCs) are poorly understood. We characterise the relationships between SARS-CoV-2 RNAaemia and disease severity, clinical deterioration, and specific EPCs.We used quantitative (qPCR) and digital (dPCR) PCR to quantify SARS-CoV-2 RNA from nasopharyngeal swabs and plasma in 191 patients presenting to the Emergency Department (ED) with COVID-19. We recorded patient symptoms, laboratory markers, and clinical outcomes, with a focus on oxygen requirements over time. We collected longitudinal plasma samples from a subset of patients. We characterised the role of RNAaemia in predicting clinical severity and EPCs using elastic net regression.23·0% (44/191) of SARS-CoV-2 positive patients had viral RNA detected in plasma by dPCR, compared to 1·4% (2/147) by qPCR. Most patients with serial measurements had undetectable RNAaemia 10 days after onset of symptoms, but took 16 days to reach maximum severity, and 33 days for symptoms to resolve. Initially RNAaemic patients were more likely to manifest severe disease (OR 6·72 [95% CI, 2·45 - 19·79]), worsening of disease severity (OR 2·43 [95% CI, 1·07 - 5·38]), and EPCs (OR 2·81 [95% CI, 1·26 - 6·36]). RNA load correlated with maximum severity ( r = 0·47 [95% CI, 0·20 - 0·67]).dPCR is more sensitive than qPCR for the detection of SARS-CoV-2 RNAaemia, which is a robust predictor of eventual COVID-19 severity and oxygen requirements, as well as EPCs. Since many COVID-19 therapies are initiated on the basis of oxygen requirements, RNAaemia on presentation might serve to direct early initiation of appropriate therapies for the patients most likely to deteriorate.NIH/NIAID (Grants R01A153133, R01AI137272, and 3U19AI057229 - 17W1 COVID SUPP #2) and a donation from Eva Grove.Evidence before this study: The varied clinical manifestations of COVID-19 have directed attention to the distribution of SARS-CoV-2 in the body. Although most concentrated and tested for in the nasopharynx, SARS-CoV-2 RNA has been found in blood, stool, and numerous tissues, raising questions about dissemination of viral RNA throughout the body, and the role of this process in disease severity and extrapulmonary complications. Recent studies have detected low levels of SARS-CoV-2 RNA in blood using either quantitative reverse transcriptase real-time PCR (qPCR) or droplet digital PCR (dPCR), and have associated RNAaemia with disease severity and biomarkers of dysregulated immune response.Added value of this study: We quantified SARS-CoV-2 RNA in the nasopharynx and plasma of patients presenting to the Emergency Department with COVID-19, and found an array-based dPCR platform to be markedly more sensitive than qPCR for detection of SARS-CoV-2 RNA, with a simplified workflow well-suited to clinical adoption. We collected serial plasma samples during patients' course of illness, and showed that SARS-CoV-2 RNAaemia peaks early, while clinical condition often continues to worsen. Our findings confirm the association between RNAaemia and disease severity, and additionally demonstrate a role for RNAaemia in predicting future deterioration and specific extrapulmonary complications.Implications of all the available evidence: Variation in SARS-CoV-2 RNAaemia may help explain disparities in disease severity and extrapulmonary complications from COVID-19. Testing for RNAaemia with dPCR early in the course of illness may help guide patient triage and management.

  View details for DOI 10.1101/2020.12.19.20248561

  View details for PubMedID 33398290

  View details for PubMedCentralID PMC7781329

• Computed tomographic quantification of periaortic adipose tissue volume as a correlate of cardiovascular disease. Cardiology journal Robbins, N., Hooker, E. A., Hart, K. W., Kapur, S., Blomkalns, A. 2019; 26 (6): 802-804

  View details for DOI 10.5603/CJ.2019.0119

  View details for PubMedID 31970740

• Innovation in Residency Selection: The AAMC Standardized Video Interview ACADEMIC MEDICINE Bird, S. B., Hern, H., Blomkalns, A., Deiorio, N. M., Haywood, Y., Hiller, K. M., Dunleavy, D., Dowd, K. 2019; 94 (10): 1489–97

  View details for DOI 10.1097/ACM.0000000000002705

  View details for Web of Science ID 000509244700024

• So the Doctor Is Burned Out: What Does It Mean for Patient Care? ACADEMIC EMERGENCY MEDICINE Lu, D. W., Blomkalns, A. L. 2019; 26 (7): 835–36

  View details for DOI 10.1111/acem.13714

  View details for Web of Science ID 000475970700015

• Innovation in Residency Selection: The AAMC Standardized Video Interview. Academic medicine : journal of the Association of American Medical Colleges Bird, S. B., Hern, H. G., Blomkalns, A., Deiorio, N. M., Haywood, Y., Hiller, K. M., Dunleavy, D., Dowd, K. 2019

  Abstract

  PURPOSE: Innovative tools are needed to help shift residency selection toward a more holistic process that balances academic achievement with other knowledge and skills important for success in residency. The authors evaluated the feasibility of the AAMC Standardized Video Interview (SVI) and evidence of the validity of SVI total scores.METHOD: The SVI, developed by the Association of American Medical Colleges, consists of six questions designed to assess applicants' interpersonal and communication skills and knowledge of professionalism. Study 1 was conducted in 2016 for research purposes. Study 2 was an operational pilot administration in 2017; SVI data were available for residency selection use by emergency medicine residency programs for the 2018 application cycle. Descriptive statistics, correlations, and standardized mean differences were used to examine data.RESULTS: Study 1 included 855 applicants; Study 2 included 3,532 applicants. SVI total scores were relatively normally distributed. There were small correlations between SVI total scores and United States Medical Licensing Examination Step exam scores, Alpha Omega Alpha Honor Medical Society membership, and Gold Humanism Honor Society membership. There were no-to-small group differences in SVI total scores by gender and race/ethnicity, and small-to-medium differences by applicant type.CONCLUSIONS: Findings provide initial evidence of the validity of SVI total scores and suggest these scores provide different information than academic metrics. Use of the SVI, as part of a holistic screening process, may help program directors widen the pool of applicants invited to in-person interviews and may signal that programs value interpersonal and communication skills and professionalism.

  View details for PubMedID 30870151

• Making Promotion Count: The Gender Perspective ACADEMIC EMERGENCY MEDICINE Madsen, T. E., Heron, S. L., Rounds, K., Kass, D., Lall, M., Sethuraman, K. N., Arbelaez, C., Blomkalns, A., Safdar, B., Soc Acad Emergency Med Equity Res 2019; 26 (3): 335–38

  View details for DOI 10.1111/acem.13680

  View details for Web of Science ID 000461220000009

• So the doctor is burned out: What does it mean for patient care? Academic emergency medicine : official journal of the Society for Academic Emergency Medicine Lu, D. W., Blomkalns, A. L. 2019

  Abstract

  The current state of physician burnout has become an increasingly popular topic of discussion and concern. Depending on how it is defined and measured by researchers, the prevalence of physician burnout ranges anywhere from 0 to 80%.1 Emergency medicine is often cited as the specialty with some of the highest reported levels of physician burnout.2 Regardless of what the "true" prevalence of physician burnout may be, most of these studies suggest the presence of a crisis. The detrimental impact of burnout on physicians is certainly of interest to physicians. What is missing from these discussions is the impact of burnout on patients, their families, and objective clinical outcomes. This article is protected by copyright. All rights reserved.

  View details for PubMedID 30768823

• Making Promotion Count: The Gender Perspective On Behalf of the Society for Academic Emergency Medicine Equity Research Taskforce. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine Madsen, T. E., Heron, S. L., Rounds, K., Kass, D., Lall, M., Sethuraman, K. N., Arbelaez, C., Blomkalns, A., Safdar, B. 2019

  Abstract

  Women in academic emergency medicine (EM) experience disparities in both compensation and advancement.1-3 Some hypothesized causes of gender disparities include lack of mentorship and resources,4-5 unequal distribution of opportunity,6-7 sexism8 and implicit bias.9-10 Gender differences in academic rank in EM may also be driven by differences in scholarly productivity, slower ascent to leadership among women, attrition from academic medicine, and potentially a lack of adequate support for faculty that have family obligations competing with work,4 though these factors are largely speculative. This article is protected by copyright. All rights reserved.

  View details for PubMedID 30628138

• Research Priorities for Physician Wellness in Academic Emergency Medicine: Consensus from the Society of Academic Emergency Medicine Wellness Committee. AEM education and training Chung, A. S., Wong, M. L., Sanchez, L. D., Lu, D. W., Manfredi, R. A., Mishkin, H., Heron, S., Blomkalns, A. L. 2018; 2 (Suppl Suppl 1): S40–S47

  Abstract

  Background: Physicians and trainees in academic health care settings face unique challenges to maintaining and enhancing their well-being compared to their community practice counterparts.Objective: Our objective was to develop a research agenda focused on well-being, resilience, and career longevity issues specific to practicing emergency medicine in an academic setting.Methods: We convened an expert group of academic emergency physicians prior to the 2018 annual meeting of the Society for Academic Emergency Medicine to determine a set of uniformly accepted research priorities in the field by consensus.Results: Three themes emerged as components of a comprehensive research agenda: 1) origins and natural history of burnout, resilience, well-being and other related concepts; 2) influence of early training and the learning environment; and 3) impact of burnout, attrition, and lack of organizational or system support for wellness on operations.Conclusion: We believe that this agenda will inform future research and effective interventions to support physician and trainee well-being.

  View details for PubMedID 30607378

• Research Priorities for Physician Wellness in Academic Emergency Medicine: Consensus from the Society of Academic Emergency Medicine Wellness Committee AEM EDUCATION AND TRAINING Chung, A. S., Wong, M. L., Sanchez, L. D., Lu, D. W., Manfredi, R. A., Mishkin, H., Heron, S., Blomkalns, A. L. 2018; 2: S40-S47

  View details for DOI 10.1002/aet2.10211

  View details for Web of Science ID 000770025100005

• Beyond Test Scores and Medical Knowledge: The Standardized Video Interview, an Innovative and Ethical Approach for Holistic Assessment of Applicants. Academic medicine : journal of the Association of American Medical Colleges Bird, S. B., Blomkalns, A., Deiorio, N. M., Gallahue, F. E. 2018; 93 (2): 151

  View details for DOI 10.1097/ACM.0000000000002040

  View details for PubMedID 29377856

• Role of myeloperoxidase in abdominal aortic aneurysm formation: mitigation by taurine. American journal of physiology. Heart and circulatory physiology Kim, H. W., Blomkalns, A. L., Ogbi, M., Thomas, M., Gavrila, D., Neltner, B. S., Cassis, L. A., Thompson, R. W., Weiss, R. M., Lindower, P. D., Blanco, V. M., McCormick, M. L., Daugherty, A., Fu, X., Hazen, S. L., Stansfield, B. K., Huo, Y., Fulton, D. J., Chatterjee, T., Weintraub, N. L. 2017; 313 (6): H1168-H1179

  Abstract

  Oxidative stress plays a fundamental role in abdominal aortic aneurysm (AAA) formation. Activated polymorphonuclear leukocytes (or neutrophils) are associated with AAA and express myeloperoxidase (MPO), which promotes inflammation, matrix degradation, and other pathological features of AAA, including enhanced oxidative stress through generation of reactive oxygen species. Both plasma and aortic MPO levels are elevated in patients with AAA, but the role of MPO in AAA pathogenesis has, heretofore, never been investigated. Here, we show that MPO gene deletion attenuates AAA formation in two animal models: ANG II infusion in apolipoprotein E-deficient mice and elastase perfusion in C57BL/6 mice. Oral administration of taurine [1% or 4% (wt/vol) in drinking water], an amino acid known to react rapidly with MPO-generated oxidants like hypochlorous acid, also prevented AAA formation in the ANG II and elastase models as well as the CaCl2 application model of AAA formation while reducing aortic peroxidase activity and aortic protein-bound dityrosine levels, an oxidative cross link formed by MPO. Both MPO gene deletion and taurine supplementation blunted aortic macrophage accumulation, elastin fragmentation, and matrix metalloproteinase activation, key features of AAA pathogenesis. Moreover, MPO gene deletion and taurine administration significantly attenuated the induction of serum amyloid A, which promotes ANG II-induced AAAs. These data implicate MPO in AAA pathogenesis and suggest that studies exploring whether taurine can serve as a potential therapeutic for the prevention or treatment of AAA in patients merit consideration.NEW & NOTEWORTHY Neutrophils are abundant in abdominal aortic aneurysm (AAA), and myeloperoxidase (MPO), prominently expressed in neutrophils, is associated with AAA in humans. This study demonstrates that MPO gene deletion or supplementation with the natural product taurine, which can scavenge MPO-generated oxidants, can prevent AAA formation, suggesting an attractive potential therapeutic strategy for AAA.

  View details for DOI 10.1152/ajpheart.00296.2017

  View details for PubMedID 28971841

  View details for PubMedCentralID PMC5814655

• Red Blood Cell Dysfunction Induced by High-Fat Diet: Potential Implications for Obesity-Related Atherosclerosis. Circulation Unruh, D., Srinivasan, R., Benson, T., Haigh, S., Coyle, D., Batra, N., Keil, R., Sturm, R., Blanco, V., Palascak, M., Franco, R. S., Tong, W., Chatterjee, T., Hui, D. Y., Davidson, W. S., Aronow, B. J., Kalfa, T., Manka, D., Peairs, A., Blomkalns, A., Fulton, D. J., Brittain, J. E., Weintraub, N. L., Bogdanov, V. Y. 2015; 132 (20): 1898-908

  Abstract

  High-fat diet (HFD) promotes endothelial dysfunction and proinflammatory monocyte activation, which contribute to atherosclerosis in obesity. We investigated whether HFD also induces the dysfunction of red blood cells (RBCs), which serve as a reservoir for chemokines via binding to Duffy antigen receptor for chemokines (DARC).A 60% HFD for 12 weeks, which produced only minor changes in lipid profile in C57/BL6 mice, markedly augmented the levels of monocyte chemoattractant protein-1 bound to RBCs, which in turn stimulated macrophage migration through an endothelial monolayer. Levels of RBC-bound KC were also increased by HFD. These effects of HFD were abolished in DARC(-/-) mice. In RBCs from HFD-fed wild-type and DARC(-/-) mice, levels of membrane cholesterol and phosphatidylserine externalization were increased, fostering RBC-macrophage inflammatory interactions and promoting macrophage phagocytosis in vitro. When labeled ex vivo and injected into wild-type mice, RBCs from HFD-fed mice exhibited ≈3-fold increase in splenic uptake. Finally, RBCs from HFD-fed mice induced increased macrophage adhesion to the endothelium when they were incubated with isolated aortic segments, indicating endothelial activation.RBC dysfunction, analogous to endothelial dysfunction, occurs early during diet-induced obesity and may serve as a mediator of atherosclerosis. These findings may have implications for the pathogenesis of atherosclerosis in obesity, a worldwide epidemic.

  View details for DOI 10.1161/CIRCULATIONAHA.115.017313

  View details for PubMedID 26467254

  View details for PubMedCentralID PMC4772773

• Unstable Angina and Non ST-Segment Elevation ACS Scientific American Emergency Medicine edited by Brown, D. 2015
• Localization, identification, and excision of murine adipose depots. Journal of visualized experiments : JoVE Mann, A., Thompson, A., Robbins, N., Blomkalns, A. L. 2014

  Abstract

  Obesity has increased dramatically in the last few decades and affects over one third of the adult US population. The economic effect of obesity in 2005 reached a staggering sum of $190.2 billion in direct medical costs alone. Obesity is a major risk factor for a wide host of diseases. Historically, little was known regarding adipose and its major and essential functions in the body. Brown and white adipose are the two main types of adipose but current literature has identified a new type of fat called brite or beige adipose. Research has shown that adipose depots have specific metabolic profiles and certain depots allow for a propensity for obesity and other related disorders. The goal of this protocol is to provide researchers the capacity to identify and excise adipose depots that will allow for the analysis of different factorial effects on adipose; as well as the beneficial or detrimental role adipose plays in disease and overall health. Isolation and excision of adipose depots allows investigators to look at gross morphological changes as well as histological changes. The adipose isolated can also be used for molecular studies to evaluate transcriptional and translational change or for in vitro experimentation to discover targets of interest and mechanisms of action. This technique is superior to other published techniques due to the design allowing for isolation of multiple depots with simplicity and minimal contamination.

  View details for DOI 10.3791/52174

  View details for PubMedID 25549006

  View details for PubMedCentralID PMC4396874

• Isolation and excision of murine aorta; a versatile technique in the study of cardiovascular disease. Journal of visualized experiments : JoVE Robbins, N., Thompson, A., Mann, A., Blomkalns, A. L. 2014: e52172

  Abstract

  Cardiovascular disease is a broad term describing disease of the heart and/or blood vessels. The main blood vessel supplying the body with oxygenated blood is the aorta. The aorta may become affected in diseases such as atherosclerosis and aneurysm. Researchers investigating these diseases would benefit from direct observation of the aorta to characterize disease progression as well as to evaluate efficacy of potential therapeutics. The goal of this protocol is to describe proper isolation and excision of the aorta to aid investigators researching cardiovascular disease. Isolation and excision of the aorta allows investigators to look at gross morphometric changes as wells as allowing them to preserve and stain the tissue to look at histologic changes if desired. The aorta may be used for molecular studies to evaluate protein and gene expression to discover targets of interest and mechanisms of action. This technique is superior to imaging modalities as they have inherent limitations in technology and cost. Additionally, primary isolated cells from a freshly isolated and excised aorta can allowing researchers to perform further in situ and in vitro assays. The isolation and excision of the aorta has the limitation of having to sacrifice the animal however, in this case the benefits outweigh the harm as it is the most versatile technique in the study of aortic disease.

  View details for DOI 10.3791/52172

  View details for PubMedID 25490214

  View details for PubMedCentralID PMC4354289

• Transplanted perivascular adipose tissue accelerates injury-induced neointimal hyperplasia: role of monocyte chemoattractant protein-1. Arteriosclerosis, thrombosis, and vascular biology Manka, D., Chatterjee, T. K., Stoll, L. L., Basford, J. E., Konaniah, E. S., Srinivasan, R., Bogdanov, V. Y., Tang, Y., Blomkalns, A. L., Hui, D. Y., Weintraub, N. L. 2014; 34 (8): 1723-30

  Abstract

  Perivascular adipose tissue (PVAT) expands during obesity, is highly inflamed, and correlates with coronary plaque burden and increased cardiovascular risk. We tested the hypothesis that PVAT contributes to the vascular response to wire injury and investigated the underlying mechanisms.We transplanted thoracic aortic PVAT from donor mice fed a high-fat diet to the carotid arteries of recipient high-fat diet-fed low-density lipoprotein receptor knockout mice. Two weeks after transplantation, wire injury was performed, and animals were euthanized 2 weeks later. Immunohistochemistry was performed to quantify adventitial macrophage infiltration and neovascularization and neointimal lesion composition and size. Transplanted PVAT accelerated neointimal hyperplasia, adventitial macrophage infiltration, and adventitial angiogenesis. The majority of neointimal cells in PVAT-transplanted animals expressed α-smooth muscle actin, consistent with smooth muscle phenotype. Deletion of monocyte chemoattractant protein-1 in PVAT substantially attenuated the effects of fat transplantation on neointimal hyperplasia and adventitial angiogenesis, but not adventitial macrophage infiltration. Conditioned medium from perivascular adipocytes induced potent monocyte chemotaxis in vitro and angiogenic responses in cultured endothelial cells.These findings indicate that PVAT contributes to the vascular response to wire injury, in part through monocyte chemoattractant protein-1-dependent mechanisms.

  View details for DOI 10.1161/ATVBAHA.114.303983

  View details for PubMedID 24947528

  View details for PubMedCentralID PMC4103955

• HDAC9 knockout mice are protected from adipose tissue dysfunction and systemic metabolic disease during high-fat feeding. Diabetes Chatterjee, T. K., Basford, J. E., Knoll, E., Tong, W. S., Blanco, V., Blomkalns, A. L., Rudich, S., Lentsch, A. B., Hui, D. Y., Weintraub, N. L. 2014; 63 (1): 176-87

  Abstract

  During chronic caloric excess, adipose tissue expands primarily by enlargement of individual adipocytes, which become stressed with lipid overloading, thereby contributing to obesity-related disease. Although adipose tissue contains numerous preadipocytes, differentiation into functionally competent adipocytes is insufficient to accommodate the chronic caloric excess and prevent adipocyte overloading. We report for the first time that a chronic high-fat diet (HFD) impairs adipogenic differentiation, leading to accumulation of inefficiently differentiated adipocytes with blunted expression of adipogenic differentiation-specific genes. Preadipocytes from these mice likewise exhibit impaired adipogenic differentiation, and this phenotype persists during in vitro cell culture. HFD-induced impaired adipogenic differentiation is associated with elevated expression of histone deacetylase 9 (HDAC9), an endogenous negative regulator of adipogenic differentiation. Genetic ablation of HDAC9 improves adipogenic differentiation and systemic metabolic state during an HFD, resulting in diminished weight gain, improved glucose tolerance and insulin sensitivity, and reduced hepatosteatosis. Moreover, compared with wild-type mice, HDAC9 knockout mice exhibit upregulated expression of beige adipocyte marker genes, particularly during an HFD, in association with increased energy expenditure and adaptive thermogenesis. These results suggest that targeting HDAC9 may be an effective strategy for combating obesity-related metabolic disease.

  View details for DOI 10.2337/db13-1148

  View details for PubMedID 24101673

  View details for PubMedCentralID PMC3868044

• Human coronary artery perivascular adipocytes overexpress genes responsible for regulating vascular morphology, inflammation, and hemostasis. Physiological genomics Chatterjee, T. K., Aronow, B. J., Tong, W. S., Manka, D., Tang, Y., Bogdanov, V. Y., Unruh, D., Blomkalns, A. L., Piegore, M. G., Weintraub, D. S., Rudich, S. M., Kuhel, D. G., Hui, D. Y., Weintraub, N. L. 2013; 45 (16): 697-709

  Abstract

  Inflammatory cross talk between perivascular adipose tissue and the blood vessel wall has been proposed to contribute to the pathogenesis of atherosclerosis. We previously reported that human perivascular (PV) adipocytes exhibit a proinflammatory phenotype and less adipogenic differentiation than do subcutaneous (SQ) adipocytes. To gain a global view of the genomic basis of biologic differences between PV and SQ adipocytes, we performed genome-wide expression analyses to identify differentially expressed genes between adipocytes derived from human SQ vs. PV adipose tissues. Although >90% of well-expressed genes were similarly regulated, we identified a signature of 307 differentially expressed genes that were highly enriched for functions associated with the regulation of angiogenesis, vascular morphology, inflammation, and blood clotting. Of the 156 PV upregulated genes, 59 associate with angiogenesis, vascular biology, or inflammation, noteworthy of which include TNFRSF11B (osteoprotegerin), PLAT, TGFB1, THBS2, HIF1A, GATA6, and SERPINE1. Of 166 PV downregulated genes, 21 associated with vascular biology and inflammation, including ANGPT1, ANGPTL1, and VEGFC. Consistent with the emergent hypothesis that PV adipocytes differentially regulate angiogenesis and inflammation, cell culture-derived adipocyte-conditioned media from PV adipocytes strongly enhanced endothelial cell tubulogenesis and monocyte migration compared with media from SQ adipocytes. These findings demonstrate that PV adipocytes have the potential to significantly modulate vascular inflammatory crosstalk in the setting of atherosclerosis by their ability to signal to both endothelial and inflammatory cells.

  View details for DOI 10.1152/physiolgenomics.00042.2013

  View details for PubMedID 23737535

  View details for PubMedCentralID PMC3742916

• CD14 directs adventitial macrophage precursor recruitment: role in early abdominal aortic aneurysm formation. Journal of the American Heart Association Blomkalns, A. L., Gavrila, D., Thomas, M., Neltner, B. S., Blanco, V. M., Benjamin, S. B., McCormick, M. L., Stoll, L. L., Denning, G. M., Collins, S. P., Qin, Z., Daugherty, A., Cassis, L. A., Thompson, R. W., Weiss, R. M., Lindower, P. D., Pinney, S. M., Chatterjee, T., Weintraub, N. L. 2013; 2 (2): e000065

  Abstract

  Recruitment of macrophage precursors to the adventitia plays a key role in the pathogenesis of abdominal aortic aneurysms (AAAs), but molecular mechanisms remain undefined. The innate immune signaling molecule CD14 was reported to be upregulated in adventitial macrophages in a murine model of AAA and in monocytes cocultured with aortic adventitial fibroblasts (AoAf) in vitro, concurrent with increased interleukin-6 (IL-6) expression. We hypothesized that CD14 plays a crucial role in adventitial macrophage precursor recruitment early during AAA formation.CD14(-/-) mice were resistant to AAA formation induced by 2 different AAA induction models: aortic elastase infusion and systemic angiotensin II (AngII) infusion. CD14 gene deletion led to reduced aortic macrophage infiltration and diminished elastin degradation. Adventitial monocyte binding to AngII-infused aorta in vitro was dependent on CD14, and incubation of human acute monocytic leukemia cell line-1 (THP-1) monocytes with IL-6 or conditioned medium from perivascular adipose tissue (PVAT) upregulated CD14 expression. Conditioned medium from AoAf and PVAT induced CD14-dependent monocyte chemotaxis, which was potentiated by IL-6. CD14 expression in aorta and plasma CD14 levels were increased in AAA patients compared with controls.These findings link CD14 innate immune signaling via a novel IL-6 amplification loop to adventitial macrophage precursor recruitment in the pathogenesis of AAA.

  View details for DOI 10.1161/JAHA.112.000065

  View details for PubMedID 23537804

  View details for PubMedCentralID PMC3647288

• Cardiac Imaging and Stress Testing, 2e Emergency Medicine Executive edited by Adams, J. 2012
• The time dependence of antithrombin initiation in patients with non-ST-segment elevation acute coronary syndromes: subgroup analysis from the ACUITY trial. Annals of emergency medicine Diercks, D. B., Pollack, C. V., Hollander, J. E., Blomkalns, A. L., Emerman, C. L., Rokos, I. C., Larson, D. M., Hoekstra, J. W., Mehran, R., Stone, G. W. 2011; 57 (3): 204-212.e1-6

  Abstract

  Antithrombins are among standard treatment agents for patients with non-ST-segment elevation acute coronary syndromes. We aimed to determine the association between time from emergency department (ED) presentation to treatment with an antithrombin and adverse cardiac events.The study cohort was a subgroup of the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial, enrolled from March 1, 2005, to December 5, 2005. The ACUITY trial enrolled patients with moderate- and high-risk non-ST-segment elevation acute coronary syndromes and who were undergoing an early invasive strategy (<72 hours from randomization). All patients received an antithrombin (unfractionated heparin, low-molecular-weight heparin, or bivalirudin), in addition to other agents. A formal ED case report form was introduced in March 2005. Time from presentation to antithrombin initiation was evaluated as a continuous variable in hours. The endpoints were defined as major ischemic events (death, myocardial infarction, unplanned revascularization) or major bleeding within 30 days, or inhospital major bleeding. Logistic regression was used to adjust for demographics, severity of disease, comorbidities, and treatment differences.Of the 2,722 patients enrolled with an ED case report form, complete time data were available in 2,632 (96%). Median time to antithrombin administration was 4.87 hours (interquartile range 2.67 to 9.83). After multivariable analysis, there was no association of major ischemic events with log time (hours) to antithrombin treatment (adjusted odds ratio [OR] 0.99; 95% confidence interval [CI] 0.97 to 1.01). There was an increase in major bleeding at 30 days and inhospital major bleeding complications with longer log time (hours) to antithrombin initiation (adjusted OR 1.44, 95% CI 1.15 to 1.80; OR 1.43, 95% CI 1.13 to 1.83, respectively).In this study of patients with non-ST-segment elevation acute coronary syndromes who were undergoing an early invasive management strategy, we were unable to demonstrate an association between adverse ischemic outcomes with the timing of antithrombin administration. However, there was an increase in bleeding outcomes as time to antithrombin administration increased.

  View details for DOI 10.1016/j.annemergmed.2010.06.567

  View details for PubMedID 20952100

• Low level bacterial endotoxin activates two distinct signaling pathways in human peripheral blood mononuclear cells. Journal of inflammation (London, England) Blomkalns, A. L., Stoll, L. L., Shaheen, W., Romig-Martin, S. A., Dickson, E. W., Weintraub, N. L., Denning, G. M. 2011; 8: 4

  Abstract

  Bacterial endotoxin, long recognized as a potent pro-inflammatory mediator in acute infectious processes, has more recently been identified as a risk factor for atherosclerosis and other cardiovascular diseases. When endotoxin enters the bloodstream, one of the first cells activated is the circulating monocyte, which exhibits a wide range of pro-inflammatory responses.We studied the effect of low doses of E. coli LPS on IL-8 release and superoxide formation by freshly isolated human peripheral blood mononuclear cells (PBMC).IL-8 release was consistently detectable at 10 pg/ml of endotoxin, reaching a maximum at 1 ng/ml, and was exclusively produced by monocytes; the lymphocytes neither produced IL-8, nor affected monocyte IL-8 release. Superoxide production was detectable at 30 pg/ml of endotoxin, reaching a maximum at 3 ng/ml. Peak respiratory burst activity was seen at 15-20 min, and superoxide levels returned to baseline by 1 h. IL-8 release was dependent on both membrane-associated CD14 (mCD14) and Toll-like receptor 4 (TLR4. Superoxide production was dependent on the presence of LBP, but was not significantly affected by a blocking antibody to TLR4. Moreover, treatment with lovastatin inhibited LPS-dependent IL-8 release and superoxide production.These findings suggest that IL-8 release and the respiratory burst are regulated by distinct endotoxin-dependent signaling pathways in PBMC in low level of endotoxin exposure. Selectively modulating these pathways could lead to new approaches to treat chronic inflammatory diseases, such as atherosclerosis, while preserving the capacity of monocytes to respond to acute bacterial infections.

  View details for DOI 10.1186/1476-9255-8-4

  View details for PubMedID 21352551

  View details for PubMedCentralID PMC3056742

• Obesity Challenging and Emerging Conditions in Emergency Medicine edited by Venkat, A. 2011
• Gender differences in time to presentation for myocardial infarction before and after a national women's cardiovascular awareness campaign: a temporal analysis from the Can Rapid Risk Stratification of Unstable Angina Patients Suppress ADverse Outcomes with Early Implementation (CRUSADE) and the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network-Get with the Guidelines (NCDR ACTION Registry-GWTG). American heart journal Diercks, D. B., Owen, K. P., Kontos, M. C., Blomkalns, A., Chen, A. Y., Miller, C., Wiviott, S., Peterson, E. D. 2010; 160 (1): 80-87.e3

  Abstract

  In 2001-2002, the American Heart Association and National Heart, Lung, and Blood Institute initiated national campaigns with the aim of increasing women's awareness of their risk of heart disease, with particular focus on women aged 40 to 60 years. Our aim is to determine if these women's awareness campaigns were associated with a reduction in the time to hospital presentation for myocardial infarction in women.The study population comprised patients who presented with a non-ST-segment elevation myocardial infarction in the Can Rapid Risk Stratification of Unstable Angina Patients Suppress ADverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines Registry and the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network-Get with the Guidelines registry. Analysis was done based on the introduction of the educational intervention: preintervention 2002-2003, intermediate 2004-2005, and post 2006-2007.Of 125,161 patients, 50,162 (40.1%) are women. The median time from symptom onset to presentation was significantly longer in women than men: 3 hours (interquartile range 1.4-7.6) versus 2.8 hours (interquartile range 1.3-7.2, P < .0001), a difference that remained significant after adjusting for clinical characteristics. There was no measurable reduction in the time from symptom onset to presentation over the period of the awareness campaigns: post- versus preintervention period (-0.18%, 95% CI -3.02% to 2.74%). After adjustment for covariates, women aged 40 to 60 years had a 3.46% longer time to presentation than men (95% CI 1.06-5.92, P = .005).There was no reduction in time from symptom onset to hospital presentation for myocardial infarction patients since national awareness campaigns in women were initiated, and a significant gender gap remains.

  View details for DOI 10.1016/j.ahj.2010.04.017

  View details for PubMedID 20598976

• The association between money and opinion in academic emergency medicine. The western journal of emergency medicine Birkhahn, R. H., Blomkalns, A., Klausner, H., Nowak, R., Raja, A. S., Summers, R., Weber, J. E., Briggs, W. M., Arkun, A., Diercks, D. 2010; 11 (2): 126-32

  Abstract

  Financial conflicts of interest have come under increasing scrutiny in medicine, but their impact has not been quantified. Our objective was to use the results of a national survey of academic emergency medicine (EM) faculty to determine if an association between money and personal opinion exists.We conducted a web-based survey of EM faculty. Opinion questions were analyzed with regard to whether the respondent had either 1) received research grant money or 2) received money from industry as a speaker, consultant, or advisor. Responses were unweighted, and tests of differences in proportions were made using Chi-squared tests, with p<0.05 set for significance.We received responses from 430 members; 98 (23%) received research grants from industry, while 145 (34%) reported fee-for-service money. Respondents with research money were more likely to be comfortable accepting gifts (40% vs. 29%) and acting as paid consultants (50% vs. 37%). They had a more favorable attitude with regard to societal interactions with industry and felt that industry-sponsored lectures could be fair and unbiased (52% vs. 29%). Faculty with fee-for-service money mirrored those with research money. They were also more likely to believe that industry-sponsored research produces fair and unbiased results (61% vs. 45%) and less likely to believe that honoraria biased speakers (49% vs. 69%).Accepting money for either service or research identified a distinct population defined by their opinions. Faculty engaged in industry-sponsored research benefitted socially (collaborations), academically (publications), and financially from the relationship.

  View details for PubMedID 20823958

  View details for PubMedCentralID PMC2908643

• Crosstalk between perivascular adipose tissue and blood vessels CURRENT OPINION IN PHARMACOLOGY Rajsheker, S., Manka, D., Blomkalns, A. L., Chatterjee, T. K., Stoll, L. L., Weintraub, N. L. 2010; 10 (2): 191-196

  Abstract

  Crosstalk between cells in the blood vessel wall is vital to normal vascular function and is perturbed in diseases such as atherosclerosis and hypertension. Perivascular adipocytes reside at the adventitial border of blood vessels but until recently were virtually ignored in studies of vascular function. However, perivascular adipocytes have been demonstrated to be powerful endocrine cells capable of responding to metabolic cues and transducing signals to adjacent blood vessels. Accordingly, crosstalk between perivascular adipose tissue (PVAT) and blood vessels is now being intensely examined. Emerging evidence suggests that PVAT regulates vascular function through numerous mechanisms, but evidence to date suggests modulation of three key aspects that are the focus of this review: inflammation, vasoreactivity, and smooth muscle cell proliferation.

  View details for DOI 10.1016/j.coph.2009.11.005

  View details for Web of Science ID 000276734600014

  View details for PubMedID 20060362

  View details for PubMedCentralID PMC2843777

• Turning ACS outside in: linking perivascular adipose tissue to acute coronary syndromes AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Blomkalns, A. L., Chatterjee, T., Weintraub, N. L. 2010; 298 (3): H734–H735

  View details for DOI 10.1152/ajpheart.00058.2010

  View details for Web of Science ID 000274931500002

  View details for PubMedID 20097767

• The usage patterns of cardiac bedside markers employing point-of-care testing for troponin in non-ST-segment elevation acute coronary syndrome: results from CRUSADE. Clinical cardiology Takakuwa, K. M., Ou, F. S., Peterson, E. D., Pollack, C. V., Peacock, W. F., Hoekstra, J. W., Ohman, E. M., Gibler, W. B., Blomkalns, A. L., Roe, M. T. 2009; 32 (9): 498-505

  Abstract

  Point-of-care (POC) testing may expedite the care of emergency department (ED) patients suspected of having acute coronary syndromes (ACS). We evaluated the use patterns of cardiac bedside markers or POC testing for troponin in patients with non-ST-segment elevation (NSTE) ACS.NSTE ACS data were collected from the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association (ACC/AHA) Guidelines (CRUSADE) registry. We compared hospital and patient characteristics, in-hospital events, and process-of-care variables between hospitals to those that did not use POC testing in > or = 50% of enrolled patients. We examined characteristics, in-hospital events, and process-of-care differences between patients with negative vs positive troponin POC testing results.Of 568 hospitals, 74 (16,276 patients) had high POC usage compared with 197 hospitals (50,782 patients) with no troponin POC usage. From the high POC usage hospitals, 12,604 patients had recorded troponin POC test results. Hospitals with high POC usage had a shorter ED length of stay and were less likely to administer aspirin, beta-blockers, and heparin during the first 24 hours of care. Patients with positive troponin POC results were more often older, minority, female, Medicare-insured, diabetic, and renally impaired. They had fewer electrocardiograms within 10 minutes but were more likely to get aspirin, beta-blockers, glycoprotein IIb/IIIa inhibitors, and heparin within 24 hours of arrival. They also had longer ED lengths of stay, received fewer in-hospital and interventional procedures, and had more adverse clinical events.Differences existed in how hospitals used POC testing and the care given based on those results. Positive POC results are associated with expedited and higher use of anti-ischemic therapies.

  View details for DOI 10.1002/clc.20626

  View details for PubMedID 19743496

• Safety and efficacy of bivalirudin in high-risk patients admitted through the emergency department. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine Miller, C. D., Blomkalns, A. L., Gersh, B. J., Pollack, C. V., Brogan, G. X., Diercks, D. B., Peacock, W. F., Stone, G. W., Hollander, J. E., Manoukian, S. V., Hoekstra, J. W. 2009; 16 (8): 717-25

  Abstract

  The objective was to assess the safety and efficacy of bivalirudin monotherapy in patients with high-risk acute coronary syndrome (ACS) presenting to the emergency department (ED).Data from the Acute Catheterization and Urgent Intervention Triage StrategY (ACUITY) trial were used to conduct a post hoc subgroup analysis of high-risk ACS patients (cardiac biomarker elevation or ST-segment deviation) who initially presented to the ED. The ACUITY trial randomized patients to receive heparin (unfractionated [UFH] or enoxaparin) plus glycoprotein IIb/IIIa inhibition (GPI), bivalirudin plus GPI, or bivalirudin monotherapy. Endpoints included composite ischemia, major bleeding (not coronary artery bypass graft (CABG) related), and net clinical outcome (major bleeding plus composite ischemia).Of 13,819 participants in the ACUITY trial, 6,441 presented initially to the ED, met high-risk criteria, and were included in the primary analysis. Bivalirudin alone when compared to heparin plus GPI, after adjusting for covariates, was associated with an improvement in net clinical outcome (12.3% vs. 14.3%, adjusted odds ratio [OR] = 0.81, 95% confidence interval [CI] = 0.66 to 0.99), similar composite ischemia (9.3% vs. 9.1%, adjusted OR = 0.98, 95% CI = 0.77 to 1.24), and less major bleeding (4.0% vs. 6.8%, adjusted OR = 0.57, 95% CI = 0.42 to 0.75). Bivalirudin plus GPI when compared to heparin plus GPI had similar net clinical outcome (13.8% vs. 14.3%, adjusted OR = 0.91, 95% CI = 0.75 to 1.11), composite ischemia (8.8% vs. 9.1%, adjusted OR = 0.87, 95% CI = 0.69 to 1.11), and major bleeding (6.8% vs. 6.8%, adjusted OR = 1.01, 95% CI = 0.79 to 1.30).Bivalirudin monotherapy decreases major bleeding while providing similar protection from ischemic events compared to heparin plus GPI in patients with high-risk ACS admitted through the ED.

  View details for DOI 10.1111/j.1553-2712.2009.00417.x

  View details for PubMedID 19673711

• Serial venous point-of-care lactate measurements for the evaluation and triage of undifferentiated patients with blunt trauma Point Care Blomkalns, A. 2009
• Academic emergency medicine faculty and industry relationships. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine Birkhahn, R. H., Blomkalns, A. L., Klausner, H. A., Nowak, R. M., Raja, A. S., Summers, R. L., Weber, J. E., Briggs, W. M., Arkun, A., Diercks, D. 2008; 15 (9): 819-24

  Abstract

  The authors surveyed the membership of the Society for Academic Emergency Medicine (SAEM) about their associations with industry and predictors of those associations.A national Web-based survey inviting faculty from the active member list of SAEM was conducted. Follow-up requests for participation were sent weekly for 3 weeks. Information was collected on respondents' personal and practice characteristics, industry interactions, and personal opinions regarding these interactions. Raw response rates were reported and a logistic regression was used to generate descriptive statistics.Responses were received from 430 members, representing 14% of the 3,183 active members. Respondents were 83% male and 86% white, with 96% holding an MD degree (24% with an additional postdoctoral degree). Most were at the assistant (37%) or associate (25%) professor rank, with 51% holding at least one leadership position. Most respondents (82%) reported some type of industry interaction, most commonly the acceptance of food or beverages (67%). Respondents at the associate professor rank or higher were more likely to receive payments from industry (51% vs. 22%, odds ratio [OR] = 3.7).This survey suggests that interactions between industry and academic EM faculty are common and increase with academic rank, but not with years in practice or leadership influence. The number and type of interactions are consistent with those reported by a national sampling of other physician specialties.

  View details for PubMedID 19244632

• Society for Academic Emergency Medicine Industry Relations Committee Academic Emergency Medicine Birkahn, R. 2008
• Guideline implementation research: exploring the gap between evidence and practice in the CRUSADE Quality Improvement Initiative. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine Blomkalns, A. L., Roe, M. T., Peterson, E. D., Ohman, E. M., Fraulo, E. S., Gibler, W. B. 2007; 14 (11): 949-54

  Abstract

  Translating research results into routine clinical practice remains difficult. Guidelines, such as the 2002 American College of Cardiology/American Heart Association Guidelines for the Management of Patients with Unstable Angina and non-ST-segment elevation myocardial infarction, have been developed to provide a streamlined, evidence-based approach to patient care that is of high quality and is reproducible. The Can Rapid Risk Stratification of Unstable Angina Patients Suppress ADverse Outcomes with Early Implementation (CRUSADE) Quality Improvement Initiative was developed as a registry for non-ST-segment elevation acute coronary syndromes to track the use of guideline-based acute and discharge treatments for hospitalized patients, as well as outcomes associated with the use of these treatments. Care for more than 200,000 patients at more than 400 high-volume acute care hospitals in the United States was tracked in CRUSADE, with feedback provided to participating physicians and hospitals regarding their performance over time and compared with similar institutions. Such access to data has proved important in stimulating improvements in non-ST-segment elevation acute coronary syndromes care at participating hospitals for delivery of acute and discharge guideline-based therapy, as well as improving outcomes for patients. Providing quality improvement methods such as protocol order sets, continuing education programs, and a CRUSADE Quality Improvement Initiative toolbox serve to actively stimulate physician providers and institutions to improve care. The CRUSADE Initiative has also proven to be a fertile source of research in translation of treatment guidelines into routine care, resulting in more than 52 published articles and 86 abstracts presented at major emergency medicine and cardiology meetings. The cycle for research of guideline implementation demonstrated by CRUSADE includes four major steps--observation, intervention, investigation, and publication--that serve as the basis for evaluating the impact of any evidence-based guideline on patient care. Due to the success of CRUSADE, the American College of Cardiology combined the CRUSADE Initiative with the National Registry for Myocardial Infarction ST-segment elevation myocardial infarction program to form the National Cardiovascular Data Registry-Acute Coronary Treatment & Intervention Outcomes Network Registry beginning in January 2007.

  View details for DOI 10.1197/j.aem.2007.06.017

  View details for PubMedID 17967956

• Emergency Department education improves patient knowledge of coronary artery disease risk factors but not the accuracy of their own risk perception. Preventive medicine Williams, A., Lindsell, C., Rue, L., Blomkalns, A. 2007; 44 (6): 520-5

  Abstract

  Coronary artery disease (CAD) is the single largest killer of both males and females in the United States. The Emergency Department (ED) represents a unique environment in which patient education may improve coronary artery disease risk factor knowledge and relative risk perception. ED patients' understanding of CAD risk factors is often limited. Patients' perception of their own risk is often not a reflection of their true risk. We hypothesized that an American Heart Association educational video intervention would improve patients' knowledge of coronary artery disease risk factors and personal risk awareness in the ED setting.IRB approval was obtained for this prospective observational cohort study. Our trial included 100 adult patients (age 18 and over), both male and female, using the ED population at an inner city tertiary care Level I trauma center hospital as our source of participants. Recruitment of patients began in January 2002 and ended in May 2004.Patients who watched the educational video did improve their knowledge of cardiac risk factors significantly when compared to patients who received no educational video intervention. In our study, this information was not retained at 30-day follow-up. However, there was still significant improvement in their knowledge when compared to baseline scores pre-intervention. Patients overestimated their risk when compared to an objective measure of risk. In both the study and control groups, patients significantly overestimated their risk pre-educational intervention, immediately post-educational intervention, and at 30-day follow-up when compared to an objective measure of risk.Simple educational intervention at a teachable moment (i.e. when a patient is experiencing chest pain in the ED) significantly improves patient's knowledge of CAD risk factors immediately post-intervention. This improvement in knowledge is not fully retained at 30-day follow-up, which suggests that patients may benefit from further educational intervention prior to 1 month follow-up. Patients overestimate their risk when compared to an objective measure of risk, regardless of whether they receive an educational intervention or not.

  View details for DOI 10.1016/j.ypmed.2007.01.011

  View details for PubMedID 17336373

• Cardiac Imaging and Stress Testing Emergency Medicine edited by Adams, J. 2007
• Evaluation of dyslipidemia in the emergency department: Impact of cholesterol testing on subsequent therapy AMERICAN HEART JOURNAL Blomkalns, A. L., O'Connell, E. M., Eady, C. E., Lindsell, C. J., Gibler, W. 2006; 152 (6): 1182–86

  Abstract

  Dyslipidemia is not routinely evaluated in emergency department (ED) patients. We hypothesized that many ED patients would qualify for lipid therapy and that methods of follow-up for patients would not achieve adequate treatment goals.We performed an observational study of ED patients with symptoms consistent with acute coronary syndrome (ACS). Lipid profiles and data about coronary heart disease risk factors were obtained. The National Institutes of Health/National Cholesterol Education Program guidelines were used to determine whether patients qualified for drug therapy. Six-week and 6-month follow-ups were performed.Three hundred ninety-four patients presenting to the ED with possible ACS were enrolled in the study; 47 patients were subsequently excluded. The remaining 347 included patients who were 63.7% African American and 53.6% female. Proportions of patients with low-density lipoprotein > or = 130 and > or = 160 were 30.8% and 10.1%, respectively. Fifty-seven (16.4%, 95% CI 12.9%-20.7%) qualified for immediate drug therapy. Of the 44 patients meeting treatment criteria for whom follow-up was obtained, only 1 (2.3%) had received lipid-lowering medications with outpatient referral within 6 weeks. At 6 months, 4 (9.5%) of 42 patients with follow-up had received lipid-lowering therapies.Dyslipidemia meeting criteria for therapy is present in a significant proportion of ED patients. Most of these patients do not get appropriately treated on medical follow-up. Our study suggests that lipid screening and subsequent appropriate lipid-lowering therapy could be considered for ED patients with possible ACS.

  View details for DOI 10.1016/j.ahj.2006.07.015

  View details for Web of Science ID 000243110400032

  View details for PubMedID 17161073

• Emergency Department Multimarker Point-of-care Testing Reduces Time to Cardiac Marker Results Without Loss of Diagnostic Accuracy POINT OF CARE Storrow, A. B., Lindsell, C. J., Collins, S. P., Fermann, G. J., Blomkalns, A. L., Williams, J. M., Goldsmith, B., Gibler, W. 2006; 5 (3): 132–36

  View details for DOI 10.1097/01.poc.0000232334.13428.7a

  View details for Web of Science ID 000218039400007

• Frequency and consequences of recording and electrocardiogram > 10 minutes after arrival in an emergency room in non-ST-segment elevation acute coronary syndromes (from the CRUSADE initiative) AMERICAN JOURNAL OF CARDIOLOGY Diercks, D. B., Peacock, W. F., Hiestand, B. C., Chen, A. Y., Pollack, C. V., Kirk, J. D., Blomkalns, A. L., Newby, L. K., Hochman, J. S., Peterson, E. D., Roe, M. T. 2006; 97 (4): 437–42

  Abstract

  We sought to determine the frequency of electrocardiographic (ECG) acquisition within 10 minutes of hospital arrival, factors associated with delayed ECG acquisition, and any relation among delayed ECG acquisition, treatment patterns, and clinical outcomes. We therefore analyzed data from 63,478 patients (26,615 women, 42%) with high-risk non-ST-segment elevation acute coronary syndromes (designated by positive cardiac markers and/or ischemic ST-segment changes) who were enrolled in the CRUSADE Quality Improvement Initiative from February 2001 to March 2004. Patients were categorized based on time to electrocardiography as delayed (>10 minutes from hospital arrival) or nondelayed (<10 minutes). Multivariable predictors of delayed ECG acquisition were determined. Overall, median time to electrocardiography was 15 minutes (25th to 75th percentile 7 to 32). ECG acquisition was delayed (median 25 minutes, 25th to 75th percentile 16 to 50) in 41,397 patients (65.2%). In the remaining 34.8%, time to electrocardiography was <10 minutes (median 5 minutes, 25th to 75th percentile 3 to 8). Women were more likely than men to have delayed ECG acquisition (69% vs 62%), and female gender was the most significant predictor of delayed ECG acquisition (odds ratio 1.29, 95% confidence interval 1.25 to 1.34). In conclusion, only 33% of high-risk patients with non-ST-segment elevation acute coronary syndrome had an initial electrocardiogram obtained <10 minutes of arrival as recommended. Women were significantly more likely than men to have delayed ECG acquisition. Emergency departments should focus on decreasing the time to initial ECG acquisition to improve treatment of acute coronary syndrome in this group.

  View details for DOI 10.1016/j.amjcard.2005.09.073

  View details for Web of Science ID 000235479200001

  View details for PubMedID 16461033

• Cyanosis; Rheumatology Emergency Medicine Handbook edited by Roppolo, L. 2006
• Chest pain unit concept: Rationale and diagnostic strategies CARDIOLOGY CLINICS Blomkalns, A. L., Gibler, W. B. 2005; 23 (4): 411-+

  Abstract

  Each year in the United States, over 8 million patients present to the emergency department(ED) with complaints of chest discomfort or other symptoms consistent with possible acute coronary syndrome (ACS). While over half of these patients are typically admitted for further diagnostic evaluation, fewer than 20% are diagnosed with ACS. With hospital beds and inpatient resources scarce, these admissions can be avoided by evaluating low- to moderate-risk patients in chest pain units. This large, undifferentiated patient population represents a potential high-risk group for emergency physicians requiring a systematic approach and specific ED resources. This evaluation is required to appropriately determine if a patient is safe to be discharged home with outpatient follow-up versus requiring admission to the hospital for monitoring and further testing.

  View details for DOI 10.1016/j.ccl.2005.08.011

  View details for Web of Science ID 000233769800004

  View details for PubMedID 16278115

• Practical implementation of the guidelines for unstable angina/non-ST-segment elevation myocardial infarction in the emergency department ANNALS OF EMERGENCY MEDICINE Gibler, W. B., Cannon, C. P., Blomkalns, A. L., Char, D. M., Drew, B. J., Hollander, J. E., Jaffe, A. S., Jesse, R. L., Newby, L. K., Ohman, E. M., Peterson, E. D., Pollack, C. V. 2005; 46 (2): 185–97

  Abstract

  In the United States each year, >5.3 million patients present to emergency departments with chest discomfort and related symptoms. Ultimately, >1.4 million individuals are hospitalized for unstable angina and non-ST-segment elevation myocardial infarction. For emergency physicians and cardiologists alike, these patients represent an enormous challenge to accurately diagnose and appropriately treat. This update of the 2002 American College of Cardiology/American Heart Association Guidelines for the Management of Patients with Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction (UA/NSTEMI) provides an evidence-based approach to the diagnosis and treatment of these patients in the emergency department, in-hospital, and after hospital discharge. Despite publication of the guidelines several years ago, many patients with UA/NSTEMI still do not receive guidelines-indicated therapy.

  View details for DOI 10.1016/j.annemergmed.2005.04.022

  View details for Web of Science ID 000230855100016

  View details for PubMedID 16046952

• Practical implementation of the guidelines for unstable angina/non-ST-segment elevation myocardial infarction in the emergency department - A Scientific Statement from the American Heart Association Council on Clinical Cardiology (Subcommittee on Acute Cardiac Care), Council on Cardiovascular Nursing, and Quality of Care and Outcomes Research Interdisciplinary Working Group, in Collaboration with the Society of Chest Pain Centers CIRCULATION Gibler, W. B., Cannon, C. P., Blomkalns, A. L., Char, D. M., Drew, B. J., Hollander, J. E., Jaffe, A. S., Jesse, R. L., Newby, L. K., Ohman, E. M., Peterson, E. D., Pollack, C. V. 2005; 111 (20): 2699–2710

  Abstract

  In the United States each year, >5.3 million patients present to emergency departments with chest discomfort and related symptoms. Ultimately, >1.4 million individuals are hospitalized for unstable angina and non-ST-segment elevation myocardial infarction. For emergency physicians and cardiologists alike, these patients represent an enormous challenge to accurately diagnose and appropriately treat. This update of the 2002 American College of Cardiology/American Heart Association Guidelines for the Management of Patients with Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction (UA/NSTEMI) provides an evidence-based approach to the diagnosis and treatment of these patients in the emergency department, in-hospital, and after hospital discharge. Despite publication of the guidelines several years ago, many patients with UA/NSTEMI still do not receive guidelines-indicated therapy.

  View details for DOI 10.1161/01.CIR.0000165556.44271.BE

  View details for Web of Science ID 000229313000021

  View details for PubMedID 15911720

• Gender disparities in the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Blomkalns, A. L., Chen, A. Y., Hochman, J. S., Peterson, E. D., Trynosky, K., Diercks, D. B., Brogan, G. X., Boden, W. E., Roe, M. T., Ohman, E. M., Gibler, W. B., Newby, L. K., CRUSADE Invest 2005; 45 (6): 832–37

  Abstract

  We hypothesized that significant disparities in gender exist in the management of patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS).Gender-related differences in the diagnosis and treatment of ACS have important healthcare implications. No large-scale examination of these disparities has been completed since the publication of the revised American College of Cardiology/American Heart Association guidelines for management of patients with NSTE ACS.Using data from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines) National Quality Improvement Initiative, we examined differences of gender in treatment and outcomes among patients with NSTE ACS.Women (41% of 35,875 patients) were older (median age 73 vs. 65 years) and more often had diabetes and hypertension. Women were less likely to receive acute heparin, angiotensin-converting enzyme inhibitors, and glycoprotein IIb/IIIa inhibitors and less commonly received aspirin, angiotensin-converting enzyme inhibitors, and statins at discharge. The use of cardiac catheterization and revascularization was higher in men, but among patients with significant coronary disease, percutaneous revascularization was performed in a similar proportion of women and men. Women were at higher risk for unadjusted in-hospital death (5.6% vs. 4.3%), reinfarction (4.0% vs. 3.5%), heart failure (12.1% vs. 8.8%), stroke (1.1% vs. 0.8%), and red blood cell transfusion (17.2% vs. 13.2%), but after adjustment, only transfusion was higher in women.Despite presenting with higher risk characteristics and having higher in-hospital risk, women with NSTE ACS are treated less aggressively than men.

  View details for DOI 10.1016/j.jacc.2004.11.055

  View details for Web of Science ID 000227586600003

  View details for PubMedID 15766815

• Chest Pain Unit Concept: Rationale and Diagnostic Strategies Cardiology Clinics edited by Amsterdam, E. 2005
• Diagnosis of Acute Coronary Syndromes in the Emergency Department: Evolution of Chest Pain Centers In Acute Coronary Syndromes, Third Edition edited by Dekker, M. 2005
• Residency training in emergency medicine: the challenges of the 21st century. The Keio journal of medicine Williams, A. L., Blomkalns, A. L., Gibler, W. B. 2004; 53 (4): 203-9

  Abstract

  Emergency Medicine is a relatively young specialty in the United States as well as in other parts of the world. It was only 36 years ago, in 1968, that the American College of Emergency Physicians was founded. Two years later, the University of Cincinnati in Cincinnati, Ohio, USA launched the first Emergency Medicine Residency Training Program. Until the inception of this program, staffing of "Emergency Rooms" consisted largely of physicians who were not trained in the specialty of Emergency Medicine. Emergency Medicine Residency training programs fulfill the need to have Emergency Medicine trained physicians staffing Emergency Departments. There are three and four year training formats for Emergency Medicine in the United States. The University of Cincinnati program is a full four-year program, which teaches residents to master the many diagnostic, procedural, and interpersonal skills required of Emergency Medicine physicians. Diagnostic skills must encompass the pathology affecting all organ systems in all age groups and both sexes. Procedural skills include airway management, vascular access, cavity access, and wound repair. Interpersonal skills are demanding as well, requiring leadership/management of the Emergency Department care team, immediate patient rapport, and dealing with patient/family grief. The Residency Review Committee of the Accreditation Council for Graduate Medical Education (ACGME) ensures that all programs have a structured curriculum complete with both didactic and bedside teaching, as well as structured methods for evaluation of both residents and faculty. According to manpower studies, a great need still exists for Emergency Physicians in many United States hospitals, particularly in rural communities.

  View details for PubMedID 15647626

• Standardized reporting guidelines for studies evaluating risk stratification of emergency department patients with potential acute coronary syndromes ANNALS OF EMERGENCY MEDICINE Hollander, J. E., Blomkains, A. L., Brogan, G. X., Diercks, D. B., Field, J. M., Garvey, J. L., Gibler, W. B., Henry, T. D., Hoekstra, J. W., Holroyd, B. R., Hong, Y. L., Kirk, J. D., O'Neil, B. J., Jackson, R. E., Hollander, J. E., Aufderheide, T., Blomkalns, A. L., Brogan, G. X., Christenson, J., Collins, S., Diercks, D. B., Fesmire, F. M., Garvey, J. L., Gibler, W. B., Green, G. B., Hoekstra, J. W., Holroyd, B. R., Kirk, J. D., Lindsell, C. J., Peacock, W. F., Pollack, C. V., Zalenski, R., Jackson, R. E. 2004; 44 (6): 589-598

  View details for DOI 10.1016/j.annemergmed.2004.08.009

  View details for Web of Science ID 000225503900005

  View details for PubMedID 15573034

• Achieving standardization in clinical research: Changing cacophony into harmony ANNALS OF EMERGENCY MEDICINE Gibler, W. B., Blomkalns, A. L. 2004; 44 (3): 213–14

  View details for DOI 10.1016/j.annemergmed.2004.03.032

  View details for Web of Science ID 000223647200003

  View details for PubMedID 15332060

• Development of the chest pain center: Rationale, implementation, efficacy, and cost-effectiveness PROGRESS IN CARDIOVASCULAR DISEASES Blomkalns, A. L., Gibler, W. B. 2004; 46 (5): 393–403

  View details for DOI 10.1016/j.pcad.2003.12.005

  View details for Web of Science ID 000221990300003

  View details for PubMedID 15179628

• Emergency department crowding: Emergency physicians and cardiac risk stratification as part of the solution ANNALS OF EMERGENCY MEDICINE Blomkalns, A. L., Gibler, W. B. 2004; 43 (1): 77–78

  View details for DOI 10.1016/j.annemergmed.2003.10.033

  View details for Web of Science ID 000187852900015

  View details for PubMedID 14707945

• The Chest Pain Center Concept Cardiovascular Emergencies edited by Peacock, F. 2004
• Basic MI Therapy Cardiovascular Emergencies edited by Peacock, F. 2004
• Evaluation of chest pain and heart failure in the emergency department: impact of multimarker strategies and B-type natriuretic peptide. Reviews in cardiovascular medicine Gibler, W. B., Blomkalns, A. L., Collins, S. P. 2003; 4 Suppl 4: S47-55

  Abstract

  In the emergency setting, acute chest pain and shortness of breath represent common patient presentations. Cardiac biomarkers including myoglobin, creatine kinase (CK)-MB, troponin, and b-type natriuretic peptide provide diagnostic and prognostic information for patients with chest pain and shortness of breath. This article reviews the use of cardiac biomarkers in the emergency department to evaluate acute coronary syndrome and congestive heart failure.

  View details for PubMedID 14564228

• Can electrocardiographic criteria predict adverse cardiac events and positive cardiac markers? Academic emergency medicine : official journal of the Society for Academic Emergency Medicine Blomkalns, A. L., Lindsell, C. J., Chandra, A., Osterlund, M. E., Gibler, W. B., Pollack, C. V., Tiffany, B. R., Hollander, J. E., Hoekstra, J. W. 2003; 10 (3): 205-10

  Abstract

  To determine electrocardiogram (ECG) predictors of positive cardiac markers and short-term adverse cardiac events in an undifferentiated chest pain population presenting to emergency departments (EDs). The authors hypothesized that specific ECG findings, other than those previously identified in higher-risk populations, would be predictive of cardiac outcomes and positive cardiac markers.This study used data from a prospectively collected, retrospectively analyzed Internet-based data registry of undifferentiated chest pain patients (i*trACS). Logistic regression modeling was performed to determine the ECG findings that were predictive of 1) positive cardiac markers and 2) short-term adverse cardiac events.ST-segment elevation (STE), ST-segment depression (STD), pathological Q-waves (PQW), and T-wave inversion were associated with increased odds of percutaneous coronary intervention or catheterization, myocardial infarction, or coronary artery bypass grafting. The odds of creatine kinase-MB (CK-MB) measuring positive were increased if STE, STD, or PQW were present [odds ratio (OR) 2.495, 2.582, and 1.295, respectively]. A right bundle branch block tended to decrease the odds of CK-MB measuring positive (OR 0.658). A similar pattern of results was observed for troponin I (OR 3.608 for STE, 3.72 for STD, 1.538 for PQW). Troponin T showed an increased odds of measuring positive if any of STE, STD, left bundle branch block, or T-wave inversion were evident (OR 2.313, 2.816, 1.80, and 1.449, respectively).Initial ECG criteria can be used to predict short-term cardiac outcomes and positive cardiac markers. These findings can be important aids in the risk-stratification and aggressive treatment regimens of chest pain patients presenting to EDs.

  View details for PubMedID 12615583

• Evaluation of Acute Chest Pain in Women. In Coronary Disease in Women edited by Shaw, L. 2003
• Selecting safe psychotropics for patients after a myocardial infarction. Current Psychiatry Deewan, N., Suresh, D., Blomkalns, A., Jenkins, W. 2003
• Markers and the initial triage and treatment of patients with chest pain. Cardiovascular toxicology Blomkalns, A. L., Gibler, W. B. 2001; 1 (2): 111-5

  Abstract

  Emergency departments evaluate nearly 8 million patients with chest pain per year. Nearly 4 million of these individuals are admitted to inpatient units for further evaluation and treatment, but only 30% of these admitted patients ultimately have the diagnosis of acute coronary syndrome (ACS). Previously, the initial evaluation of patients with chest discomfort presenting to the emergency department (ED) involved the triad of history, physical, and ECG. Current evidence demonstrates that a fourth element, cardiac markers, serves as a valuable aid in not only determining initial diagnosis but also providing risk stratification and dictating initial patient treatment. Chest pain units (CPUs) using serial marker determinations have been successful in identifying patients with or at risk for adverse cardiac events in a timely and cost- efficient manner. New point-of-care-testing (POCT) of cardiac markers at the patient's bedside allows for even more timely determination. This article will review the use of cardiac markers in heterogeneous patients presenting to EDs with chest discomfort. We will focus on the use of markers in the risk stratification and initial treatment of the ED chest pain population and emphasize the role of CPUs and POCT.

  View details for PubMedID 12213982

• Diagnosis of Acute Coronary Syndromes in the Emergency Department – The Evolution of Chest Pain Centers Acute Coronary Syndromes: Second edition, Revised and Expanded edited by Topol, E. 2001
• Venomous Animal Injuries In Emergency Medicine: Concepts and Clinical Practice, 5th edition edited by Rosen, P. 2001
• The Diagnosis of Acute Coronary Syndromes in the Emergency Department In Acute Coronary Syndromes edited by Bassan, R. 2000
• The Diagnosis of Acute Cornoary Syndromes in the Emergency Department: The Evolution of Chest Pain Centers. In Acute Coronary Syndromes edited by Topol, E. 2000
• Catfish spine envenomation: a case report and literature review WILDERNESS & ENVIRONMENTAL MEDICINE Blomkalns, A. L., Otten, E. J. 1999; 10 (4): 242–46

  Abstract

  Catfish spine envenomations are common injuries, reported in both freshwater and saltwater. Such injuries are complex puncture wounds, often complicated by severe infection. Signs and symptoms range from simple local pain and bleeding to systemic manifestations with hemodynamic compromise. Care and treatment involve aggressive pain management, judicious wound cleansing, prophylactic antibiotics, and close follow-up. A case of catfish spine envenomation from a freshwater catfish is presented here.

  View details for DOI 10.1580/1080-6032(1999)010[0242:CSEACR]2.3.CO;2

  View details for Web of Science ID 000084397600006

  View details for PubMedID 10628284

• Purification of bovine alpha-lactalbumin by immobilized metal ion affinity chromatography PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY Blomkalns, A. L., Gomez, M. R. 1997; 27 (4): 219–26

  Abstract

  The milk protein alpha-lactalbumin was isolated from bovine whey protein concentrate solution by immobilized metal ion affinity chromatography (IMAC) using Cu(II)-Chelating Sepharose Fast Flow. Stepwise pH (5.5-3.8) changes in sodium acetate buffer were used to elute the protein selectively, at which time it was concentrated and reapplied to an uncharged Chelating Sepharose Fast Flow column to remove the contaminating Cu(II) ions. A purity of 90% and recovery of 80% was achieved. The described method appears to be suitable for isolation of alpha-lactalbumin in a form adequate for milk formula engineering.

  View details for DOI 10.1080/10826069708001280

  View details for Web of Science ID A1997YK08800002

  View details for PubMedID 9413555