Publications by authors named "Laura Walker"

120 Publications

Six years of gender equity in emergency medicine chief resident selection.

AEM Educ Train 2021 Apr 1;5(2):e10595. Epub 2021 Apr 1.

Department of Emergency Medicine Mayo Clinic Rochester Minnesota USA.

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http://dx.doi.org/10.1002/aet2.10595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035632PMC
April 2021

A myeloid-stromal niche and gp130 rescue in NOD2-driven Crohn's disease.

Nature 2021 Mar 31. Epub 2021 Mar 31.

The Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Crohn's disease is a chronic inflammatory intestinal disease that is frequently accompanied by aberrant healing and stricturing complications. Crosstalk between activated myeloid and stromal cells is critical in the pathogenicity of Crohn's disease, and increases in intravasating monocytes are correlated with a lack of response to anti-TNF treatment. The risk alleles with the highest effect on Crohn's disease are loss-of-function mutations in NOD2, which increase the risk of stricturing. However, the mechanisms that underlie pathogenicity driven by NOD2 mutations and the pathways that might rescue a lack of response to anti-TNF treatment remain largely uncharacterized. Here we use direct ex vivo analyses of patients who carry risk alleles of NOD2 to show that loss of NOD2 leads to dysregulated homeostasis of activated fibroblasts and macrophages. CD14 peripheral blood mononuclear cells from carriers of NOD2 risk alleles produce cells that express high levels of collagen, and elevation of conserved signatures is observed in nod2-deficient zebrafish models of intestinal injury. The enrichment of STAT3 regulation and gp130 ligands in activated fibroblasts and macrophages suggested that gp130 blockade might rescue the activated program in NOD2-deficient cells. We show that post-treatment induction of the STAT3 pathway is correlated with a lack of response to anti-TNF treatment in patients, and demonstrate in vivo in zebrafish the amelioration of the activated myeloid-stromal niche using the specific gp130 inhibitor bazedoxifene. Our results provide insights into NOD2-driven fibrosis in Crohn's disease, and suggest that gp130 blockade may benefit some patients with Crohn's disease-potentially as a complement to anti-TNF therapy.
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http://dx.doi.org/10.1038/s41586-021-03484-5DOI Listing
March 2021

Prolonged evolution of the human B cell response to SARS-CoV-2 infection.

Sci Immunol 2021 02;6(56)

Adimab LLC, Lebanon, NH 03766, USA.

A comprehensive understanding of the kinetics and evolution of the human B cell response to SARS-CoV-2 infection will facilitate the development of next-generation vaccines and therapies. Here, we longitudinally profiled this response in mild and severe COVID-19 patients over a period of five months. Serum neutralizing antibody (nAb) responses waned rapidly but spike (S)-specific IgG memory B cells (MBCs) remained stable or increased over time. Analysis of 1,213 monoclonal antibodies (mAbs) isolated from S-specific MBCs revealed a primarily de novo response that displayed increased somatic hypermutation, binding affinity, and neutralization potency over time, providing evidence for prolonged antibody affinity maturation. B cell immunodominance hierarchies were similar across donor repertoires and remained relatively stable as the immune response progressed. Cross-reactive B cell populations, likely re-called from prior endemic beta-coronavirus exposures, comprised a small but stable fraction of the repertoires and did not contribute to the neutralizing response. The neutralizing antibody response was dominated by public clonotypes that displayed significantly reduced activity against SARS-CoV-2 variants emerging in Brazil and South Africa that harbor mutations at positions 501, 484 and 417 in the S protein. Overall, the results provide insight into the dynamics, durability, and functional properties of the human B cell response to SARS-CoV-2 infection and have implications for the design of immunogens that preferentially stimulate protective B cell responses.
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http://dx.doi.org/10.1126/sciimmunol.abg6916DOI Listing
February 2021

[Tinea capitis: clinical features and therapeutic alternatives].

Rev Argent Microbiol 2021 Feb 19. Epub 2021 Feb 19.

Unidad Micología, Hospital de Infecciosas Francisco Javier Muñiz, Ciudad Autónoma de Buenos Aires, Argentina.

A descriptive observational and cross-sectional study was carried out. The clinical characteristics, etiologic agents, treatments and outcome of 33 cases of tinea capitis in the Mycology Unit at Francisco J. Muñiz Hospital of Buenos Aires City between January 2015 and December 2019 were analyzed. The median age of the patients was 7 years, 21 of whom were male, 3 were HIV-positive and 22 had pets. The isolated etiologic agents were the following: Microsporum canis in 22 cases, Trichophyton tonsurans in 8, Nannizzia gypsea in 2 and Trichophyton mentagrophytes in one patient. Suppurative tinea capitis (krion Celsi) was detected in 10 cases and the same number of patients presented other skin locations of their dermatophytosis in addition to those in the scalp. Twenty-one cases were orally treated with griseofulvin and 12 with terbinafine. Those patients with suppurative tinea capitis received drops of betamethasone by mouth besides the antifungal drugs. All patients had good clinical and mycological response to the treatments, all lesions disappeared, and mycological studies turned negative by the end of the treatments. We conclude that both drugs were effective for the treatment of tinea capitis; however, lesions in those cases receiving terbinafine involuted more slowly.
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http://dx.doi.org/10.1016/j.ram.2021.01.004DOI Listing
February 2021

The Multifaceted Impact of COVID-19 on the Female Academic Emergency Physician: A National Conversation.

AEM Educ Train 2021 Jan 21;5(1):91-98. Epub 2020 Oct 21.

and the Department of Emergency Medicine Yale University New Haven CT USA.

COVID-19 has impacted all health care professionals in every aspect of life. Female academic emergency physicians have been uniquely affected and continue to face challenges related to clinical workloads, work-life integration, academic productivity, leadership and visibility within departments, and mental health. This white paper, prepared on behalf of the Academy for Women in Academic Emergency Medicine (AWAEM), describes the differential impact of COVID-19 on female academic emergency physicians explored during a virtual panel discussion at the 2020 Society for Academic Emergency Medicine Annual Meeting. AWAEM convened a virtual panel of women to begin a discussion to share experiences and challenges and formulate consensus guidelines regarding best practices and mitigation strategies. The authors describe the unique ways in which female academic physicians have been affected, identify ongoing and intensified gender gaps, and delineate strategies to address the identified problems. Specific recommendations include individual, as well as, institutional and systems-level approaches to combat the inequities.
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http://dx.doi.org/10.1002/aet2.10539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849338PMC
January 2021

Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody.

Science 2021 02 25;371(6531):823-829. Epub 2021 Jan 25.

Adimab, LLC, Lebanon, NH 03766, USA.

The recurrent zoonotic spillover of coronaviruses (CoVs) into the human population underscores the need for broadly active countermeasures. We employed a directed evolution approach to engineer three severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies for enhanced neutralization breadth and potency. One of the affinity-matured variants, ADG-2, displays strong binding activity to a large panel of sarbecovirus receptor binding domains and neutralizes representative epidemic sarbecoviruses with high potency. Structural and biochemical studies demonstrate that ADG-2 employs a distinct angle of approach to recognize a highly conserved epitope that overlaps the receptor binding site. In immunocompetent mouse models of SARS and COVID-19, prophylactic administration of ADG-2 provided complete protection against respiratory burden, viral replication in the lungs, and lung pathology. Altogether, ADG-2 represents a promising broad-spectrum therapeutic candidate against clade 1 sarbecoviruses.
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http://dx.doi.org/10.1126/science.abf4830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963221PMC
February 2021

Tongue lesion due to Cryptococcus neoformans as the first finding in an HIV-positive patient.

Rev Iberoam Micol 2021 Jan-Mar;38(1):19-22. Epub 2020 Dec 30.

Unidad Micología del Hospital de Infecciosas F. J. Muñiz, Buenos Aires, Argentina.

Background: Cryptococcosis is a severe universally distributed mycosis which mainly affects immunocompromised hosts. This mycosis is caused by yeasts of two species complex of the genus Cryptococcus: Cryptococcus neoformans and Cryptococcus gattii. Meningeal cryptococcosis is the most frequent clinical presentation of this disseminated mycosis. The oral mucosa involvement is extremely unusual.

Case Report: We present a case of cryptococcosis with an unusual clinical form. The patient was assisted because she had an ulcerated lesion on the lingual mucosa. Encapsulated yeasts compatible with Cryptococcus were found in microscopic exams of wet preparations from lingual ulcer clinical samples obtained for cytodiagnosis and mycological studies. Cryptococcus neoformans (C. neoformans var. grubii VNI) was isolated in culture. This patient did not know her condition of HIV seropositive before the appearance of the tongue lesion.

Conclusions: The involvement of the oral mucosa is uncommon in this fungal infection, but is important to include it in the differential diagnosis in HIV positive patients.
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http://dx.doi.org/10.1016/j.riam.2020.10.003DOI Listing
December 2020

Structural Basis of Zika Virus Specific Neutralization in Subsequent Flavivirus Infections.

Viruses 2020 11 24;12(12). Epub 2020 Nov 24.

Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.

Zika virus (ZIKV), a mosquito-borne human flavivirus that causes microcephaly and other neurological disorders, has been a recent focus for the development of flavivirus vaccines and therapeutics. We report here a 4.0 Å resolution structure of the mature ZIKV in complex with ADI-30056, a ZIKV-specific human monoclonal antibody (hMAb) isolated from a ZIKV infected donor with a prior dengue virus infection. The structure shows that the hMAb interactions span across the E protein dimers on the virus surface, inhibiting conformational changes required for the formation of infectious fusogenic trimers similar to the hMAb, ZIKV-117. Structure-based functional analysis, and structure and sequence comparisons, identified ZIKV residues essential for neutralization and crucial for the evolution of highly potent E protein crosslinking Abs in ZIKV. Thus, this epitope, ZIKV's "Achilles heel", defined by the contacts between ZIKV and ADI-30056, could be a suitable target for the design of therapeutic antibodies.
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http://dx.doi.org/10.3390/v12121346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760643PMC
November 2020

An Engineered Antibody with Broad Protective Efficacy in Murine Models of SARS and COVID-19.

bioRxiv 2020 Nov 17. Epub 2020 Nov 17.

The recurrent zoonotic spillover of coronaviruses (CoVs) into the human population underscores the need for broadly active countermeasures. Here, we employed a directed evolution approach to engineer three SARS-CoV-2 antibodies for enhanced neutralization breadth and potency. One of the affinity-matured variants, ADG-2, displays strong binding activity to a large panel of sarbecovirus receptor binding domains (RBDs) and neutralizes representative epidemic sarbecoviruses with remarkable potency. Structural and biochemical studies demonstrate that ADG-2 employs a unique angle of approach to recognize a highly conserved epitope overlapping the receptor binding site. In murine models of SARS-CoV and SARS-CoV-2 infection, passive transfer of ADG-2 provided complete protection against respiratory burden, viral replication in the lungs, and lung pathology. Altogether, ADG-2 represents a promising broad-spectrum therapeutic candidate for the treatment and prevention of SARS-CoV-2 and future emerging SARS-like CoVs.
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http://dx.doi.org/10.1101/2020.11.17.385500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685319PMC
November 2020

Impact of the SARS-CoV-2 Pandemic on Emergency Department Presentations in an Integrated Health System.

Mayo Clin Proc 2020 11 19;95(11):2395-2407. Epub 2020 Sep 19.

Department of Emergency Medicine, Mayo Clinic, Rochester, MN.

Objective: To quantify the impact of the severe acute respiratory syndrome coronavirus 2 pandemic on emergency department volumes and patient presentations and evaluate changes in community mortality for the purpose of characterizing new patterns of emergency care use.

Patients And Methods: This is an observational cross-sectional study using electronic health records for emergency department visits in an integrated multihospital system with academic and community practices across 4 states for visits between March 17 and April 21, 2019, and February 9 and April 21, 2020. We compared numbers and proportions of common and critical chief symptoms and diagnoses, triage assessments, throughput, disposition, and selected hospital lengths of stay and out-of-hospital deaths.

Results: In the period of interest, emergency department visits decreased by nearly 50% (35037 to 18646). Total numbers of patients with myocardial infarctions, stroke, appendicitis, and cholecystitis diagnosed decreased. The percentage of visits for mental health symptoms increased. There was an increase in deaths, driven by out-of-hospital mortality.

Conclusion: Fewer patients presenting with acute and time-sensitive diagnoses suggests that patients are deferring care. This may be further supported by an increase in out-of-hospital mortality. Understanding which patients are deferring care and why will allow us to develop outreach strategies and ensure that those in need of rapid assessment and treatment will do so, preventing downstream morbidity and mortality.
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http://dx.doi.org/10.1016/j.mayocp.2020.09.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501771PMC
November 2020

Cytotoxic lymphocytes are dysregulated in multisystem inflammatory syndrome in children.

medRxiv 2020 Sep 2. Epub 2020 Sep 2.

Multisystem inflammatory syndrome in children (MIS-C) presents with fever, inflammation and multiple organ involvement in individuals under 21 years following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To identify genes, pathways and cell types driving MIS-C, we sequenced the blood transcriptomes of MIS-C cases, pediatric cases of coronavirus disease 2019, and healthy controls. We define a MIS-C transcriptional signature partially shared with the transcriptional response to SARS-CoV-2 infection and with the signature of Kawasaki disease, a clinically similar condition. By projecting the MIS-C signature onto a co-expression network, we identified disease gene modules and found genes downregulated in MIS-C clustered in a module enriched for the transcriptional signatures of exhausted CD8 T-cells and CD56 CD57 NK cells. Bayesian network analyses revealed nine key regulators of this module, including , a central coordinator of exhausted CD8 T-cell differentiation. Together, these findings suggest dysregulated cytotoxic lymphocyte response to SARS-Cov-2 infection in MIS-C.
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http://dx.doi.org/10.1101/2020.08.29.20182899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480058PMC
September 2020

Palliative care in the emergency department: A survey assessment of patient and provider perspectives.

Palliat Med 2020 10 15;34(9):1279-1285. Epub 2020 Jul 15.

Department of Emergency Medicine, Mayo Clinic, Rochester, MN, USA.

Background: Palliative care has been identified as an area of low outpatient referral from our emergency department, yet palliative care has been shown to improve the quality of patient's lives.

Aim: This study investigates both provider and patient perspectives on palliative care for the purpose of identifying barriers to increased palliative care utilization within our healthcare system.

Design: Two surveys were developed, one for patients/caregivers and one for healthcare providers.

Setting/participants: This was a single-center study completed at a quaternary academic emergency department. A survey was sent to emergency medicine providers with 47% response rate. Research staff approached Emergency Department patients who had been identified to be high risk to fill out paper surveys with 76% response rate.

Results: Only 28% of patients had already undergone palliative care, with an additional 25% interested in palliative care. Nearly half of the patients felt that they needed more resources to prevent hospital visits. Patients identified low understanding of palliative care and difficulty accessing appointments as barriers to consultation. Among providers, 98% indicated that they had patients who would benefit from palliative care. A majority of providers highlighted patient understanding of palliative care and access to appointments as barriers to palliative care. Notably, 52% of providers reported that emergency medicine provider knowledge was a barrier to palliative care consultation.

Conclusions: Despite emergency department patients' self-identified need for resources and emergency medicine providers' recognition of patients who would benefit from palliative care, few patients receive palliative care consultation.
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http://dx.doi.org/10.1177/0269216320942453DOI Listing
October 2020

Broad neutralization of SARS-related viruses by human monoclonal antibodies.

Science 2020 08 15;369(6504):731-736. Epub 2020 Jun 15.

Adimab LLC, Lebanon, NH 03766, USA.

Broadly protective vaccines against known and preemergent human coronaviruses (HCoVs) are urgently needed. To gain a deeper understanding of cross-neutralizing antibody responses, we mined the memory B cell repertoire of a convalescent severe acute respiratory syndrome (SARS) donor and identified 200 SARS coronavirus 2 (SARS-CoV-2) binding antibodies that target multiple conserved sites on the spike (S) protein. A large proportion of the non-neutralizing antibodies display high levels of somatic hypermutation and cross-react with circulating HCoVs, suggesting recall of preexisting memory B cells elicited by prior HCoV infections. Several antibodies potently cross-neutralize SARS-CoV, SARS-CoV-2, and the bat SARS-like virus WIV1 by blocking receptor attachment and inducing S1 shedding. These antibodies represent promising candidates for therapeutic intervention and reveal a target for the rational design of pan-sarbecovirus vaccines.
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http://dx.doi.org/10.1126/science.abc7424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299279PMC
August 2020

Broad sarbecovirus neutralizing antibodies define a key site of vulnerability on the SARS-CoV-2 spike protein.

bioRxiv 2020 May 16. Epub 2020 May 16.

Adimab LLC, Lebanon, NH 03766, USA.

Broadly protective vaccines against known and pre-emergent coronaviruses are urgently needed. Critical to their development is a deeper understanding of cross-neutralizing antibody responses induced by natural human coronavirus (HCoV) infections. Here, we mined the memory B cell repertoire of a convalescent SARS donor and identified 200 SARS-CoV-2 binding antibodies that target multiple conserved sites on the spike (S) protein. A large proportion of the antibodies display high levels of somatic hypermutation and cross-react with circulating HCoVs, suggesting recall of pre-existing memory B cells (MBCs) elicited by prior HCoV infections. Several antibodies potently cross-neutralize SARS-CoV, SARS-CoV-2, and the bat SARS-like virus WIV1 by blocking receptor attachment and inducing S1 shedding. These antibodies represent promising candidates for therapeutic intervention and reveal a new target for the rational design of pan-sarbecovirus vaccines.
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http://dx.doi.org/10.1101/2020.05.15.096511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241100PMC
May 2020

Non-pharmacologic interventions improve comfort and experience among older adults in the Emergency Department.

Am J Emerg Med 2021 01 4;39:15-20. Epub 2020 May 4.

Department of Emergency Medicine, Mayo Clinic, Rochester, MN, USA; Department Health Science Research, Division of Health Care Policy and Research, Mayo Clinic, Rochester, MN, USA. Electronic address:

Objective: Determine if a comfort cart would improve older adults' comfort and facilitate communication during Emergency Department (ED) visits.

Methods: A comfort cart containing low-cost, non-pharmacological interventions to improve patient comfort and ability to communicate (e.g., hearing amplifiers, reading glasses) were made available to patients aged ≥65 years. Patients and clinicians were surveyed to assess effectiveness. We followed the Standards for Quality Improvement Reporting Excellence: SQUIRE 2.0 guidelines.

Results: Three hundred patients and 100 providers were surveyed. Among patients, 98.0%, 95.1%, and 67.5% somewhat or strongly agreed that the comfort cart improved comfort, overall experience, and independence, respectively. Among providers, 97.0%, 95.0%, 87.0%, and 83% somewhat or strongly agreed that the comfort cart provided comfort, improved patient satisfaction, increased ability to give compassionate care, and increased patient orientation.

Conclusion: The comfort cart was an affordable and effective intervention that improved patients' comfort by facilitating communication, wellbeing, and compassionate care delivery.
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http://dx.doi.org/10.1016/j.ajem.2020.04.089DOI Listing
January 2021

Rational Vaccine Design in the Time of COVID-19.

Cell Host Microbe 2020 05;27(5):695-698

Adimab, Lebanon, NH 03766, USA. Electronic address:

As scientists consider SARS-CoV-2 vaccine design, we discuss problems that may be encountered and how to tackle them by what we term "rational vaccine design." We further discuss approaches to pan-coronavirus vaccines. We draw on experiences from recent research on several viruses including HIV and influenza, as well as coronaviruses.
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http://dx.doi.org/10.1016/j.chom.2020.04.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219357PMC
May 2020

A conserved dendritic-cell regulatory program limits antitumour immunity.

Nature 2020 04 25;580(7802):257-262. Epub 2020 Mar 25.

The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Checkpoint blockade therapies have improved cancer treatment, but such immunotherapy regimens fail in a large subset of patients. Conventional type 1 dendritic cells (DC1s) control the response to checkpoint blockade in preclinical models and are associated with better overall survival in patients with cancer, reflecting the specialized ability of these cells to prime the responses of CD8 T cells. Paradoxically, however, DC1s can be found in tumours that resist checkpoint blockade, suggesting that the functions of these cells may be altered in some lesions. Here, using single-cell RNA sequencing in human and mouse non-small-cell lung cancers, we identify a cluster of dendritic cells (DCs) that we name 'mature DCs enriched in immunoregulatory molecules' (mregDCs), owing to their coexpression of immunoregulatory genes (Cd274, Pdcd1lg2 and Cd200) and maturation genes (Cd40, Ccr7 and Il12b). We find that the mregDC program is expressed by canonical DC1s and DC2s upon uptake of tumour antigens. We further find that upregulation of the programmed death ligand 1 protein-a key checkpoint molecule-in mregDCs is induced by the receptor tyrosine kinase AXL, while upregulation of interleukin (IL)-12 depends strictly on interferon-γ and is controlled negatively by IL-4 signalling. Blocking IL-4 enhances IL-12 production by tumour-antigen-bearing mregDC1s, expands the pool of tumour-infiltrating effector T cells and reduces tumour burden. We have therefore uncovered a regulatory module associated with tumour-antigen uptake that reduces DC1 functionality in human and mouse cancers.
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http://dx.doi.org/10.1038/s41586-020-2134-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787191PMC
April 2020

Interventions to improve older adults' Emergency Department patient experience: A systematic review.

Am J Emerg Med 2020 06 12;38(6):1257-1269. Epub 2020 Mar 12.

Department of Emergency Medicine, Mayo Clinic, Rochester, MN, United States of America; Department of Health Science Research, Division of Health Care Policy and Research, Mayo Clinic, Rochester, MN, United States of America. Electronic address:

Study Objective: To summarize interventions that impact the experience of older adults in the emergency department (ED) as measured by patient experience instruments.

Methods: This is a systematic review to evaluate interventions aimed to improve geriatric patient experience in the ED. We searched Ovid CENTRAL, Ovid EMBASE, Ovid MEDLINE and PsycINFO from inception to January 2019. The main outcome was patient experience measured through instruments to assess patient experience or satisfaction. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to evaluate the confidence in the evidence available.

Results: The search strategy identified 992 studies through comprehensive literature search and hand-search of reference lists. A total of 21 studies and 3163 older adults receiving an intervention strategy aimed at improve patient experience in the ED were included. Department-wide interventions, including geriatric ED and comprehensive geriatric assessment unit, focused care coordination with discharge planning and referral for community services, were associated with improved patient experience. Providing an assistive listening device to those with hearing loss and having a pharmacist reviewing the medication list showed an improved patient perception of quality of care provided. The confidence in the evidence available for the outcome of patient experience was deemed to be very low.

Conclusion: While all studies reported an outcome of patient experience, there was significant heterogeneity in the tools used to measure it. The very low certainty in the evidence available highlights the need for more reliable tools to measure patient experience and studies designed to measure the effect of the interventions.
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http://dx.doi.org/10.1016/j.ajem.2020.03.012DOI Listing
June 2020

Longitudinal dynamics of the human B cell response to the yellow fever 17D vaccine.

Proc Natl Acad Sci U S A 2020 03 9;117(12):6675-6685. Epub 2020 Mar 9.

Adimab, LLC, Lebanon, NH 03766;

A comprehensive understanding of the development and evolution of human B cell responses induced by pathogen exposure will facilitate the design of next-generation vaccines. Here, we utilized a high-throughput single B cell cloning technology to longitudinally track the human B cell response to the yellow fever virus 17D (YFV-17D) vaccine. The early memory B cell (MBC) response was mediated by both classical immunoglobulin M (IgM) (IgMCD27) and switched immunoglobulin (swIg) MBC populations; however, classical IgM MBCs waned rapidly, whereas swIg and atypical IgM and IgD MBCs were stable over time. Affinity maturation continued for 6 to 9 mo following vaccination, providing evidence for the persistence of germinal center activity long after the period of active viral replication in peripheral blood. Finally, a substantial fraction of the neutralizing antibody response was mediated by public clones that recognize a fusion loop-proximal antigenic site within domain II of the viral envelope glycoprotein. Overall, our findings provide a framework for understanding the dynamics and complexity of human B cell responses elicited by infection and vaccination.
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http://dx.doi.org/10.1073/pnas.1921388117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104296PMC
March 2020

Validation of the Elderly Risk Assessment Index in the Emergency Department.

Am J Emerg Med 2020 07 9;38(7):1441-1445. Epub 2019 Dec 9.

Department of Emergency Medicine, Mayo Clinic, Rochester, MN, USA; Department Health Science Research, Division of Health Care Policy and Research, Mayo Clinic, Rochester, MN, USA. Electronic address:

Objectives: The Elderly Risk Assessment (ERA) score is a validated index for primary care patients that predict hospitalizations, mortality, and Emergency Department (ED) visits. The score incorporates age, prior hospital days, marital status, and comorbidities. Our aim was to validate the ERA score in ED patients.

Methods: Observational cohort study of patients age ≥ 60 presenting to an academic ED over a 1-year period. Regression analyses were performed for associations with outcomes (hospitalization, return visits and death). Medians, interquartile range (IQR), odds ratios (OR) and 95% confidence intervals (CI) were calculated.

Results: The cohort included 27,397 visits among 18,607 patients. Median age 74 years (66-82), 48% were female and 59% were married. Patients from 54% of visits were admitted to the hospital, 16% returned to the ED within 30 days, and 18% died within one year. Higher ERA scores were associated with: hospital admission (score 10 [4-16] vs 5 [1-11], p < 0.0001), return visits (11 [5-17] vs 7 [2-13], p < 0.0001); and death within one year (14 [7-20] vs 6 [2-13], p < 0.0001). Patients with ERA score ≥ 16 were more likely to be admitted to the hospital, OR 2.14 (2.02-2.28, p < 0.0001), return within 30 days OR 1.99 (1.85-2.14), and to die within a year, OR 2.69 (2.54-2.85).

Conclusion: The ERA score can be automatically calculated within the electronic health record and helps identify patients at increased risk of death, hospitalization and return ED visits. The ERA score can be applied to ED patients, and may help prognosticate the need for advanced care planning.
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http://dx.doi.org/10.1016/j.ajem.2019.11.048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280072PMC
July 2020

The sticking points: Improving sharps safety practices.

Nurs Manage 2019 11;50(11):43-50

At Lehigh Valley Health Network in Allentown, Pa., Laura J. Walker is the clinical safety programs manager, Kristina Holleran is a patient care specialist, Joanna McKnight is a products nurse specialist, and Mary Jean Potylycki is the patient care specialists manager.

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http://dx.doi.org/10.1097/01.NUMA.0000602828.72807.18DOI Listing
November 2019

Affinity Maturation Enhances Antibody Specificity but Compromises Conformational Stability.

Cell Rep 2019 Sep;28(13):3300-3308.e4

Adimab, LLC, Lebanon, NH 03766, USA. Electronic address:

Monoclonal antibodies (mAbs) have recently emerged as one of the most promising classes of biotherapeutics. A potential advantage of B cell-derived mAbs as therapeutic agents is that they have been subjected to natural filtering mechanisms, which may enrich for B cell receptors (BCRs) with favorable biophysical properties. Here, we evaluated 400 human mAbs for polyreactivity, hydrophobicity, and thermal stability using high-throughput screening assays. Overall, mAbs derived from memory B cells and long-lived plasma cells (LLPCs) display reduced levels of polyreactivity, hydrophobicity, and thermal stability compared with naive B cell-derived mAbs. Somatic hypermutation (SHM) is inversely associated with all three biophysical properties, as well as BCR expression levels. Finally, the developability profiles of the human B cell-derived mAbs are comparable with those observed for clinical mAbs, suggesting their high therapeutic potential. The results provide insight into the biophysical consequences of affinity maturation and have implications for therapeutic antibody engineering and development.
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http://dx.doi.org/10.1016/j.celrep.2019.08.056DOI Listing
September 2019

Progression of Emergency Medicine Resident Patient Experience Scores by Level of Training.

J Patient Exp 2019 Sep 4;6(3):210-215. Epub 2018 Sep 4.

Mayo Clinic, Rochester, MN, USA.

Background: Patient satisfaction surveys are vital to measuring a patient's experience of care. How scores of patients managed by emergency medicine (EM) residents change as residents progress through training is not known.

Objectives: To evaluate whether EM residents' patient satisfaction scores improve as residency training progresses, similar to clinical skill improvement.

Methods: A retrospective cross-sectional study evaluated the correlation of patient satisfaction scores with EM resident year of training from 2015 through 2017. We evaluated for a change in score over time for the 4 "physician questions" and the "overall" score.

Results: We evaluated 1684 Press Ganey surveys linked to 40 EM resident physicians during the study period. The mean top box scores for the 4 physician questions (concern for comfort [ = .72], courtesy [ = .55], informative about treatment [ = .46], and listening [ = .91]) and overall assessment of emergency department care ( = .51) were not significantly improved over the course of resident.

Conclusion: We did not observe a difference in EM residents' patient experience scores as their level of training progressed. Comprehensive patient experience training for residents might be needed.
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http://dx.doi.org/10.1177/2374373518798098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739686PMC
September 2019

Impact of scribes on throughput metrics and billing during an electronic medical record transition.

Am J Emerg Med 2020 08 10;38(8):1594-1598. Epub 2019 Sep 10.

Department of Emergency Medicine, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, United States of America.

Objective: Evaluate an established scribe program on throughput and revenue capture in an Emergency Department (ED) undergoing an EMR transition.

Methods: A prospective cohort design comparing patients managed with and without scribes in an academic ED. Throughput metrics (medians, min) and relative value units (RVUs, means) were collected. Data was evaluated in its entirety (three months), as well as in two subsets: go live (immediate two weeks) and adoption (two weeks post implementation to end).

Results: All patients: There was no significant difference in throughput or RVUs during the three month period. During go-live, scribes showed improvement in total RVUs per patient (4.63 vs 4.40, p = 0.048). During adoption, scribed patients had decreased length of stay (LOS, 221 vs 231, p = 0.023). Adults: Door to provider (28 vs 37, p = 0.014) and total RVUs (5.20 vs 4.92, p = 0.042) were improved with scribes in the go-live period. Scribes improved go-live morning and overnight shifts, while lengthening provider to disposition during afternoon shifts. No significant differences were seen in the adoption period, except for increased provider to disposition time overnight with scribes (154 vs 146, p = 0.030). Pediatrics: When all pediatric patients were compared, scribe patients had a decreased professional RVU charge (2.78 vs 2.90, p = 0.037). During go live and adoption, no significant differences were found in any other parameter or subgrouping.

Conclusions: A scribe's ability to mitigate operational inefficiencies introduced by an EMR transition seems limited in an academic hospital. Previous research highlighting the impact of scribes on revenue was not replicated during this study.
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http://dx.doi.org/10.1016/j.ajem.2019.158433DOI Listing
August 2020

Ongoing and Focused Provider Performance Evaluations in Emergency Medicine: Current Practices and Modified Delphi to Guide Future Practice.

Am J Med Qual 2020 Jul/Aug;35(4):306-314. Epub 2019 Sep 13.

Mayo Clinic Department of Emergency Medicine, Rochester, MN.

The Joint Commission requires ongoing and focused provider performance evaluations (OPPEs/FPPEs). The authors aim to describe current approaches in emergency medicine (EM) and identify consensus-based best practice recommendations. An online survey was distributed to leaders in EM to gain insight into current practices. A modified Delphi approach was then used to develop consensus to recommend best practice. A variety of strategies are currently in use for OPPE/FPPE. "Peer reviewed cases with opportunity for improvement" was identified as a preferred metric for OPPE. Although the preference was for use of peer review in OPPE, a consistent and standard adoption of robust internal care review processes is needed to establish expected norms. National benchmarking is not available currently. This was a limited survey of self-identified leaders, and there is an opportunity for additional engagement of leaders in EM to identify a unified approach that appropriately relates to patient outcomes.
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http://dx.doi.org/10.1177/1062860619874113DOI Listing
September 2019

Single-Cell Analysis of Crohn's Disease Lesions Identifies a Pathogenic Cellular Module Associated with Resistance to Anti-TNF Therapy.

Cell 2019 09 29;178(6):1493-1508.e20. Epub 2019 Aug 29.

Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address:

Clinical benefits of cytokine blockade in ileal Crohn's disease (iCD) are limited to a subset of patients. Here, we applied single-cell technologies to iCD lesions to address whether cellular heterogeneity contributes to treatment resistance. We found that a subset of patients expressed a unique cellular module in inflamed tissues that consisted of IgG plasma cells, inflammatory mononuclear phagocytes, activated T cells, and stromal cells, which we named the GIMATS module. Analysis of ligand-receptor interaction pairs identified a distinct network connectivity that likely drives the GIMATS module. Strikingly, the GIMATS module was also present in a subset of patients in four independent iCD cohorts (n = 441), and its presence at diagnosis correlated with failure to achieve durable corticosteroid-free remission upon anti-TNF therapy. These results emphasize the limitations of current diagnostic assays and the potential for single-cell mapping tools to identify novel biomarkers of treatment response and tailored therapeutic opportunities.
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http://dx.doi.org/10.1016/j.cell.2019.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060942PMC
September 2019