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Results: 1 to 10 of 460

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Risk-stratified Management to Remove Low-Risk Penicillin Allergy Labels in the ICU.
Stone CA, Stollings JL, Lindsell CJ, Dear ML, Buie RB, Rice TW, Phillips EJ
(2020) Am J Respir Crit Care Med 201: 1572-1575
MeSH Terms: Amoxicillin, Anti-Bacterial Agents, Diagnostic Errors, Drug Hypersensitivity, Humans, Intensive Care Units, Penicillins, Risk Assessment, Skin Tests
Added March 30, 2020
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9 MeSH Terms
An autoimmune-based, paraneoplastic neurologic syndrome following checkpoint inhibition and concurrent radiotherapy for merkel cell carcinoma: case report.
Sherry AD, Bezzerides M, Khattab MH, Luo G, Ancell KK, Kirschner AN
(2020) Strahlenther Onkol 196: 664-670
MeSH Terms: Aged, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Immunological, Antineoplastic Combined Chemotherapy Protocols, Autoimmune Diseases of the Nervous System, Axilla, Carboplatin, Carcinoma, Merkel Cell, Combined Modality Therapy, Deglutition Disorders, Etoposide, Fatal Outcome, Fingers, Hallucinations, Humans, Lymphatic Metastasis, Male, Neuralgia, Palliative Care, Paraneoplastic Syndromes, Nervous System, Parenteral Nutrition, Total, Pneumonia, Aspiration, Positron Emission Tomography Computed Tomography, Radioimmunotherapy, Radiotherapy, High-Energy, Radiotherapy, Intensity-Modulated, Skin Neoplasms
Show Abstract · Added March 3, 2020
PURPOSE - Merkel cell carcinoma is highly sensitive to both radiation and immunotherapy. Moreover, concurrent radioimmunotherapy may capitalize on anti-tumor immune activity and improve Merkel cell treatment response, although an enhanced immune system may cross-react with native tissues and lead to significant sequelae.
METHODS - Here we present a case study of a patient with metastatic Merkel cell carcinoma treated with radiotherapy concurrent with pembrolizumab.
RESULTS - After radioimmunotherapy, the patient developed sensory neuropathy, visual hallucinations, and mixed motor neuron findings. Neurologic dysfunction progressed to profound gastrointestinal dysmotility necessitating parenteral nutrition and intubation with eventual expiration.
CONCLUSION - This case represents a unique autoimmune paraneoplastic neurologic syndrome, likely specific to neuroendocrine tumors and motivated by concurrent radioimmunotherapy. Recognition of the potential role of radioimmunotherapy may provide an advantage in anticipating these severe sequelae.
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27 MeSH Terms
Regulation of tissue iron homeostasis: the macrophage "ferrostat".
Winn NC, Volk KM, Hasty AH
(2020) JCI Insight 5:
MeSH Terms: Adipose Tissue, Animals, Bone Marrow, Bone and Bones, Central Nervous System, Disease, Erythropoiesis, Health, Homeostasis, Humans, Iron, Liver, Macrophages, Muscle, Skeletal, Myocardium, Pancreas, Skin, Spleen, Wound Healing
Show Abstract · Added March 3, 2020
Iron is an essential element for multiple fundamental biological processes required for life; yet iron overload can be cytotoxic. Consequently, iron concentrations at the cellular and tissue level must be exquisitely governed by mechanisms that complement and fine-tune systemic control. It is well appreciated that macrophages are vital for systemic iron homeostasis, supplying or sequestering iron as needed for erythropoiesis or bacteriostasis, respectively. Indeed, recycling of iron through erythrophagocytosis by splenic macrophages is a major contributor to systemic iron homeostasis. However, accumulating evidence suggests that tissue-resident macrophages regulate local iron availability and modulate the tissue microenvironment, contributing to cellular and tissue function. Here, we summarize the significance of tissue-specific regulation of iron availability and highlight how resident macrophages are critical for this process. This tissue-dependent regulation has broad implications for understanding both resident macrophage function and tissue iron homeostasis in health and disease.
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19 MeSH Terms
Penicillin Allergy.
Castells M, Khan DA, Phillips EJ
(2019) N Engl J Med 381: 2338-2351
MeSH Terms: Adult, Anaphylaxis, Anti-Bacterial Agents, Child, Desensitization, Immunologic, Drug Hypersensitivity, Humans, Immunologic Tests, Penicillins, Skin Tests
Added March 30, 2020
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MeSH Terms
Single-cell transcriptomics reveal polyclonal memory T-cell responses in skin with positive abacavir patch test results.
Redwood AJ, Rwandamuriye F, Chopra A, Leary S, Ram R, McDonnell W, Konvinse K, White K, Pavlos R, Koelle DM, Mallal S, Phillips EJ
(2019) J Allergy Clin Immunol 144: 1413-1416.e7
MeSH Terms: Aged, Anti-HIV Agents, Arthralgia, CD8-Positive T-Lymphocytes, Dideoxynucleosides, Drug Hypersensitivity, Drug-Related Side Effects and Adverse Reactions, Gene Expression Profiling, HLA-B Antigens, Headache, Humans, Immunologic Memory, Lymphocyte Activation, Male, Myalgia, Patch Tests, Single-Cell Analysis, Skin
Added March 30, 2020
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18 MeSH Terms
Cephalosporin Allergy: Current Understanding and Future Challenges.
Khan DA, Banerji A, Bernstein JA, Bilgicer B, Blumenthal K, Castells M, Ein D, Lang DM, Phillips E
(2019) J Allergy Clin Immunol Pract 7: 2105-2114
MeSH Terms: Anaphylaxis, Basophil Degranulation Test, Cephalosporins, Cross Reactions, Desensitization, Immunologic, Drug Eruptions, Drug Hypersensitivity, Humans, Perioperative Period, Pharmacogenomic Variants, Serum Sickness, Skin Tests, beta-Lactams
Show Abstract · Added March 30, 2020
Cephalosporins are commonly used antibiotics both in hospitalized patients and in outpatients. Hypersensitivity reactions to cephalosporins are becoming increasingly common with a wide range of immunopathologic mechanisms. Cephalosporins are one of the leading causes for perioperative anaphylaxis and severe cutaneous adverse reactions. Patients allergic to cephalosporins tend to tolerate cephalosporins with disparate R1 side chains but may react to other beta-lactams with common R1 side chains. Skin testing for cephalosporins has not been well validated but appears to have a good negative predictive value for cephalosporins with disparate R1 side chains. In vitro tests including basophil activation tests have lower sensitivity when compared with skin testing. Rapid drug desensitization procedures are safe and effective and have been used successfully for immediate and some nonimmediate cephalosporin reactions. Many gaps in knowledge still exist regarding cephalosporin hypersensitivity.
Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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13 MeSH Terms
Immune-mediated adverse reactions to vaccines.
Stone CA, Rukasin CRF, Beachkofsky TM, Phillips EJ
(2019) Br J Clin Pharmacol 85: 2694-2706
MeSH Terms: Guillain-Barre Syndrome, Humans, Hypersensitivity, Delayed, Hypersensitivity, Immediate, Immunocompromised Host, Immunoglobulin E, Skin Tests, T-Lymphocytes, Vaccination, Vaccine Excipients, Vaccines
Show Abstract · Added March 30, 2020
Vaccination continues to be the single most important and successful public health intervention, due to its prevention of morbidity and mortality from prevalent infectious diseases. Severe immunologically mediated reactions are rare and less common with the vaccine than the true infection. However, these events can cause public fearfulness and loss of confidence in the safety of vaccination. In this paper, we perform a systematic literature search and narrative review of immune-mediated vaccine adverse events and their known and proposed mechanisms, and outline directions for future research. Improving our knowledge base of severe immunologically mediated vaccine reactions and their management drives better vaccine safety and efficacy outcomes.
© 2019 The British Pharmacological Society.
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11 MeSH Terms
Identification of drug-specific public TCR driving severe cutaneous adverse reactions.
Pan RY, Chu MT, Wang CW, Lee YS, Lemonnier F, Michels AW, Schutte R, Ostrov DA, Chen CB, Phillips EJ, Mallal SA, Mockenhaupt M, Bellón T, Tassaneeyakul W, White KD, Roujeau JC, Chung WH, Hung SI
(2019) Nat Commun 10: 3569
MeSH Terms: Adoptive Transfer, Adult, Aged, Animals, Carbamazepine, Disease Models, Animal, Female, HLA-B15 Antigen, Humans, Male, Mice, Transgenic, Middle Aged, Receptor-CD3 Complex, Antigen, T-Cell, Receptors, Antigen, T-Cell, alpha-beta, Severity of Illness Index, Skin, Stevens-Johnson Syndrome, T-Lymphocytes, Cytotoxic
Show Abstract · Added March 30, 2020
Drug hypersensitivity such as severe cutaneous adverse reactions (SCAR), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), could be life-threatening. Here, we enroll SCAR patients to investigate the T cell receptor (TCR) repertoire by next-generation sequencing. A public αβTCR is identified from the cytotoxic T lymphocytes of patients with carbamazepine-SJS/TEN, with its expression showing drug/phenotype-specificity and an bias for HLA-B*15:02. This public αβTCR has binding affinity for carbamazepine and its structural analogs, thereby mediating the immune response. Adoptive transfer of T cell expressing this public αβTCR to HLA-B*15:02 transgenic mice receiving oral administration of carbamazepine induces multi-organ injuries and symptoms mimicking SCAR, including hair loss, erythema, increase of inflammatory lymphocytes in the skin and blood, and liver and kidney dysfunction. Our results not only demonstrate an essential role of TCR in the immune synapse mediating SCAR, but also implicate potential clinical applications and development of therapeutics.
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MeSH Terms
Beta-Lactam and Sulfonamide Allergy Testing Should Be a Standard of Care in Immunocompromised Hosts.
Trubiano JA, Slavin MA, Thursky KA, Grayson ML, Phillips EJ
(2019) J Allergy Clin Immunol Pract 7: 2151-2153
MeSH Terms: Anti-Bacterial Agents, Chemoprevention, Drug Hypersensitivity, Humans, Immunocompromised Host, Penicillins, Self Report, Skin Tests, Sulfonamides, Trimethoprim, Sulfamethoxazole Drug Combination, beta-Lactams
Show Abstract · Added March 30, 2020
Antibiotic allergies are reported in up to 1 in 4 immunocompromised hosts with significant impacts on antibiotic utilization and patient outcomes. Health services programs focused on de-labeling beta-lactam and sulfonamide allergy labels should be a standard of care in immunocompromised hosts.
Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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11 MeSH Terms
p73 regulates epidermal wound healing and induced keratinocyte programming.
Beeler JS, Marshall CB, Gonzalez-Ericsson PI, Shaver TM, Santos Guasch GL, Lea ST, Johnson KN, Jin H, Venters BJ, Sanders ME, Pietenpol JA
(2019) PLoS One 14: e0218458
MeSH Terms: Animals, Cell Proliferation, DNA Damage, Ectoderm, Epithelial Cells, Gene Expression Regulation, Developmental, Hair Follicle, Humans, Keratinocytes, Mice, Mice, Knockout, Single-Cell Analysis, Skin, Stem Cell Niche, Trans-Activators, Tumor Protein p73, Wound Healing
Show Abstract · Added June 28, 2019
p63 is a transcriptional regulator of ectodermal development that is required for basal cell proliferation and stem cell maintenance. p73 is a closely related p53 family member that is expressed in select p63-positive basal cells and can heterodimerize with p63. p73-/- mice lack multiciliated cells and have reduced numbers of basal epithelial cells in select tissues; however, the role of p73 in basal epithelial cells is unknown. Herein, we show that p73-deficient mice exhibit delayed wound healing despite morphologically normal-appearing skin. The delay in wound healing is accompanied by decreased proliferation and increased levels of biomarkers of the DNA damage response in basal keratinocytes at the epidermal wound edge. In wild-type mice, this same cell population exhibited increased p73 expression after wounding. Analyzing single-cell transcriptomic data, we found that p73 was expressed by epidermal and hair follicle stem cells, cell types required for wound healing. Moreover, we discovered that p73 isoforms expressed in the skin (ΔNp73) enhance p63-mediated expression of keratinocyte genes during cellular reprogramming from a mesenchymal to basal keratinocyte-like cell. We identified a set of 44 genes directly or indirectly regulated by ΔNp73 that are involved in skin development, cell junctions, cornification, proliferation, and wound healing. Our results establish a role for p73 in cutaneous wound healing through regulation of basal keratinocyte function.
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17 MeSH Terms