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Drug allergy delabeling programs have become an essential element of antibiotic stewardship. Development of delabeling programs involves careful selection of target patient population, thoughtful design of delabeling approach, stakeholder engagement, assembly of key team members, implementation, and evaluation of clinical and safety outcomes. Recent programs have targeted patients thought to be most likely to benefit from removal of inaccurate antibiotic allergy labels, those with β-lactam antibiotic allergies and high-risk populations likely to need β-lactam antibiotics as first-line treatment. This review provides an overview of current risk stratification methods and β-lactam cross-reactivity data and summarizes how different inpatient and outpatient delabeling programs have used these concepts in delabeling algorithms. β-Lactam delabeling programs for inpatients, pediatric patients, and programs utilizing telehealth have been implemented with good outcomes. This review also focuses on delabeling programs for high-risk populations likely to benefit from first-line β-lactam antibiotics. These populations include perioperative, prenatal, and immunocompromised patients. Delabeling programs have been successful in the inpatient and outpatient settings at enabling appropriate antibiotic use. This article reviews delabeling strategies utilized by these programs with a focus on highlighting elements key to their success and future areas for innovation.

BackgroundPolyethylene glycol (PEG) and polysorbate reactions were initially implicated as a likely risk factor for reacting to coronavirus disease 2019 (COVID-19) vaccines and remain a source of vaccine hesitancy despite increasing evidence that they do not pose an increased risk for COVID-19 vaccine reactions.ObjectiveTo investigate COVID-19 vaccine safety outcomes in patients with reported reactions to PEG- and polysorbate-containing medications and vaccines.MethodsCOVID-19 vaccine safety was reviewed in patients with PEG or polysorbate reactions documented in their electronic medical records at a tertiary academic medical center (cohort 1) and patients referred to Allergy and Immunology with reported PEG or polysorbate reactions (cohort 2). COVID-19 vaccine safety was also reviewed following reported symptoms (onset ≤ 12 hours) to first-dose PEG-containing messenger RNA (mRNA) COVID-19 vaccine (cohort 3).ResultsOf 252 patients in cohort 1 (n=202) and cohort 2 (n=50), 236 (94%) received mRNA COVID-19 vaccines (106 Pfizer, 130 Moderna); 235 received both doses. Only 3 patients from cohort 2 developed mild rash following vaccination. None of the 44 patients in cohort 3 with acute symptoms following first-dose mRNA COVID-19 vaccine (27 Pfizer, 17 Moderna) had previously reported PEG or polysorbate reactions. Of these 44 patients, 43 received the second dose and all 3 who developed symptoms following the second dose (1 required epinephrine) had negative PEG skin testing.ConclusionPatients with reported reactions to PEG and polysorbate safely received COVID-19 vaccines. PEG and polysorbate skin testing did not identify patients at risk for first dose or recurrent reactions to COVID-19 vaccines. Screening for PEG and polysorbate allergy may only increase vaccine hesitancy without identifying patients at risk for COVID-19 vaccine reactions.

Secondary hypogammaglobulinemia (SHG) is characterized by reduced immunoglobulin levels due to acquired causes of decreased antibody production or increased antibody loss. Clarification regarding whether the hypogammaglobulinemia is secondary or primary is important because this has implications for evaluation and management. Prior receipt of immunosuppressive medications and/or presence of conditions associated with SHG development, including protein loss syndromes, are histories that raise suspicion for SHG. In patients with these histories, a thorough investigation of potential etiologies of SHG reviewed in this report is needed to devise an effective treatment plan focused on removal of iatrogenic causes (eg, discontinuation of an offending drug) or treatment of the underlying condition (eg, management of nephrotic syndrome). When iatrogenic causes cannot be removed or underlying conditions cannot be reversed, therapeutic options are not clearly delineated but include heightened monitoring for clinical infections, supportive antimicrobials, and in some cases, immunoglobulin replacement therapy. This report serves to summarize the existing literature regarding immunosuppressive medications and populations (autoimmune, neurologic, hematologic/oncologic, pulmonary, posttransplant, protein-losing) associated with SHG and highlights key areas for future investigation.

OBJECTIVE: To review the virology, immunology, epidemiology, clinical manifestations, and treatment of the three major zoonotic coronavirus epidemics: severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19). DATA SOURCES: Published literature obtained through PubMed database searches and reports from national and international public health agencies. STUDY SELECTIONS: Studies relevant to the basic science, epidemiology, clinical characteristics, and treatment of SARS, MERS, and COVID-19 with a focus on patients with asthma, allergy, and primary immunodeficiency. RESULTS: Whereas SARS and MERS each caused less than a thousand deaths, COVID-19 has caused a worldwide pandemic with nearly 1 million deaths. Diagnosing COVID-19 relies of nucleic acid amplification tests, and infection has broad clinical manifestations that can affect almost every organ system. Asthma and atopy do not appear to predispose patients to COVID-19 infection, but their effects on COVID-19 clinical outcomes remain mixed and inconclusive. It is recommended that effective therapies, including inhaled corticosteroids and biologic therapy, be continued to maintain disease control. There are no reports of COVID-19 among patients with primary innate and T-cell deficiencies. The presentation of COVID-19 among patients with primary antibody deficiencies is variable, with some experiencing mild clinical courses while others experiencing fatal. The landscape of treatment for COVID-19 is rapidly evolving, with both antivirals and immunomodulators currently with demonstrated efficacy. CONCLUSION: Further data is needed to better understand the role of asthma, allergy, and primary immunodeficiency on COVID-19 infection and outcomes.

Background Patients with cystic fibrosis (CF) often have a history of antibiotic adverse drug reactions (ADRs) that pose a barrier to receiving recommended first-line treatment. Targeted antibiotic allergy evaluations are increasingly recognized as an important strategy for optimization of antimicrobial stewardship. Objective To improve first-line antibiotic use in patients with CF with antibiotic ADRs by streamlining access to antibiotic allergy evaluations and standardizing documentation of plans for antibiotic reintroduction. Methods We incorporated allergy evaluations into a multidisciplinary CF clinic and used telemedicine when allergy evaluations could not be performed during CF clinic. Standard documentation of antibiotic allergy plans was used to enable safe reintroduction of first-line antibiotics by CF providers. Results Strategies used in this study allowed 81.3% (26 of 32) of patients with CF to receive allergy evaluations and antibiotic allergy plans for prioritized antibiotics (penicillin, cephalosporin, sulfonamide), with removal of 41.0% (16 of 39) of prioritized antibiotic ADRs. Only 5.1% (2 of 39) of prioritized antibiotic ADRs evaluated required strict avoidance after evaluation. There were 9 patients who received at least 1 prioritized antibiotic, with 66.6% (6 of 9) of these patients given the antibiotic after only 1 allergy evaluation visit. Furthermore, these strategies allowed allergy evaluations of 23 nonprioritized antibiotics to occur, with removal of the ADR in 39.1% (9 of 23) and use of 77.8% (7 of 9) of nonprioritized antibiotics after removal. Conclusion Incorporating allergy evaluations into a multidisciplinary CF clinic can liberalize first-line antibiotic use in patients with CF. Standard documentation of antibiotic allergy plans allowed antibiotic reintroduction to occur even before complete removal of documented antibiotic ADRs.

BACKGROUND: Coronavirus disease 2019 (COVID-19) necessitated wide-scale adoption of telemedicine (TM) and restriction of in-person care. The impacts on allergy/immunology (A/I) care delivery are still being studied. OBJECTIVE: To describe the outcomes of rapid transition to TM-based care (video visit followed by in-person visits dedicated to diagnostic and therapeutic procedures when needed) at an academic A/I practice during COVID-19. METHODS: Demographic data were compared for patients originally scheduled for in-person visits between March 10, 2020, and April 30, 2020, who completed a video visit instead between March 10, 2020, and June 30, 2020, and those who did not. Appointment completion, diagnoses, and drug allergy and skin testing completion were compared for visits between March 10, 2020, and June 30, 2020, and 1 year prior (March 10, 2019-June 30, 2019). RESULTS: Sixty-nine percent (265 of 382) of patients originally scheduled between March 10, 2020, and April 30, 2020, were able to complete video visits. Patients who completed video visits were more likely to be white (52% vs 33%; P < .001), English-speaking (96% vs 89%; P = .01), and privately insured (70% vs 54%; P = .004). With TM-based care compared with in-person care, there were significant decreases in environmental and food skin testing completion rates (91% and 92% in 2019 vs 60% and 64% in 2020, respectively, P < .001). Drug allergy testing completed after internal referral remained low but comparable (51% in 2019 vs 52% in 2020). Transitioning nonprocedural visits to video allowed allergen immunotherapy and biologic injection visits to resume at a volume similar to pre-COVID. No COVID-19 infections resulted from in-clinic exposure. CONCLUSIONS: Although transitioning to TM-based care allowed continued A/I care delivery, strategies are needed to achieve higher testing completion rates and ensure video visits do not exacerbate existing health disparities.

Muons have been utilized to see through large structures such as the pyramids. The accelerated muons can have high intensity and monochromatic energy, allowing for better resolution imaging in less time.

Background Percutaneous coronary intervention (PCI) is often complicated by periprocedural myocardial injury (PMI) manifested by elevated cardiac biomarkers. The occurrence of PMI has been shown to be associated with worse clinical outcome over short- and long-term. Purpose We performed multidetector computed tomography (MDCT) and cardiac magnetic resonance imaging (CMR) to evaluate the relationship between culprit plaque characteristics and PMI. Methods A total of 90 patients who underwent elective PCI were underwent CMR and multidetector coronary tomography before PCI. The high intensity plaque (HIP) on CMR was defined as a coronary plaque to myocardium signal intensity ratio (PMR) of >1.4. The plaque characteristics and the presence of napkin-ring sign (NRS) were analyzed on MDCT. PMI was defined as an increase in cardiac Troponin T levels to more than 5 times the upper limit of normal at 24 h after PCI. Patients were divided into 2 groups according to the presence (Group I, n=26) or absence (Group II, n=64) of PMI. Results Spotty calcification, positive remodeling, low attenuation plaque and NRS on MDCT were significantly more observed in Group I than in Group II. HIP on CMR was significantly more observed in Group I than in Group II. In the multivariable logistic regression analysis, the presence of NRS and HIP were significantly independent predictors of PMI (odds ratio (OR) 4.82, 95% confidence interval 1.13–20.60, P=0.034 and OR 3.66, 95% CI 1.09–12.30, P=0.036, respectively). Moreover, for prediction of PMI, NRS and HIP showed a high positive predictive value of 81%, and their absence showed a high negative predictive value of 91%. Conclusions MDCT and CMR may play an important role in detecting which lesions are high risks for myocardial necrosis after PCI in elective coronary stenting. Funding Acknowledgement Type of funding source: None

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The interplay among magnetism, electronic nematicity, and superconductivity is the key issue in strongly correlated materials including iron-based, cuprate, and heavy-fermion superconductors. Magnetic fluctuations have been widely discussed as a pairing mechanism of unconventional superconductivity, but recent theory predicts that quantum fluctuations of nematic order may also promote high-temperature superconductivity. This has been studied in FeSe1−xSx superconductors exhibiting nonmagnetic nematic and pressure-induced antiferromagnetic orders, but its abrupt suppression of superconductivity at the nematic end point leaves the nematic-fluctuation driven superconductivity unconfirmed. Here we report on systematic studies of high-pressure phase diagrams up to 8 GPa in high-quality single crystals of FeSe1−xTex. When Te composition x(Te) becomes larger than 0.1, the high-pressure magnetic order disappears, whereas the pressure-induced superconducting dome near the nematic end point is continuously found up to x(Te) ≈ 0.5. In contrast to FeSe1−xSx, enhanced superconductivity in FeSe1−xTex does not correlate with magnetism but with the suppression of nematicity, highlighting the paramount role of nonmagnetic nematic fluctuations for high-temperature superconductivity in this system., Despite studies in FeSe1−xSx, it is yet unconfirmed whether nematic fluctuation can induce superconductivity. Here, the authors study single crystals of FeSe1−xTex showing enhanced superconductivity upon suppression of nematicity.

Key Clinical Message Diffuse cutaneous mastocytosis (DCM) is a rare but potentially fatal condition when diagnosis and targeted treatments are delayed. This case illustrates the life‐threatening complications in DCM and reviews the currently available treatments. To our knowledge, this is the first report of mastocytosis with somatic K509I mutation and concomitant tuberous sclerosis.

Purpose Severe hypogammaglobulinemia (HG) in lung transplant recipients is associated with increased infections and one-year mortality. As standard protocols for HG screening and management do not exist, we surveyed lung transplant centers to characterize current practices in HG screening and management. Methods We created a survey which was reviewed by three experts in Lung Transplant Pulmonology and Allergy/Immunology. The survey consisted of eight long-answer questions, four yes/no questions, and three checkbox questions focused on IgG measurement and HG treatment practices pre- and post-lung transplant. We sent the survey to 50 physicians at 40 transplant centers internationally using Google Forms on February 4th, 2020. Results There were 24 (48%, 24/50) respondents from 19 lung transplant centers. Responses were tabulated for individual respondents as answers varied within centers. Respondents reported routinely measuring IgG levels in 54% (13/24) of pre-transplant patients and 38% (9/24) of post-transplant patients, with time points for checking IgG levels varying widely. In post-transplant patients with frequent infections, respondents reported routinely measuring IgG levels (83%, 20/24), routinely not measuring (13%, 3/24), or not having a protocol (4%, 1/24). Reported criteria for initiating IgG replacement therapy (IgG-RT) were infection frequency only (n=2), IgG level only (n=6), or some combination of the two (n=9). IgG level cutoffs utilized to initiate IgG-RT ranged from Conclusion HG screening and management practices in lung transplant recipients vary greatly, potentially leaving patients vulnerable to worse clinical outcomes. Reported barriers include lack of guidance regarding HG treatment criteria and difficulties obtaining IgG-RT. Involving immunologists in screening and treatment decision-making could mitigate some of these barriers.

Hypersensitivity reactions to platinum agents are common. For carboplatin and cisplatin, the first hypersensitivity reaction typically occurs around the second and third re-exposure during the second line of therapy (eighth and ninth courses overall). For oxaliplatin, the first hypersensitivity reaction can occur throughout the treatment course. Skin testing helps risk stratify patients to appropriate desensitization protocols and assess risk for breakthrough HSRs during desensitization. A risk-stratification protocol using 3 serial skin tests and desensitization protocols enables patients with platinum agent hypersensitivity to receive first-line chemotherapy treatment safely.

Acquired angioedema due to C1-INH deficiency (C1-INH-AAE) can occur when there are acquired (not inherited) deficiencies of C1-INH. A quantitative or functional C1-INH deficiency with negative family history and low C1q is diagnostic of C1-INH-AAE. The most common conditions associated with C1-INH-AAE are autoimmunity and B-cell lymphoproliferative disorders. A diagnosis of C1-INH-AAE can precede a diagnosis of lymphoproliferative disease and confers an increased risk for developing non-Hodgkin lymphoma. Treatment focuses on symptom control with therapies that regulate bradykinin activity (C1-INH concentrate, icatibant, ecallantide, tranexamic acid, androgens) and treatment of any underlying conditions.

Purpose Severe hypogammaglobulinemia (HG), IgG Methods We developed and implemented standard pre-/post-LT IgG screening protocols through iterative PDSA cycles starting 1/1/19. We collected pre-/post- IgG levels for LT recipients between 1/1/94-10/15/20 to measure process outcomes and inform future improvements. Results Both pre- and post-LT IgG screening increased after screening protocols were implemented (Table). Of 45 patients who underwent LT between 1/1/17-10/15/20 and had pre-LT IgG checked, 0% (0) had severe HG, 11% (5) HG (IgG 400-700 mg/dL), 9% (4) isolated low IgG subclasses, 4% (2) isolated low IgA, and 13% (6) isolated low IgM. All 5 patients with pre-LT HG, 2 with associated low IgA and/or IgM, developed severe or clinically significant HG post-LT requiring IgG Replacement Therapy (IgG-RT). Of 249 patients who underwent LT before 6/30/20 and had post-LT IgG checked, severe HG rates were 17% (8/48), 7% (4/60), 5% (3/56), 14% (8/56), 11% (6/53), 6% (3/48), 3% (1/34), and 3% (1/35) at 0.5, 1, 2, 3, 6, 12, 18, and 24 months. Median [range] time from LT to severe HG onset was 90 [14-730] days. Time from severe HG onset to recovery was 31 [16-184] days in 9 patients whose severe HG resolved without IgG-RT. IgG-RT was started in 28 patients 212 [0-3533] days after LT per immunology recommendation. Pre-LT IgG (r=0.78, p=0) and IgG3 (r=0.82, p=0) correlated with the lowest IgG level post-LT. Pre-LT CD27+ (r=-0.58, p=0.007) and CD27+IgM+IgD+ (r=-0.52, p=0.02) B cells inversely correlated with the lowest IgG level post-LT. Conclusion Implementation of standard HG screening protocols increased detection of severe HG post-LT and revealed novel findings regarding the significance of immunologic abnormalities in LT recipients.

The goal of this paper is to review the major adverse cutaneous reactions that have been reported to the most commonly used biologics. Anti-TNF agents and immune checkpoint inhibitors have significant, immune-mediated cutaneous manifestations that can necessitate discontinuation. Anti-TNF agents, IL-6 inhibitors, and IL-12/23 inhibitors can paradoxically cause psoriasis flares or unmask previously undiagnosed psoriasis. IL-17 inhibitors are unique in increasing risk for Candida infections. Benign injection site reactions, non-specific rash, cellulitis, and hypersensitivity reactions are relatively common adverse events. A wide variety of cutaneous reactions caused by biologics have been reported, ranging from benign injection site reactions to life-threatening cutaneous reactions necessitating discontinuation of the implicated biologic agent.

Measurement of the longitudinal bunch size is important for the stable beam operation. Especially in a medium energy beam transport (MEBT) located after a radio-frequency quadrupole in J-PARC, it is necessary to measure the bunch size with minimum set of equipment to avoid subsequent emittance growth due to space charge. We had proposed a longitudinal size measurement with an rf deflector normally used for deflecting theμbunch; phase spread is migrated to spatial one if the reference particle arrives at the deflector when the voltage is rising in time and is zero. Then a buncher cavity located upstream of the deflector is utilized to scan the phase spread to measure the longitudinal beam parameters. In this poster, recent measurement results are presented., Proceedings of the 9th Int. Particle Accelerator Conf., IPAC2018, Vancouver, BC, Canada

Corticosteroids can cause both immediate and delayed immune hypersensitivity reactions. Adverse immune reactions to corticosteroids can be triggered by the corticosteroid itself, or by ingredients contained in corticosteroid preparations. Immediate hypersensitivity reactions manifest with IgE-mediated symptoms, including anaphylaxis, urticaria and bronchospasm, typically within an hour after corticosteroid administration. Skin testing and graded challenge can be useful diagnostic tools when evaluating immediate hypersensitivity reactions. Cross-reactivity patterns have not been observed between corticosteroid classes for immediate hypersensitivity reactions. Delayed hypersensitivity reactions typically present as a contact dermatitis to topical corticosteroids. Patch testing can help identify the culprit agent(s), and cross-reactivity patterns based on corticosteroid structure have been observed for delayed hypersensitivity.

Hypersensitivity reactions to platinum agents are common. For carboplatin and cisplatin, the first hypersensitivity reaction typically occurs around the second and third re-exposure during the second line of therapy (eighth and ninth courses overall). For oxaliplatin, the first hypersensitivity reaction can occur throughout the treatment course. Skin testing helps risk stratify patients to appropriate desensitization protocols and assess risk for breakthrough HSRs during desensitization. A risk-stratification protocol using 3 serial skin tests and desensitization protocols enables patients with platinum agent hypersensitivity to receive first-line chemotherapy treatment safely.

Immunoglobulin (Ig) E-mediated food allergy and eosinophilic esophagitis (EoE) are chronic, allergen-mediated disorders characterized by an aberrant TH2 immune response. The development and investigation of biologics for the treatment of IgE-mediated food allergy and eosinophilic esophagitis have provided further insight into the pathophysiology and management of these disorders. This article provides an overview of biologic therapies that are being investigated or have potential as treatments for IgE-mediated food allergy and eosinophilic esophagitis. Identification of EoE phenotypes that are responsive to biologics and investigation of biologics combined with other therapies may help elucidate a role for biologics in EoE.

Background Hypersensitivity reactions (HSRs) are a common impediment to paclitaxel therapy. Management strategies to guide care after a paclitaxel-induced HSR are needed. Objective The objective was to evaluate the utility and safety of risk stratification on the basis of severity of the initial HSR. Methods A risk stratification pathway was developed on the basis of a retrospective review of the management and outcome of 130 patients with paclitaxel-induced HSRs at Massachusetts General Hospital. This pathway was then studied prospectively in patients referred to Allergy/Immunology with paclitaxel-induced HSRs. Results The study population (n = 35) had a mean age of 56.1 ± 12 years and most were women (n = 33 [94%]). All 5 patients (15%) with grade 1 initial HSRs were successfully reexposed to paclitaxel, 1 patient at the standard infusion rate and 4 patients at 50% of the standard infusion rate. Thirty patients (85%) with grade 2 to 4 initial HSRs underwent initial paclitaxel desensitization based on the risk stratification pathway. No patients developed severe HSRs using the pathway. Eleven (31%) patients had HSRs that were mild to moderate in nature (grade 1, n = 4 [11%]; grade 2, n = 6 [17%]; grade 3, n = 1 [3%]) during their first desensitization. Sixteen (46%) of the 35 patients safely returned to the outpatient infusion setting for paclitaxel treatment at 50% of the standard infusion rate. Seven (20%) discontinued paclitaxel before the completion of the risk stratification pathway because of disease progression, completion of therapy, or death. Conclusions A management strategy using the initial HSR severity for risk stratification allowed patients to receive paclitaxel safely.