Chronic Spontaneous Urticaria: An Update on the Evaluation and Management.

Chronic spontaneous urticaria (CSU) affects 0.5% to 1% of the general population and is often managed by allergy and immunology specialists. Guidelines have evolved over the past several decades with an emphasis on decreasing extensive screening laboratory testing as they are of low-yield and cost-ineffective. The utility of biomarkers remains under investigation but total immunoglobulin E may be helpful in determining specific endotypes and response to omalizumab. Antihistamines and omalizumab remain the primary therapeutic options for CSU, but an expanding body of evidence supports the use of immunosuppressants and anti-inflammatory medications in refractory cases.

The Impact of Prior Authorization on Clinical Practice and Patient Care Outcomes: A Work Group Report of the AAAAI Prior Authorization Task Force.

The Prior Authorization Task Force of the American Academy of Allergy, Asthma & Immunology (AAAAI), a presidential initiative of David Khan, MD, FAAAI, was established to develop an AAAAI position statement outlining ways to improve health care for our patients, to support legislation that advocates for prior authorization (PA) reform and identify the impact PA has on its membership using a questionnaire survey. This article describes the results of this survey. An electronic anonymous survey questionnaire was developed to assess the impact and burden of PA on AAAAI members and their staff and patients. Surveys were sent to randomly selected members and fellows of the AAAAI in the United States. Descriptive statistics were used to analyze the results by the Information Services team of the AAAAI and the authors of this work group report. The questionnaire responses from allergy immunology specialists demographically reflected the AAAAI membership and indicate that PAs can significantly affect patient care delivery and increase administrative burden to clinical practices, leading to serious adverse events in some circumstances. Differential responses regarding PAs for various medication classes likely reflect the physician's patient population, which can shift prescribing patterns. Prior authorization is a serious health care problem that is wasting financial resources and needlessly placing patients in danger when they are unable to access medications or medical services required for clinical management. The results of this questionnaire study support the recommendations made in the recent AAAAI position statement on PA.

Valorization of cellulosic fiber derived from waste biomass of constructed wetland as a potential reinforcement in polymeric composites: A technological approach to achieve circular economy.

This study establishes the suitability of cellulosic fibers derived from Canna indica waste biomass for utilization as a reinforcement in natural fiber polymeric composites. The waste biomass was harvested from constructed wetlands engaged in the treatment of municipal wastewater from a gated community. The extracted Canna indica (CI) fibers were studied for their physicochemical, mechanical, structural, crystallographic, and thermal characteristics and proposed as a potential alternative to synthetic fiber. The CI fibers contained a relatively higher amount of cellulose (60 wt%) and a low wax fraction (0.5 wt%) - which is advantageous for its gainful utilization as a reinforcement. The CI fibers were thermally stable up to 237 °C and have an average fiber length, diameter, and density of 4.3 mm, 842 µm, and 0.75 g/cm3, respectively. The mean maximum tensile strength and Young's modulus were found to be 113 ± 6.82 MPa and 0.8 ± 7.91 GPa, respectively. The nano-indentation test displayed the nano hardness and modulus as 0.3 ± 0.6 GPa and 1.62 ± 0.2 GPa, respectively. The crystallographic properties of CI fibers consisted of an 87.45% crystallinity index and 3.2 nm crystallite size. The morphological attributes of CI fibers showed rough surfaces and shallow cavities on the surfaces of the fibers suggesting the suitability for its utilization as a reinforcement. It is argued that this technological approach can potentially achieve circular economy through valorization of Canna indica biomass harvested from natural wastewater treatment plants.

Current and future management of chronic spontaneous urticaria and chronic inducible urticaria.

Background: Chronic urticaria (CU), characterized by ≥6 weeks of intense pruritus, remains a debilitating condition for patients. New and safe treatments are needed to manage CU recalcitrant to standard therapy. Objective: A review of the current literature of standard and novel therapeutics in the management of CU was conducted. Methods: A literature search via a medical literature data base and clinical trial data base was conducted to identify treatment options for CU and current clinical trials. Results: Second-generation antihistamines, omalizumab, and cyclosporine remain the most proven therapeutic options for CU. Dupilumab, mepolizumab, benralizumab, tezepelumab, and CDX-0159 are all undergoing clinical trials for CU. Although ligelizumab demonstrated initial promising results, a phase III study was discontinued due to a nonsuperior clinical impact compared with omalizumab. Conclusion: Novel therapies are needed for the treatment of recalcitrant CU. With a deeper understanding of the pathophysiology of CU, promising therapeutics are in clinical trials for CU.

Management paradigms for chronic rhinosinusitis in individuals with asthma: An evidence-based review with recommendations.

BACKGROUND: Despite the significant morbidity associated with chronic rhinosinusitis (CRS) in individuals with asthma (CRSwA), there is a paucity of codified, evidence-based management strategies for CRS in this population. METHODS: Using PubMed, Embase, and Cochrane Review Databases, a systematic review was performed covering management strategies for CRSwA. A total of 5903 articles were screened, and 70 were included for full-text analysis. After application of exclusion criteria, 53 articles comprised the qualitative synthesis. The level of evidence was graded and benefit-harm assessments, as well as value judgment and recommendations, were provided RESULTS: Strong evidence confirms the benefit of oral and topical medications on sinonasal-specific outcomes in individuals with CRSwA; there is low-grade evidence demonstrating that these agents improve lung function and/or asthma control. Moderate to strong evidence suggests that endoscopic sinus surgery (ESS) improves both sinonasal- and asthma-specific quality of life. Although there is insufficient to low evidence to indicate that ESS improves pulmonary function in this population, data indicate a positive impact of this intervention on asthma control. Biologic medications strongly improve both subjective and objective sinonasal- and asthma-specific outcomes. CONCLUSION: Evidence supports managing CRS in individuals with CRSwA in a stepwise fashion, starting with traditional nonbiologic oral and topical medication, and escalating to second-line treatments, such as ESS and biologics. Optimal treatment of individuals who have CRSwA often requires concurrent, directed management of asthma, as not all CRS interventions impact asthma status.

A Review of Adverse Reactions to Biologics Used in Allergy-Immunology Practice.

Biologic agents have become an integral therapeutic option for practicing allergists-immunologists for the management of asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, and various immunologic conditions. As these agents vary considerably from traditional small-molecule drugs, various adverse reactions have been noted. A different approach must be used to classify these reactions beyond the classic Gell-Coombs classification system as it does not capture many of the adverse events seen with biologic therapy. This article addresses the available literature on proposed classification systems and diagnostic modalities for adverse events associated with biologics and reviews each approved agent used frequently in allergy-immunology practice.

Deciphering the sensing of α-amyrin acetate with hs-DNA: a multipronged biological probe.

In this study, we focus on the biomimetic development of small molecules and their biological sensing with DNA. The binding of herring sperm deoxyribonucleic acid (hs-DNA) with naturally occurring bioactive small molecule α-amyrin acetate (α-AA), a biomimetic - isolated from the leaves of Ficus (F.) arnottiana is investigated. Collective information from various imaging, spectroscopic and biophysical experiments provides evidence that α-AA is a minor groove sensor of hs-DNA and preferentially binds to the A-T-rich regions. Interactions of different concentrations of small molecule α-AA with hsDNA were evaluated via various analytical techniques such as UV-Vis, circular dichroism (CD) and fluorescence emission spectroscopy. Fluorescence emission spectroscopy results suggest that α-AA decreases the emission level of hsDNA. DNA minor groove sensor Hoechst 33258 and intercalative sensor EB, melting transition analysis (T M) and viscosity analysis clarified that α-AA binds to hs-DNA via a groove site. Biophysical chemistry and molecular docking studies show that hydrophobic interactions play a major role in this binding. The present research deals with a natural product biosynthesis-linked chemical-biology interface sensor as a biological probe for α-AA: hs-DNA.

Non-IgE-Mediated Drug Hypersensitivity Reactions.

PURPOSE OF REVIEW: Non-IgE-mediated drug reactions have traditionally been poorly defined and studied, though they are the most common form of hypersensitivity. Their presentations are highly variable and can range in severity from mild, cutaneous-only reactions to severe systemic disease. RECENT FINDINGS: The most notable advance in non-IgE-mediated hypersensitivity reactions is in diagnostics. HLA alleles have traditionally been used for identifying certain patients at risk for abacavir hypersensitivity syndrome, but more recent studies have shown several other HLA alleles associated with severe cutaneous adverse reactions with various medications. This article also highlights the use of delayed intradermal testing for radiocontrast media and patch testing for delayed antibiotic reactions. Drug reactions remain a major cause of morbidity and reason for treatment changes. Non-IgE-mediated reactions have had an increase in research interest over the past decade with an increased emphasis on better understanding the clinical presentation and underlying pathophysiology.

Intelligent Spacecraft Visual GNC Architecture With the State-Of-the-Art AI Components for On-Orbit Manipulation.

Conventional spacecraft Guidance, Navigation, and Control (GNC) architectures have been designed to receive and execute commands from ground control with minimal automation and autonomy onboard spacecraft. In contrast, Artificial Intelligence (AI)-based systems can allow real-time decision-making by considering system information that is difficult to model and incorporate in the conventional decision-making process involving ground control or human operators. With growing interests in on-orbit services with manipulation, the conventional GNC faces numerous challenges in adapting to a wide range of possible scenarios, such as removing unknown debris, potentially addressed using emerging AI-enabled robotic technologies. However, a complete paradigm shift may need years' efforts. As an intermediate solution, we introduce a novel visual GNC system with two state-of-the-art AI modules to replace the corresponding functions in the conventional GNC system for on-orbit manipulation. The AI components are as follows: (i) A Deep Learning (DL)-based pose estimation algorithm that can estimate a target's pose from two-dimensional images using a pre-trained neural network without requiring any prior information on the dynamics or state of the target. (ii) A technique for modeling and controlling space robot manipulator trajectories using probabilistic modeling and reproduction to previously unseen situations to avoid complex trajectory optimizations on board. This also minimizes the attitude disturbances of spacecraft induced on it due to the motion of the robot arm. This architecture uses a centralized camera network as the main sensor, and the trajectory learning module of the 7 degrees of freedom robotic arm is integrated into the GNC system. The intelligent visual GNC system is demonstrated by simulation of a conceptual mission-AISAT. The mission is a micro-satellite to carry out on-orbit manipulation around a non-cooperative CubeSat. The simulation shows how the GNC system works in discrete-time simulation with the control and trajectory planning are generated in Matlab/Simulink. The physics rendering engine, Eevee, renders the whole simulation to provide a graphic realism for the DL pose estimation. In the end, the testbeds developed to evaluate and demonstrate the GNC system are also introduced. The novel intelligent GNC system can be a stepping stone toward future fully autonomous orbital robot systems.

Autonomous Robots for Space: Trajectory Learning and Adaptation Using Imitation.

This paper adds on to the on-going efforts to provide more autonomy to space robots and introduces the concept of programming by demonstration or imitation learning for trajectory planning of manipulators on free-floating spacecraft. A redundant 7-DoF robotic arm is mounted on small spacecraft dedicated for debris removal, on-orbit servicing and assembly, autonomous and rendezvous docking. The motion of robot (or manipulator) arm induces reaction forces on the spacecraft and hence its attitude changes prompting the Attitude Determination and Control System (ADCS) to take large corrective action. The method introduced here is capable of finding the trajectory that minimizes the attitudinal changes thereby reducing the load on ADCS. One of the critical elements in spacecraft trajectory planning and control is the power consumption. The approach introduced in this work carry out trajectory learning offline by collecting data from demonstrations and encoding it as a probabilistic distribution of trajectories. The learned trajectory distribution can be used for planning in previously unseen situations by conditioning the probabilistic distribution. Hence almost no power is required for computations after deployment. Sampling from a conditioned distribution provides several possible trajectories from the same start to goal state. To determine the trajectory that minimizes attitudinal changes, a cost term is defined and the trajectory which minimizes this cost is considered the optimal one.

Direct coordination of pterin to FeII enables neurotransmitter biosynthesis in the pterin-dependent hydroxylases.

The pterin-dependent nonheme iron enzymes hydroxylate aromatic amino acids to perform the biosynthesis of neurotransmitters to maintain proper brain function. These enzymes activate oxygen using a pterin cofactor and an aromatic amino acid substrate bound to the FeII active site to form a highly reactive FeIV = O species that initiates substrate oxidation. In this study, using tryptophan hydroxylase, we have kinetically generated a pre-FeIV = O intermediate and characterized its structure as a FeII-peroxy-pterin species using absorption, Mössbauer, resonance Raman, and nuclear resonance vibrational spectroscopies. From parallel characterization of the pterin cofactor and tryptophan substrate-bound ternary FeII active site before the O2 reaction (including magnetic circular dichroism spectroscopy), these studies both experimentally define the mechanism of FeIV = O formation and demonstrate that the carbonyl functional group on the pterin is directly coordinated to the FeII site in both the ternary complex and the peroxo intermediate. Reaction coordinate calculations predict a 14 kcal/mol reduction in the oxygen activation barrier due to the direct binding of the pterin carbonyl to the FeII site, as this interaction provides an orbital pathway for efficient electron transfer from the pterin cofactor to the iron center. This direct coordination of the pterin cofactor enables the biological function of the pterin-dependent hydroxylases and demonstrates a unified mechanism for oxygen activation by the cofactor-dependent nonheme iron enzymes.

Safety and efficacy of direct two-step penicillin challenges with an inpatient pharmacist-driven allergy evaluation.

Background: Penicillin allergy is commonly reported and has clinical and financial consequences for patients and hospitals. A penicillin evaluation program can safely delabel patients and optimize antibiotic therapy. Pharmacists who perform this task have focused on a detailed interview or penicillin skin testing (PST). Antibiotic graded challenge after PST requires more resources and is more costly than going directly to a two-step challenge. Objective: To determine whether a pharmacist-driven penicillin allergy evaluation and a testing protocol that primarily uses direct oral challenges can safely delabel patients. Methods: Adult patients (ages >18 years) with a penicillin allergy in their electronic medical record (EMR) who were admitted between September 2019 and June 2020 were eligible. Although all patients with penicillin allergy were eligible, priority was given to patients who required antibiotics. Patients were interviewed, and, if indicated, based on an institutional protocol, were tested by using PST and/or two-step oral challenge. If the patient passed the challenge, then the penicillin allergy label was removed in the EMR and the patient counseled. Demographic information, allergy questionnaire results, testing results, and changes in antimicrobial therapy were collected. Results: Fifty patients were evaluated from September 2019 to June 2020. Ninety-six percent of the patients were delabeled, and antibiotic therapy changed for 54%. Twenty patients were delabeled with an interview alone, and 30 patients underwent oral two-step challenge. Only one patient required PST. Conclusion: A pharmacist-driven penicillin allergy evaluation program focused on direct oral graded challenges and bypassing PST can effectively delabel admitted patients. However, more safety data are needed before implementation of similar programs to optimize antibiotic treatment.