Six-Food Elimination Diet Is Less Effective During Pollen Season in Adults With Eosinophilic Esophagitis Sensitized to Pollens.

INTRODUCTION: The role of inhaled and swallowed aeroallergens in treatment outcomes of adult patients with eosinophilic esophagitis (EoE) is unclear. We hypothesized that the pollen season contributes to the failure of the 6-food elimination diet (SFED) in EoE. METHODS: We compared outcomes of patients with EoE who underwent SFED during vs outside of the pollen season. Consecutive adult patients with EoE who underwent SFED and skin prick test (SPT) for birch and grass pollen were included. Individual pollen sensitization and pollen count data were analyzed to define whether each patient had been assessed during or outside of the pollen season after SFED. All patients had active EoE (≥15 eosinophils/high-power field) before SFED and adhered to the diet under the supervision of a dietitian. RESULTS: Fifty-eight patients were included, 62.0% had positive SPT for birch and/or grass, whereas 37.9% had negative SPT. Overall, SFED response was 56.9% (95% confidence interval, 44.1%-68.8%). When stratifying response according to whether the assessment had been performed during or outside of the pollen season, patients sensitized to pollens showed significantly lower response to SFED during compared with outside of the pollen season (21.4% vs 77.3%; P = 0.003). In addition, during the pollen season, patients with pollen sensitization had significantly lower response to SFED compared with those without sensitization (21.4% vs 77.8%; P = 0.01). DISCUSSION: Pollens may have a role in sustaining esophageal eosinophilia in sensitized adults with EoE despite avoidance of trigger foods. The SPT for pollens may identify patients less likely to respond to the diet during the pollen season.

Food allergy-A holistic approach to dietary management. A joint EAACI Research & Outreach Committee and INDANA review.

Following a diagnosis of IgE-mediated food allergy, to secure the best outcome, the patient should receive individualized advice tailored to their specific needs, which considers the type and presentation of the food involved, level of exclusion required, risk of cross-contamination and any variance required for age, ethnicity, financial issues, and lifestyle. Issues such as food labels "may contain" statements, and variation in the threshold of reaction and impact of cofactors should also be considered. Most important is the need to ensure that the diagnosis is robust, especially given the nutritional, psychological, and socioeconomic issues that can affect an individual with a diagnosis of food allergy. Unnecessary exclusion of one or more foods that have not triggered allergic reactions, especially in individuals with allergic comorbidities, can result in severe IgE-mediated reactions on re-exposure. Given that food allergies may change over time, the diagnosis should be reviewed, to determine whether resolution is likely, or new-food triggers are reported. Regular assessment is vital, especially during childhood, to ensure reintroduction occurs at an appropriate time, thus enabling increased diversity of the diet and improvement in the quality of life. For some, an IgE-mediated food allergy may necessitate the life-long exclusion of foods, and for others, a food habitually eaten suddenly triggers an allergic reaction in adult life. People of all ages, ethnicities, and socioeconomic backgrounds deserve individual advice on the management of their food allergy to support a healthy diet and improve quality of life.

British Society of Gastroenterology (BSG) and British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) joint consensus guidelines on the diagnosis and management of eosinophilic oesophagitis in children and adults.

BACKGROUND: Eosinophilic oesophagitis (EoE) is an increasingly common cause of dysphagia in both children and adults, as well as one of the most prevalent oesophageal diseases with a significant impact on physical health and quality of life. We have provided a single comprehensive guideline for both paediatric and adult gastroenterologists on current best practice for the evaluation and management of EoE. METHODS: The Oesophageal Section of the British Society of Gastroenterology was commissioned by the Clinical Standards Service Committee to develop these guidelines. The Guideline Development Group included adult and paediatric gastroenterologists, surgeons, dietitians, allergists, pathologists and patient representatives. The Population, Intervention, Comparator and Outcomes process was used to generate questions for a systematic review of the evidence. Published evidence was reviewed and updated to June 2021. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was used to assess the evidence and make recommendations. Two rounds of voting were held to assess the level of agreement and the strength of recommendations, with 80% consensus required for acceptance. RESULTS: Fifty-seven statements on EoE presentation, diagnosis, investigation, management and complications were produced with further statements created on areas for future research. CONCLUSIONS: These comprehensive adult and paediatric guidelines of the British Society of Gastroenterology and British Society of Paediatric Gastroenterology, Hepatology and Nutrition are based on evidence and expert consensus from a multidisciplinary group of healthcare professionals, including patient advocates and patient support groups, to help clinicians with the management patients with EoE and its complications.

A novel algorithmic approach to generate consensus treatment guidelines in adult acute myeloid leukaemia.

Induction therapy for acute myeloid leukaemia (AML) has changed with the approval of a number of new agents. Clinical guidelines can struggle to keep pace with an evolving treatment and evidence landscape and therefore identifying the most appropriate front-line treatment is challenging for clinicians. Here, we combined drug eligibility criteria and genetic risk stratification into a digital format, allowing the full range of possible treatment eligibility scenarios to be defined. Using exemplar cases representing each of the 22 identified scenarios, we sought to generate consensus on treatment choice from a panel of nine aUK AML experts. We then analysed >2500 real-world cases using the same algorithm, confirming the existence of 21/22 of these scenarios and demonstrating that our novel approach could generate a consensus AML induction treatment in 98% of cases. Our approach, driven by the use of decision trees, is an efficient way to develop consensus guidance rapidly and could be applied to other disease areas. It has the potential to be updated frequently to capture changes in eligibility criteria, novel therapies and emerging trial data. An interactive digital version of the consensus guideline is available.

BSACI guideline for the diagnosis and management of pollen food syndrome in the UK.

Pollen food syndrome (PFS) is a highly prevalent food allergy affecting pollen-sensitized children and adults. Sufferers experience allergic symptoms when consuming raw plant foods, due to the homology between the pollen allergens and unstable proteins in these foods. The triggers involved can vary depending on the pollen sensitization, which in turn is affected by geographical location. The British Society of Allergy and Clinical Immunology (BSACI) Standards of Care Committee (SOCC) identified a need to develop a guideline for the diagnosis and management of PFS in the United Kingdom (UK). Guidelines produced by the BSACI use either the GRADE or SIGN methodology; due to a lack of high-quality evidence these recommendations were formulated using the SIGN guidelines, which is acknowledged to be less robust than the GRADE approach. The correct diagnosis of PFS ensures the avoidance of a misdiagnosis of a primary peanut or tree nut allergy or confusion with another plant food allergy to non-specific lipid transfer proteins. The characteristic foods involved, and rapid-onset oropharyngeal symptoms, mean PFS can often be diagnosed from the clinical history alone. However, reactions involving tree nuts, peanuts and soya milk or severe/atypical reactions to fruits and vegetables may require additional diagnostic tests. Management is through the exclusion of known trigger foods, which may appear to be simple, but is highly problematic if coupled with a pre-existing food allergy or for individuals following a vegetarian/vegan diet. Immunotherapy to pollens is not an effective treatment for PFS, and although oral or sublingual immunotherapy to foods seems more promising, large, controlled studies are needed. The typically mild symptoms of PFS can lead to an erroneous perception that this condition is always easily managed, but severe reactions can occur, and anxiety about the onset of symptoms to new foods can have a profound effect on quality of life.

An optimal acquisition scheme for Q-band EPR distance measurements using Cu2+-based protein labels.

Recent advances in site-directed Cu2+ labeling of proteins and nucleic acids have added an attractive new methodology to measure the structure-function relationship in biomolecules. Despite the promise, accessing the higher sensitivity of Q-band Double Electron Electron Resonance (DEER) has been challenging for Cu2+ labels designed for proteins. Q-band DEER experiments on this label typically require many measurements at different magnetic fields, since the pulses can excite only a few orientations at a given magnetic field. Herein, we analyze such orientational effects through simulations and show that three DEER measurements, at strategically selected magnetic fields, are generally sufficient to acquire an orientational-averaged DEER time trace for this spin label at Q-band. The modeling results are experimentally verified on Cu2+ labeled human glutathione S-transferase (hGSTA1-1). The DEER distance distribution measured at the Q-band shows good agreement with the distance distribution sampled by molecular dynamics (MD) simulations and X-band experiments. The concordance of MD sampled distances and experimentally measured distances adds growing evidence that MD simulations can accurately predict distances for the Cu2+ labels, which remains a key bottleneck for the commonly used nitroxide label. In all, this minimal collection scheme reduces data collection time by as much as six-fold and is generally applicable to many octahedrally coordinated Cu2+ systems. Furthermore, the concepts presented here may be applied to other metals and pulsed EPR experiments.

Examining the bidirectional relationships between maternal intrusiveness and child internalizing symptoms in a community sample: A longitudinal study from infancy to middle childhood.

BACKGROUND: Myriad parenting behaviors have been linked to the development of internalizing disorders in children. Intrusive parenting, characterized by autonomy-limiting behaviors that hold the parent's agenda above that of the child, may uniquely contribute to the development of child internalizing symptoms. The current study investigates bidirectional effects between maternal intrusiveness and internalizing symptomology from infancy to middle childhood. METHODS: Participants were a community sample of 218 infant-mother dyads assessed at 7 time points (5 and 10 months; 2, 3, 4, 6, and 9 years). Maternal intrusiveness was behaviorally coded at all timepoints; mothers completed the CBCL for their child at ages 3, 4, 6, and 9 years. The empirically derived Internalizing subscale was used to assess child internalizing symptoms. RESULTS: About 1/3 to ½ of mothers displayed maternal intrusiveness across infancy and childhood, with the exception of ages 2-3 years, when an increase in the number of mothers displaying intrusiveness was observed. A cross-lagged panel model showed that intrusiveness and internalizing symptoms were concurrently related at 3 years, but this relationship disappeared when we controlled for maternal education. There was no evidence of prospective relationships between our constructs. CONCLUSIONS: Mothers in a community-based sample may increase intrusiveness in the toddler and early preschool years as children strive for more autonomy. Intrusiveness may play more of a maintenance role in child internalizing symptoms, and associations between maternal intrusiveness and child internalizing symptomatology may be weaker than hypothesized, varying by maternal education. Suggestions for assessing intrusive parenting in future studies are discussed.

The impact of cytogenetics on duration of response and overall survival in patients with relapsed multiple myeloma (long-term follow-up results from BSBMT/UKMF Myeloma X Relapse [Intensive]): a randomised, open-label, phase 3 trial.

The Myeloma X trial (ISCRTN60123120) registered patients with relapsed multiple myeloma. Participants were randomised between salvage autologous stem cell transplantation (ASCT) or weekly cyclophosphamide following re-induction therapy. Cytogenetic analysis performed at trial registration defined t(4;14), t(14;16) and del(17p) as high-risk. The effect of cytogenetics on time to progression (TTP) and overall survival was investigated. At 76 months median follow-up, ASCT improved TTP compared to cyclophosphamide (19 months (95% confidence interval [95% CI] 16-26) vs. 11 months (9-12), hazard ratio [HR]: 0·40, 95% CI: 0·29-0·56, P < 0·001), on which the presence of any single high-risk lesion had a detrimental impact [likelihood ratio test (LRT): P = 0·011]. ASCT also improved OS [67 months (95% CI 59-not reached) vs. 55 months (44-67), HR: 0·64, 95% CI: 0·42-0·99, P = 0·0435], with evidence of a detrimental impact with MYC rearrangement (LRT: P = 0·021). Twenty-one (24·7%) cyclophosphamide patients received an ASCT post-trial, median OS was not reached (95% CI: 39-not reached) for these participants compared to 31 months (22-39), in those who did not receive a post-trial ASCT. The analysis further supports the benefit of salvage ASCT, which may still be beneficial after second relapse in surviving patients. There is evidence that this benefit reduces in cytogenetic high-risk patients, highlighting the need for targeted study in this patient group.

Mesenchymal stromal cells for acute graft-versus-host disease: response at 1 week predicts probability of survival.

Mesenchymal stromal cells (MSCs) have been successfully used for the treatment of steroid-resistant graft-versus-host-disease (GvHD). However, the lack of early predictors of clinical responses impacts on the time at which to add further treatment and consequently the design of informative clinical trials. Here, we present the UK experience of one of the largest cohorts of GvHD patients undergoing MSC infusions so far reported. We show that clinical responses assessed as early as 1 week after MSC infusion predict patients' overall survival. In our cohort, cell dose, patients' age and type of organ involvement are crucial factors associated with clinical responses.

Food avoidance strategies in eosinophilic oesophagitis.

Eosinophilic oesophagitis (EoE) is a chronic disease associated with significant morbidity that can result in permanent fibrosis and stricture formation. Given the complexity, a multidisciplinary approach is recommended to manage these patients. In the majority of children with EoE not responsive to proton-pump inhibitor (PPI), inflammation is driven by sensitivity to foods and treatment with an elimination diet can be effective. Foods most commonly identified to trigger EoE in children are milk and wheat, but egg, soy, meats and grains can also be triggers. Foods can be eliminated using a step-down or step-up approach. If the goal is to achieve quick remission, elemental diet or six food elimination diets are the most effective. A step-up approach starting from a 1-2 food elimination diet and increasing the number of foods based on a personalized dietary approach is recommended if the goal is to achieve remission using the least number of endoscopies and with increased acceptability to the patient. Children with EoE on elimination diets require frequent monitoring of growth and nutrition, as well as screening for symptoms of EoE, allergy and mindfulness regarding psychosocial impact of chronic disease on the family and child. Current research focused on tools to select patients who mostly will benefit from dietary treatment, identify relevant food allergens, obtain oesophageal tissue non-invasively and induce tolerance will greatly improve the treatment of EoE.

UK consensus statement on the use of plerixafor to facilitate autologous peripheral blood stem cell collection to support high-dose chemoradiotherapy for patients with malignancy.

Plerixafor is a CXC chemokine receptor (CXCR4) antagonist that mobilizes stem cells in the peripheral blood. It is indicated (in combination with granulocyte-colony stimulating factor [G-CSF]) to enhance the harvest of adequate quantities of cluster differentiation (CD) 34+ cells for autologous transplantation in patients with lymphoma or multiple myeloma whose cells mobilize poorly. Strategies for use include delayed re-mobilization after a failed mobilization attempt with G-CSF, and rescue or pre-emptive mobilization in patients in whom mobilization with G-CSF is likely to fail. Pre-emptive use has the advantage that it avoids the need to re-schedule the transplant procedure, with its attendant inconvenience, quality-of-life issues for the patient and cost of additional admissions to the transplant unit. UK experience from 2 major centers suggests that pre-emptive plerixafor is associated with an incremental drug cost of less than £2000 when averaged over all patients undergoing peripheral blood stem cell (PBSC) transplant. A CD34+ cell count of <15 µl-1 at the time of recovery after chemomobilization or after four days of G-CSF treatment, or an apheresis yield of <1 × 106 CD34+ cells/kg on the first day of apheresis, could be used to predict the need for pre-emptive plerixafor.

Stem Cell Harvesting after Bortezomib-Based Reinduction for Myeloma Relapsing after Autologous Transplantation: Results from the British Society of Blood and Marrow Transplantation/United Kingdom Myeloma Forum Myeloma X (Intensive) Trial.

The phase III British Society of Blood and Marrow Transplantation/United Kingdom Myeloma Forum Myeloma X trial (MMX) demonstrated prospectively, for the first time, superiority of salvage autologous stem cell transplantation over chemotherapy maintenance for multiple myeloma (MM) in first relapse after previous ASCT. However, many patients have stored insufficient stem cells (PBSC) for second ASCT and robust evidence for remobilization after first ASCT is lacking. We report the feasibility, safety, and efficacy of remobilization after bortezomib-doxorubicin-dexamethasone reinduction in MMX and outcomes of second ASCT with these cells. One hundred ten patients underwent ≥1 remobilization with 32 and 4, undergoing second and third attempts, respectively. Toxicities of remobilization were similar to those seen in first-line mobilization. After all attempts, 52% of those with insufficient previously stored PBSC had harvested a sufficient quantity to proceed to second ASCT. Median PBSC doses infused, neutrophil engraftment, and time to discharge after second ASCT were similar regardless of stem cell source, as were the toxicities of second ASCT. No significant differences between PBSC sources were noted in depth of response to ASCT or time to progression. Harvesting after bortezomib-doxorubicin-dexamethasone reinduction for MM at first relapse is safe and feasible and yields a reliable cell product for second ASCT. The study is registered with ClinicalTrials.gov (NCT00747877) and EudraCT (2006-005890-24).

Postextinction Geographies: Audiovisual Afterlives of the Bucardo and the Ivory-Billed Woodpecker.

How do technologies animate more-than-human geographies after extinction? How can geographical scholarship evoke, or bring presence to, extinct biota? In an epoch simultaneously characterized by biotic loss at an unthinkable scale and the increased presence of representations depicting nonhuman life through mass media and digitization, we examine the epistemic, affective, and ethical possibilities of extinct animal traces to shape more-than-human geographies. We show how technological apparatuses inaugurate afterlives of extinction troubling binaries of extinct-extant and absence-presence. Specifically, we consider audio and visual remains of two taxa producing awkward and unsettling postextinction geographies: the ivory-billed woodpecker and the bucardo. Sound recordings and other historical traces continue to forge contemporary connections between human searchers and the ivory-billed woodpecker, although no sighting of the ghost bird has been universally accepted since 1944. The bucardo was declared extinct in 2000, but it was tentatively reanimated through a failed 2003 cloning project; in this milieu, visual technologies and representations conjure alternative presence and speculative futures beyond technoscientific spectacle. Through conversing our own situated, speculative, and technologically mediated relations with these taxa-and situating the technological assemblages themselves-we present some of the lively, contested, and dispersed ways technological apparatuses affect and inaugurate animated geographies after extinction.

¿Cómo animan las tecnologías a las geografías más-que-humanas después de la extinción? ¿Cómo puede la erudición geográfica evocar o darle existencia a la biota extinta? En una época que simultáneamente se caracteriza por la pérdida biótica a una escala impensable, y la creciente presencia de representaciones que muestran la vida no humana a través de los medios masivos y la digitalización, examinamos las posibilidades epistémicas, afectivas y éticas de las huellas de animales extintos para configurar las geografías más-que-humanas. Mostramos cómo los aparatos tecnológicos inauguran las posvidas de la extinción cuestionando los binarios de lo extinto­existente y de la ausencia­presencia. Específicamente, tomamos en consideración los restos sonoros y visuales de dos taxones que producen geografías postextincionales hoscas e inquietantes: el pájaro carpintero pico de marfil y el bucardo. Las grabaciones de sonidos y otros relictos históricos siguen forjando conexiones contemporáneas entre las búsquedas humanas y el pájaro carpintero pico de marfil, así desde 1944 no haya sido universalmente aceptado avistamiento alguno de esta ave fantasmal. El bucardo se declaró extinto en 2000, pero fue tentativamente revivido por medio de un fallido proyecto de clonación en 2003; en este entorno ambiental las tecnologías y representaciones visuales conjuran una presencia alternativa y unos futuros especulativos más allá del espectáculo tecnocientífico. A través de nuestras propias relaciones situadas, especulativas y tecnológicamente mediadas con aquellos taxones ­y situando los propios ensamblajes tecnológicos­ presentamos algunas de las formas vivas, controvertidas y dispersas en que los aparatos tecnológicos afectan e inauguran geografías animadas después de la extinción.

Listening for the Ivory-billed Woodpecker: Sonic geography and the making of extinction knowledge.

If an apparently extinct bird calls in a forest, and there are people there to hear it-to record it, even-is it still extinct? The Ivory-billed Woodpecker was last 'officially' seen in the United States in 1944, but its extinction continues to be a subject of intense debate between conservation authorities, scientists, and grassroots activists. Tensions peaked around 2005, when scientists from the Cornell Laboratory of Ornithology announced their rediscovery of the species. However, their evidence received significant challenge from other ornithologists, and this apparent rediscovery has since been generally dismissed. In 2021, the United States Fish and Wildlife Service recommended the ivorybill be declared officially extinct. Still, many people continue to trawl the Southeastern forests in search of ivorybills. In this article, I investigate the methods, debates, and results of efforts to locate this species, with a focus on sound. In doing so, I explore the interconnected roles of sound and space in the making of extinction knowledge. Sonic search methods of listening, sounding, and translating are core ways that searchers attempt to attune to, communicate with, and establish evidence of ivorybills. Additionally, sonic search practices are critical spaces of negotiation and contestation between different searchers, between searchers and ivorybills, and between searchers and skeptics. Ultimately, this article argues that sonic geographies affect the production of extinction knowledge, and vice versa-extinction knowledge making practices produce distinct sonic geographies.

A new 13C trityl-based spin label enables the use of DEER for distance measurements.

Triarylmethyl (TAM)-based labels, while still underutilized, are a powerful class of labels for pulsed-Electron Spin Resonance (ESR) distance measurements. They feature slow relaxation rates for long-lasting signals, high stability for cellular experiments, and narrow spectral features for efficient excitation of the spins. However, the typical narrow line shape limits the available distance measurements to only single-frequency experiments, such as Double Quantum Coherence (DQC) and Relaxation Induced Dipolar Modulation Enhancement (RIDME), which can be complicated to perform or hard to process. Therefore, widespread usage of TAM labels can be enhanced by the use of Double Electron-Electron Resonance (DEER) distance measurements. In this work, we developed a new spin label, 13C1-mOX063-d24, with a 13C isotope as the radical center. Due to the resolved hyperfine splitting, the spectrum is sufficiently broadened to permit DEER-based experiments at Q-band spectrometers. Additionally, this new label can be incorporated orthogonally with Cu(II)-based protein label. The orthogonal labeling scheme enables DEER distance measurement at X-band frequencies. Overall, the new trityl label allows for DEER-based distance measurements that complement existing TAM-label DQC and RIDME experiments.

"Store-bought is fine": Sensitivity considerations using shaped pulses for DEER measurements on Cu(II) labels.

The narrow excitation bandwidth of monochromic pulses is a sensitivity limitation for pulsed dipolar spectroscopy on Cu(II)-based measurements. In response, frequency-swept pulses with large excitation bandwidths have been adopted to probe a greater range of the EPR spectrum. However, much of the work utilizing frequency-swept pulses in Cu(II) distance measurements has been carried out on home-built spectrometers and equipment. Herein, we carry out systematic Cu(II) based distance measurements to demonstrate the capability of chirp pulses on commercial instrumentation. More importantly we delineate sensitivity considerations under acquisition schemes that are necessary for robust distance measurements using Cu(II) labels for proteins. We show that a 200 MHz sweeping bandwidth chirp pulse can improve the sensitivity of long-range distance measurements by factors of three to four. The sensitivity of short-range distances only increases slightly due to special considerations for the chirp pulse duration relative to the period length of the modulated dipolar signal. Enhancements in sensitivity also dramatically reduce measurement collection times enabling rapid collection of orientationally averaged Cu(II) distance measurements in under two hours.

An Integrative Model of Youth Anxiety: Cognitive-Affective Processes and Parenting in Developmental Context.

Multiple theoretical frameworks have been proposed to provide a more comprehensive picture of the risk factors that influence anxiety-related developmental trajectories. Nonetheless, there remains a need for an integrative model that outlines: (1) which risk factors may be most pertinent at different points in development, and (2) how parenting may maintain, exacerbate, or attenuate an affective style that is characterized by high negative emotional reactivity to unfamiliar, uncertain, and threatening situations. A developmentally informed, integrative model has the potential to guide treatment development and delivery, which is critical to reducing the public health burden associated with these disorders. This paper outlines a model integrating research on many well-established risk mechanisms for anxiety disorders, focusing on (1) the developmental progression from emotional reactivity constructs early in life to those involving higher-level cognitive processes later in youth, and (2) potential pathways by which parenting may impact the stability of youth's cognitive-affective responses to threat-relevant information across development.