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Alessandro Fiocchi,1 R Sharon Chinthrajah,2 Ignacio J Ansotegui,3 Panida Sriaroon,4 S Shahzad Mustafa,5 Pranil Raut,6 Briana Cameron,6 Sachin Gupta,1 David M Fleischer7 1Bambino Gesù Childrens’ Hospital IRCCS, Rome, Italy; 2Stanford University, Stanford, CA, USA; 3Hospital Quironsalud Bizkaia, Bilbao, Spain; 4University of South Florida, Tampa, FL, USA; 5Rochester Regional Health & University of Rochester, Rochester, NY, USA; 6Genentech Inc., South San Francisco, CA, USA; 7Children’s Hospital Colorado, University of Colorado School of Medicine, Aurora, CO, USACorrespondence: David M Fleischer, Section Head, Allergy & Immunology, University of Colorado School of Medicine and Children’s Hospital Colorado, 13123 East 16th Avenue, B518, Aurora, CO, 80045, USA, Tel +1-720-777-4393, Email David.Fleischer@childrenscolorado.orgBackground: The intrinsic link between food allergy and asthma is well-established, and comorbidity can exacerbate both conditions. Omalizumab, an anti-immunoglobulin E (IgE) antibody, has the biological plausibility to manage both conditions, but only a few small studies have assessed omalizumab in patients with comorbid asthma and food allergy.Patients and Methods: We conducted a post hoc analysis of placebo-controlled, randomized clinical trials (IA05 in children and 008/009 in adolescents/adults) and real-world observational studies (EXCELS and PROSPERO). For each study, patients with asthma were stratified by whether they had physician-reported food allergy, as per baseline characteristics data.Results: For patients with comorbid food allergy, there was evidence for increased atopy at baseline (numerically higher total IgE levels and atopic comorbidities). The collective body of evidence found that omalizumab consistently improved general and asthma-specific patient-centered outcomes (food allergy-specific outcomes were not available). For patients with asthma, omalizumab improved healthcare resource use (emergency room visits, hospitalizations, unscheduled doctor visits), quality of life (asthma-specific Asthma Quality of Life Questionnaire), productivity (missed work/school days and the Work Productivity and Activity Impairment: Asthma), and asthma outcomes (asthma exacerbations and Asthma Control Test score) regardless of comorbid food allergy.Conclusion: There was no loss of omalizumab efficacy even though patients with both asthma and food allergy appeared to be generally more atopic. Omalizumab may be a viable management option for patients with these comorbidities.Clinical trial registration: NCT00079937; NCT01922037; NCT00252135.Plain Language Summary: Food allergy and asthma are linked and if you have both conditions then you can feel worse. There is a treatment available, called omalizumab, that helps people with asthma and helps people with food allergy, but it’s not clear if it can help people with both conditions. Here, we look at whether omalizumab can help people with bad to very bad asthma (also called moderate to severe asthma) who also have food allergy. We found that omalizumab improved many aspects of a person’s life, including whether they visited the emergency room, were admitted to hospital, their quality of life, whether they missed school or work, and whether their asthma improved. These improvements occurred in all people with moderate to severe asthma, whether they had food allergy or did not have food allergy. This suggests that omalizumab can help people with both conditions.Keywords: asthma, food allergy, food hypersensitivity, healthcare resource use, omalizumab, productivity, quality of life

Minimally invasive medical treatments for peripheral nerve stimulation are critically needed to minimize surgical risks, enhance the precision of therapeutic interventions, and reduce patient recovery time. Magnetoelectric nanoparticles (MENPs), known for their unique ability to respond to both magnetic and electric fields, offer promising potential for precision medicine due to their dual tunable functionality. In this study a multi-physics modeling of the MENPs was performed, assessing their capability to be targeted through external magnetic fields and become electrically activated. In particular, by integrating electromagnetic, fluid dynamics, and biological models, the efficacy of MENPs as wireless nano-tools to trigger electrical stimulation in the peripheral Nervous system present within the dermal microenvironment was assessed. The simulations replicate the blood venous capillary network, accounting for the complex interactions between MENPs, blood flow, and vessel walls. Results demonstrate the precise steering of MENPs (>95%) toward target sites under a low-intensity external magnetic field (78 mT) even with a low susceptibility value (0.45). Furthermore, the extravasation and electrical activation of MENPs within the dermal tissue are analyzed, revealing the generation of high-induced electric fields in the surrounding area when MENPs are subjected to external magnetic fields. Overall, these findings predict that MENPs can be targeted in a tissue site when intravenously administrated, dragged through the microvessels of the venous system, and activated by generating high electric fields for the stimulation of the peripheral nervous system.

Background: Children allergic to milk and egg, but tolerant to baked products, display higher reactivity thresholds than the general population of children allergic to milk and egg. We sought to verify the reactivity thresholds of milk- and egg-allergic children who also react to baked milk and baked egg, respectively. Methods: We retrospectively assessed consecutive oral food challenge (OFC) for baked milk and egg between January 2018 and March 2022 in a population of baked milk- and baked-egg allergic children. Results: Among 407 children included (median age 56 - IQR 31.1–103.7 months, 67.1% male), 93 (23.6%) returned positive OFC results, 41 with baked milk, and 52 with baked egg. The most conservative ED01 was 0.4 mg total protein (IQR 0.1–2.7) for milk and 2.2 mg total protein (IQR 0.6–7.3) for egg. The respective ED05 was 3.9 (IQR 1.1–14) mg for milk and 11.7 (IQR 5–27.2) mg for egg. Such thresholds are consistent to those found for fresh milk (0.8 times for ED01, 1.1 times for ED05). For egg, they are 6.5 (egg ED01), and 7.5 (egg ED05) times lower than for native form.Compared to the currently used thresholds, they are 1.3 (milk ED01), 1.3 (milk ED05), 11 (egg ED01), and 4.9 (egg ED05) times higher. Conclusions: Milk thresholds are similar to those already observed in baked allergic versus baked tolerant children, while EDs for egg are at least 1.6 times higher than those currently indicated.Egg-allergic patients could be exempt from the recommendations of absolute avoidance of foods when present in infinitesimal quantities, represented by precautionary allergen labelling based on current EDs.

Abstract This Anaphylaxis Manifesto calls on communities to prioritise 10 practical actions to improve the lives of people at risk of serious allergic reactions. The Global Allergy and Asthma European Network and the European Federation of Allergy and Airways Diseases Patients' Associations (EFA) compiled patient‐centric priorities. We used qualitative consensus methods, research evidence and feedback from over 200 patient groups, stakeholder organisations and healthcare professionals. We encourage healthcare, education and food organisations to collaborate with people at risk of serious allergic reactions to tackle safety, anxiety and financial burdens for individuals and societies. Key priorities for prevention include awareness‐raising campaigns for the public and professionals, school and workplace initiatives and mandatory precautionary allergen labels on food. Priorities for improving immediate and long‐term management include educating healthcare professionals, patients and schools about when and how to use adrenaline, funding two approved adrenaline devices for everyone at risk, and facilitating access to allergy specialists. Integrated care pathways should include clinical and non‐clinical management options such as individualised risk assessment and quality of life assessment, self‐management plans, dietetic and psychosocial support and peer support. Organisations around the world are committing to work together towards these priorities.

Background:. The breast-sharing technique uses the lower quadrants discarded from a contralateral symmetrizing reduction mammoplasty to reconstruct the breast after mastectomy. The aim of our study was to revisit this old technique and to improve its vascular predictability by preoperative computed tomography angiography (angio-CT) and intraoperative indocyanine green (ICG) imaging. Methods:. Twenty-six patients were enrolled and assessed by a preoperative angio-CT to localize and evaluate the internal mammary artery perforator (IMAP). In the selected patients, a Wise skin-pattern reduction was designed to allow elevation of a transversely oriented flap including both inferior poles. The flap was based medially on the IMAP. After elevation, evaluation of its arterial and venous perfusion was assessed with ICG. Results:. Eight patients were excluded after pre- and intraoperative studies. Sixteen breast-sharing flaps were performed. A distal flap venous compromise appeared in 2 cases, requiring debridement and flap repositioning, and an infection occurred in 1 case. Four patients had detectable firm lumps that resolved. There were no issues with donor site healing, and a repositioning of the areola was necessary in 2 patients. Conclusions:. Breast-sharing techniques have not gained popularity for many reasons. By combining current understanding of breast cancer behavior, experience with perforator anatomy, and angio-CT and ICG, we believe this study gives a second life to this flap, identifying its weaknesses and improving them. The IMAP propeller flap, simpler and safer in the presence of comorbidities than a free flap, can be a good choice for well-selected candidates.

Background: Allergic rhinitis (AR) is a highly prevalent disease. We aimed to assess the symptoms that physicians who see patients with AR perceive as the most bothersome in their patients. Methods: We performed a cross-sectional study based on an online questionnaire sent to all members of the Allergic Rhinitis and its Impact on Asthma (ARIA) initiative. The survey included questions on the physicians' perceptions of patients’ AR symptoms as well as of their own AR symptoms. Results: Among 401 respondents, 155 (38.7%) reported having AR. ARIA members reported nasal symptoms to be the most frequent (89.7%) and bothersome (80.0%) symptoms experienced by themselves. Likewise, nasal symptoms were reported by ARIA members as the most frequent (94.8% in members with AR vs 96.0% in members without AR) and bothersome (57.0% in members with AR vs 67.9% in members without AR) in their patients. We found a significant association (p = 0.001) between physicians’ own symptoms and those perceived as the most bothersome in their patients. Conclusion: Physicians perceive nasal symptoms to be the most frequent and the most bothersome symptoms in AR patients. The physicians' personal experiences with AR may influence their perception of patients’ symptoms.

Additive manufacturing of architected materials, particularly lattice or porous structures, has garnered significant interest in recent years due to its ability to enhance weight-to-strength performance, load-bearing capabilities, and superior energy absorption. Integrating these structures with shape memory alloys (SMAs) introduces unique functionality, enabling them to revert to their original shape after unloading. This paper offers a comprehensive review of the capabilities and challenges associated with additively manufactured architected SMAs. Several examples are presented to illustrate the functional and thermomechanical performance of these structures. Additionally, potential applications are examined, and future trends in this innovative field are explored.

Abstract Immunoglobulin E (IgE)‐mediated food allergies are the most common type of food allergy, often causing rapid symptoms after exposure to allergens posing a serious health risk and a high impact on patient's and caregiver's quality of life. Omalizumab, a humanized anti‐IgE monoclonal antibody, reduces allergic reactions by binding to circulating IgE. Omalizumab has been successfully used in allergic asthma, chronic rhinosinusitis with nasal polyps, and chronic urticaria, and was recently approved for treating IgE‐mediated food allergies by the US Food and Drug Administration (FDA). This GA2LEN ANACARE Consensus Statement presents our position on the use of omalizumab for treating IgE‐mediated food allergies, based on a systematic review and meta‐analysis, experience with use for other conditions, and expert consensus achieved via an eDelphi process. Following publication of the recent OUtMATCH study (stage 1) results and subsequent FDA approval, we propose that there is now sufficient evidence to recommend omalizumab as the only drug currently available that can mechanistically reduce IgE‐mediated food allergic reactions. We acknowledge that the evidence does not reach the highest level of evidence which would be needed for a guideline recommendation.

Abstract Total protein levels in fish are widely used in health and welfare studies, providing a simple and accessible measure. However, the multifaceted role of blood proteins makes it sometimes challenging to link total protein content to specific health issues, while specific protein fractions may offer more precise insights into fish biology and health, particularly in farmed fish species where such data is often lacking. Data were gathered from two experiments involving Dicentrarchus labrax and Sparus aurata, key species in European marine aquaculture. The aim was (1) to assess how different globulin fractions contribute to total protein content in blood and (2) how these contributions vary across different sampling times in healthy animals. In D. labrax, the beta1 globulin fraction emerged as the major contributor (34.16%), followed by albumin and alpha2 globulins (18.24% and 16.41%, respectively). In contrast, pre-albumins and alpha1 fractions had the least contribution (5.49% and 7.71%). S. aurata exhibited albumin as the primary contributor (23.39%), followed by beta1 and alpha2 globulins (19.71% and 19.15%, respectively), with gamma and alpha1 fractions contributing the least (5.34% and 8.63%). Notably, the study revealed relatively stable contributions of globulin fractions to total proteins within both species, albeit with minor variations over time, potentially linked to environmental and individual factors. Furthermore, larger fish displayed higher total protein levels. This research underscores the need for further investigation into the diverse factors influencing globulin contributions to total proteins, ultimately enhancing health and welfare monitoring for farmed fish species.

Background: Precautionary Allergen (“may contain”) Labelling (PAL) is used by industry to communicate potential risk to food-allergic individuals posed by unintended allergen presence (UAP). In 2014, the World Allergy Organization (WAO) highlighted that PAL use was increasing, but often applied inconsistently and without regulation — which reduces its usefulness to consumers with food allergy and those purchasing food for them. WAO proposed the need for a regulated, international framework to underpin application of PAL. In 2019, the World Health Organization (WHO) and the Food and Agriculture Organization (FAO) of the United Nations convened an expert consultation to address the issue of PAL, the outputs of which are now being considered by the Codex Committee on Food Labelling (CCFL). Objectives: To summarise the latest data to inform the application of PAL in a more systematic way, for implementation into global food standards. Methods: A non-systematic review of issues surrounding precautionary labelling and food allergens in pre-packaged products. Results: Approximately, 100 countries around the world have legislation on the declaration of allergenic ingredients. Just a few have legislation on UAP. Given the risks that UAP entails, non-regulated PAL creates inconvenience in real life due to its unequal, difficult interpretation by patients. The attempts made so far to rationalize PAL present lights and shadows. Conclusions: At a time when CCFL is considering the results of the FAO/WHO Expert Consultation 2020–2023, we summarise the prospects to develop an effective and homogeneous legislation at a global level, and the areas of uncertainty that might hinder international agreement on a regulated framework for PAL of food allergens.

Abstract Patient‐reported outcome measures (PROMs) are used to assess a patient's health status at a particular point in time. They are essential in the development of person‐centred care. This paper reviews studies performed on PROMs for assessing AR and asthma control, in particular VAS scales that are included in the app MASK‐air® (Mobile Airways Sentinel networK) for asthma and rhinitis. VASs were initially developed on paper and pencil and tested for their criterion validity, cut‐offs and responsiveness. Then, a multicentric, multinational, double‐blind, placebo‐controlled, randomised control trial (DB‐PC‐RCT) using an electronic VAS form was carried out. Finally, with the development of MASK‐air® in 2015, previously validated VAS questions were adapted to the digital format and further methodologic evaluations were performed. VAS for asthma, rhinitis, conjunctivitis, work and EQ‐5D are included in the app. Additionally, two control‐medication scores for allergic symptoms of asthma (e‐DASTHMA) were validated for their criterion validity, cut‐offs and responsiveness.

The delicate balance between discrimination and generalization of responses is crucial for survival in our ever-changing environment. In particular, it is important to understand how stimulus discrimination affects the level of stimulus generalization. For example, when we use non-differential training for Pavlovian eyeblink conditioning to investigate generalization of cerebellar-related eyelid motor responses, we find generalization effects on amount, amplitude and timing of the conditioned responses. However, it is unknown what the generalization effects are following differential training. We trained mice to close their eyelids to a 10 kHz tone with an air-puff as the reinforcing stimulus (CS+), while alternatingly exposing them to a tone frequency of either 4 kHz, 9 kHz or 9.5 kHz without the air-puff (CS−) during the training blocks. We tested the generalization effects during the expression of the responses after the training period with tones ranging from 2 kHz to 20 kHz. Our results show that the level of generalization tended to positively correlate with the difference between the CS+ and the CS− training stimuli. These effects of generalization were found for the probability, amplitude but not for the timing of the conditioned eyelid responses. These data indicate the specificity of the generalization effects following differential versus non-differential training, highlighting the relevance of discrimination learning for stimulus generalization.

Background: Type 2 inflammation is the principal determinant of asthma in children, and it leads to the downstream activation of eosinophils (EOS), the production of immunoglobulin-E (IgE), and increased levels of fraction of exhaled nitric oxide (FeNO). Dupilumab received the approval for the treatment of uncontrolled severe Type 2 asthma in children. Objective: The aim of this analysis was to calculate the Type 2 severe asthma paediatric population who would be eligible for treatment with dupilumab in Italy and characterize them by expected biomarker status. Methods: The calculation of the dupilumab-eligible population employed a two-phase approach: 1) estimating the total number of children aged 6–11 years with uncontrolled severe asthma; and 2) stratifying the severe uncontrolled asthma population, based on appropriate biomarker levels, thus identifying patients eligible for treatment with dupilumab. The VOYAGE study provided the data for this analysis. Results: The two-phase approach utilizing VOYAGE data revealed that the average number of paediatric patients with uncontrolled severe asthma was N = 1007. Stratification of these patients, as per VOYAGE data, indicated that the majority (N = 740; 73.5%) would have ≥2 elevated biomarkers, and over one-third patients (N = 434, 43.1%) would exhibit simultaneously elevated levels of EOS, FeNO and IgE. Of the paediatric patients, N = 864 were identified as eligible to dupilumab treatment, constituting 85.8% of the target population. Notably, nearly half eligible patients (N = 454) displayed elevated levels of both EOS and FeNO biomarkers, while the substantial majority (81.1%) exhibited at least an increase of EOS levels (N = 817). Patients with increased FeNO levels without a concurrent increase in EOS were less frequent (N = 47; 5.4% of the eligible population). Conclusion: The simultaneous testing of multiple biomarkers during baseline patient assessment and disease follow-up is highly recommended. Utilizing cost-effective tests, physicians can estimate the prevalence of severe Type 2 asthma, categorize patients into distinct phenotypes (eosinophilic, allergic, or mixed), and consequently identify and prescribe the most suitable therapeutic interventions. This approach also facilitates the ongoing evaluation and adjustment of the treatment strategies based on individual patient responses.

Cow's milk allergy (CMA) is one of the most common presentations of food allergy in early childhood. Management of CMA involves individualized avoidance of cow's milk and other mammalian milk and foods containing these. Optimal elimination of cow's milk avoidance includes: label reading; information about safe and nutritious substitute foods; appropriate choice of infant formula or a plant-based food; establishing tolerance to baked milk and monitoring nutritional intake and growth. Substitute formulas are divided into soy formula (not hydrolyzed), milk-based extensively hydrolyzed formulas, rice based extensive, and partially hydrolyzed formulas and amino acid-based formulas. The use of other mammalian milks is not recommended for the management of cow's milk allergy due to a high level of cross-reactivity and nutritional concerns. For toddlers who are eating well, children, and adults, a suitable plant-based beverage may be a suitable alternative to a specialized formula, following careful nutritional considerations. Families need to be instructed on finding suitable nutritious foods and how to prepare suitable meals at home. Individuals with CMA also need to know how to identify and treat acute severe reactions.

Theresa W Guilbert,1 Alberto Tolcachier,2 Alessandro G Fiocchi,3 Constance H Katelaris,4,5 Wanda Phipatanakul,6,7 Philippe Begin,8 Inés de Mir,9 Arman Altincatal,10 Rebecca Gall,11 Olivier Ledanois,12 Amr Radwan,11 Juby A Jacob-Nara,13 Yamo Deniz,11 Paul J Rowe13 1Department of Pediatrics, Cincinnati Children’s Hospital and University of Cincinnati, Cincinnati, OH, USA; 2Center for Allergy and Respiratory Diseases, Buenos Aires, Argentina; 3Bambino Gesù Children’s Hospital IRCCS, Rome, Italy; 4Department of Medicine, Campbelltown Hospital, Campbelltown, NSW, Australia; 5Immunology & Allergy Unit, Western Sydney University, Sydney, NSW, Australia; 6Department of Allergy and Immunology, Boston Children’s Hospital, Boston, MA, USA; 7Department of Pediatrics, Harvard Medical School, Boston, MA, USA; 8Centre Hospitalier Universitaire (CHU) Sainte-Justine, Montreal, QC, Canada; 9Pediatric Pulmonary Unit, Hospital Universitari Vall d’Hebron, Barcelona, Spain; 10Sanofi, Cambridge, MA, USA; 11Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA; 12Sanofi, Paris, France; 13Sanofi, Bridgewater, NJ, USACorrespondence: Theresa W Guilbert, Cincinnati Children’s Hospital and University of Cincinnati, 3333 Burnet Ave, Cincinnati, OH, 45229, USA, Tel +1 513-636-6771, Email theresa.guilbert@cchmc.orgPurpose: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukins-4/-13, key and central drivers of type 2 inflammation in multiple diseases. This post hoc analysis of the Phase 3 LIBERTY ASTHMA VOYAGE study (NCT02948959) evaluated the efficacy of dupilumab in children aged 6 to 11 years with moderate-to-severe asthma with a type 2 inflammatory phenotype (blood eosinophil count ≥ 150 cells/μL or fractional exhaled nitric oxide [FeNO] ≥ 20 ppb) and a history of 1, 2, or ≥ 3 prior exacerbations. The impact of baseline type 2 biomarker levels on the efficacy of dupilumab in this population was also investigated.Patients and Methods: Patients were stratified by the number of exacerbations in the prior year (1, 2, or ≥ 3) and level of FeNO or blood eosinophil count at baseline. Endpoints included rate of severe exacerbations, percentage of non-exacerbators, and change from baseline in both lung function parameters (pre- and post-bronchodilator [BD] percent predicted forced expiratory volume in 1 s (ppFEV1) and ppFEV1/forced vital capacity [FVC] ratio) and Asthma Control Questionnaire 7 Interviewer-Administered (ACQ-7-IA) score.Results: A total of 350 patients were included in this analysis. Across patients with 1, 2, or ≥ 3 prior exacerbations and different levels of type 2 biomarkers, dupilumab reduced the risk of severe asthma exacerbations vs placebo by 53.0– 96.0% and improved both pre-BD ppFEV1 and pre-BD FEV1/FVC ratio at Week 52. Dupilumab led to significant reductions in ACQ-7-IA scores in all groups of patients by Week 52.Conclusion: In children with uncontrolled, moderate-to-severe asthma with a type 2 phenotype, dupilumab consistently reduced the risk of asthma exacerbations, improved lung function, and reduced ACQ-7-IA scores, regardless of exacerbation history. Keywords: pediatric asthma, type 2 asthma, lung function, asthma control, biologics, anti-interleukin-4 and -13

Abstract Objective We present the cases of two sisters, both harboring the same ALDH18A1 gene mutations, who presented with a complex clinical phenotype characterized by spastic paraparesis with ataxia, epileptic encephalopathy, severe psychomotor deficits, and behavioral abnormalities. Methods Case description of two sisters with ALDH18A1 gene mutations. Results The older patient, a 12‐year‐old girl, exhibited spastic paraparesis with ataxia, microcephaly, facial dysmorphisms, and severe intellectual disability, with an absence of verbal language. An electroencephalogram (EEG) revealed marked spike‐and‐wave activation during sleep (SWAS), although no clinically documented seizures were observed. The younger sister, who was 9 years old, displayed a similar clinical presentation, including spastic paraparesis with ataxia, microcephaly, dysmorphisms, however, she displayed slightly more severe intellectual deficits and polymorphic seizures. EEG revealed a SWAS pattern in this case. Magnetic resonance imaging scans in both cases showed only a thin corpus callosum. Whole exome sequencing unveiled the presence of two likely pathogenic variants in compound heterozygosity within the ALDH18A1 gene. Specifically, these variants included the splice site variant c.88 + 1c.88+1G>A of paternal origin and the variant c.1364c.1364T>C (p.Leu455Ser) of maternal origin. Both sisters displayed normal blood levels of ammonia, ornithine, citrulline, arginine, and other amino acids. Interpretation These findings were compatible with ALDH18A1‐related HSP complicated with a clinical and EEG pattern reminiscent of DEE‐SWAS. We present the first report of DEE‐SWAS in ALDH18A1‐related HSP, expanding the clinical manifestations of this complex neurodevelopmental condition.

Theresa W Guilbert,1 Kevin R Murphy,2 Eckard Hamelmann,3 Kristie R Ross,4 Atul Gupta,5 Alessandro Fiocchi,6 Changming Xia,7 Rebecca Gall,7 Olivier Ledanois,8 Amr Radwan,7 Juby A Jacob-Nara,9 Paul J Rowe,9 Yamo Deniz7 1Cincinnati Children’s Hospital and University of Cincinnati, Cincinnati, OH, USA; 2Boys Town National Research Hospital, Omaha, NE, USA; 3Department of Pediatrics, Children’s Center Bethel, University of Bielefeld, Bielefeld, Germany; 4UH Rainbow Babies and Children’s Hospital, Cleveland, OH, USA; 5King’s College Hospital, London, UK; 6Bambino Gesù Children’s Hospital IRCCS, Rome, Italy; 7Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA; 8Sanofi, Paris, France; 9Sanofi, Bridgewater, NJ, USACorrespondence: Theresa W Guilbert, Cincinnati Children’s Hospital and University of Cincinnati, Cincinnati, OH, USA, Tel +1 513-636-6771, Email theresa.guilbert@cchmc.orgBackground: Severe, uncontrolled asthma and asthma exacerbations in children are associated with abnormal lung function and airway development, and increased risk of chronic obstructive lung disease in adulthood. The rationale for this post hoc analysis was to explore the relationship between changes in asthma exacerbation rates and lung function in children treated with dupilumab.Methods: This post hoc analysis included children aged 6 to 11 years with uncontrolled, moderate-to-severe type 2 asthma (blood eosinophils ≥ 150 cells/μL or fractional exhaled nitric oxide ≥ 20 ppb) who received dupilumab or placebo in the phase 3 LIBERTY ASTHMA VOYAGE study (NCT02948959). Endpoints were the proportion of patients achieving clinically meaningful improvements (≥ 5% or ≥ 10%) in pre-bronchodilator percent-predicted forced expiratory volume in 1 second (ppFEV1) by Week 12, annualized severe asthma exacerbation rates from Week 12– 52, and mean change from baseline in ppFEV1 to Week 12.Results: At Week 12 of VOYAGE, 141/236 (60%) of children treated with dupilumab and 57/114 (50%) of children receiving placebo showed improvements of ≥ 5% in ppFEV1; 106/236 (45%) children receiving dupilumab and 36/114 (32%) receiving placebo achieved improvements in ppFEV1 ≥ 10%. During the Week 12– 52 treatment period, dupilumab vs placebo significantly reduced severe exacerbation rates in all subgroups by 52– 60% (all P< 0.05). Dupilumab treatment resulted in rapid and sustained improvements in ppFEV1 (Week 12 least squares mean difference [95% CI] vs placebo: 3.54 [0.30, 6.78] percentage points; P=0.03) in children who achieved improvements of ≥ 5%.Conclusion: Dupilumab vs placebo significantly improved pre-bronchodilator ppFEV1, with a higher proportion of patients achieving a clinically meaningful response at Week 12. Dupilumab also significantly reduced severe exacerbation rates, independent of pre-bronchodilator ppFEV1 response at Week 12.Trial Registration: NCT02948959.Keywords: asthma, children, dupilumab, exacerbations, lung function, moderate-to-severe asthma, percent-predicted FEV1, uncontrolled asthma

Additive manufacturing has revolutionized the creation of complex and intrinsic structures, offering tailored designs for enhanced product performance across various applications. Architected cellular or lattice structures exemplify this innovation, customizable for specific mechanical or functional requirements, boasting advantages such as reduced mass, heightened load-bearing capabilities, and superior energy absorption. Nonetheless, their single-use limitation arises from plastic deformation resulting from localized yield damage or plastic buckling. Incorporating NiTi shape memory alloys (SMAs) presents a solution, enabling structures to recover their original shape post-unloading. In this study, an NiTi architected metastructure, featuring auxetic behavior and a negative Poisson's ratio, was designed and fabricated via laser powder bed fusion (LPBF). The samples exhibit promising superelastic performance with recoverable deformation strains at room temperature. Comprehensive characterization processes evaluated the functional performance of the fabricated metastructures. The metastructure geometry promoted microstructure formation primarily along the wall thickness. Cycling compression tests, conducted at three applied force levels, demonstrated stable cyclic behavior with up to 3.8 % reversible deformation strain, devoid of plastic buckling or yielding damage. Furthermore, the NiTi metastructures displayed robust energy absorption capacity and damping behavior, underscoring their potential for reusable energy dissipators in various industries including aerospace, automotive, construction, and etc.

BackgroundPrimary ciliary dyskinesia (PCD) is considered a rare cause of chronic rhinosinusitis with nasal polyposis (CRSwNP), which is reported in 6% of children with PCD. The forms of PCD associated with the variants of the GAS8 gene identified so far seem to be linked to recurrent respiratory infections (sinusitis, otitis, and bronchiectasis) without situs inversus.Case presentationWe report a case of an 11-year-old girl with recurrent otitis media, productive cough, and chronic rhinosinusitis with nasal polyposis with homozygosity for a novel nonsense mutation in the GAS8.ConclusionChildren with CRSwNP should be treated in a multidisciplinary manner (ENT, pulmonologist, allergist, pathologist, pediatrician, and geneticist) because nasal polyposis often hides etiologies that must be recognized.

Abstract The large use of fish meal/fish oil in carnivorous fish feeds is the main concern regarding environmental sustainability of aquaculture. Here, we evaluated the effects of an innovative diet, designed to be (1) environmentally sustainable by lowering the marine protein content while being (2) cost effective by using sustainable alternative raw materials with acceptable cost and produced on an industrial scale, on growth performance, gut microbiota composition, health and welfare of European sea bass (Dicentrarchus labrax), a key species of the Mediterranean marine aquaculture, reared in sea cages. Results show that the specific growth rate of fish fed the low marine protein diet was significantly lower than those fed conventional diet (0.67% vs 0.69%). Fatty acid profile of fillets from fish fed a low marine protein diet presented significant lower n-6 and higher n-3 content when compared to conventional ones. Then, a significant increase in the abundance of Vibrio and reduction of Photobacterium were found in the gut of fish fed with the low marine protein diet but effects on sea bass health needs further investigation. Finally, no major health and welfare alterations for fish fed the low marine protein diet were observed, combined with a potential slight benefit related to humoral immunity. Overall, these results suggest that despite the low marine protein diet moderately affects growth performance, it nevertheless may enhance environmental and economic sustainability of the sea bass aquaculture.