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Dysregulation of the renin-angiotensin-aldosterone-system (RAAS) in sepsis is a complex and early phenomenon with a likely significant contribution to organ failure and patient outcomes. A better understanding of the pathophysiology and intricacies of the RAAS in septic shock has led to the use of exogenous angiotensin II as a new therapeutic agent. In this review, we report a multinational and multi-disciplinary expert panel discussion on the role and implications of RAAS modulation in sepsis and the use of exogenous angiotensin II. The panel proposed guidance regarding patient selection and treatment options with exogenous angiotensin II which should trigger further research., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The organization of the consensus meeting was sponsored by Viatris, which commercialized Giapreza. Mathieu Legrand is supported by grant number R01-GM151494-01 from NIGMS/NIH and received consulting fees from Alexion, Radiometer, Viatris and La Jolla. Giovanni Landoni received speaker fees from Medis, Paion and Viatris, and consultancy fees from Paion and Viatris. PMW received consultant fees from Viatris. AKK has previously received consulting fees from La Jolla Pharma, including grant funding for the ATHOS3 trial. He has also previously received consulting fees from Innoviva Therapeutics and Viatris Pharmaceuticals. He is supported by a Wake Forest Cardiovascular Sciences Center Award and a NIH/NCATS Award “Dysfunction Renin in Septic Shock”. He has received consulting fees on advisory boards for Medtronic, Edwards Life Sciences, Philips Research North America, Baxter, GE Healthcare, Potrero Medical, Retia Medical, Pharmazz Inc., Trevena Pharma and Caretaker Medical for activities unrelated to the current manuscript. Katarzyna Kotfis is National Consultant in Anesthesiology and Critical Care in Poland, Associate Editor for Intensive Care Medicine (ISSN 1432-1238), Advisory board member for Critical Care (ISSN: 1364-8535) and Member of the Advisory Board for Viatris. Alexander Zarbock has received consulting fees from Astute-Biomerieux, Baxter, Bayer, Novartis, Guard Therapeutics, AM Pharma, Paion, Viatris, Renibus, Alexion, Fresenius, research funding from Astute-Biomerieux, Fresenius, Baxter, and speakers fees from Astute-Biomerieux, Fresenius, Baxter. Daniel De Backer has received consulting fees from Edwards Lifesciences, Philips, Baxter, Viatris, Pharmazz. Other authors had not disclosures to declare., (© 2024. The Author(s).)

Background: Sphingosine-1-phosphate (S1P) is a signalling molecule that has an inhibitory role in atherosclerosis, inflammation, cell proliferation, and immunity. Cenerimod is a selective S1P 1 receptor modulator under investigation for the treatment of systemic lupus erythematosus (SLE). We aimed to determine the efficacy, safety, and tolerability of four doses of cenerimod in adults with moderate-to-severe SLE receiving standard of care background therapy., Methods: CARE was a double-blind, randomised, placebo-controlled, phase 2 trial, in adults (aged 18-75 years) with moderate-to-severe SLE (a score of at least 6 out of 105 on the SLE disease activity index-2000, modified to exclude leukopenia [mSLEDAI-2K] score). Participants were recruited from 189 hospitals, specialist centres, and outpatient clinics in 22 countries in Asia Pacific, Latin America, Europe, and the USA. Participants were randomly assigned (1:1:1:1:1), using an interactive response technology via balanced block randomisation (block size of 5) and stratified by oral glucocorticoid dose at randomisation and disease activity at screening, to once-daily oral cenerimod at 0·5 mg, 1·0 mg, 2·0 mg, or 4·0 mg or placebo, in addition to stable background SLE therapy, and followed up for 12 months. After 6 months, participants assigned to cenerimod 4·0 mg were randomly assigned again (1:1) to either cenerimod 2.0 mg or placebo for a further 6 months. The primary endpoint was change from baseline to month 6 in mSLEDAI-2K score, assessed in all participants randomly assigned to treatment (full analysis set). To meet the primary endpoint, the doses had to show a significant improvement over placebo, when adjusting for multiplicity, considering the hierarchical testing strategy, per a prespecified plan. Safety analyses included all participants who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03742037, and is complete., Findings: Between Dec 21, 2018, and Aug 25, 2022, 810 patients were screened and 427 were randomly assigned to 0·5 mg (n=85), 1·0 mg (n=85), 2·0 mg (n=86), and 4·0 mg (n=85) cenerimod or placebo (n=86). Median age was 42 years (IQR 33-51), 406 (95%) of 427 participants were women, 21 (5%) were men, and 337 (79%) were White. At month 6, the least squares mean change from baseline in mSLEDAI-2K score was -2·85 (95% CI -3·60 to -2·10) for the placebo group and -3·24 (-3·98 to -2·49; difference vs placebo -0·39 [95% CI -1·45 to 0·68]; p=0·47) for the cenerimod 0·5 mg group, -3·41 (-4·16 to -2·67; difference vs placebo -0·57 [-1·62 to 0·49]; p=0·29) for the 1·0 mg group, -2·84 (-3·58 to -2·09; difference vs placebo 0·01 [-1·05 to 1·08]; p=0·98) for the 2·0 mg group, and -4·04 (-4·79 to -3·28; difference vs placebo -1·19 [-2·25 to -0·12]; p=0·029) for the 4·0 mg group; hence, the primary endpoint was not met. Treatment-emergent adverse events up to 12 months had no clear treatment-related or dose-related pattern across the groups. At month 6, treatment-emergent lymphopenia was reported in one (1%) of 85 patients who received cenerimod 0·5 mg, five (6%) of 85 patients who received 1·0 mg, nine (10%) of 86 patients who received 2·0 mg, 12 (14%) of 84 patients who received 4·0 mg, and no patients who received placebo. Two deaths due to adverse events occurred (both in the cenerimod 1·0 mg group; one due to acute coronary syndrome and the other due to upper gastrointestinal haemorrhage), and were determined to be unrelated to study treatment., Interpretation: The primary endpoint was not met. Cenerimod was well tolerated over 12 months. Cenerimod 4·0 mg is being investigated for the treatment of SLE in two ongoing phase 3 trials (NCT05648500, NCT05672576)., Funding: Idorsia Pharmaceuticals., Competing Interests: Declaration of interests ADA is a consultant for Amgen, AstraZeneca, Aurinia, Biogen, Bristol Myers Squibb, Cabaletta, Celgene, Eli Lilly, Idorsia, Janssen, Genentech, GSK, Sana, Sanofi, and UCB; has received grants from AstraZeneca, Biogen, BMS, Cabaletta, Idorsia, Genentech, NKARTA, Pfizer, Sana, Sanofi, and UCB; and has been a participant on advisory boards for Amgen and BMS. DD is a consultant advisor for GSK, UCB, and CSL Vifor; has received speaker fees from GSK and UCB; and has received support from CSL Vifor for attending European Alliance of Associations for Rheumatology 2023. CC was an employee of Idorsia Pharmaceuticals at the time the work was performed. KK is a consultant for BMS, GSK, Genentech/Roche, Equillium, AstraZeneca, Biogen, Eli Lilly, Amgen, Aurinia, Cabaletta, Shoreline, Ventyx, and Mirador; has been a participant on an advisory board for Genentech/Roche; holds a leadership or fiduciary role in Lupus Therapeutics and Lupus Foundation of America; and hold stocks in Artiva Bio and Bento Bio. JTM is a consultant for AbbVie, Alexion, Alumis, Amgen, Astra Zeneca, Aurinia, BMS, EMD Serono, Genentech, Gilead, GSK, Lilly, Merck, Pfizer, Provention, Remegen, Sanofi, UCB, and Zenas; has received grants from BMS, GSK, and AstraZeneca; has received speaker fees from AbbVie, BMS, Merck, and Remegen; and is Chief Advisor for Clinical Development for Lupus Foundation of America. SVN is aconsultant for Biogen, Idorsia, and AstraZeneca; has received speaker fees from Astellas, AstraZeneca, Aurinia, Pfizer, GSK, and Roche; has participated on advisory boards and data safety monitoring boards for Roche; and is President and Chief Executive Officer of Rheumatology Educational Trust Foundation. PC, MJM, DSS and OB are employees of Idorsia Pharmaceuticals and shareholders in the company. LT was an employee of Idorsia Pharmaceuticals and a shareholder in the company at the time the work was performed., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Food allergy represents an increasing global health issue, significantly impacting society on a personal and on a systems-wide level. The gold standard for diagnosing food allergy, the oral food challenge, is time-consuming, expensive, and carries risks of allergic reactions, with unpredictable severity. There is, therefore, an urgent need for more accurate, scalable, predictive diagnostic techniques. In this review, we discuss possible future directions in the world of food allergy diagnosis. We start by describing the current clinical approach to food allergy diagnosis, highlighting novel diagnostic methods recommended for use in clinical practice, such as the basophil activation test and molecular allergology, and go on to discuss tests that require more research before they can be applied to routine clinical use, including the mast cell activation test and bead-based epitope assay. Finally, we consider exploratory approaches, such as IgE glycosylation, IgG4, T and B cell assays, microbiome analysis, and plasma cytokines. Artificial intelligence is assessed for potential integrated interpretation of panels of diagnostic tests. Overall, a framework is proposed suggesting how combining established and emerging technologies can effectively enhance the accuracy of food allergy diagnosis in the future., Competing Interests: AS reports grants from Medical Research Council (MR/M008517/1; MC/PC/18052; MR/T032081/1), Food Allergy Research and Education (FARE), the Immune Tolerance Network/National Institute of Allergy and Infectious Diseases (NIAID, NIH), Asthma UK (AUK-BC-2015-01), BBSRC, Rosetrees Trust and the NIHR through the Biomedical Research Centre (BRC) award to Guy's and St Thomas' NHS Foundation Trust, during the conduct of the study; personal fees from Thermo Scientific, Nestle, Nutricia, Infomed, Novartis, Allergy Therapeutics, IgGenix, Buhlmann, as well as research support from IgGenix, Buhlmann and Thermo Fisher Scientific through a collaboration agreement with King's College London. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Wong and Santos.)

Food Protein-Induced Enterocolitis (FPIES) is a non-IgE mediated GI food allergy characterized by delayed, protracted vomiting, accompanied by lethargy and pallor, usually 1-4 hours following ingestion of the food allergen. The pathophysiology of FPIES remains unknown and currently there are no diagnostic biomarkers available to assess disease activity or its resolution. Over the last two decades, FPIES has become increasingly recognized in both pediatric and adult patients. Forty years later after the initial FPIES description, the first international classification of diseases (ICD-10) code for FPIES was established and the first international consensus guidelines for diagnosis and management of FPIES was published. On June 22, 2022, the National Institute of Allergy and Infectious Diseases (NIAID) held its first virtual multidisciplinary workshop on FPIES. Various clinical and translational aspects of FPIES, as well as the important areas of unmet needs were discussed as priorities for future research during this 2-day virtual workshop. The following report provides a summary of content of the workshop, including updated literature on the topic areas, as well as providing a critical commentary on the state of FPIES., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Breast pseudoaneurysm is a rare complication following breast interventional procedures such as core biopsies and vacuum-assisted biopsies. The occurrence of pseudoaneurysm increases with the conditions of increased breast vascularity like cancer, pregnancy and lactation., Case Report: We present two cases of pseudoaneurysm formation secondary to core biopsies of the breasts. The first patient was an 82-year-old female patient who presented with breast swelling and bruising after multiple clinical core biopsies of the left breast. Our second patient was a 47-year-old lady who presented with a palpable lump following ultrasound-guided core biopsies of the left breast. Ultrasound showed hypoechoic pulsating area with evidence of internal colour flow in connection with a vessel in both cases. Imaging appearances were in keeping with a pseudoaneurysm of the breast., Discussion: Most pseudoaneurysms are secondary to interventional procedures in the breast. Common clinical presentation is a pulsatile, palpable mass at the biopsy site soon after the biopsy or later. On B mode imaging, it presents as a well-circumscribed mass of mixed echogenicity. Typical waveform in spectral Doppler and 'yin-yang' sign in colour Doppler is demonstrated with a turbulent internal flow. There are different treatment options to manage pseudoaneurysms of the breast., Conclusion: Pseudoaneurysm of the breast should be considered if a patient presents with a breast mass/lump close to a recent biopsy site. On clinical examination, pulsatility of the mass should raise the suspicion and definite diagnosis can be made with spectral and colour Doppler US scan., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2024.)

Background: Feeding intolerance is common in critically ill patients and can lead to malnutrition. Prokinetic agents may be used to enhance the uptake of nutrition. However, the evidence on the effectiveness and safety of prokinetic agents is sparse, and there is a lack of data on their use in intensive care units (ICU)., Methods: We will conduct an international 14-day inception cohort study of 1000 acutely admitted adult ICU patients. Data will be collected from ICU admission and daily during ICU stay for up to 90 days. The primary outcome will be the proportion of ICU patients who receive prokinetic agents. Secondary outcomes include mortality, days alive without life support, days alive out of ICU, days alive out of hospital (all within 90 days) and the number of patients with one or more serious adverse events., Results: We will present data on the use of prokinetic agents descriptively and use Cox regressions with death and ICU discharge as competing events to evaluate the association between patient characteristics and the use of prokinetic agents. We will use extended Cox models with time-varying covariates and linear regression models to assess the associations between the use of prokinetic agents and the secondary outcomes., Conclusion: The outlined international cohort study will provide valuable epidemiological data on the use of prokinetic agents in adult, acutely admitted ICU patients., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Background: Short-lasting unilateral neuralgiform headache attacks (SUNHA) are trigeminal autonomic cephalalgias that feature intense and recurrent paroxysms of pain and autonomic symptoms. Many patients are left with debilitating symptoms despite best-available treatment. Psychedelics, such as the serotonin 2A partial agonist psilocybin, have shown promise in related disorders such as migraine and cluster headache. In this open-label phase Ib ascending dose study, we aimed to assess the effects of low-dose oral psilocybin with psychological support in six to 12 patients with chronic SUNHA. Study objectives were to determine effects on cognition, as well as safety, tolerability, and effects on headache severity and frequency., Methods: Oral psilocybin in ascending doses of 5, 7.5, and 10 mg (one dose per session; three dosing sessions in total) were administered. Cognition was assessed via the Cambridge Neuropsychological Tests Automated Battery. Headache attacks were assessed via headache diaries and the six-item Headache Impact Test (HIT-6). Subjective dose intensity was assessed via the five-Dimensional Altered States of Consciousness Questionnaire (5D-ASC). The study was terminated early due to recruitment difficulties; four patients were enrolled, three of whom were study completers. Post hoc, we undertook a thematic analysis of the applicable free-text clinical trial notes from the dosing and subsequent visits (n = 22). An inductive method was employed to establish emergent themes., Results: No significant adverse events were recorded. We were unable to collect data as planned on cognitive function during the acute experience due to high ratings of subjective dose intensity (mean 5D-ASC scores 37.8-45.7). The impact of the headaches remained severe throughout the duration of the trial (HIT-6 mean scores 64.3-65.7). There were limited effects on headache duration and severity based on the diaries; however, mean daily attack frequency decreased by >50% in two participants at final follow-up (22.9 to 11.0 and 56.4 to 28.0, respectively). Completing participants and their clinicians recorded "much" (two participants) or "minimal" improvements (one participant) at final follow-up via the Clinical Global Impression rating scale. Thematic analysis indicated that psychological insights were key features of participants' experience; these insights included re-configured relationships to their headache pain., Conclusion: The study met with recruitment difficulties and cognition could not be assessed during the acute experience due to subjective dose intensity, likely mediated in part by expectancy effects. The clinical results provide no conclusive evidence for the use of psilocybin in SUNHA. We suggest that accounting for psychological factors in chronic SUNHA may be an important facet of treatment., (© 2024 The Author(s). Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Background: Existing therapeutic strategies are challenged by long times to achieve effect and often require frequent administration. Peanut-allergic individuals would benefit from a therapeutic that provides rapid protection against accidental exposure within days of administration while carrying little risk of adverse reactions., Objective: Guided by the repertoire of human IgE mAbs from allergic individuals, we sought to develop a treatment approach leveraging the known protective effects of allergen-specific IgG4 antibodies., Methods: We applied our single-cell RNA-sequencing SEQ SIFTER platform (IgGenix, Inc, South San Francisco, Calif) to whole blood samples from peanut-allergic individuals to discover IgE mAbs. These were then class-switched by replacing the IgE constant region with IgG4 while retaining the allergen-specific variable regions. In vitro mast cell activation tests, basophil activation tests, ELISAs, and an in vivo peanut allergy mouse model were used to evaluate the specificity, affinity, and activity of these recombinant IgG4 mAbs., Results: We determined that human peanut-specific IgE mAbs predominantly target immunodominant epitopes on Ara h 2 and Ara h 6 and that recombinant IgG4 mAbs effectively block these epitopes. IGNX001, a mixture of 2 such high-affinity IgG4 mAbs, provided robust protection against peanut-mediated mast cell activation in vitro as well as against anaphylaxis upon intragastric peanut challenge in a peanut allergy mouse model., Conclusions: We developed a peanut-specific IgG4 antibody therapeutic with convincing preclinical efficacy starting from a large repertoire of human IgE mAbs from demographically and geographically diverse individuals. These results warrant further clinical investigation of IGNX001 and underscore the opportunity for the application of this therapeutic development strategy in other food and environmental allergies., Competing Interests: Disclosure statement The study was supported by IgGenix. A.F.S. acknowledges grants from the Medical Research Council (grant nos. MR/M008517/1, MC/PC/18052, and MR/T032081/1), Food Allergy Research and Education, the Immune Tolerance Network/National Institute of Allergy and Infectious Diseases, Asthma UK (grant no. AUK-BC-2015-01), Biotechnology and Biological Sciences Research Council (BBSRC), Rosetrees Trust, and the National Institute for Health and Care Research (NIHR) through the Biomedical Research Centre award to Guy’s and St Thomas’ National Health Service Foundation Trust during the conduct of the study. Disclosure of potential conflict of interest: D. Croote, J. J. W. Wong, P. Creeks, V. Aruva, R. Ferrini, G. R. Thomas, and H. B. Lowman are employees of, and/or stakeholders in, IgGenix. Patent applications assigned to IgGenix have been filed covering aspects of this work. R. G. Hamilton is a consultant for IgGenix. A. F. Santos received personal fees from Thermo Fisher Scientific, Novartis, Allergy Therapeutics, Nestle, and IgGenix; and received research support from IgGenix and Thermo Fisher Scientific through collaboration agreements with King’s College London. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

With the widespread use of 18F-fluorodeoxyglucose positron emission tomography (FDG PET/CT) in the investigation and staging of cancers, incidental discovery of FDG-avid thyroid nodules is becoming increasingly common, with a reported incidence in the range 1%-4% of FDG PET/CT scans. The risk of malignancy in an incidentally discovered FDG avid thyroid nodule is not clear due to selection bias in reported retrospective series but is likely to be less than 15%. Even in cases where the nodule is found to be malignant, the majority will be differentiated thyroid cancers with an excellent prognosis even without treatment. If, due to index cancer diagnosis, age and co-morbidities, it is unlikely that the patient will survive 5 years, further investigation of an incidental FDG avid thyroid nodule is unlikely to be warranted. We provide a consensus statement on the circumstances in which further investigation of FDG avid thyroid nodules with ultrasound and fine needle aspiration might be appropriate., (© 2023 John Wiley & Sons Ltd.)

Introduction: The basophil activation test (BAT) has shown evidence of high sensitivity and high specificity to support the diagnosis of IgE-mediated allergy. It is a functional test that uses live cells analyzed by flow cytometry and thus needs to be performed within 24h of blood collection. BAT has shown to be reproducible and reliable when tested in a clinical diagnostic laboratory with standardized protocols and flow cytometry settings., Areas Covered: In this review, we summarize the evidence to support clinical use of BAT and the next steps required for clinical implementation for an improve clinical care for patients with suspected IgE-mediated food allergy., Expert Opinion: BAT has recently been included in Clinical Guidelines of Food Allergy Diagnosis and its implementation in clinical practice depends largely on availability. Proposed clinical applications of the BAT include: distinction between food allergy and asymptomatic IgE sensitization; determination of food allergic status to peanut, tree nuts and seeds in polysensitized children; evaluation of tolerance to baked egg and baked milk in egg and milk allergic children; identification of patients at high-risk of severe allergic reactions; monitoring for spontaneous resolution of food allergy; confirmation of eligibility for specific treatments of food allergy; prediction and monitoring of response to immunomodulatory treatments.

This European Academy of Allergy and Clinical Immunology (EAACI) guideline provides recommendations for the management of IgE-mediated food allergy and was developed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Following the confirmation of IgE-mediated food allergy diagnosis, allergen avoidance and dietary advice (with support of a specialised dietitian, if possible) together with the provision of a written treatment plan, education on the recognition of allergic symptoms and prescription of medication including adrenaline using an auto-injector are essential. Patients with significant anxiety and requirement for coping strategies may benefit from support from a clinical psychologist. As immunomodulatory interventions, omalizumab is suggested for treatment of IgE-mediated food allergy in children from the age of 1 and adults; and oral allergen-specific immunotherapy is recommended for children and adolescents with peanut allergy and suggested for milk and egg allergies (generally after 4 years of age for milk and egg). Sublingual and epicutaneous immunotherapy are suggested for peanut allergy but are not yet available at the point of care. Future research into disease modifying treatments for IgE-mediated food allergy are highly needed, with standardised and patient-focused protocols and outcomes., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: CRUSE® is an app that allows patients with chronic spontaneous urticaria (CSU) to monitor their daily disease activity through the use of visual analogue scales (VASs). We aimed to determine the concurrent validity, reliability, responsiveness and minimal important difference (MID) of CRUSE® VASs., Methods: We evaluated the properties of three daily VASs: VAS for how much patients were affected by their CSU ('VAS urticaria'), VAS for the impact of urticaria on work/school productivity ('VAS productivity') and the VAS of EQ-5D. Concurrent validity was assessed by measuring the association between each VAS and the Urticaria Activity Score (UAS). Intra-rater reliability was determined based on the data of users providing multiple daily questionnaires within the same day. Test-retest reliability and responsiveness (ability to change), respectively, were tested in clinically stable and clinically unstable users. MIDs were determined using distribution-based methods., Results: We included 5938 patients (67,380 days). Concurrent validity was high, with VAS urticaria being more strongly associated with the UAS score than the remaining VASs. Intra-rater reliability was also high, with intraclass correlation coefficients (ICC) being above 0.950 for all VASs. Moderate-high test-retest reliability and responsiveness were observed, with reliability ICC being highest for VAS EQ-5D and responsiveness being highest for VAS urticaria. The MID for VAS urticaria was 17 (out of 100) units, compared to 15 units for VAS productivity and 11 units for VAS EQ-5D., Conclusion: Daily VASs for CSU available in the CRUSE® app display high concurrent validity and intra-rater reliability and moderate-high test-retest reliability and responsiveness., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

A growing and significant number of people with diabetes develop chronic kidney disease (CKD). Diabetes-related CKD is a leading cause of end-stage kidney disease (ESKD) and people with diabetes and CKD have high morbidity and mortality, predominantly related to cardiovascular disease (CVD). Despite advances in care over the recent decades, most people with CKD and type 2 diabetes are likely to die of CVD before developing ESKD. Hyperglycaemia and hypertension are modifiable risk factors to prevent onset and progression of CKD and related CVD. People with type 2 diabetes often have dyslipidaemia and CKD per se is an independent risk factor for CVD, therefore people with CKD and type 2 diabetes require intensive lipid lowering to reduce burden of CVD. Recent clinical trials of people with type 2 diabetes and CKD have demonstrated a reduction in composite kidney end point events (significant decline in kidney function, need for kidney replacement therapy and kidney death) with sodium-glucose co-transporter-2 (SGLT-2) inhibitors, non-steroidal mineralocorticoid receptor antagonist finerenone and glucagon-like peptide 1 receptor agonists. The Association of British Clinical Diabetologists (ABCD) and UK Kidney Association (UKKA) Diabetic Kidney Disease Clinical Speciality Group have previously undertaken a narrative review and critical appraisal of the available evidence to inform clinical practice guidelines for the management of hyperglycaemia, hyperlipidaemia and hypertension in adults with type 2 diabetes and CKD. This 2024 abbreviated updated guidance summarises the recommendations and the implications for clinical practice for healthcare professionals who treat people with diabetes and CKD in primary, community and secondary care settings., (© 2024 The Author(s). Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Abstract: The ultimate goal of bringing most new drugs to the clinic in hematologic malignancy is to improve overall survival. However, the use of surrogate end points for overall survival is increasingly considered standard practice, because a well validated surrogate end point can accelerate the outcome assessment and facilitate better clinical trial design. Established examples include monitoring minimal residual disease in chronic myeloid leukemia and acute leukemia, and metabolic response assessment in lymphoma. However, what happens when a clinical trial end point that is not a good surrogate for disease-modifying potential becomes ingrained as an expected outcome, and new agents are expected or required to meet this end point to demonstrate "efficacy"? Janus kinase (JAK) inhibitors for myelofibrosis (MF) have a specific impact on reducing symptom burden and splenomegaly but limited impact on the natural history of the disease. Since the introduction of ruxolitinib more than a decade ago there has been modest incremental success in clinical trials for MF but no major leap forward to alter the natural history of the disease. We argue that the clinical development of novel agents for MF will be accelerated by moving away from using end points that are specifically tailored to measure the beneficial effects of JAK inhibitors. We propose that specific measures of relevant disease burden, such as reduction in mutation burden as determined by molecular end points, should replace established end points. Careful reanalysis of existing data and trials in progress is needed to identify the most useful surrogate end points for future MF trials and better serve patient interest., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Marfan syndrome (MFS) is a hereditary connective tissue disorder with an estimated prevalence of 1:5000-1:10 000 individuals. It is a pleiotropic disease characterized by specific ocular, cardiovascular, and skeletal features. The most common cardiovascular complication is aortic root dilatation which untreated can lead to life-threatening aortic root dissection, mainly occurring in adult patients. Prompt diagnosis, appropriate follow-up, and timely treatment can prevent aortic events. Currently there are no specific recommendations for treatment of children with MFS, and management is greatly based on adult guidelines. Furthermore, due to the scarcity of studies including children, there is a lack of uniform treatment across different centres. This consensus document aims at bridging these gaps of knowledge. This work is a joint collaboration between the paediatric subgroup of the European Network of Vascular Diseases (VASCERN, Heritable Thoracic Aortic Disease Working Group) and the Association for European Paediatric and Congenital Cardiology (AEPC). A group of experts from 12 different centres and 8 different countries participated in this effort. This document reviews four main subjects, namely, (i) imaging of the aorta at diagnosis and follow-up, (ii) recommendations on medical treatment, (iii) recommendations on surgical treatment, and (iv) recommendations on sport participation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide. It attributes their onset to a functionally impaired epithelial barrier triggered by the toxicity of the exposed substances, associated with microbial dysbiosis, immune system activation, and inflammation. Diseases encompassed by the epithelial barrier theory share common features such as an increased prevalence after the 1960s or 2000s that cannot (solely) be accounted for by the emergence of improved diagnostic methods. Other common traits include epithelial barrier defects, microbial dysbiosis with loss of commensals and colonization of opportunistic pathogens, and circulating inflammatory cells and cytokines. In addition, practically unrelated diseases that fulfill these criteria have started to emerge as multimorbidities during the last decades. Here, we provide a comprehensive overview of diseases encompassed by the epithelial barrier theory and discuss evidence and similarities for their epidemiology, genetic susceptibility, epithelial barrier dysfunction, microbial dysbiosis, and tissue inflammation., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Purpose of Review: Recognition of the importance of innate lymphoid cells (ILCs) in the immune mechanisms of food allergy has grown in recent years. This review summarizes recent findings of ILCs in immunoglobulin E (IgE)-mediated food allergy. New research on ILCs in the context of the microbiome and other atopic diseases are also considered with respect to how they can inform understanding of the role of ILCs in food allergy., Recent Findings: ILCs can mediate allergic and tolerogenic responses through multiple pathways. A novel subset of interleukin (IL)-10 producing ILC2s are associated with tolerance following immunotherapy to grass pollen, house dust mite allergy and lipid transfer protein allergy. ILC2s can drive food allergen-specific T cell responses in an antigen-specific manner. A memory subset of ILC2s has been identified through studies of other atopic diseases and is associated with effectiveness of response to therapy., Summary: The role of ILCs in food allergy and oral tolerance is relatively understudied compared to other diseases. ILCs can modulate immune responses through several mechanisms, and it is likely that these are of importance in the context of food allergy. Better understanding of theses pathways may help to answer fundamental questions regarding the development of food allergy and lead to novel therapeutic targets and treatment., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

The advent of immunological therapies has revolutionized the treatment of solid and haematological cancers over the last decade. Licensed therapies which activate the immune system to target cancer cells can be broadly divided into two classes. The first class are antibodies that inhibit immune checkpoint signalling, known as immune checkpoint inhibitors (ICIs). The second class are cell-based immune therapies including chimeric antigen receptor T lymphocyte (CAR-T) cell therapies, natural killer (NK) cell therapies, and tumour infiltrating lymphocyte (TIL) therapies. The clinical efficacy of all these treatments generally outweighs the risks, but there is a high rate of immune-related adverse events (irAEs), which are often unpredictable in timing with clinical sequalae ranging from mild (e.g. rash) to severe or even fatal (e.g. myocarditis, cytokine release syndrome) and reversible to permanent (e.g. endocrinopathies).The mechanisms underpinning irAE pathology vary across different irAE complications and syndromes, reflecting the broad clinical phenotypes observed and the variability of different individual immune responses, and are poorly understood overall. Immune-related cardiovascular toxicities have emerged, and our understanding has evolved from focussing initially on rare but fatal ICI-related myocarditis with cardiogenic shock to more common complications including less severe ICI-related myocarditis, pericarditis, arrhythmias, including conduction system disease and heart block, non-inflammatory heart failure, takotsubo syndrome and coronary artery disease. In this scientific statement on the cardiovascular toxicities of immune therapies for cancer, we summarize the pathophysiology, epidemiology, diagnosis, and management of ICI, CAR-T, NK, and TIL therapies. We also highlight gaps in the literature and where future research should focus., (© 2024 European Society of Cardiology.)

Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide and remains a major cause of morbidity and mortality. Unfortunately, a significant proportion of patients have persistent AF, for which conventional catheter ablation is less effective. However, convergent ablation has emerged in recent years as a hybrid treatment targeting both the epicardium and endocardium in a multidisciplinary joint cardiothoracic and electrophysiology procedure, with promising efficacy outcomes in recent studies. This treatment is increasingly being performed in the United Kingdom. This review article discusses the rationale and evidence behind convergent ablation, along with factors that need to be considered when setting up a successful ablation service., (© 2024 The Author(s). Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Background: Ensuring equitable access to adequate standard of care for patients with rare hematological disease is one of the aims of the European Reference Network (ERN) EuroBloodNet. Stroke is one of the most devastating complications for children with sickle cell disease (SCD). For effective prevention of stroke risk, annual transcranial Doppler (TCD) according to a defined protocol is recommended for patients aged 2-16 years, with red blood cell transfusion therapy for those at risk. There is no information regarding screening for stroke risk and stroke prevention programs in Europe., Methods: Seven SCD experts of five healthcare providers (HCPs) of ERN EuroBloodNet developed an online survey to assess the access to TCD screening and stroke prevention programs for children with SCD in Europe., Results: Eighty-one experts in 77 HCPs from 16 European countries responded to 16 online questions. Thirty-two of 77 (51%) HCPs were EuroBloodNet reference centers, and 36% physicians reported not having a dedicated TCD/TCD imaging service for children with SCD. Only 30% of physicians provided estimates that all their patients received annual TCD according to the standard protocol due to lack of trained staff (43%), lack of TCD instruments (11%), refusal of patients due to logistical difficulties (22%), and lack of funds for dedicated staff or equipment (11%)., Conclusions: This multinational European survey provides the first comprehensive picture of access to TCD screening and stroke prevention in European countries. Identifying the potential underlying causes of the lack of effective standardized screening, this survey also addresses possible dedicated actions to cover these needs., (© 2024 Wiley Periodicals LLC.)

Introduction: Co-morbid anxiety and depression (distress) in inflammatory bowel disease (IBD) results in poorer outcomes and increased healthcare burden. IBD services require scalable treatment pathways for distress to meet this need. This real-world longitudinal study evaluates the implementation of a new integrated care pathway for distress including: 1) routine mental health screening and 2) therapist-guided, digital CBT tailored to the challenges of living with IBD (compass with adaptations for IBD: COMPASS-IBD) in a UK National Health Service (NHS) large gastroenterology service (∼ 5000 patients)., Methods: We describe a mixed-methods, observational, real-world longitudinal study. Routine mental health screening in the IBD service will identify patients with distress (using pre-defined clinical cut-offs), who will be triaged to determine appropriate treatment pathways (including participation in the COMPASS-IBD study). Participants will receive COMPASS-IBD online for ∼12 weeks (including 6 × 30-min therapist sessions). Key implementation outcomes will assess reach and adoption of the new pathway using aggregate data on uptake of mental health screening, eligibility, and consent rates for COMPASS-IBD, and number of COMPASS-IBD sessions completed. Interviews with patients and healthcare providers will primarily assess acceptability of the new pathway. Potential effectiveness will be assessed using participant questionnaires at pre-intervention, 12-weeks (post-intervention), and 6-month follow-up. The primary effectiveness outcome will be pre-post changes in distress (PHQ-ADS scores). Quantitative data will be summarised using descriptive statistics and qualitative data analysed using reflexive thematic analysis., Conclusion: Study findings will inform treatment pathways for co-morbid distress in IBD, and highlight adaptations required to increase future scalability and effectiveness., Trial Registration Number: NCT05330299 (clinicaltrials.gov)., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RMM reports personal fees from training in CBT for irritable bowel syndrome outside the submitted work. She received payment for consultancy to Mahana Therapeutics, has share options in Mahana therapeutics, and is a beneficiary of a licence agreement between Mahana therapeutics and King's College London. She has received reimbursement for travel and speaker fees from EABM, APS and BABCP conferences. All other authors report no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Various biomarkers are used to define peanut allergy (PA). We aimed to observe changes in PA resolution and persistence over time comparing biomarkers in PA and peanut sensitised but tolerant (PS) children in a population-based cohort., Methods: Participants were recruited from the EAT and EAT-On studies, conducted across England and Wales, and were exclusively breastfeed babies recruited at 3 months old and followed up until 7-12 years old. Clinical characteristics, skin prick test (SPT), sIgE to peanut and peanut components and mast cell activation tests (MAT) were assessed at 12 months, 36 months and 7-12 years. PA status was determined at the 7-12 year time point., Results: The prevalence of PA was 2.1% at 7-12 years. Between 3 and 7-12 year, two children developed PA and one outgrew PA. PA children had larger SPT, higher peanut-sIgE, Ara h 2-sIgE and MAT (all p < .001) compared to PS children from 12 months onwards. SPT, peanut-sIgE, Ara h 2-sIgE and MAT between children with persistent PA, new PA, outgrown PA and PS were statistically significant from 12 months onwards (p < .001). Those with persistent PA had SPT, peanut-sIgE and Ara h 2-sIgE that increased over time and MAT which was highest at 36 months. New PA children had increased SPT and peanut-sIgE from 36 months to 7-12 years, but MAT remained low. PS children had low biomarkers across time., Conclusions: In this cohort, few children outgrow or develop new PA between 36 months and 7-12 years. Children with persistent PA have raised SPT, peanut-sIgE, Ara h 2-sIgE and MAT evident from infancy that consistently increase over time., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Cow's milk allergy (CMA) remains one of the most common and complex paediatric food allergies. In the last decade, our understanding has advanced in terms of immunoglobulin E (IgE)-mediated CMA and focus is now also paid to non-IgE-mediated CMA, particularly in some Western countries where incidence rates are high. We have had significant progress in the last 10 years in relation to our understanding of existing supportive tests for IgE-mediated CMA, with the advancement of newer tests, such as the basophil activation test (BAT), which have shown great promise. However, little advancement has been made in terms of tests for non-IgE-mediated CMA, and controversy still exists around symptoms. Our understanding of the natural history of CMA has also advanced with more awareness of different phenotypes. While the mainstay of management remains cow's milk elimination, the importance of supporting breastfeeding and avoidance of unwarranted cow's milk elimination diets in breastfeeding mothers has been highlighted. For non-breastfed children, there has been some advancement in the formulas offered for the management of CMA, including the recognition of hydrolysed rice-based formulas and increased demand for nutritionally complete plant-based options, some of which are currently being assessed. The addition of pro, pre and synbiotics is considered safe to use, although research and guidance on routine use remain absent. Knowledge of tolerance induction from studies on the early introduction of peanuts has also highlighted the importance of a more active approach to managing CMA with the use of milk ladders, primarily in non-IgE-mediated CMA and baked milk (BM) introduction in IgE-mediated CMA. In addition, modulation of the microbiome and diet diversity during complementary feeding has been a major advancement in the last 10 years. While data on poor growth and feeding difficulties in children with CMA has not changed much, increased rates of obesity are now also reported. Finally, novel approaches, including oral immunotherapy, the use of milk ladders and earlier consideration of BM, have advanced somewhat in the last decade, although the risks and benefits of these novel approaches require further research. While CMA remains a complicated allergy to diagnose and manage, the evolution of science has advanced our knowledge and brought some novel innovations, which combined have enhanced our practice., (© 2024 The Author(s). Journal of Human Nutrition and Dietetics published by John Wiley & Sons Ltd on behalf of British Dietetic Association.)

Proton pump inhibitors (PPIs) are a commonly used class of drugs with a good safety profile. However, their use is associated with rare cases of severe skin reaction. Herein, we present details of a patient who developed two episodes of omeprazole-induced delayed-onset hypersensitivity (atypical drug reaction with eosinophilia and systemic symptoms [DRESS]). Lymphocytes from the patient were stimulated to proliferate and secrete cytokines and cytolytic molecules when treated with the drug. T-cell cross-reactivity was observed with structurally related PPIs. Hence, other PPIs have the potential to cause further serious immune-related adverse events in patients who present with hypersensitivity to a primary PPI.

Background: Consumption of ultra-processed foods [UPFs] may be associated with negative health outcomes. Limited data exist regarding the potential role of UPFs in the occurrence of allergic diseases. The underlying mechanisms underpinning any such associations are also poorly elucidated., Methods: We performed a systematic review and narrative evidence synthesis of the available literature to assess associations between UPF consumption and pediatric allergy outcomes (n = 26 papers), including data on the association seen with the gut microbiome (n = 16 papers) or immune system (n = 3 papers) structure and function following PRISMA guidelines., Results: Dietary exposure to fructose, carbonated soft drinks, and sugar intake was associated with an increased risk of asthma, allergic rhinitis, and food allergies in children. Commercial baby food intake was associated with childhood food allergy. Childhood intake of fructose, fruit juices, sugar-sweetened beverages, high carbohydrate UPFs, monosodium glutamate, UPFs, and advanced glycated end-products (AGEs) was associated with the occurrence of allergic diseases. Exposure to UPFs and common ingredients in UPFs seem to be associated with increased occurrence of allergic diseases such as asthma, wheezing, food allergies, atopic dermatitis, and allergic rhinitis, in many, but not all studies., Conclusion: More preclinical and clinical studies are required to better define the link between UPF consumption and the risk of allergies and asthma. These observational studies ideally require supporting data with clearly defined UPF consumption, validated dietary measures, and mechanistic assessments to definitively link UPFs with the risk of allergies and asthma., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Derived from the myeloid lineage, granulocytes, including basophils, eosinophils, and neutrophils, along with mast cells, play important, often disparate, roles across the allergic disease spectrum. While these cells and their mediators are commonly associated with allergic inflammation, they also exhibit several functions either promoting or restricting tumor growth. In this Position Paper we discuss common granulocyte and mast cell features relating to immunomodulatory functions in allergy and in cancer. We highlight key mechanisms which may inform cancer treatment and propose pertinent areas for future research. We suggest areas where understanding the communication between granulocytes, mast cells, and the tumor microenvironment, will be crucial for identifying immune mechanisms that may be harnessed to counteract tumor development. For example, a comprehensive understanding of allergic and immune factors driving distinct neutrophil states and those mechanisms that link mast cells with immunotherapy resistance, might enable targeted manipulation of specific subpopulations, leading to precision immunotherapy in cancer. We recommend specific areas of investigation in AllergoOncology and knowledge exchange across disease contexts to uncover pertinent reciprocal functions in allergy and cancer and allow therapeutic manipulation of these powerful cell populations. These will help address the unmet needs in stratifying and managing patients with allergic diseases and cancer., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Objectives: To evaluate the diagnostic performance and reliability of MRI descriptors used for the detection of Ménière's disease (MD) on delayed post-gadolinium MRI. To determine which combination of descriptors should be optimally applied and whether analysis of the vestibular aqueduct (VA) contributes to the diagnosis., Materials and Methods: This retrospective single centre case-control study evaluated delayed post-gadolinium MRI of patients with Ménièriform symptoms examined consecutively between Dec 2017 and March 2023. Two observers evaluated 17 MRI descriptors of MD and quantified perilymphatic enhancement (PLE) in the cochlea. Definite MD ears according to the 2015 Barany Society criteria were compared to control ears. Cohen's kappa and diagnostic odds ratio (DORs) were calculated for each descriptor. Forward stepwise logistic regression determined which combination of MRI descriptors would best predict MD ears, and the area under the receiver operating characteristic curve for this model was measured., Results: A total of 227 patients (mean age 48.3 ± 14.6, 99 men) with 96 definite MD and 78 control ears were evaluated. The presence of saccular abnormality (absent, as large as or confluent with the utricle) performed best with a DOR of 292.6 (95% confidence interval (CI), 38.305-2235.058). All VA descriptors demonstrated excellent reliability and with DORs of 7.761 (95% CI, 3.517-17.125) to 18.1 (95% CI, 8.445-39.170). Combining these saccular abnormalities with asymmetric cochlear PLE and an incompletely visualised VA correctly classified 90.2% of cases (sensitivity 84.4%, specificity 97.4%, AUC 0.938)., Conclusion: Either absent, enlarged or confluent saccules are the best predictors of MD. Incomplete visualisation of the VA adds value to the diagnosis., Clinical Relevance Statement: A number of different MRI descriptors have been proposed for the diagnosis of Ménière's disease, but by establishing the optimally performing MRI features and highlighting new useful descriptors, there is an opportunity to improve the diagnostic performance of Ménière's disease imaging., Key Points: • A comprehensive range of existing and novel vestibular aqueduct delayed post-gadolinium MRI descriptors were compared for their diagnostic performance in Ménière's disease. • Saccular abnormality (absent, confluent with or larger than the utricle) is a reliable descriptor and is the optimal individual MRI predictor of Ménière's disease. • The presence of this saccule descriptor or asymmetric perilymphatic enhancement and incomplete vestibular aqueduct visualisation will optimise the MRI diagnosis of Ménière's disease., (© 2024. Crown.)

Background: A paucity of data exists to inform the use of interleukin (IL)-6 receptor antibodies (anti-IL-6) in pregnancy, particularly in the third trimester. This study aimed to describe outcomes of pregnant women and their neonates exposed to these medications given after the first trimester to treat COVID-19., Methods: In this retrospective cohort study, we included all women with COVID-19 who were treated with an anti-IL-6 during pregnancy at two tertiary hospitals in London, UK-Guy's and St Thomas' NHS Foundation Trust and Imperial College Healthcare NHS Trust-between March 1, 2020, and Sept 30, 2022. Maternal demographics, clinical data, administered medications, and maternal and neonatal outcomes were assessed for all included women via a review of medical records and through maternal medicine networks., Findings: 25 women received an anti-IL-6 for COVID-19 in pregnancy during the study period and were followed up for 12 months. The group described were a population at high risk, with 24 requiring level two or three critical care. 24 women received tocilizumab and one received sarilumab. All women were prescribed at least three concomitant medications. 16 received the anti-IL-6 in the third trimester of pregnancy and nine during the seocnd trimester. There were no women with maternal neutropenia or pancytopenia; increases in liver enzymes in 16 of 20 women with available alanine aminotransferase data were in keeping with the severity of COVID-19 reported and all three women who developed a secondary bacterial infection mounted a C-reactive protein response. There was one maternal death due to COVID-19. All pregnancies resulted in livebirths and there was one twin pregnancy. 16 of 26 babies were born preterm. One baby died at age 6 months due to complications of extreme prematurity. A transient neonatal cytopenia was described in six of 19 babies in whom a full blood count was performed. Although these findings are likely to be in keeping with prematurity alone, we cannot exclude the possibility that transplacental transfer of anti-IL-6 was contributory., Interpretation: We report further data on the use of anti-IL-6 in the second and third trimesters of pregnancy for the management of COVID-19. When extrapolated, our data can inform shared decision making for individuals who would benefit from the use of anti-IL-6 into the third trimester of pregnancy for management of rheumatological disease., Funding: None., Competing Interests: Declaration of interests MN reports speakers fees from Exeltis, grants from the National Institute for Health and Care Research's Clinical Research Training Fellowship, and is co-chair of Royal College of Physicians Trainee Committee. BG reports speakers fees from GSK and grants from Versus Arthritis Clinical Research Fellowship (reference 22975). CN-P reports consultancy fees from UCB; speakers fees from UCB, Sanofi, Bristol Myers Squib, and Otsuka; and participation on advisory board for UCB. MKD reports an unpaid obstetric representative role for the UK MacDonald Obstetric Medicine Society. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objective: To compile and evaluate the heritability and inheritance patterns of lower urinary tract symptoms (LUTS) in adult cohorts., Methods: Searches of five databases (PubMed, Embase, APA PsycInfo, Global Health, and OVID Medline) commenced on 6 July 2024, resulting in 736 articles retrieved after deduplication. Studies evaluating heritability patterns, gene frequencies, and familial aggregation of symptoms were included for review. Screening and predefined eligibility criteria produced 34 studies for final review. A descriptive analysis of synthesised data was performed, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Cochrane Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool and the Johanna Briggs Institute checklist were used to evaluate these studies., Results: Ten of the 34 studies (29%) described general LUTS, 14 (41%) described symptoms due to benign prostatic enlargement (BPE), nine (26%) described urinary incontinence (UI; urge UI [UUI], stress UI [SUI] and mixed UI [MUI]), four (12%) described nocturia alone, two (6%) described overactive bladder (OAB), and four (13%) described other specific symptoms (frequency, postvoid residual urine volume). BPE symptoms, UI (MUI and UUI), nocturia alone, and frequency alone were associated with genetic predisposition, whilst OAB and SUI had more modest inheritance., Conclusion: The pathogenetic and pharmacological mechanisms fundamental to LUTS manifestation are highly heterogeneous. Further work is required to evaluate the inheritance patterns of LUTS more extensively., (© 2024 The Author(s). BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Introduction: Lymphocytic esophagitis (LyE) and eosinophilic esophagitis (EoE) are immune-mediated esophageal diseases. Clinical characteristics, endoscopic findings, and treatment outcomes of LyE were compared with EoE., Methods: This was an international retrospective study on adults enrolled at 3 centers in Europe. We recorded clinical characteristics and endoscopy findings at baseline and symptoms, histology, and endoscopy outcomes after treatment of patients with LyE and EoE., Results: Demographics, clinical presentation, comorbidities, and endoscopy findings were largely different in 35 patients with LyE compared with 59 patients with EoE. Proton pump inhibitor response was generally lower in LyE., Discussion: LyE is clinically different from EoE, but differences in treatment response need further investigation., (Copyright © 2024 by The American College of Gastroenterology.)

Purpose: To compare the calibre of the cochlear (CN), superior vestibular (SVN) and inferior vestibular (IVN) nerves on magnetic resonance imaging (MRI), both between Ménière's Disease (MD) ears and clinical controls, and between inner ears with and without endolymphatic hydrops (EH) on MRI., Methods: A retrospective case-control study evaluated patients undergoing MRI for suspected hydropic ear disease from 9/2017 to 8/2022. The CN, SVN, IVN and facial nerve (FN) diameters and cross-sectional areas (CSA) were measured on T2-weighted sequences whilst EH was evaluated on delayed post-gadolinium MRI. Absolute nerve calibre (and that relative to the FN) in unilateral definite MD ears (2015 Barany criteria) was compared to that in both asymptomatic contralateral ears and clinical control ears. Nerve calibre in ears with severe cochlear and vestibular EH was compared to ears without EH. t tests or Wilcoxon signed-rank test/Mann-Whitney U test were applied (p < 0.001)., Results: 173 patients (mean age 51.3 ± 15.1, 65 men) with 84 MD (62 unilateral) and 62 clinical control ears were studied. Absolute and relative CN dimensions were decreased in both MD ears (CSA and diameter) and the contralateral asymptomatic ears (CSA) when compared to clinical controls (p < 0.001). Absolute nerve dimensions were reduced in both severe vestibular EH (CN, IVN and SVN) and severe cochlear EH (CN) (p < 0.001), however this was not evident when adjusted according to facial nerve calibre., Conclusion: There is decreased absolute CN calibre in both symptomatic and asymptomatic MD ears as well as ears with severe cochlear and vestibular EH on MRI., (© 2024. Crown.)

Food allergy (FA) is a potentially life-threatening chronic condition that is becoming an increasing public health problem worldwide. This systematic review (SR) was carried out to inform the development of clinical recommendations on the treatment of IgE-mediated FA with biologics and/or IT for the update of the EAACI guidelines. A SR of randomized-controlled trials or quasi-controlled trials was carried out. Studies were identified via comprehensive search strategies in Medline, Embase, and Cochrane Library, up to April 2022., Population: Human adults, children, and adolescents with IgE-mediated FA., Intervention: IT and/or biologics., Comparator: Placebo or standard-of-care (allergen avoidance)., Outcome: Efficacy (desensitization, sustained unresponsiveness (SU), remission), quality of life, and safety (systemic and local adverse reactions (AR)). The Cochrane RoB tool was used to assess the risk of bias. It was reported according to PRISMA and registered in PROSPERO CRD4202229828. After screening, 121 studies were included (111 for IT and 10 for biologics). Most studies had a high risk of bias and showed high heterogeneity in design and results. Metanalysis showed a positive effect of biologics and IT in terms of relative risk (RR) for achieving tolerance to the culprit food compared to avoidance or placebo. Omalizumab for any FA showed a RR of 2.17 [95% confidence interval: 1.22, 3.85]. For peanut allergy, oral IT (OIT) had a RR of 11.94 [1.76, 80.84] versus avoidance or placebo, sublingual IT (SLIT) had a RR of 3.00 [1.04, 8.66], and epicutaneous IT (EPIT) of 2.16 [1.56, 3.00]. OIT had a RR of 5.88 [2.27, 15.18] for cow's milk allergy, and of 3.43 [2.24, 5.27] for egg allergy. There was insufficient data on SLIT or EPIT for the treatment of egg and milk allergies. Most ARs reported were mild. For OIT the most common AR involved the gastrointestinal system and for EPIT, AR's most commonly affected the skin. There was limited data on severe or life-threatening ARs. There was limited evidence for long term efficacy and quality of life. In conclusion, biologics and IT, alone or in combination, are effective in achieving desensitization while on active treatment but more evidence is needed on long-term tolerance as current evidence is not of high quality. Adverse events while on therapy are generally mild to moderate but a long-term comprehensive safety profile is missing. There is a critical need to optimize and standardize desensitization protocols and outcome measures to facilitate our understanding of the efficacy and safety as well as to allow for comparison between interventions., (© 2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Active inflammatory arthritis in pregnancy is associated with an increased risk of adverse pregnancy outcomes. Treatment of active inflammation and maintenance of low disease activity with medication reduces these risks. Therapeutic decisions on disease-modifying antirheumatic drugs (DMARDs) in pregnancy are complicated by safety concerns, which have led to inappropriate withdrawal of treatment and consequential harm to mother and fetus. Studies of inflammatory arthritis in pregnancy have consistently shown minimal safety concerns with the use of biological DMARDs and an increased risk of disease flare with discontinuation of biological DMARDs. It is our opinion that during pregnancy, the benefits of disease control with biological DMARDs, when required in addition to conventional synthetic DMARDs, outweigh the risks. In this Series paper, we review the reasons for reconsideration of equipoise and propose an agenda for future research to optimise the use of biological DMARDs in inflammatory arthritis during pregnancy., Competing Interests: Declaration of interests IG has received grants from Union Chimique Belge (UCB), honoraria from MGP as a coauthor on an educational review article in 2020, and speaker fees from UCB, and has participated in advisory boards for UCB. IT has received speaker fees from UCB. CN-P has received speaker fees from UCB and participated in advisory boards for UCB. CT has received honoraria to provide an online lecture in a related area in 2022 and to be coauthor on an educational review article in 2020 (from MGP), and has acted as an expert witness for obstetric cases in the UK. SD has received speaker and consulting fees from UCB. NF has received consulting fees from ALK, Sanofi Aventis, Gideon Richter, Abbot, Galderma, AstraZeneca, Ipsen, Vertex, Thea, Novo Nordisk, Aimmune, and Ipsen; speaker fees from Abbott Singapore; and has participated in advisory boards for Orion. RJEMD has received grants paid to his department from the Dutch Arthritis Association, ZonMw, UCB, and Galapagos; consulting fees from Galapagos and UCB; and speaker fees from UCB, Roche, AbbVie, Genzyme, Novartis, AstraZeneca, and Eli Lilly; and has participated in advisory boards for Galapagos and UCB. MEBC has received grants and consulting fees from GSK and UCB and has participated in advisory boards for MotherToBaby. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Introduction: Despite the success of immunotherapies for melanoma in recent years, there remains a significant proportion of patients who do not yet derive benefit from available treatments. Immunotherapies currently licensed for clinical use target the adaptive immune system, focussing on Tcell interactions and functions. However, the most prevalent immune cells within the tumor microenvironment (TME) of melanoma are macrophages, a diverse immune cell subset displaying high plasticity, to which no current therapies are yet directly targeted. Macrophages have been shown not only to activate the adaptive immune response, and enhance cancer cell killing, but, when influenced by factors within the TME of melanoma, these cells also promote melanoma tumorigenesis and metastasis., Areas Covered: We present a review of the most up-to-date literatureavailable on PubMed, focussing on studies from within the last 10 years. We also include data from ongoing and recent clinical trials targeting macrophages in melanoma listed on clinicaltrials.gov., Expert Opinion: Understanding the multifaceted role of macrophages in melanoma, including their interactions with immune and cancer cells, the influence of current therapies on macrophage phenotype and functions and how macrophages could be targeted with novel treatment approaches, are all critical for improving outcomes for patients with melanoma.

As a component of myeloablative conditioning before allogeneic hematopoietic stem cell transplantation (HSCT), Total Body Irradiation (TBI) is employed in radiotherapy centers all over the world. In recent and coming years, many centers are changing their technical setup from a conventional TBI technique to multi-isocenter conformal arc therapy techniques such as Volumetric Modulated Arc Therapy (VMAT) or Helical Tomotherapy (HT). These techniques allow better homogeneity and control of the target prescription dose, and provide more freedom for individualized organ-at-risk sparing. The technical design of multi-isocenter/multi-plan conformal TBI is complex and should be developed carefully. A group of early adopters with conformal TBI experience using different treatment machines and treatment planning systems came together to develop technical recommendations and share experiences, in order to assist departments wishing to implement conformal TBI, and to provide ideas for standardization of practices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Aims: No endoscopic scoring system has been established for immune-mediated colitis (IMC). This study aimed to establish such a system for IMC and explore its utility in guiding future selective immunosuppressive therapy (SIT) use compared to clinical symptoms., Methods: This retrospective, international, 14-center study included 674 patients who developed IMC after immunotherapy and underwent endoscopic evaluation. Ten endoscopic features were selected by group consensus and assigned 1 point each to calculate an IMC endoscopic score (IMCES). IMCES cutoffs were chosen to maximize specificity for SIT use. This specificity was compared between IMCESs, and clinical symptoms were graded according to a standardized instrument., Results: A total of 309 (45.8%) patients received SIT. IMCES specificity for SIT use was 82.8% with a cutoff of 4. The inclusion of ulceration as a mandatory criterion resulted in higher specificity (85.0% for a cutoff of 4). In comparison, the specificity of a Mayo endoscopic subscore of 3 was 74.6%, and the specificity of clinical symptom grading was much lower at 27.4% and 12.3%, respectively. Early endoscopy was associated with timely SIT use (P < .001; r = 0.4084)., Conclusions: This is the largest multicenter study to devise an endoscopic scoring system to guide IMC management. An IMCES cutoff of 4 has a higher specificity for SIT use than clinical symptoms, supporting early endoscopic evaluation for IMC., Competing Interests: Disclosure The following authors disclosed financial relationships: Y. Wang: Consultant for Sorriso Pharma, MabQuest, AzurRx, Sanarentero, Janssen, IOTA, Ilyapharma, Biontech, and Mallinckrodt Pharma. D. Faleck: Consultant for Kaleido Biosciences, AzurRx, Mallinckrodt Pharmaceuticals, Janssen, Teva, Gilead, Ferring, and Equillium. M. Dougan: Research funding Eli Lilly; consulting fees from Genentech, Partner Therapeutics, SQZ Biotech, AzurRx, Eli Lilly, Mallinckrodt Pharmaceuticals, Aditum, Foghorn Therapeutics, Palleon, Sorriso Pharmaceuticals, Generate Biomedicines, Asher Bio, Neoleukin Therapeutics, Moderna, Alloy Therapeutics, Third Rock Ventures, DE Shaw Research, Agenus, and Curie Bio; member of the Scientific Advisory Board for Veravas, Monod Bio, Axxis Bio, and Cerberus Therapeutics. D. B. Johnson: Served on advisory boards or as a consultant for BMS, Catalyst Biopharma, Iovance, Jansen, Mallinckrodt, Merck, Mosaic ImmunoEngineering, Novartis, Oncosec, Pfizer, Targovax, and Teiko; research funding from BMS and Incyte; patents pending for the use of MHC-II as a biomarker for immune checkpoint inhibitor response and abatacept as a treatment for immune-related adverse events. P. Grivas: Funding from Acrivon Therapeutics, ALX Oncology, Bavarian Nordic, Bristol-Myers Squibb, Clovis Oncology, Debiopharm; Genentech, Gilead, GlaxoSmithKline, G1 Therapeutics, Merck KGaA, Mirati Therapeutics, MSD, Pfizer, and QED Therapeutics. Consultant for Aadi Bioscience, Abbvie, AstraZeneca, Asieris Pharmaceuticals, Astellas Pharma, Bristol-Myers Squibb, Boston Gene, CG Oncology, Dyania Health, Lucence Health, Fresenius Kabi, G1 Therapeutics, Gilead, Guardant Health, ImmunityBio, Janssen, Merck KGaA, MSD, Pfizer, PureTech, Roche, SeaGen, Strata Oncology, and Silverback Therapeutics. D. Owen: Research funding (to institution) from Merck, BMS, Pfizer, Genentech, Palobiofarma, and Onc.AI. N. Powell: Speaker for Allergan, Bristol Myers Squibb, Falk, Ferring, Janssen, Pfizer, Tillotts, and Takeda; consultant and/or advisory board member for AbbVie, Allergan, Celgene, Bristol Myers Squibb, Ferring, and Vifor Pharma. J. Philpott: Speaker for AbbVie. S. Sandhu: Grants from Novartis/AAA, Astra Zeneca, Merck Sharp and Dohme, and Genentech; personal fees from Astra Zeneca; and personal fees to the institution from Merck Sharp and Dohme, Bristol Myer Squibb, and personal fees to the institution from Astra Zeneca, outside the submitted work. D. J. Pinato: Grant funding from the Wellcome Trust Strategic Fund (PS3416), the Foundation for Liver Research, and the Associazione Italiana per la Ricerca sul Cancro (AIRC MFAG grant ID 25697); support from the NIHR Imperial Biomedical Research Centre, Imperial Experimental Cancer Medicine Centre, and Imperial College Tissue Bank; lecture fees from ViiV Healthcare, Bayer Healthcare, Bristol Myers Squibb, Roche, EISAI, and Falk Foundation; travel expenses from Bristol Myers Squibb, Bayer Healthcare, and Viiv Healthcare; consultant for Bayer Healthcare, Bristol Myers Squibb, Mina Therapeutics, H3B, EISAI, Roche, DaVolterra, Mursla, Exact Sciences, Avamune, and AstraZeneca; and research funding (to his institution) from MSD, Bristol Myers Squibb, and GSK. A. Olsson-Brown: Speaker/consultant for Bristol Myers Squibb, MSD, Novartis, Eiasi, and Merck/Pfizer; speaker for Roche, AZ, GSK, Ipsen, and Boehringer Ingram. C. Cassol: Grant funding from Novartis, Iptacopan Educational Steering Committee, Nephrology, and SBIR. All other authors disclosed no financial relationships. This study was supported by the National Institutes of Health/National Cancer Institute under award number P30CA016672 for institutional review board review service; otherwise, no additional grant support was received for conducting the study., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)