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Abstract: Descemet membrane (DM) endothelial keratoplasty is considered the gold standard for treating corneal endothelial decompensation and is a true like-for-like replacement. Not all causes of endothelial dysfunction are global, with conditions such as viral endotheliitis affecting discrete populations of endothelial cells. In this study, endothelial grafts matching the area of dysfunction were produced to preserve healthy host cells and limit the immunological burden of new grafts. We have termed this modified DM endothelial keratoplasty procedure DM endothelial patching., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Context: De Novo nephrolithiasis in renal transplant can have severe consequences since renal transplantation involves a single functioning kidney with medical and anatomical specificities (heterotopic transplantation on iliac vessels, immunosuppressive treatments, and comorbidities)., Objective: To systematically review all available evidence on the prevalence of de novo nephrolithiasis in renal transplant, presentation, and stone characteristics, and to report in a meta-analysis the efficacy of stone treatments (extracorporeal shock wave lithotripsy [ESWL], medical treatment, percutaneous nephrolithotomy [PCNL], open surgery, and ureteroscopy)., Evidence Acquisition: Medline, Embase, and the Cochrane Library were searched up to November 2021 for all relevant publications reporting the management of de novo nephrolithiasis in renal allografts. The primary outcome was stone-free rate (SFR) at 3 mo. Secondary outcomes included prevalence, stone characteristics (size, density, and composition), symptoms on presentation, need for drainage, complications, and recurrence. Data were narratively synthesized in light of methodological and clinical heterogeneity, and a meta-analysis was performed for SFR. The risk of bias of each included study was assessed., Evidence Synthesis: We included 37 retrospective studies with 553 patients and 612 procedures; of the 612 procedures 20 were antegrade ureteroscopy, 154 retrograde ureteroscopy, 118 PCNL, 25 open surgery, 155 ESWL, and 140 surveillance/medical treatment. The prevalence of nephrolithiasis in renal transplant was 1.0%. The mean stone size on diagnosis was 11 mm (2-50). The overall SFR at 3 mo was 82%: 96% with open surgery, 95% with antegrade ureteroscopy, 86% with PCNL, 81% with retrograde ureteroscopy, and 75% with ESWL., Conclusions: De novo nephrolithiasis in renal transplant is an infrequent condition. A high SFR were obtained with an antegrade approach (ureteroscopy, PCNL, and open approach) that should be considered in renal transplant patients owing to the heterotopic position of the renal graft. The choice of technique was correlated with stone size: generally ureteroscopy and ESWL for stones 11-12 mm (mean stone size) versus PCNL and open surgery for 17-25 mm stones., Patient Summary: De novo nephrolithiasis in renal transplants is an infrequent situation that can have severe consequences on the function of the renal graft. We evaluated the efficacy of each treatment and noted that antegrade approaches (open surgery, percutaneous nephrolithotomy, and antegrade ureteroscopy) were associated with the highest stone-free rate. As opposed to the management of nephrolithiasis in native kidney, an antegrade approach should be considered more in renal transplant patients., (Copyright © 2022. Published by Elsevier B.V.)

Background and Aims: The utility of real-world data is dependent on the quality and homogeneity of reporting. We aimed to develop a core outcome set for real-world studies in adult patients with inflammatory bowel disease [IBD]., Methods: Candidate outcomes and outcome measures were identified and categorised in a systematic review. An international panel including patients, dietitians, epidemiologists, gastroenterologists, nurses, pathologists, radiologists, and surgeons participated in a modified Delphi consensus process. A consensus meeting was held to ratify the final core outcome set., Results: A total of 26 panellists from 13 countries participated in the consensus process. A total of 271 items [130 outcomes, 141 outcome measures] in nine study domains were included in the first-round survey. Panellists agreed that real-world studies on disease activity should report clinical, endoscopic, and biomarker disease activity. A disease-specific clinical index [Harvey-Bradshaw Index, Partial Mayo Score, Simple Clinical Colitis Activity Index] should be used, rather than physician global assessment. In ulcerative colitis [UC], either the UC Endoscopic Index of Severity or the Mayo Endoscopic Score can be used, but there was no consensus on an endoscopic index for Crohn's disease, nor was there consensus on the use of the presence of ulcers. There was consensus on using faecal calprotectin and C-reactive protein. There was no consensus on the use of histology in real-world studies., Conclusions: A core outcome set for real-world studies in IBD has been developed based on international multidisciplinary consensus. Its adoption will facilitate synthesis in the generation of real-world evidence., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Objective: Whether benefits and risks of intravenous (IV) infliximab combotherapy with immunosuppressants versus infliximab monotherapy apply to subcutaneous (SC) infliximab is unknown. This post hoc analysis of a pivotal randomised CT-P13 SC 1.6 trial aimed to compare SC infliximab monotherapy with combotherapy in inflammatory bowel disease (IBD)., Methods: Biologic-naïve patients with active Crohn's disease or ulcerative colitis received CT-P13 IV 5 mg/kg at Week (W) 0 and 2 (dose-loading phase). At W6, patients were randomised (1:1) to receive CT-P13 SC 120 or 240 mg (patients < 80 or ≥ 80 kg) every 2 weeks until W54 (maintenance phase), or to continue CT-P13 IV every 8 weeks until switching to CT-P13 SC from W30. The primary endpoint-non-inferiority of trough serum concentrations-was assessed at W22. We report a post hoc analysis comparing pharmacokinetic, efficacy, safety and immunogenicity outcomes up to W54 for patients randomised to CT-P13 SC, stratified by concomitant immunosuppressant use., Results: Sixty-six patients were randomised to CT-P13 SC (37 monotherapy, 29 combotherapy). At W54, there were no significant differences in the proportions of patients achieving target exposure (5 µg/mL; 96.6% monotherapy vs 95.8% combotherapy; p > 0.999) or meeting efficacy or biomarker outcomes including clinical remission (62.9% vs 74.1%; p = 0.418). Monotherapy and combotherapy groups had comparable immunogenicity (anti-drug antibodies [ADAs]: 65.5% vs 48.0% [p = 0.271], neutralising antibodies [in ADA-positive patients]: 10.5% vs 16.7% [p = 0.630], respectively)., Conclusions: Pharmacokinetics, efficacy and immunogenicity were potentially comparable between SC infliximab monotherapy and combotherapy in biologic-naïve IBD patients., Trial Registration: ClinicalTrials.gov: NCT02883452., (© 2023. The Author(s).)

Background: A growing number of studies have shown encouraging results with omalizumab (OMA) as monotherapy and as an adjunct to oral immunotherapy (OMA+OIT) in patients with single/multiple food allergies., Objectives: To evaluate the efficacy and safety of OMA or OMA+OIT in patients with immunoglobulin E (IgE)-mediated food allergy., Methods: An extensive literature search (inception to December 31, 2020) was performed to identify randomized, controlled, and observational studies that assessed OMA as monotherapy or OMA+OIT in patients with IgE-mediated food allergy. The outcomes were an increase in tolerated dose of foods, successful desensitization, sustained unresponsiveness, immunological biomarkers, severity of allergic reactions to food, quality of life (QoL), and safety. A P less than .05 was considered significant., Results: In total, 36 studies were included. The OMA monotherapy (vs pre-OMA) significantly increased the tolerated dose of multiple foods; increased the threshold of tolerated dose for milk, egg, wheat, and baked milk; improved QoL; and reduced food-induced allergic reactions (all P < .01). The OMA+OIT significantly increased the tolerated dose of multiple foods (vs placebo and pre-OMA), desensitization (vs placebo+OIT and pre-OMA) (all P ≤ .01), and improved QoL (vs pre-OMA) and immunoglobulin G4 levels (both P < .01). No major safety concerns were identified., Conclusions: In IgE-mediated food allergy, OMA can help patients consume multiple foods and allow for food dose escalation. As an adjunct to OIT, OMA can also support high-dose desensitization and higher maintenance doses. Further studies are warranted to empirically evaluate the effect of OMA and confirm these findings., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Ara h 2-specific IgE (Arah2-sIgE) is an excellent serologic marker for peanut allergy. However, not all subjects with detectable Arah2-sIgE react clinically., Objective: To assess the importance of functional characteristics of Arah2-sIgE for Ara h 2-induced mast cell activation., Methods: We studied a cohort of children assessed for peanut allergy. We determined Arah2-sIgE levels, Ara h 2/total IgE ratios and IgE avidity for Ara h 2 using ImmunoCAP (Thermo Fisher) and mast cell activation to Ara h 2 using flow cytometry., Results: Samples from 61 of 100 children (46 peanut-allergic [PA] and 15 peanut-sensitized tolerant) who had Arah2-sIgE levels 0.10 kU/L or greater were studied. Arah2-sIgE and Ara h 6-specific IgE levels, Ara h 2/total IgE ratios, and the diversity of IgE for Ara h 2 epitopes were higher in PA compared with peanut-sensitized tolerant samples. The levels of IgE to peanut, Ara h 1, and Ara h 3 were not significantly different between groups. Results from the mast cell activation test to Ara h 2 strongly correlated with Arah2-sIgE levels (r = 0.722; P < .001) and Ara h 2/total IgE ratios (r = 0.697; P < .001) and moderately with Arah2-sIgE diversity (r = 0.540; P < .001). On a linear regression model, Arah2-sIgE levels (standardized β-coefficient = 0.396; P = .008) and Ara h 2/total IgE ratios (standardized β-coefficient = 0.0.669; P = .002) were the main determinants of mast cell response to Ara h 2., Conclusions: Most children sensitized to Ara h 2 are PA. Ara h 2-specific IgE titers and specific activity are the major determinants of mast cell response to Ara h 2., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: To survey past and current radiology academic clinical fellows (ACFs) for feedback on their experiences, academic achievements, challenges faced in balancing academic and clinical responsibilities, and opinion on how to optimise the fellowship programme., Materials & Methods: A 26-question online survey approved by the Royal College of Radiologists (RCR) Academic Committee was distributed over a 7-month period (June 2021 to January 2022) to current and past radiology ACFs via the National Institute for Health and Care Research (NIHR) integrated academic training imaging leads, radiology training programme directors, and social media., Results: Thirty-five survey responses were received from past or present ACFs. Of the respondents, 42.8% (15/35) entered ACF training from another research post, and most continued their academic interests after ACF training (59.3%, 16/27 that had completed the post). The majority (22/35, 63%) had or were in the process of obtaining a postgraduate research degree. The most common academic outputs were scientific publications and national/international conference presentations. Most (23/35, 66%) would recommend the ACF post to colleagues, although some found it challenging balancing on-call and examination commitments during training., Conclusions: Entry into the radiology ACF programme is often after a prior academic post. Many ACFs appear to enjoy their fellowship experience and continue academic interests after training, some achieving higher research degrees. Challenges in balancing clinical workload require some flexibility from local clinical and academic supervisors. Suggestions for alternative structuring of the ACF pathway and how to optimise entry into these competitive posts are also outlined., (Copyright © 2023 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Introduction: Recurrent chromosome 16p13.11 microduplication has been characterised in the literature as a cause of developmental delay, learning difficulties and behavioural abnormalities. It is a neurosusceptibility locus and has incomplete penetrance and variable expression. Other clinical features, such as cardiac abnormalities have also been reported. The duplicated region contains the MYH11 gene, which encodes the protein myosin-11 and is a component of the myosin heavy chain in smooth muscle. Recent literature has suggested 16p13.11 microduplication as one of the possible risk factors for thoracic aortic aneurysms and dissection (TAAD). Therefore, we studied the detailed phenotype of cases of chromosome 16p13.11 microduplication from seven centres in the United Kingdom (UK) to expand the phenotype, focusing on the cardiac abnormalities., Methods: All individuals with a chromosome 16p13.11 microduplication seen in Clinical Genetics prior to June 2017 in 6 centres (prior to 2018 in the seventh centre) were identified through the regional genetics laboratory databases. A Microsoft Excel® proforma was created and clinical data was collected retrospectively from clinical genetics databases from the seven genetics services in the UK. The data was collated and analysed collectively., Results: The majority of the individuals presented with (72%) developmental delay and (62%) behavioural abnormalities, in keeping with the published literature. 27% had some dysmorphic features, 14% had visual impairment and 8% had congenital cardiac abnormalities. Echocardiograms were performed in 50% of patients, and only 3.8% patients had aortic dilatation and no one had aortic dissection. 9.7% of patients were found to have a second genetic/chromosomal diagnosis, especially where there were additional phenotypic features., Conclusion: 16p13.11 microduplication is a neurosusceptibility locus and is associated with variable expression. It may be helpful to refer children with 16p13.11 microduplication for a cardiac review for congenital cardiac abnormalities and also for ophthalmological assessment. Further prospective studies with cardiac assessments are recommended in this cohort of patients to determine whether ongoing aortic surveillance is indicated. Guidelines about the frequency of surveillance are indicated, especially in individuals with normal cardiac findings. We also highlight the importance of considering a second diagnosis if the phenotype is inconsistent with that reported., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Simultaneousinvolvement of the supraclavicular and axillary lymphatic basins is known to occur in metastatic skin cancers. We present the case of a 35-year-old male with metastatic melanoma present in the right neck and axillary lymph nodes. He underwent a combined, in-continuity dissection of both basins using intraoperative ultrasound to ensure full clearance of lymph nodes from the cervicoaxillary canal, which otherwise would have been impossible to achieve without clavicle osteotomy. This allowed us to avoid a division of the clavicle and related morbidity. Postoperative imaging confirmed no residual disease, and no local recurrence subsequently. We conclude that intraoperative use of ultrasound can help guide surgeons trying to achieve clearance of metastatic disease in anatomically complex regions, avoiding unnecessary morbidity., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Oral food challenges (OFCs) are currently the definitive diagnostic procedure in food allergy. Their design has evolved over the decades to maximize safety, optimize convenience, and address several specific clinical questions. However, they are a resource-intensive investigation that carry a risk for severe allergic reaction in which fatal outcomes, although rare, have been reported. In this review, we explore the many roles that OFC fulfil in the clinical and research settings. We also discuss progress that has been made in developing alternative diagnostic tools and how far these have reached in offering a viable replacement to OFC in clinical practice. Finally, we discuss the ongoing importance of research OFC to improve the future diagnostic capabilities of novel diagnostic tools., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest the authors declare they have no conflicts of interest.

Background: Causes and precipitating factors of sudden cardiac death (SCD) in adolescents are poorly understood., Objectives: The authors sought to investigate the etiologies of SCD and their association with physical activity in a large cohort of adolescents., Methods: Between 1994 and June 2022, 7,675 cases of SCD were consecutively referred to our national cardiac pathology center; 756 (10%) were adolescents. All cases underwent detailed autopsy evaluation by expert cardiac pathologists. Clinical information was obtained from referring coroners., Results: A structurally normal heart, indicative of sudden arrhythmic death syndrome was the most common autopsy finding (n = 474; 63%). Myocardial diseases were detected in 163 cases (22%), including arrhythmogenic cardiomyopathy (n = 36; 5%), hypertrophic cardiomyopathy (n = 31; 4%), idiopathic left ventricular hypertrophy (n = 31; 4%), and myocarditis (n = 30; 4%). Coronary artery anomalies were identified in 17 cases (2%). Decedents were competitive athletes in 128 cases (17%), and 159 decedents (21%) died during exercise. Arrhythmogenic cardiomyopathy was diagnosed in 8% of athletes compared with 4% of nonathletes (P = 0.05); coronary artery anomalies were significantly more common in athletes (9% vs 1%; P < 0.001), as well as commotio cordis (5% compared with 1% in nonathletes; P = 0.001). The 3 main comorbidities were asthma (n = 58; 8%), epilepsy (n = 44; 6%), and obesity (n = 40; 5%)., Conclusions: Sudden arrhythmic death syndrome and myocardial diseases are the most common conditions diagnosed at autopsy in adolescent victims of SCD. Among causes of SCD, arrhythmogenic cardiomyopathy, coronary artery anomalies, and commotio cordis are more common in young athletes than in similar age sedentary individuals., Competing Interests: Funding Support and Author Disclosures The charity Cardiac Risk in the Young fund the Cardiac Risk in the Young Cardiovascular Pathology Laboratories. Dr Finocchiaro is partly funded by the charity Cardiac Risk in the Young. Dr Westaby is funded by the National Institute for Health and Care Research. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: While several scoring systems for the severity of anaphylactic reactions have been developed, there is a lack of consensus on definition and categorisation of severity of food allergy disease as a whole., Aim: To develop an international consensus on the severity of food allergy (DEfinition of Food Allergy Severity, DEFASE) scoring system, to be used globally., Methods Phase 1: We conducted a mixed-method systematic review (SR) of 11 databases for published and unpublished literature on severity of food allergy management and set up a panel of international experts., Phase 2: Based on our findings in Phase 1, we drafted statements for a two-round modified electronic Delphi (e-Delphi) survey. A purposefully selected multidisciplinary international expert panel on food allergy (n = 60) was identified and sent a structured questionnaire, including a set of statements on different domains of food allergy severity related to symptoms, health-related quality of life, and economic impact. Participants were asked to score their agreement on each statement on a 5-point Likert scale ranging from "strongly agree" to "strongly disagree". Median scores and percentage agreements were calculated. Consensus was defined a priori as being achieved if 70% or more of panel members rated a statement as "strongly agree" to "agree" after the second round. Based on feedback, 2 additional online voting rounds were conducted., Results: We received responses from 92% of Delphi panel members in round 1 and 85% in round 2. Consensus was achieved on the overall score and in all of the 5 specific key domains as essential components of the DEFASE score., Conclusions: The DEFASE score is the first comprehensive grading of food allergy severity that considers not only the severity of a single reaction, but the whole disease spectrum. An international consensus has been achieved regarding a scoring system for food allergy disease. It offers an evaluation grid, which may help to rate the severity of food allergy. Phase 3 will involve validating the scoring system in research settings, and implementing it in clinical practice., (© 2023 The Authors.)

Autoimmune rheumatic diseases (ARD) can affect women and men during fertile age, therefore reproductive health is a priority issue in rheumatology. Many topics need to be considered during preconception counselling: fertility, the impact of disease-related factors on pregnancy outcomes, the influence of pregnancy on disease activity, the compatibility of medications with pregnancy and breastfeeding. Risk stratification and individualized treatment approach elaborated by a multidisciplinary team minimize the risk of adverse pregnancy outcomes (APO). Research has been focused on identifying biomarkers that can be predictive of APO. Specifically, preeclampsia and hypertensive disorders of pregnancy tend to develop more frequently in women with ARD. Placental insufficiency can lead to intrauterine growth restriction and small-for-gestational age newborns. Such APO have been shown to be associated with maternal disease activity in different ARD. Therefore, a key message to be addressed to the woman wishing for a pregnancy and to her family is that treatment with compatible drugs is the best way to ensure maternal and fetal wellbeing. An increasing number of medications have entered the management of ARD, but data about their use in pregnancy and lactation are scarce. More information is needed for most biologic drugs and their biosimilars, and for the so-called small molecules, while there is sufficient evidence to recommend the use of TNF inhibitors if needed for keeping maternal disease under control. Other issues related to the reproductive journey have emerged as "unmet needs", such as sexual dysfunction, contraception, medically assisted reproduction techniques, long-term outcome of children, and they will be addressed in this review paper. Collaborative research has been instrumental to reach current knowledge and the future will bring novel insights thanks to pregnancy registries and prospective studies that have been established in several Countries and to their joint efforts in merging data., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: To investigate the effectiveness of an intraoperative surgical technique to reduce the incidence of immediate postoperative cavity hemorrhage in patients undergoing vitrectomy for complications of proliferative diabetic retinopathy., Methods: A single-center, prospective study of 20 consecutive patients who underwent vitrectomy for proliferative diabetic retinopathy-related complications. A standard 3-port pars plana vitrectomy with either 23 g or 25 g was performed. At the end of surgery, the infusion was switched off to create transient hypotony and endolaser photocoagulation with long-duration burns were applied to actively leaking blood vessel., Results: The average age was 56.2 + 12.8 years. Eleven eyes had actively bleeding vessels at the end of surgery and received endolaser photocoagulation. No patients were found to have hypotony at Day 1 postoperative. Preoperative median visual acuity was 20/1,600 improving to 20/40 at a median of 2.3 weeks post-op (range 0.4-8.5 weeks). Two eyes (10%) had a small postoperative cavity hemorrhage with 20/40 vision, which did not require further intervention., Conclusion: The described technique was found to be effective in reducing the incidence of postoperative cavity hemorrhage from up to 75% reported in literature to 10% in our pilot study. Further study with a larger number of patients is required.

The atopic march was described more than 20 years ago on the basis of initial observations, and it is now seen in prospective studies. The concept has evolved and is now considered to be the progression of atopic dermatitis to other atopic conditions, including asthma, allergic rhinitis, food allergy, and eosinophilic esophagitis in a nonlinear fashion. The progression can include some or all of the aforementioned atopic conditions. The pathogenesis is part of the classic type 2 inflammatory process involving IL-4, IL-5, and IL-13 preceded by induction of the alarmins (thymic stromal lymphopoietin, IL-33, and IL-25), leading to production of IgE in a genetically predisposed individual. The development of new biologics that interact with T2 pathway represent possible ways to prevent or modify the atopic march., (Copyright © 2023 American Academy of Allergy, Asthma Immunology. Published by Elsevier Inc. All rights reserved.)

Since the discovery of immunoglobulin E (IgE) as a mediator of allergic diseases in 1967, our knowledge about the immunological mechanisms of IgE-mediated allergies has remarkably increased. In addition to understanding the immune response and clinical symptoms, allergy diagnosis and management depend strongly on the precise identification of the elicitors of the IgE-mediated allergic reaction. In the past four decades, innovations in bioscience and technology have facilitated the identification and production of well-defined, highly pure molecules for component-resolved diagnosis (CRD), allowing a personalized diagnosis and management of the allergic disease for individual patients. The first edition of the "EAACI Molecular Allergology User's Guide" (MAUG) in 2016 rapidly became a key reference for clinicians, scientists, and interested readers with a background in allergology, immunology, biology, and medicine. Nevertheless, the field of molecular allergology is moving fast, and after 6 years, a new EAACI Taskforce was established to provide an updated document. The Molecular Allergology User's Guide 2.0 summarizes state-of-the-art information on allergen molecules, their clinical relevance, and their application in diagnostic algorithms for clinical practice. It is designed for both, clinicians and scientists, guiding health care professionals through the overwhelming list of different allergen molecules available for testing. Further, it provides diagnostic algorithms on the clinical relevance of allergenic molecules and gives an overview of their biology, the basic mechanisms of test formats, and the application of tests to measure allergen exposure., (© 2023 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Long-term sequelae are frequent and often disabling after epidermal necrolysis (Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)). However, consensus on the modalities of management of these sequelae is lacking., Objectives: We conducted an international multicentric DELPHI exercise to establish a multidisciplinary expert consensus to standardize recommendations regarding management of SJS/TEN sequelae., Methods: Participants were sent a survey via the online tool "Survey Monkey" consisting of 54 statements organized into 8 topics: general recommendations, professionals involved, skin, oral mucosa and teeth, eyes, genital area, mental health, and allergy workup. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). Results were analyzed according to the RAND/UCLA Appropriateness Method., Results: Fifty-two healthcare professionals participated. After the first round, a consensus was obtained for 100% of 54 initially proposed statements (disagreement index < 1). Among them, 50 statements were agreed upon as 'appropriate'; four statements were considered 'uncertain', and ultimately finally discarded., Conclusions: Our DELPHI-based expert consensus should help guide physicians in conducting a prolonged multidisciplinary follow-up of sequelae in SJS-TEN., (© 2023. The Author(s).)

Background: An infodemic is excess information, including false or misleading information, that spreads in digital and physical environments during a public health emergency. The COVID-19 pandemic has been accompanied by an unprecedented global infodemic that has led to confusion about the benefits of medical and public health interventions, with substantial impact on risk-taking and health-seeking behaviors, eroding trust in health authorities and compromising the effectiveness of public health responses and policies. Standardized measures are needed to quantify the harmful impacts of the infodemic in a systematic and methodologically robust manner, as well as harmonizing highly divergent approaches currently explored for this purpose. This can serve as a foundation for a systematic, evidence-based approach to monitoring, identifying, and mitigating future infodemic harms in emergency preparedness and prevention., Objective: In this paper, we summarize the Fifth World Health Organization (WHO) Infodemic Management Conference structure, proceedings, outcomes, and proposed actions seeking to identify the interdisciplinary approaches and frameworks needed to enable the measurement of the burden of infodemics., Methods: An iterative human-centered design (HCD) approach and concept mapping were used to facilitate focused discussions and allow for the generation of actionable outcomes and recommendations. The discussions included 86 participants representing diverse scientific disciplines and health authorities from 28 countries across all WHO regions, along with observers from civil society and global public health-implementing partners. A thematic map capturing the concepts matching the key contributing factors to the public health burden of infodemics was used throughout the conference to frame and contextualize discussions. Five key areas for immediate action were identified., Results: The 5 key areas for the development of metrics to assess the burden of infodemics and associated interventions included (1) developing standardized definitions and ensuring the adoption thereof; (2) improving the map of concepts influencing the burden of infodemics; (3) conducting a review of evidence, tools, and data sources; (4) setting up a technical working group; and (5) addressing immediate priorities for postpandemic recovery and resilience building. The summary report consolidated group input toward a common vocabulary with standardized terms, concepts, study designs, measures, and tools to estimate the burden of infodemics and the effectiveness of infodemic management interventions., Conclusions: Standardizing measurement is the basis for documenting the burden of infodemics on health systems and population health during emergencies. Investment is needed into the development of practical, affordable, evidence-based, and systematic methods that are legally and ethically balanced for monitoring infodemics; generating diagnostics, infodemic insights, and recommendations; and developing interventions, action-oriented guidance, policies, support options, mechanisms, and tools for infodemic managers and emergency program managers., Competing Interests: Conflicts of Interest: SB, SBr, NG, SH, AI, MK, RL, TN, TDP, and BY are staff of the World Health Organization (WHO); CBF and BKW are consultants with WHO; SK and CV are staff of the US Centers for Disease Control and Prevention (US CDC). These authors alone are responsible for the views expressed in this paper, and they do not represent the views of their organizations. The conflicts of interest were reviewed and managed as per WHO procedures. AD declared that his university received research support on information diet measurement by WHO for the product owned by WHO. He was not part of the consensus driving during the closing session of the meeting. TM is the current Editor-in-Chief of JMIR Infodemiology and declared ownership interest in a company for work not related to the deliberation in this publication. LMB works for Immunize Canada/the Canadian Public Health Association, which has received educational grants/funding from Merck Canada, Pfizer Canada, Pfizer Global, Moderna Canada, Seqirus, Sanofi Canada, GSK Canada, and the Public Health Agency of Canada (PHAC). These funds are not related to the paper. CW was executive director of the nonprofit organization First Draft, which received funds for research and advocacy work from Google, and research project support on the effectiveness of SMS-based social inoculation from WHO. She chaired the first 3 days of the conference but was not part of the consensus driving during the closing session of the meeting. EP declared receiving conference stipends, training fees, and publication fees from the Medical Research Council. He was not part of the consensus driving during the closing session of the meeting. IB is director of the WHO Collaborating Center on information systems for health, which supports WHO with broader digital health analytics and policy analysis. The center has supported the Pan American Health Organization (PAHO)/WHO with infodemic analytics during COVID-19. SMR declared receiving consultancy fees from the EURO Health Group research consortium and is currently a consultant in infodemic management for WHO. JR and SVDL declared that their university received research funding from NATO Strategic Communications Centre of Excellence, Google Jigsaw, WhatsApp, British Academy, the Economic and Social Research Council (ESRC), the UK Cabinet Office, and EU Horizon 2020. They were not part of the consensus driving during the closing session of the meeting. AG declared that his university received research funds from the Canadian Institutes of Health Research (CIHR). AS declared receiving consultancy fees from Euro Health Group A/S – Denmark for services unrelated to the topic of the conference. PB is founder and CEO of HealthEnabled, which received past funding from Gavi, the Vaccine Alliance, to conduct digital social listening. JN declared employment with Harvard University, working in the field of medical misinformation. MG and MEB declared no conflicts of interest for this paper., (©Elisabeth Wilhelm, Isabella Ballalai, Marie-Eve Belanger, Peter Benjamin, Catherine Bertrand-Ferrandis, Supriya Bezbaruah, Sylvie Briand, Ian Brooks, Richard Bruns, Lucie M Bucci, Neville Calleja, Howard Chiou, Abhinav Devaria, Lorena Dini, Hyjel D'Souza, Adam G Dunn, Johannes C Eichstaedt, Silvia M A A Evers, Nina Gobat, Mika Gissler, Ian Christian Gonzales, Anatoliy Gruzd, Sarah Hess, Atsuyoshi Ishizumi, Oommen John, Ashish Joshi, Benjamin Kaluza, Nagwa Khamis, Monika Kosinska, Shibani Kulkarni, Dimitra Lingri, Ramona Ludolph, Tim Mackey, Stefan Mandić-Rajčević, Filippo Menczer, Vijaybabu Mudaliar, Shruti Murthy, Syed Nazakat, Tim Nguyen, Jennifer Nilsen, Elena Pallari, Natalia Pasternak Taschner, Elena Petelos, Mitchell J Prinstein, Jon Roozenbeek, Anton Schneider, Varadharajan Srinivasan, Aleksandar Stevanović, Brigitte Strahwald, Shabbir Syed Abdul, Sandra Varaidzo Machiri, Sander van der Linden, Christopher Voegeli, Claire Wardle, Odette Wegwarth, Becky K White, Estelle Willie, Brian Yau, Tina D Purnat. Originally published in JMIR Infodemiology (https://infodemiology.jmir.org), 20.02.2023.)

Aims: Existing strategies that identify post-infarct ventricular tachycardia (VT) ablation target either employ invasive electrophysiological (EP) mapping or non-invasive modalities utilizing the electrocardiogram (ECG). Their success relies on localizing sites critical to the maintenance of the clinical arrhythmia, not always recorded on the 12-lead ECG. Targeting the clinical VT by utilizing electrograms (EGM) recordings stored in implanted devices may aid ablation planning, enhancing safety and speed and potentially reducing the need of VT induction. In this context, we aim to develop a non-invasive computational-deep learning (DL) platform to localize VT exit sites from surface ECGs and implanted device intracardiac EGMs., Methods and Results: A library of ECGs and EGMs from simulated paced beats and representative post-infarct VTs was generated across five torso models. Traces were used to train DL algorithms to localize VT sites of earliest systolic activation; first tested on simulated data and then on a clinically induced VT to show applicability of our platform in clinical settings. Localization performance was estimated via localization errors (LEs) against known VT exit sites from simulations or clinical ablation targets. Surface ECGs successfully localized post-infarct VTs from simulated data with mean LE = 9.61 ± 2.61 mm across torsos. VT localization was successfully achieved from implanted device intracardiac EGMs with mean LE = 13.10 ± 2.36 mm. Finally, the clinically induced VT localization was in agreement with the clinical ablation volume., Conclusion: The proposed framework may be utilized for direct localization of post-infarct VTs from surface ECGs and/or implanted device EGMs, or in conjunction with efficient, patient-specific modelling, enhancing safety and speed of ablation planning., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Anti-tachycardia pacing (ATP) is a reliable electrotherapy to painlessly terminate ventricular tachycardia (VT). However, ATP is often ineffective, particularly for fast VTs. The efficacy may be enhanced by optimized delivery closer to the re-entrant circuit driving the VT. This study aims to compare ATP efficacy for different delivery locations with respect to the re-entrant circuit, and further optimize ATP by minimizing failure through re-initiation., Methods and Results: Seventy-three sustained VTs were induced in a cohort of seven infarcted porcine ventricular computational models, largely dominated by a single re-entrant pathway. The efficacy of burst ATP delivered from three locations proximal to the re-entrant circuit (septum) and three distal locations (lateral/posterior left ventricle) was compared. Re-initiation episodes were used to develop an algorithm utilizing correlations between successive sensed electrogram morphologies to automatically truncate ATP pulse delivery. Anti-tachycardia pacing was more efficacious at terminating slow compared with fast VTs (65 vs. 46%, P = 0.000039). A separate analysis of slow VTs showed that the efficacy was significantly higher when delivered from distal compared with proximal locations (distal 72%, proximal 59%), being reversed for fast VTs (distal 41%, proximal 51%). Application of our early termination detection algorithm (ETDA) accurately detected VT termination in 79% of re-initiated cases, improving the overall efficacy for proximal delivery with delivery inside the critical isthmus (CI) itself being overall most effective., Conclusion: Anti-tachycardia pacing delivery proximal to the re-entrant circuit is more effective at terminating fast VTs, but less so slow VTs, due to frequent re-initiation. Attenuating re-initiation, through ETDA, increases the efficacy of delivery within the CI for all VTs., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Fluid overload is a risk factor for increased morbidity and mortality, especially in patients with heart disease. The treatment options are limited to diuretics and mechanical fluid removal using ultrafiltration or renal replacement therapy. This paper provides an overview of the challenges of managing fluid overload, outlines the risks and benefits of different pharmacological options and extracorporeal techniques, and provides guidance for clinical practice., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Adolescence is a critical stage of rapid biological, emotional and social change and development. Adolescents and young adults (AYA) with asthma and allergies need to develop the knowledge and skills to self-manage their health independently. Healthcare professionals (HCP), parents and their wider network play an essential role in supporting AYA in this process. Previous work showed significant limitations in transition care across Europe. In 2020, the first evidence-based guideline on effective transition for AYA with asthma and allergies was published by EAACI., Aim: We herein summarize practical resources to support this guideline's implementation in clinical practice., Methods: For this purpose, multi-stakeholder Task Force members searched for resources in peer review journals and grey literature. These resources were included if relevant and of good quality and were pragmatically rated for their evidence-basis and user friendliness., Results: Resources identified covered a range of topics and targeted healthcare professionals, AYA, parents/carers, schools, workplace and wider community. Most resources were in English, web-based and had limited evidence-basis., Conclusions: This position paper provides a valuable selection of practical resources for all stakeholders to support effective transitional care for AYA with asthma and allergies. Future research should focus on developing validated, patient-centred tools to further assist evidence-based transition care., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Context: No algorithm exists for structured follow-up of urolithiasis patients., Objective: To provide a discharge time point during follow-up of urolithiasis patients after treatment., Evidence Acquisition: We performed a systematic review of PubMed/Medline, EMBASE, Cochrane Library, clinicaltrials.gov, and reference lists according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Fifty studies were eligible., Evidence Synthesis: From a pooled analysis of 5467 stone-free patients, we estimated that for a safety margin of 80% for remaining stone free, patients should be followed up using imaging, for at least 2 yr (radiopaque stones) or 3 yr (radiolucent stones) before being discharged. Patients should be discharged after 5 yr of no recurrence with a safety margin of 90%. Regarding residual disease, patients with fragments ≤4 mm could be offered surveillance up to 4 yr since intervention rates range between 17% and 29%, disease progression between 9% and 34%, and spontaneous passage between 21% and 34% at 49 mo. Patients with larger residual fragments should be offered further definitive intervention since intervention rates are high (24-100%). Insufficient data exist for high-risk patients, but the current literature dictates that patients who are adherent to targeted medical treatment seem to experience less stone growth or regrowth of residual fragments, and may be discharged after 36-48 mo of nonprogressive disease on imaging., Conclusions: This systematic review and meta-analysis indicates that stone-free patients with radiopaque or radiolucent stones should be followed up to 2 or 3 yr, respectively. In patients with residual fragments ≤4 mm, surveillance or intervention can be advised according to patient preferences and characteristics, while for those with larger residual fragments, reintervention should be scheduled., Patient Summary: Here, we review the literature regarding follow-up of urolithiasis patients. Patients who have no stones after treatment should be seen up to 2-3 yr, those with large fragments should be reoperated, and those with small fragments could be offered surveillance with imaging., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background and Aim: The evidence on isolated oligohydramnios (IO) patients and their postnatal outcomes are inconsistent. Recent research has clarified the connection between that IO and negative outcomes in the postnatal period. Our goal was to analyze the correlation between Doppler measurements and postnatal outcomes in oligohydramnios patients, with a focus on the cerebroplacental ratio (CPR)., Methodology: A cohort study was conducted in the Radiology Department of Khan Research Laboratories (KRL) Hospital from October 2021 to July 2022. One hundred women were chosen as the sample size. For this study, we used the Raosoft sample size calculator with a 95% confidence interval and a 5% margin of error. Both the middle cerebral artery and the umbilical artery were imaged using ultrasound, and the systolic-to-diastolic ratio and peak systolic velocity are recorded. Pulsatility index (PI) and resistive index (RI) were also calculated. If the amniotic fluid index (AFI) is less than 5 cm, the condition is known as oligohydramnios. The newborn's APGAR score was taken immediately after birth as well as after 5 minutes., Results: We have determined that, on average, mothers are 35.45 weeks/248.15 days pregnant. When compared to the reference standard, CPR diagnostic features showed a sensitivity of 92% and a specificity of 77.27. Overall diagnostic accuracy is predicted to be 93.0%, with a 93.50% positive prognosis and a 73.91% negative prognosis. The effect size for the change in APGAR scores before and after the test was -2.38 1.03, with a 95% confidence interval of -2.58 to -2.17 and a significance level of 0.00., Conclusion: This study concludes that CPR is an effective screening tool and that it can be used to predict postnatal outcomes in patients with oligohydramnios. Clinical prediction rules were found to be a more effective screening tool, with a sensitivity of 92%, a specificity of 77.27%, and a diagnostic accuracy of 92.3%., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Mughal et al.)

Background: COVID-19 vaccines are found to be effective interventions to tackle COVID-19. However, the hesitancy towards its acceptance has been rising in Pakistan. This study highlights the opinion of the general population in Pakistan regarding the acceptance and hesitancy of COVID-19 vaccination., Methods: A descriptive cross-sectional survey study was conducted among Pakistanis from December 2021 to January 2022. Adult respondents that have and have not received COVID-19 vaccinations were included in this study. Data collection was obtained through questionnaires that assessed acceptance and hesitancy toward COVID-19 vaccines. Statistical analysis was performed using IBM SPSS software version 25 for Windows., Results: We obtained 367 respondents with 333 respondents completing the questionnaire. There were 259 respondents who have been vaccinated. A total of 67.9% of responses agreed that vaccines could control the COVID-19 pandemic. The reasons for not getting vaccination were afraid of adverse effects (48.6%) and COVID-19 vaccines not being tested thoroughly (30.9%). The main reason for vaccine acceptance was awareness about vaccines (23.1%), a belief that vaccines can stop severe COVID-19 disease (16.8%), and self-protection (14.7%)., Conclusion: Most Pakistanis agreed that vaccines could manage the pandemic. Vaccine acceptance was contributed by the awareness and belief regarding the protective effects of vaccines while vaccine hesitancy was due to the public's doubt about the vaccines' side effects and testing. The Pakistan government should focus on emphasizing knowledge about vaccines, educating the vaccines' adverse effects, and utilizing social media in doing so., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Rasheed et al.)

Objectives: Atrial fibrillation (AF) is common and can cause significant morbidity and detriment to quality of life. Success rates for conventional catheter ablation are suboptimal in persistent AF (PsAF), especially when longstanding. Convergent hybrid ablation combines endoscopic surgical epicardial and endocardial catheter ablation. It offers promise in treating PsAF. We aimed to evaluate outcomes at our centre following convergent ablation., Methods: We conducted an observational study of patients undergoing ablation from 2012 to 2019 at a London cardiac centre. Sixty-seven patients underwent convergent ablation entailing epicardial ablation, mostly via sub-xiphoid access, followed by endocardial left atrial catheter ablation. Baseline and follow-up data were obtained retrospectively from clinical records. Primary outcome was freedom from AF on/off anti-arrhythmic drugs after 12-month follow-up. Secondary outcomes included freedom from AF over the entire follow-up, freedom from anti-arrhythmic drugs, freedom from atrial arrhythmias, symptom status, repeat ablation and complications., Results: At baseline, 80.6% had PsAF >1 year (80.6%), 49.3% had body mass index >30 kg/m2 at baseline and 19.4% had left ventricular ejection fraction of 40% or less. The median follow-up was 2.3 (1.4-3.7) years. Freedom from AF recurrence was 81.3% at 1 year and 61.5% over overall follow-up. Eleven patients (16.4%) required redo AF ablation. Prolonged AF duration was associated with increased recurrence at 12 months and duration >5 years with a shorter time to recurrence on Kaplan-Meier analysis, but this and other factors did not significantly impact the AF recurrence during the overall follow-up period., Conclusions: Convergent ablation had good 1-year and overall success rates for treating PsAF. Our results in a diverse, real-world population support the potential of convergent ablation in patients with challenging to treat PsAF., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background: Brain metastasis (BM) is a major clinical problem in metastatic breast cancer (MBC), occurring in 50% of patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer. Historically omitted from clinical trials, recent studies of novel HER2-targeted agents have focused on HER2+ BM patients, addressing stable but also progressing BM and leptomeningeal carcinomatosis (LMC)., Summary: This review aimed to summarize the most relevant data on treating patients with HER2+ BM and LMC., Key Messages: The treatment paradigm for patients with HER2+ MBC has changed. Local therapies play an important role, but accumulating evidence on the intracranial activity and clinical benefit of anti-HER2 targeting therapies might lead to a shift in the paradigm on treating BM in the next few years towards more widespread use of systemic therapy., Competing Interests: Marta Filipa Freire Vaz Batista: consulting/advisory board: AstraZeneca; speaker/conferences: Daiichi-Sankyo and Nutricia; travel fees: AstraZeneca, Daiichi-Sankyo, Pfizer, and GSK. Inês Eiriz: speaker/sonferences: Novartis; travel fees: Gilead, Novartis, and Pierre Fabre. Amanda Fitzpatrick: no conflict of interest to declare. Fanny Le Du: consulting/advisory board: Daiichi-Sankyo, Lilly, Seagen Inc., Novartis, Pfizer, Roche, and Sandoz; speaker/conferences: Amgen, Lilly, Novartis, and Pierre Fabre; travel fees: Daiichi-Sankyo, Lilly, Novartis, Pierre Fabre, and Pfizer. Sofia Braga: consulting/advisory board: Daiichi-Sankyo, AstraZeneca, Novartis, and Roche; speaker/conferences: Daiichi-Sankyo, AstraZeneca, Novartis, and Roche; travel fees: Daiichi-Sankyo, AstraZeneca, Novartis, and Roche. Diogo Alpuim Costa has received honoraria from the Portuguese Navy, CUF Oncologia, and NTT DATA and has served as a speaker, advisory board member, or has received research or education funding from AstraZeneca, CUF Oncologia, Daiichi-Sankyo, Gilead, Hoffmann-La Roche, Merck KGaA, Merck Sharp & Dohme, Nestlé, Novartis, Pfizer, Nanobiotix, Puma Biotechnology Inc., Sanofi, Seagen Inc., and Uriage., (Copyright © 2022 by S. Karger AG, Basel.)

There is a well-known association between the connective tissue disorders (CTDs) and lung disease. In addition to interstitial lung disease, the CTDs may affect the air spaces and pulmonary vasculature. Imaging tests are important not only in diagnosis but also in management of these complex disorders. In the present review, key aspects of the imaging of CTD-reated diseases are discussed., Competing Interests: None declared., (Thieme. All rights reserved.)

A hybrid quality control (QC) program was developed that integrates automated and conventional Linac QC, realizing the benefits of both automated and conventional QC, increasing efficiency and maintaining independent measurement methods. Failure mode and effects analysis (FMEA) was then applied in order to validate the program prior to clinical implementation. The hybrid QC program consists of automated QC with machine performance check and DailyQA3 array on the TrueBeam Linac, and Delta4 volumetric modulated arc therapy (VMAT) standard plan measurements, alongside conventional monthly QC at a reduced frequency. The FMEA followed the method outlined in TG-100. Process maps were created for each treatment type at our center: VMAT, stereotactic body radiotherapy (SBRT), conformal, and palliative. Possible failure modes were established by evaluating each stage in the process map. The FMEA followed semiquantitative methods, using data from our QC records from eight Linacs over 3 years for the occurrence estimates, and simulation of failure modes in the treatment planning system, with scoring surveys for severity and detectability. The risk priority number (RPN) was calculated from the product of the occurrence, severity, and detectability scores and then normalized to the maximum and ranked to determine the most critical failure modes. The highest normalized RPN values (100, 90) were found to be for MLC position dynamic for both VMAT and SBRT treatments. The next highest score was 35 for beam position for SBRT, and the majority of scores were less than 20. Overall, these RPN scores for the hybrid Linac QC program indicated that it would be acceptable, but the high RPN score associated with the dynamic MLC failure mode indicates that it would be valuable to perform more rigorous testing of the MLC. The FMEA proved to be a useful tool in validating hybrid QC., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Purpose of the Review: Left ventricular non-compaction (LVNC) is characterised by prominent left ventricular trabeculae and deep inter-trabecular recesses. Although considered a distinct cardiomyopathy, prominent trabeculations may also be found in other cardiomyopathies, in athletes or during pregnancy. Clinical presentation includes heart failure symptoms, systemic embolic events, arrhythmias and sudden cardiac death. Currently, LVNC diagnosis relies on imaging criteria, and clinicians face several challenges in the assessment of patients with prominent trabeculations. In this review, we summarise the available information on the role of the ECG in the diagnosis and management of LVNC., Recent Findings: ECG abnormalities have been reported in 75-94% of adults and children with LVNC. The lack of specificity of these ECG abnormalities does not allow (in isolation) to diagnose the condition. However, when considered in a set of diagnostic criteria including family history, clinical information, and imaging features, the ECG may differentiate between physiological and pathological findings or may provide clues raising the possibility of specific underlying conditions. Finally, some ECG features in LVNC constitute ominous signs that require a stricter patient surveillance or specific therapeutic measures. The ECG remains a cornerstone in the diagnosis and management of patients with cardiomyopathies, including LVNC., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To assess predicting factors that might influence systemic lupus erythematosus (SLE) disease activity in women in an extended follow-up period of two years after giving birth with clinical assessments every three months., Methods: The study was design as an international retrospective study, enrolling 119 women with a first birth and with a two years follow-up., Results: Joint involvement was present in 80% of patients, acute cutaneous in 64%, haematological in 54%, renal in 41% and 75% of patients were positive for anti-dsDNA. The mean SLE disease activity index 2000 (SLEDAI-2K) at diagnosis was 13.5±6.8 and at first birth was 2.8±4.4. At follow-up, 51.3% of patients had at least one flare after a mean time after birth of 9±6.3 months (mean flare per patient 0.94±1.1). The most frequent flare manifestations were joint involvement (48%), renal (33%), cutaneous (28%) and haematologic (20%). Patients with remission of disease (SLEDAI-2K=0; no clinical or laboratory manifestations of SLE) at conception had significantly lower rates of flares (18/49-37% vs. 43/70-61%; p=0.008). Patients who experienced a flare during pregnancy (17 patients) had higher rates of flares during follow-up (76% vs. 47%; p=0.019), lower time for first flare (4.4±2.3 months vs. 10.3±6.5; p<0.001), lower rate of remission of disease at conception (12% vs. 46%; p<0.001), lower rates of SLEDAI-2K at conception (5.9±5.6 vs. 2.3±4; p<0.001) and lower rates of exclusive breastfeeding (24% vs. 57%: p=0.009). Results were confirmed after performing multivariate analysis., Conclusion: Remission at conception can influence SLE disease positively, even at long-term. Planned pregnancy counseling is fundamental when managing SLE patients., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Heterogeneity exists in reported outcomes and outcome measurement instruments [OMI] from observational studies. A core outcome set [COS] for observational and real-world evidence [RWE] in inflammatory bowel disease [IBD] will facilitate pooling large datasets. This systematic review describes and classifies clinical and patient-reported outcomes, for COS development., Methods: The systematic review of MEDLINE, EMBASE, and CINAHL databases identified observational studies published between 2000 and 2021 using the population exposure outcome [PEO] framework. Studies meeting eligibility criteria were included. After titles and abstracts screening, full-text articles were extracted by two independent reviewers. Primary and secondary outcomes with corresponding OMI were extracted and categorised in accordance with OMERACT Filter 2.1 framework. The frequency of outcomes and OMIs are described., Results: From 5854 studies, 315 were included: 129 [41%] Crohn's disease [CD], 60 [19%] ulcerative colitis [UC], and 126 [40%] inflammatory bowel disease [IBD] studies with 600 552 participants. Totals of 1632 outcomes and 1929 OMI were extracted mainly from medical therapy [181; 72%], surgical [34; 11%], and endoscopic [6; 2%] studies. Clinical and medical therapy-related safety were frequent outcome domains recorded in 194 and 100 studies. Medical therapy-related adverse events [n = 74] and need for surgery [n = 71] were the commonest outcomes. The most frequently reported OMI were patient or event numbers [n = 914], Harvey-Bradshaw Index [n = 45], and Montreal classification [n = 42]., Conclusions: There is substantial variability in outcomes reporting and OMI types. Categorised outcomes and OMI from this review will inform a Delphi consensus on a COS for future RWE in IBD. Data collection standardisation may enhance the quality of RWE applied to decision-making., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Variants in genes encoding nuclear pore complex (NPC) proteins are a newly identified cause of paediatric steroid-resistant nephrotic syndrome (SRNS). Recent reports describing NUP93 variants suggest these could be a significant cause of paediatric onset SRNS. We report NUP93 cases in the UK and demonstrate in vivo functional effects of Nup93 depletion in a fly (Drosophila melanogaster) nephrocyte model., Methods: Three hundred thirty-seven paediatric SRNS patients from the National cohort of patients with Nephrotic Syndrome (NephroS) were whole exome and/or whole genome sequenced. Patients were screened for over 70 genes known to be associated with Nephrotic Syndrome (NS). D. melanogaster Nup93 knockdown was achieved by RNA interference using nephrocyte-restricted drivers., Results: Six novel homozygous and compound heterozygous NUP93 variants were detected in 3 sporadic and 2 familial paediatric onset SRNS characterised histologically by focal segmental glomerulosclerosis (FSGS) and progressing to kidney failure by 12 months from clinical diagnosis. Silencing of the two orthologs of human NUP93 expressed in D. melanogaster, Nup93-1, and Nup93-2 resulted in significant signal reduction of up to 82% in adult pericardial nephrocytes with concomitant disruption of NPC protein expression. Additionally, nephrocyte morphology was highly abnormal in Nup93-1 and Nup93-2 silenced flies surviving to adulthood., Conclusion: We expand the spectrum of NUP93 variants detected in paediatric onset SRNS and demonstrate its incidence within a national cohort. Silencing of either D. melanogaster Nup93 ortholog caused a severe nephrocyte phenotype, signaling an important role for the nucleoporin complex in podocyte biology. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s).)

Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://tgh.amegroups.com/article/view/10.21037/tgh-21-87/coif). The authors have no conflicts of interest to declare.

Intensive care unit (ICU) patients with end-organ failure will require specialised machines or extracorporeal therapies to support the failing organs that would otherwise lead to death. ICU patients with severe acute kidney injury may require renal replacement therapy (RRT) to remove fluid and wastes from the body, and patients with severe cardiorespiratory failure will require extracorporeal membrane oxygenation (ECMO) to maintain adequate oxygen delivery whilst the underlying pathology is evaluated and managed. The presence of ECMO and RRT machines can further augment the existing pharmacokinetic (PK) alterations during critical illness. Significant changes in the apparent volume of distribution (V d ) and drug clearance (CL) for many important drugs have been reported during ECMO and RRT. Conventional antimicrobial dosing regimens rarely consider the impact of these changes and consequently, are unlikely to achieve effective antimicrobial exposures in critically ill patients receiving ECMO and/or RRT. Therefore, an in-depth understanding on potential PK changes during ECMO and/or RRT is required to inform antimicrobial dosing strategies in patients receiving ECMO and/or RRT. In this narrative review, we aim to discuss the potential impact of ECMO and RRT on the PK of antimicrobials and antimicrobial dosing requirements whilst receiving these extracorporeal therapies. The potential benefits of therapeutic drug monitoring (TDM) and dosing software to facilitate antimicrobial therapy for critically ill patients receiving ECMO and/or RRT are also reviewed and highlighted., (© 2022. The Author(s).)

By the April 12, 2022, the COVID-19 pandemic had resulted in over half a billion people being infected worldwide. There have been 6.1 million deaths directly due to the infection, but the pandemic has had many more short- and long-term pervasive effects on the physical and mental health of the population. Allergic diseases are among the most prevalent noncommunicable chronic diseases in the pediatric population, and health-care professionals and researchers were seeking answers since the beginning of pandemic. Children are at lower risk of developing severe COVID-19 or dying from infection. Allergic diseases are not associated with a higher COVID-19 severity and mortality, apart from severe/poorly controlled asthma. The pandemic disrupted routine health care, but many mitigation strategies, including but not limited to telemedicine, were successfully implemented to continue delivery of high-standard care. Although children faced a multitude of pandemic-related issues, allergic conditions were effectively treated remotely while reduction in air pollution and lack of contact with outdoor allergens resulted in improvement, particularly respiratory allergies. There is no evidence to recommend substantial changes to usual management modalities of allergic conditions in children, including allergen immunotherapy and use of biologicals. Allergic children are not at greater risk of multisystem inflammatory syndrome development, but some associations with Long COVID were reported, although the data are limited, and further research is needed. This statement of the EAACI Section on Pediatrics provides recommendations based on the lessons learnt from the pandemic, as available evidence., (© 2022 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Implicit biases may lead to subconscious evaluations of a person based on irrelevant characteristics such as race or gender. This audit investigates the presence of implicit bias in the management of patients who missed appointments in our department., Methods: This study retrospectively analysed discharge rates in 285 patients who missed an out-patient appointment between 1 May 2020 and 1 April 2021 at Guy's and St Thomas' Hospital. After reading the patients' names, 285 patients were categorised into genders, and ethnic categories of: White British; Black, Asian and minority (non-White) ethnic ('BAME'); and other White., Results: There were no differences in discharge rates in terms of self-reported ethnic and gender groups. However, patients perceived as White British were less likely to be discharged when compared to patients perceived as Black, Asian and minority ethnic (35 per cent vs 58 per cent). Discharge rates for perceived gender did not differ., Conclusion: Implicit bias may influence decision-making regarding whether to rebook a patient after missing an appointment.

Background: The basophil activation test (BAT) has high accuracy to diagnose peanut allergy and can reduce the need for oral food challenges (OFC); however, so far it has not been incorporated in clinical practice., Methods: We assessed the reproducibility of BAT within the same laboratory and between two different laboratories and the feasibility of using BAT in the clinical setting., Results: One hundred and two children being assessed for peanut allergy were tested on BAT (72 allergic, 30 sensitized tolerant). There was little internal variation (coefficient of variation <15%) in the BAT and a very strong correlation (R s  > .95) between BAT performed across laboratories. The 2 BAT methods were strongly correlated but not interchangeable. In the cases of discrepancy, our in house BAT method was 100% accurate. BAT was feasible and well-accepted by clinicians: no patient with positive BAT was referred for OFC, leading to reduction in the number of OFC required. Twenty one percent of patients who underwent OFC reacted to peanut. A negative BAT also encouraged the performance of OFC in sensitized children who would otherwise be considered allergic, 50% of whom did not react and incorporated peanut in the diet., Conclusions: The BAT is a robust test that can reliably be transferred between laboratories; however, different BAT methods are not interchangeable. BAT was well integrated in the clinical decision-making process in a specialized center., (© 2022 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)