The role of aortic compliance in determination of coarctation severity: Lumped parameter modeling, in vitro study and clinical evaluation

Early detection and accurate estimation of the extent of coarctation of the aorta (COA) is critical to long-term outcome. Peak-to-peak trans-coarctation pressure gradient (PKdP) higher than 20 mmHg is an indication for interventional/surgical repair. Patients with COA have reduced proximal and distal aortic compliances. A comprehensive study investigating the effects of variations of proximal COA and systemic compliances on PKdP, and consequently on the COA severity evaluation has never been done. This study evaluates the effect of aortic compliance on diagnostic accuracy of PKdP. Lumped parameter modeling and in vitro experiments were performed for COA severities of 50%, 75% and 90% by area. Modeling and in vitro results were validated against retrospective clinical data of PKdP, measured in 54 patients with COA. Modeling and in vitro. PKdP increases with reduced proximal COA compliance (+36%, +38% and +53% for COA severities of 50%, 75% and 90%, respectively; p<0.05), but decreases with reduced systemic compliance (−62%, −41% and −36% for COA severities of 50%, 75% and 90%, respectively; p<0.01). Clinical study. PKdP has a modest correlation with COA severity (R=0.29). The main determinants of PKdP are COA severity, stroke volume index and systemic compliance. Systemic compliance was found to be as influential as COA severity in PKdP determination (R=0.30 vs. R =0.34). In conclusion, PKdP is highly influenced by both stroke volume index and arterial compliance. Low values of PKdP cannot be used to exclude the severe COA presence since COA severity may be masked by reduced systemic compliance and/or low flow conditions

A systematic review of quality and consistency of clinical practice guidelines on the primary prevention of food allergy and atopic dermatitis

Background and aims: With an increasing number of Clinical Practice Guidelines (CPGs) addressing primary prevention of food allergy and atopic dermatitis, it is timely to undertake a comprehensive assessment of the quality and consistency of recommendations and evaluation of their implementability in different geographical settings. Methods: We systematically reviewed CPGs from 8 international databases and extensive website searches. Seven reviewers screened records in any language and then used the AGREE II and AGREE REX instruments to critically appraise CPGs published between January 2011 and April 2022. Results: Our search identified 2138 relevant articles, of which 30 CPGs were eventually included. Eight (27%) CPGs were shortlisted based on our predefined quality criteria of achieving scores \u3e70% in the “Scope and Purpose” and “Rigour of Development” domains of the AGREE II instrument. Among the shortlisted CPGs, scores on the “Applicability” domain were generally low, and only 3 CPGs rated highly in the “Implementability” domain of AGREE-REX, suggesting that the majority of CPGs fared poorly on global applicability. Recommendations on maternal diet and complementary feeding in infants were mostly consistent, but recommendations on use of hydrolysed formula and supplements varied considerably. Conclusion: The overall quality of a CPG for Food Allergy and Atopic Dermatitis prevention did not correlate well with its global applicability. It is imperative that CPG developers consider stakeholders’ preferences, local applicability, and adapt existing recommendations to each individual population and healthcare system to ensure successful implementation. There is a need for development of high-quality CPGs for allergy prevention outside of North America and Europe. PROSPERO registration number: CRD42021265689

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines update – I – Plan and definitions

Since the World Allergy Organization (WAO) Diagnosis and Rationale against Cow's Milk Allergy (DRACMA) Guidelines were published 10 years ago, new evidence has accumulated about the diagnosis, therapy, and specific immunotherapy for cow's milk allergy (CMA). For this reason, WAO has felt the need to update the guidelines. We introduce here this update. The new DRACMA guidelines aim to comprehensively address the guidance on diagnosis and therapy of both IgE non-IgE-mediated forms of cow's milk allergy in children and adults. They will be divided into 18 chapters, each of which will be dedicated to an aspect. The focus will be on the meta-analyzes and recommendations that will be expressed for the 3 most relevant clinical aspects: (a) the diagnostic identification of the condition; (b) the choice of the replacement formula in case of CMA in infancy when the mother is not able to breastfeed, and (c) the use of specific immunotherapy for cow's milk protein allergy

Remission of obesity and insulin resistance is not sufficient to restore mitochondrial homeostasis in visceral adipose tissue

Metabolic plasticity is the ability of a biological system to adapt its metabolic phenotype to different environmental stressors. We used a whole-body and tissue-specific phenotypic, functional, proteomic, metabolomic and transcriptomic approach to systematically assess metabolic plasticity in diet-induced obese mice after a combined nutritional and exercise intervention. Although most obesity and overnutrition-related pathological features were successfully reverted, we observed a high degree of metabolic dysfunction in visceral white adipose tissue, characterized by abnormal mitochondrial morphology and functionality. Despite two sequential therapeutic interventions and an apparent global healthy phenotype, obesity triggered a cascade of events in visceral adipose tissue progressing from mitochondrial metabolic and proteostatic alterations to widespread cellular stress, which compromises its biosynthetic and recycling capacity. In humans, weight loss after bariatric surgery showed a transcriptional signature in visceral adipose tissue similar to our mouse model of obesity reversion. Overall, our data indicate that obesity prompts a lasting metabolic fingerprint that leads to a progressive breakdown of metabolic plasticity in visceral adipose tissue

A systematic review of quality and consistency of clinical practice guidelines on the primary prevention of food allergy and atopic dermatitis

BACKGROUND AND AIMS : With an increasing number of Clinical Practice Guidelines (CPGs) addressing primary prevention of food allergy and atopic dermatitis, it is timely to undertake a comprehensive assessment of the quality and consistency of recommendations and evaluation of their implementability in different geographical settings. METHODS : We systematically reviewed CPGs from 8 international databases and extensive website searches. Seven reviewers screened records in any language and then used the AGREE II and AGREE REX instruments to critically appraise CPGs published between January 2011 and April 2022. RESULTS : Our search identified 2138 relevant articles, of which 30 CPGs were eventually included. Eight (27%) CPGs were shortlisted based on our predefined quality criteria of achieving scores >70% in the “Scope and Purpose” and “Rigour of Development” domains of the AGREE II instrument. Among the shortlisted CPGs, scores on the “Applicability” domain were generally low, and only 3 CPGs rated highly in the “Implementability” domain of AGREE-REX, suggesting that the majority of CPGs fared poorly on global applicability. Recommendations on maternal diet and complementary feeding in infants were mostly consistent, but recommendations on use of hydrolysed formula and supplements varied considerably. CONCLUSION : The overall quality of a CPG for Food Allergy and Atopic Dermatitis prevention did not correlate well with its global applicability. It is imperative that CPG developers consider stakeholders’ preferences, local applicability, and adapt existing individual population and healthcare system to ensure successful implementation. There is a need for development of high-quality CPGs for allergy prevention outside of North America and Europehttps://www.journals.elsevier.com/world-allergy-organization-journal/Paediatrics and Child Healt

Quality and consistency of clinical practice guidelines on the prevention of food allergy and atopic dermatitis : systematic review protocol

BACKGROUND AND AIMS : Allergy prevention strategies have gained significant traction as a means to attenuate the growing burden of allergic diseases over the past decade. As the evidence base for primary prevention of food allergy (FA) and atopic dermatitis (AD) is constantly advancing, clinical practice guideline (CPG) recommendations on interventions for FA and AD prevention vary in quality and consistency among professional organizations. We present a protocol for a systematic review of CPGs on primary prevention of FA and AD. METHODS : We will systematically review and appraise all CPGs addressing primary prevention of FA and AD and report our findings according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Electronic databases and manual website searches from January 2011 to March 2021 without language or geographical restrictions, and supplemented by author contact, will generate the list of potentially relevant CPGs to screen. Evaluation of the methodological quality, consistency, and global applicability of shortlisted CPGs will be performed by members of the Allergy Prevention Work Group of the World Allergy Organization (WAO) using the Appraisal of Guidelines for Research and Evaluation (AGREE) II and AGREE-REX (Recommendations EXcellence). instruments. Guideline contents, consistency, and quality of the recommendations will be summarised in tabular and narrative formats. We aim to present consolidated recommendations from international guidelines of the highest methodological quality and applicability, as determined by AGREE II and AGREE-REX. DISSEMINATION : This systematic review will provide a succinct overview of the quality and consistency of recommendations across all existing CPGs for FA and AD prevention, as well as crucial perspectives on applicability of individual recommendations in different geographical contexts. Results from this systematic review will be reported in a peer-reviewed journal. It will also inform a position statement by WAO to provide a practical framework to guide the development of future guidelines for allergy prevention worldwide. PROSPERO REGISTRATION NUMBER : CRD42021265689.Hong Kong Research Grant Council & TS Lo Foundation; the Hong Kong Health and Medical Research Fund – Research Fellowship Scheme and the National Medical Research Council (NMRC).https://www.journals.elsevier.com/world-allergy-organization-journalhj2022Paediatrics and Child Healt

Peanut‐induced anaphylaxis in children and adolescents: Data from the European Anaphylaxis Registry

Background Peanut allergy has a rising prevalence in high-income countries, affecting 0.5%-1.4% of children. This study aimed to better understand peanut anaphylaxis in comparison to anaphylaxis to other food triggers in European children and adolescents. Methods Data was sourced from the European Anaphylaxis Registry via an online questionnaire, after in-depth review of food-induced anaphylaxis cases in a tertiary paediatric allergy centre. Results 3514 cases of food anaphylaxis were reported between July 2007 - March 2018, 56% in patients younger than 18 years. Peanut anaphylaxis was recorded in 459 children and adolescents (85% of all peanut anaphylaxis cases). Previous reactions (42% vs. 38%; p = .001), asthma comorbidity (47% vs. 35%; p < .001), relevant cofactors (29% vs. 22%; p = .004) and biphasic reactions (10% vs. 4%; p = .001) were more commonly reported in peanut anaphylaxis. Most cases were labelled as severe anaphylaxis (Ring&Messmer grade III 65% vs. 56% and grade IV 1.1% vs. 0.9%; p = .001). Self-administration of intramuscular adrenaline was low (17% vs. 15%), professional adrenaline administration was higher in non-peanut food anaphylaxis (34% vs. 26%; p = .003). Hospitalization was higher for peanut anaphylaxis (67% vs. 54%; p = .004). Conclusions The European Anaphylaxis Registry data confirmed peanut as one of the major causes of severe, potentially life-threatening allergic reactions in European children, with some characteristic features e.g., presence of asthma comorbidity and increased rate of biphasic reactions. Usage of intramuscular adrenaline as first-line treatment is low and needs to be improved. The Registry, designed as the largest database on anaphylaxis, allows continuous assessment of this condition

Extensive ethnic variation and linkage disequilibrium at the FCGR2/3 locus: Different genetic associations revealed in Kawasaki Disease

The human Fc-gamma receptors (FcγRs) link adaptive and innate immunity by binding immunoglobulin G (IgG). All human low-affinity FcγRs are encoded by the FCGR2/3 locus containing functional single nucleotide polymorphisms (SNPs) and gene copy number variants. This locus is notoriously difficult to genotype and high-throughput methods commonly used focus on only a few SNPs. We performed multiplex ligation-dependent probe amplification for all relevant genetic variations at the FCGR2/3 locus in >4,000 individuals to define linkage disequilibrium (LD) and allele frequencies in different populations. Strong LD and extensive ethnic variation in allele frequencies was found across the locus. LD was strongest for the FCGR2C-ORF haplotype (rs759550223+rs76277413), which leads to expression of FcγRIIc. In Europeans, the FCGR2C-ORF haplotype showed strong LD with, among others, rs201218628 (FCGR2A-Q27W, r2 = 0.63). LD between these two variants was weaker (r2 = 0.17) in Africans, whereas the FCGR2C-ORF haplotype was nearly absent in Asians (minor allele frequency <0.005%). The FCGR2C-ORF haplotype and rs1801274 (FCGR2A-H131R) were in weak LD (r2 = 0.08) in Europeans. We evaluated the importance of ethnic variation and LD in Kawasaki Disease (KD), an acute vasculitis in children with increased incidence in Asians. An association of rs1801274 with KD was previously shown in ethnically diverse genome-wide association studies. Now, we show in 1,028 European KD patients that the FCGR2C-ORF haplotype, although nearly absent in Asians, was more strongly associated with susceptibility to KD than rs1801274 in Europeans. Our data illustrate the importance of interpreting findings of association studies concerning the FCGR2/3 locus with knowledge of LD and ethnic variation

Extensive Ethnic Variation and Linkage Disequilibrium at the FCGR2/3 Locus: Different Genetic Associations Revealed in Kawasaki Disease.

The human Fc-gamma receptors (FcγRs) link adaptive and innate immunity by binding immunoglobulin G (IgG). All human low-affinity FcγRs are encoded by the FCGR2/3 locus containing functional single nucleotide polymorphisms (SNPs) and gene copy number variants. This locus is notoriously difficult to genotype and high-throughput methods commonly used focus on only a few SNPs. We performed multiplex ligation-dependent probe amplification for all relevant genetic variations at the FCGR2/3 locus in >4,000 individuals to define linkage disequilibrium (LD) and allele frequencies in different populations. Strong LD and extensive ethnic variation in allele frequencies was found across the locus. LD was strongest for the FCGR2C-ORF haplotype (rs759550223+rs76277413), which leads to expression of FcγRIIc. In Europeans, the FCGR2C-ORF haplotype showed strong LD with, among others, rs201218628 (FCGR2A-Q27W, r 2 = 0.63). LD between these two variants was weaker (r 2 = 0.17) in Africans, whereas the FCGR2C-ORF haplotype was nearly absent in Asians (minor allele frequency <0.005%). The FCGR2C-ORF haplotype and rs1801274 (FCGR2A-H131R) were in weak LD (r 2 = 0.08) in Europeans. We evaluated the importance of ethnic variation and LD in Kawasaki Disease (KD), an acute vasculitis in children with increased incidence in Asians. An association of rs1801274 with KD was previously shown in ethnically diverse genome-wide association studies. Now, we show in 1,028 European KD patients that the FCGR2C-ORF haplotype, although nearly absent in Asians, was more strongly associated with susceptibility to KD than rs1801274 in Europeans. Our data illustrate the importance of interpreting findings of association studies concerning the FCGR2/3 locus with knowledge of LD and ethnic variation