Chronic Disease Patterns and Their Relationship With Health-Related Quality of Life in South Korean Older Adults With the 2021 Korean National Health and Nutrition Examination Survey: Latent Class Analysis.

BACKGROUND: Improved life expectancy has increased the prevalence of older adults living with multimorbidities, which likely deteriorates their health-related quality of life (HRQoL). Understanding which chronic conditions frequently co-occur can facilitate person-centered care tailored to the needs of individuals with specific multimorbidity profiles. OBJECTIVE: The study objectives were to (1) examine the prevalence of multimorbidity among Korean older adults (ie, those aged 65 years and older), (2) investigate chronic disease patterns using latent class analysis, and (3) assess which chronic disease patterns are more strongly associated with HRQoL. METHODS: A sample of 1806 individuals aged 65 years and older from the 2021 Korean National Health and Nutrition Examination Survey was analyzed. Latent class analysis was conducted to identify the clustering pattern of chronic diseases. HRQoL was assessed by an 8-item health-related quality of life scale (HINT-8). Multiple linear regression was used to analyze the association with the total score of the HINT-8. Logistic regression analysis was performed to evaluate the odds ratio of having problems according to the HINT-8 items. RESULTS: The prevalence of multimorbidity in the sample was 54.8%. Three chronic disease patterns were identified: relatively healthy, cardiometabolic condition, arthritis, allergy, or asthma. The total scores of the HINT-8 were the highest in participants characterized as arthritis, allergy, or asthma group, indicating the lowest quality of life. CONCLUSIONS: Current health care models are disease-oriented, meaning that the management of chronic conditions applies to a single condition and may not be relevant to those with multimorbidities. Identifying chronic disease patterns and their impact on overall health and well-being is critical for guiding integrated care.

The safety signal detection and analysis of monoclonal antibodies against SARS-CoV-2 based on real-world evidence - the suitable selectivity for different populations.

OBJECTIVE: Bebtelovimab (BEB), Tixagevimab/Cilgavimab (TIX/CIL), and Sotrovimab (SOT) are important agents against the severe acute respiratory syndrome coronavirus 2-Omicron strain. However, due to their short duration of application, little is known about their safety profiles. This research aimed to explore the safety profile of these monoclonal antibodies (mAbs) via real-world evidence databases and data mining tools. MATERIALS AND METHODS: Safety reports were retrieved from the database of the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System from April 2022 to March 2023. To detect the safety signal, the disproportionality analysis was performed using the reporting odds ratio method. RESULTS: SOT had the greatest proportion of "skin and subcutaneous tissue disorders" and "disorders of investigations"; BEB showed significant associations with "gastrointestinal disorders" and "nervous system disorders"; TIX/CIL had the weakest correlation with "skin and subcutaneous tissue disorders" and "general disorders and administration site conditions". Furthermore, there were still other signals related to nervous system disorders, gastrointestinal disorders only caused by BEB. TIX/CIL has been reported solely to be associated with multiple types of cardiovascular disorders. As for SOT alone, signals were strongly related to infusion reactions and hypersensitivity. CONCLUSIONS: In summary, SOT may be unsuitable for allergic patients and may lead to abnormal test results. BEB showed the highest correlations with gastrointestinal and neuropsychiatric events. In addition, its infusion reactions should also be noted. TIX/CIL can lead to a variety of cardiovascular events.

[Inappropriate treatment of asymptomatic bacteriuria]. / 5 minutes pour apprendre. Traitement problématique d'une bactériurie asymptomatique.

Asymptomatic bacteriuria is frequently encountered in clinical practice and should be treated only in pregnant women and before invasive urological procedures. Inappropriate treatment of asymptomatic bacteriuria is associated with numerous adverse effects including allergic reactions, increased antibiotics resistance and increase risk of Clostridioides difficile infection. Positive urinary culture often leads to antimicrobial treatment, irrespective of urinary symptoms. Therefore, urine analysis and culture should be performed only in symptomatic individuals or in asymptomatic individuals with a clear indication for treatment.

Root Cause Analysis of Delayed Emergency Department Computed Tomography Scans.

Introduction: A solution for emergency department (ED) congestion remains elusive. As reliance on imaging grows, computed tomography (CT) turnaround time has been identified as a major bottleneck. In this study we sought to identify factors associated with significantly delayed CT in the ED. Methods: We performed a retrospective analysis of all CT imaging completed at an urban, tertiary care ED from May 1-July 31, 2021. During that period, 5,685 CTs were performed on 4,344 patients, with a median time from CT order to completion of 108 minutes (Quartile 1 [Q1]: 57 minutes, Quartile 3 [Q3]: 182 minutes, interquartile range [IQR]: 125 minutes). Outliers were defined as studies that took longer than 369 minutes to complete (Q3 + 1.5 × IQR). We systematically reviewed outlier charts to determine factors associated with delay and identified five factors: behaviorally non-compliant or medically unstable patients; intravenous (IV) line issues; contrast allergies; glomerular filtration rate (GFR) concerns; and delays related to imaging protocol (eg, need for IV contrast, request for oral and/or rectal contrast). We calculated confidence intervals (CI) using the modified Wald method. Inter-rater reliability was assessed with a kappa analysis. Results: We identified a total of 182 outliers (4.2% of total patients). Fifteen (8.2%) cases were excluded for CT time-stamp inconsistencies. Of the 167 outliers analyzed, 38 delays (22.8%, 95% confidence interval [CI] 17.0-29.7) were due to behaviorally non-compliant or medically unstable patients; 30 (18.0%, 95% CI 12.8-24.5) were due to IV issues; 24 (14.4%, 95% CI 9.8-20.6) were due to contrast allergies; 21 (12.6%, 95% CI 8.3-18.5) were due to GFR concerns; and 20 (12.0%, 95% CI 7.8-17.9) were related to imaging study protocols. The cause of the delay was unknown in 55 cases (32.9%, 95% CI 26.3-40.4). Conclusion: Our review identified both modifiable and non-modifiable factors associated with significantly delayed CT in the ED. Patient factors such as behavior, allergies, and medical acuity cannot be controlled. However, institutional policies regarding difficult IV access, contrast administration in low GFR settings, and study protocols may be modified, capturing up to 42.6% of outliers.

Individuals with JAK1 variants are affected by syndromic features encompassing autoimmunity, atopy, colitis, and dermatitis.

Inborn errors of immunity lead to autoimmunity, inflammation, allergy, infection, and/or malignancy. Disease-causing JAK1 gain-of-function (GoF) mutations are considered exceedingly rare and have been identified in only four families. Here, we use forward and reverse genetics to identify 59 individuals harboring one of four heterozygous JAK1 variants. In vitro and ex vivo analysis of these variants revealed hyperactive baseline and cytokine-induced STAT phosphorylation and interferon-stimulated gene (ISG) levels compared with wild-type JAK1. A systematic review of electronic health records from the BioME Biobank revealed increased likelihood of clinical presentation with autoimmunity, atopy, colitis, and/or dermatitis in JAK1 variant-positive individuals. Finally, treatment of one affected patient with severe atopic dermatitis using the JAK1/JAK2-selective inhibitor, baricitinib, resulted in clinically significant improvement. These findings suggest that individually rare JAK1 GoF variants may underlie an emerging syndrome with more common presentations of autoimmune and inflammatory disease (JAACD syndrome). More broadly, individuals who present with such conditions may benefit from genetic testing for the presence of JAK1 GoF variants.

[Understanding hypersensitivity reactions to monoclonal antibodies]. / Comprendre les réactions d'hypersensibilité aux anticorps monoclonaux.

Biologic drugs are complex molecules synthesized by a living organism. Their use is increasingly prevalent across all medical specialties, exposing a growing number of patients to potential adverse reactions. In this review, we discuss the new classification of hypersensitivity reactions, along with the specific characteristics of monoclonal antibodies. We also address the available diagnostic tools and discuss the management of those reactions, including for patients requiring the continuation of these biologic drugs.

Les médicaments biologiques sont des molécules complexes synthétisées par un organisme vivant. Ils sont de plus en plus utilisés dans toutes les spécialités médicales, exposant ainsi les patients à des réactions indésirables. Dans cet article, nous abordons la nouvelle classification des réactions d'hypersensibilité ainsi que les caractéristiques spécifiques des anticorps monoclonaux. Nous évoquons également les outils diagnostiques disponibles et discutons de la prise en charge, y compris pour les patients nécessitant la poursuite de l'administration des médicaments biologiques.

Global assessment of the knowledge and confidence in managing allergic disorders among primary care pediatricians across Europe: An EAACI task force report.

BACKGROUND: Pediatricians are often the first point of contact for children in Primary Care (PC), but still perceive gaps in their allergy knowledge. We investigated self-perceived knowledge gaps and educational needs in pediatricians across healthcare systems in Europe so that future educational initiatives may better support the delivery of allergy services in PC. METHOD: A multinational survey was circulated to pediatricians who care for children and adolescents with allergy problems in PC by the EAACI Allergy Educational Needs in Primary Care Pediatricians Task Force from February to March 2023. A 5-point Likert scale was used to assess the level of agreement with questionnaire statements. Thirty surveys per country were the cut-off for inclusion and statistical analysis. RESULTS: In this study, 1991 respondents were obtained from 56 countries across Europe and 210 responses were from countries with a cut-off below 30 participants per country. Primary care pediatricians (PCPs) comprised 74.4% of the respondents. The majority (65.3%) were contracted to state or district health services. 61.7% had awareness of guidelines for onward allergy referral in their countries but only 22.3% were aware of the EAACI competencies document for allied health professionals for allergy. Total sample respondents versus PCPs showed 52% and 47% of them have access to allergy investigations in their PC facility (mainly specific IgE and skin prick tests); 67.6% and 58.9% have access to immunotherapy, respectively. The main barrier to referral to a specialist was a consideration that the patient's condition could be diagnosed and treated in this PC facility, (57.8% and 63.6% respectively). The main reasons for referral were the need for hospital assessment, and partial response to first-line treatment (55.4% and 59.2%, 47% and 50.7%, respectively). Learning and assessment methods preference was fairly equally divided between Traditional methods (45.7% and 50.1% respectively) and e-learning 45.5% and 44.9%, respectively. Generalist physicians (GPs) have the poorest access to allergy investigations (32.7%, p = .000). The majority of the total sample (91.9%) assess patients with allergic pathology. 868 (43.6%) and 1117 (46.1%), received allergy training as undergraduates and postgraduates respectively [these proportions in PCPs were higher (45% and 59%), respectively]. PCPs with a special interest in allergology experienced greater exposure to allergy teaching as postgraduates. GPs received the largest amount of allergy teaching as undergraduates. Identifying allergic disease based on clinical presentation, respondents felt most confident in the management of eczema/atopic dermatitis (87.4%) and rhinitis/asthma (86.2%), and least confident in allergen immunotherapy (36.9%) and latex allergy (30.8%). CONCLUSION: This study exploring the confidence of PCPs to diagnose, manage, and refer patients with allergies, demonstrated knowledge gaps and educational needs for allergy clinical practice. It detects areas in need of urgent improvement especially in latex and allergen immunotherapy. It is important to ensure the dissemination of allergy guidelines and supporting EAACI documents since the majority of PCPs lack awareness of them. This survey has enabled us to identify what the educational priorities of PCPs are and how they would like to have them met.

Peeking into the Stingers: A Comprehensive SWATH-MS Study of the European Hornet Vespa crabro (Linnaeus, 1758) (Hymenoptera: Vespidae) Venom Sac Extracts.

This study aimed to investigate the venom sac extracts (VSEs) of the European hornet (EH) Vespa crabro (Linnaeus, 1758) (Hymenoptera: Vespidae), focusing on the differences between stinging females, gynes (G), and workers (W), at the protein level. Using a quantitative "Sequential Window Acquisition of all Theoretical Fragment Ion Mass Spectra" (SWATH-MS) analysis, we identified and quantified a total of 240 proteins. Notably, within the group, 45.8% (n = 110) showed significant differential expression between VSE-G and VSE-W. In this set, 57.3% (n = 63) were upregulated and 42.7% (n = 47) downregulated in the G. Additionally, the two-hundred quantified proteins from the class Insecta belong to sixteen different species, six of them to the Hymenoptera/Apidae lineage, comprising seven proteins with known potential allergenicity. Thus, phospholipase A1 (Vesp v 1), phospholipase A1 verutoxin 2b (VT-2b), hyaluronidase A (Vesp v 2A), hyaluronidase B (Vesp v 2B), and venom allergen 5 (Vesp v 5) were significantly downregulated in the G, and vitellogenin (Vesp v 6) was upregulated. Overall, 46% of the VSE proteins showed differential expression, with a majority being upregulated in G. Data are available via ProteomeXchange with identifier PXD047955. These findings shed light on the proteomic differences in VSE between EH castes, potentially contributing to our understanding of their behavior and offering insights for allergy research.

The Plight of the Metabolite: Oxidative Stress and Tear Film Destabilisation Evident in Ocular Allergy Sufferers across Seasons in Victoria, Australia.

Ocular allergy (OA) is characterised by ocular surface itchiness, redness, and inflammation in response to allergen exposure. The primary aim of this study was to assess differences in the human tear metabolome and lipidome between OA and healthy controls (HCs) across peak allergy (spring-summer) and off-peak (autumn-winter) seasons in Victoria, Australia. A total of 19 participants (14 OA, 5 HCs) aged 18-45 were recruited and grouped by allergy questionnaire score. Metabolites and lipids from tear samples were analysed using mass spectrometry. Data were analysed using TraceFinder and Metaboanalyst. Metabolomics analysis showed 12 differentially expressed (DE) metabolites between those with OA and the HCs during the peak allergy season, and 24 DE metabolites were found in the off-peak season. The expression of niacinamide was upregulated in OA sufferers vs. HCs across both seasons (p ≤ 0.05). A total of 6 DE lipids were DE between those with OA and the HCs during the peak season, and 24 were DE in the off-peak season. Dysregulated metabolites affected oxidative stress, inflammation, and homeostasis across seasons, suggesting a link between OA-associated itch and ocular surface damage via eye rubbing. Tear lipidome changes were minimal between but suggested tear film destabilisation and thinning. Such metabolipodome findings may pave new and exciting ways for effective diagnostics and therapeutics for OA sufferers in the future.

Reducing Immunoreactivity of Gluten Peptides by Probiotic Lactic Acid Bacteria for Dietary Management of Gluten-Related Diseases.

Immunoreactive gluten peptides that are not digested by peptidases produced by humans can trigger celiac disease, allergy and non-celiac gluten hypersensitivity. The aim of this study was to evaluate the ability of selected probiotic strains to hydrolyze immunoreactive gliadin peptides and to identify peptidase-encoding genes in the genomes of the most efficient strains. Residual gliadin immunoreactivity was measured after one- or two-step hydrolysis using commercial enzymes and bacterial peptidase preparations by G12 and R5 immunoenzymatic assays. Peptidase preparations from Lacticaseibacillus casei LC130, Lacticaseibacillus paracasei LPC100 and Streptococcus thermophilus ST250 strains significantly reduced the immunoreactivity of gliadin peptides, including 33-mer, and this effect was markedly higher when a mixture of these strains was used. In silico genome analyses of L. casei LC130 and L. paracasei LPC100 revealed the presence of genes encoding peptidases with the potential to hydrolyze bonds in proline-rich peptides. This suggests that L. casei LC130, L. paracasei LPC100 and S. thermophilus ST250, especially when used as a mixture, have the ability to hydrolyze immunoreactive gliadin peptides and could be administered to patients on a restricted gluten-free diet to help treat gluten-related diseases.

Early-life house dust mite aeroallergen exposure augments cigarette smoke-induced myeloid inflammation and emphysema in mice.

BACKGROUND: Longitudinal studies have identified childhood asthma as a risk factor for obstructive pulmonary disease (COPD) and asthma-COPD overlap (ACO) where persistent airflow limitation can develop more aggressively. However, a causal link between childhood asthma and COPD/ACO remains to be established. Our study aimed to model the natural history of childhood asthma and COPD and to investigate the cellular/molecular mechanisms that drive disease progression. METHODS: Allergic airways disease was established in three-week-old young C57BL/6 mice using house dust mite (HDM) extract. Mice were subsequently exposed to cigarette smoke (CS) and HDM for 8 weeks. Airspace enlargement (emphysema) was measured by the mean linear intercept method. Flow cytometry was utilised to phenotype lung immune cells. Bulk RNA-sequencing was performed on lung tissue. Volatile organic compounds (VOCs) in bronchoalveolar lavage-fluid were analysed to screen for disease-specific biomarkers. RESULTS: Chronic CS exposure induced emphysema that was significantly augmented by HDM challenge. Increased emphysematous changes were associated with more abundant immune cell lung infiltration consisting of neutrophils, interstitial macrophages, eosinophils and lymphocytes. Transcriptomic analyses identified a gene signature where disease-specific changes induced by HDM or CS alone were conserved in the HDM-CS group, and further revealed an enrichment of Mmp12, Il33 and Il13, and gene expression consistent with greater expansion of alternatively activated macrophages. VOC analysis also identified four compounds increased by CS exposure that were paradoxically reduced in the HDM-CS group. CONCLUSIONS: Early-life allergic airways disease worsened emphysematous lung pathology in CS-exposed mice and markedly alters the lung transcriptome.

Neural circuits regulating visceral pain.

Visceral hypersensitivity, a common clinical manifestation of irritable bowel syndrome, may contribute to the development of chronic visceral pain, which is a major challenge for both patients and health providers. Neural circuits in the brain encode, store, and transfer pain information across brain regions. In this review, we focus on the anterior cingulate cortex and paraventricular nucleus of the hypothalamus to highlight the progress in identifying the neural circuits involved in visceral pain. We also discuss several neural circuit mechanisms and emphasize the importance of cross-species, multiangle approaches and the identification of specific neurons in determining the neural circuits that control visceral pain.

Construction by artificial intelligence and immunovalidation of hypoallergenic mite allergen Der f 36 vaccine.

Background: The house dust mite (HDM) is widely recognized as the most prevalent allergen in allergic diseases. Allergen-specific immunotherapy (AIT) has been successfully implemented in clinical treatment for HDM. Hypoallergenic B-cell epitope-based vaccine designed by artificial intelligence (AI) represents a significant progression of recombinant hypoallergenic allergen derivatives. Method: The three-dimensional protein structure of Der f 36 was constructed using Alphafold2. AI-based tools were employed to predict B-cell epitopes, which were subsequently verified through IgE-reaction testing. Hypoallergenic Der f 36 was then synthesized, expressed, and purified. The reduced allergenicity was assessed by enzyme-linked immunosorbent assay (ELISA), immunoblotting, and basophil activation test. T-cell response to hypoallergenic Der f 36 and Der f 36 was evaluated based on cytokine expression in the peripheral blood mononuclear cells (PBMCs) of patients. The immunogenicity was evaluated and compared through rabbit immunization with hypoallergenic Der f 36 and Der f 36, respectively. The inhibitory effect of the blocking IgG antibody on the specific IgE-binding activity and basophil activation of Der f 36 allergen was also examined. Results: The final selected non-allergic B-cell epitopes were 25-48, 57-67, 107-112, 142-151, and 176-184. Hypoallergenic Der f 36 showed significant reduction in IgE-binding activity. The competitive inhibition of IgE-binding to Der f 36 was investigated using the hypoallergenic Der f 36, and only 20% inhibition could be achieved, which is greatly reduced when compared with inhibition by Der f 36 (98%). The hypoallergenic Der f 36 exhibited a low basophil-stimulating ratio similar to that of the negative control, and it could induce an increasing level of IFN-γ but not Th2 cytokines IL-5 and IL-13 in PBMCs. The vaccine-specific rabbit blocking IgG antibodies could inhibit the patients' IgE binding and basophil stimulation activity of Derf 36. Conclusion: This study represents the first application of an AI strategy to facilitate the development of a B-cell epitope-based hypoallergenic Der f 36 vaccine, which may become a promising immunotherapy for HDM-allergic patients due to its reduced allergenicity and its high immunogenicity in inducing blocking of IgG.

Positive association between chlorinated paraffins and the risk of allergic diseases in children and adolescents.

Contaminants may induce immune response polarization, leading to immune diseases, such as allergic diseases. Evidence concerning the effects of chlorinated paraffins (CPs), an emerging persistent organic pollutant, on immune system is scarce, particularly for epidemiological evidence. This study explores the association between CPs exposure and allergic diseases (allergic rhinitis, atopic eczema, and allergic conjunctivitis) in children and adolescents in the Pearl River Delta (PRD) in China. Herein, 131,304 children and adolescents from primary and secondary schools in the PRD were included and completed the questionnaire survey. The particulate matter (PM) samples were collected in the PRD and the PM2.5-bound CP concentrations were analyzed. In the multivarious adjustment mixed effect model (MEM), an IQR increase in ∑CPs was significantly associated with allergic diseases (rhinitis, eczema, and conjunctivitis) with the estimated odds ratios (ORs) for 1.11 (95% CI: 1.10, 1.13), 1.17 (95% CI: 1.15, 1.19), and 1.82 (95% CI: 1.76, 1.88), respectively. Interaction analysis indicated that overweight and obese individuals might have greater risk. Similar effect estimates were observed in several sensitivity analyses. This study provided epidemiological evidence on the immunotoxicity of CPs. More studies to confirm our findings and investigate mechanisms are needed.