Search Results (7,148)

Approximately 1–2% of infants have cow’s milk protein allergy (CMPA). From a clinical perspective, diagnosing CMPA using the oral food challenge (OFC) is high risk, necessitating safer alternatives. One possible alternative is component-resolved diagnostics (CRD). This narrative review examines specific IgE (sIgE) thresholds for cow’s milk protein in predicting outcomes of OFCs in European children. Eligible studies focusing on CRD in European pediatric populations were identified through PubMed and Scopus databases. Our findings highlight the crucial role of Bos d 8 (casein) in the diagnostic process. Among the analyzed milk components, Bos d 8 appeared to be a promising marker for predicting positive OFC outcomes in several cohorts. However, due to significant population heterogeneity, conflicting findings exist, with some studies indicating that no single molecular component is consistently superior to whole cow’s milk specific IgE. While other molecules, such as Bos d 6 and lactoferrin, showed limited diagnostic utility, specific IgE to Bos d 8 demonstrated the highest clinical value. Although the double-blind, placebo-controlled food challenge (DBPCFC) remains the gold standard for CMPA diagnosis, the use of Bos d 8 in CRD is a key step toward risk stratification and may help reduce the need for high-risk OFCs in selected patients. Full article

A homologous classification for vespid venoms is missing. This study compared Polistes dominula and Vespula spp. venoms to evaluate their homology level. P. dominula and Vespula spp. extracts, including V. germanica, V. maculifrons, V. pensylvanica, V. alascensis, and V. squamosa in equal proportions, were generated from venom sacs and were subjected to sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot using Vespula-positive sera. Bands described as allergenic were excised and sequenced through Liquid Chromatography–Mass Spectrometry tandem analysis (LC-MS/MS) to confirm their identity. Phospholipase (group 1) and hyaluronidase (group 2) enzymatic activities were measured. Group 1 and 5 3-D structures and sequence identity were analyzed in silico. The results showed that the P. dominula and Vespula spp. venom extracts exhibit similar protein profiles and comparable allergen composition, with phospholipase and hyaluronidase activities. The structures of Pol d 1 and Ves v 1 and Pol d 5 and Ves v 5 were highly similar, and the identity levels were high across and within the Polistes and Vespula genera (≥50%). These results suggest the inclusion of venoms from Polistes and Vespula genera as candidates to create a new homologous group for wasp venoms and indicate that the currently described homologous groups require revision. Full article

Background: Prenatal vitamin D exposure has been proposed as a potential determinant of immune development and subsequent allergic disease risk in offspring; however, long-term cohort data remain inconsistent. Methods: We analyzed data from the KLOTHO birth cohort, including 98 adolescents with available allergic outcome assessment. A maternal–neonatal sub-cohort of mother–child pairs with available maternal and neonatal serum total 25-hydroxyvitamin D₃ [25(OH)D] measurements at delivery was used for vitamin D analyses. Allergic outcomes included asthma, allergic rhinitis, and eczema in offspring. Associations were evaluated using descriptive statistics, Spearman correlation analyses, and logistic regression models. Results: Maternal 25(OH)D concentrations were not significantly associated with asthma (ρ = 0.075, p = 0.652), allergic rhinitis (ρ = 0.100, p = 0.556), or eczema (ρ = 0.131, p = 0.426). In crude logistic regression models, vitamin D concentrations were not associated with asthma (odds ratio (OR) per 10 nmol/L: 1.07, 95% confidence interval (CI): 0.78–1.48, p = 0.67), allergic rhinitis (OR: 1.05, 95% CI: 0.76–1.45, p = 0.77), or eczema (OR: 1.17, 95% CI: 0.86–1.60, p = 0.31). Adjusted models including maternal age, pre-pregnancy body mass index (BMI), season of delivery, and ultraviolet exposure yielded similar non-significant findings, although analyses were limited by a reduced complete-case sample size. Conclusions: In this prospective cohort with follow-up into early adolescence, vitamin D status at delivery was not associated with asthma, allergic rhinitis, or eczema in offspring. These findings support a lack of statistically significant association; however, potential non-linear relationships should be interpreted cautiously, given the modest sample size. Full article

Background/Objectives: Several recent human studies have associated the use of certain medicines, such as antibiotics and antacids, with allergic conditions, potentially through microbiome disruption. In contrast, probiotics which may prevent dysbiosis, could have protective effects. Our meta-analysis aimed to evaluate the impact of these drugs (consumed during pregnancy or early life) on the risk of childhood food allergy, based on the available literature. Methods: Literature searches were conducted in the EMBASE, PubMed, Cochrane, and Web of Science databases using predefined PICO criteria. Overall, our meta-analysis included 25 studies involving 1,662,861 mothers and 5,164,280 children. Results: Using the random-effects model, we found that prenatal and early life antibiotic use (up to 2 years of age) was associated with higher odds of food allergy in childhood (OR: 1.34; 95% CI [1.10, 1.63], OR: 1.53; 95% CI [1.18, 1.98], respectively). Proton pump inhibitors were also associated with a risk of food allergies (OR: 2.65; 95% CI [1.22–5.77]), whereas the impact of H2-receptor antagonists was non-significant (OR: 2.07; 95% CI [0.96–4.45]). Probiotic use during the first two years of life was not associated with decreased risk for food allergy in children (OR: 1.25; 95% CI [0.46, 3.38]). Conclusions: These findings suggest an association between microbiome-disrupting medications during pregnancy and early childhood and an increased risk of childhood food allergy, especially those with a family history of food allergy. However, due to the predominantly observational design of the included studies, causality cannot be established. These results highlight the need for cautious and judicious use of such medications in these populations. Full article

Introduction: Cow’s milk protein allergy (CMPA) is one of the most common food allergies in early infancy and poses important clinical and economic challenges for affected children, their families, and healthcare systems. In Latin America, variability in diagnostic and therapeutic approaches remains substantial. Objective: We aim to systematically review the available evidence on CMPA, with emphasis on clinical characteristics, diagnosis, management, and economic impact, and to provide a complementary cost analysis of specialized formulas in the Colombian context. Methods: A systematic review was conducted according to PRISMA guidelines to synthesize current evidence on CMPA in pediatric populations. Studies published between 2010 and 2023 were screened using predefined eligibility criteria, and 46 studies were included in the qualitative synthesis. A complementary cost analysis was also performed to estimate the six-month costs associated with specialized infant formulas in Colombia, based on average age-specific formula consumption and standardized 2025 market prices. Results: The reviewed evidence confirms that CMPA is a heterogeneous condition with variable clinical manifestations and persistent diagnostic challenges, particularly in non-IgE-mediated presentations. Elimination of cow’s milk protein followed by oral food challenge remains the reference diagnostic approach. Breastfeeding with maternal dairy exclusion is consistently recommended as the preferred first-line strategy, whereas extensively hydrolyzed and amino-acid-based formulas are used when breastfeeding is not feasible or is insufficient. Estimated six-month costs ranged from COP 4,337,640 to COP 14,480,700 (approximately USD 1100–3600), depending on formula type. Conclusions: CMPA requires early recognition, careful clinical evaluation, individualized nutritional management, and improved access to effective and affordable treatment strategies. Full article

Background/Objectives: Ventilator weaning imposes profound hemodynamic stress, unmasking cardiopulmonary vulnerability. Since conventional predictors of post-tracheostomy weaning failure remain elusive, biomarker-driven risk stratification offers a translational approach. We evaluated the prognostic utility of admission N-terminal pro-B-type natriuretic peptide (NT-proBNP) as an early triaging tool for weaning failure and explored its therapeutic implications alongside optimal tracheostomy timing. Methods: In this large-scale retrospective cohort study, we analyzed 707 critically ill patients who underwent tracheostomy in a medical intensive care unit. We investigated the association between baseline NT-proBNP levels—measured as a molecular surrogate of cardiovascular stress at ICU admission; echocardiographic parameters; and weaning outcomes. Multivariable logistic regression analysis was utilized to identify independent pathophysiological predictors associated with weaning failure. Results: Patients experiencing weaning failure exhibited significantly elevated admission NT-proBNP levels compared to those successfully weaned (3077.0 vs. 1410.0 pg/mL, p < 0.001). High admission NT-proBNP (>3271 pg/mL) was independently associated with an increased risk of weaning failure (adjusted odds ratio [aOR] 2.86, 95% confidence interval [CI] 1.81–4.53, p < 0.001). Conversely, an early clinical intervention—tracheostomy performed within 10 days of mechanical ventilation initiation—was associated with a significantly lower risk of weaning failure (aOR 0.55, 95% CI 0.35–0.87, p = 0.010). Furthermore, elevated biomarker levels strongly correlated with prolonged intensive care unit stays and higher 90-day mortality. Conclusions: Admission NT-proBNP serves as a powerful biomarker associated with cardiopulmonary vulnerability from the earliest stages of critical illness. Integrating this diagnostic biomarker with interventional strategies like optimal tracheostomy timing has significant prognostic implications. This biomarker-guided approach facilitates personalized risk stratification from ICU admission, potentially optimizing weaning pathways for mechanically ventilated patients. Full article

Background: Central compartment atopic disease (CCAD) is a recently developed terminology used to describe a specific phenotype of chronic rhinosinusitis (CRS). The aim of this study is to provide a thorough analysis of the clinical and radiological characteristics by assessing the prevalence of symptoms, asthma, allergy, aeroallergen sensitization and radiological sinus involvement. Methods: The authors searched for articles on PubMed, Cochrane, and Embase databases. A review of the articles was carried out following PRISMA guidelines; all articles were assessed for quality according to NICE criteria. Afterwards, the meta-analysis was performed with STATA 18SE software. Studies were also assessed for heterogeneity and risk of publication bias. Mean Lund-Mackay (LMK) score of patients with and without CCAD was compared. Results: A total of 16 studies were included, including 1254 patients with CRS; 537 of these were diagnosed with CCAD. The most prevalent symptoms were obstruction at 78% and congestion at 70%, followed by rhinorrhea at 66%, hyposmia at 54%, and facial pain at 24%. Dust mite at 71% was the most prevalent sensitization. Overall, the prevalence of asthma in patients with CCAD was 26%, prevalence of allergy was 67%. The mean difference in LMK scores was −3.38 in CCAD. Conclusions: Patients frequently present with nasal obstruction and congestion; the most common allergen sensitization is to dust mites. Findings on allergy and asthma prevalence support the “Unified Airway Disease” concept and emphasize the importance of a multidisciplinary approach to managing this phenotype. CCAD patients usually do not develop very high LMK scores; high scores may rule out this diagnosis. PROSPERO registration number: CRD420261361696. Full article

Background: Cow’s milk protein allergy (CMPA) is a common cause of gastrointestinal and dermatologic symptoms in infancy. In clinical practice, infants with atopic dermatitis (AD) and suspected non-IgE-mediated CMPA are frequently managed with formula modification, although real-world comparative data across different formula strategies remain limited. Aim: To evaluate gastrointestinal symptom resolution, improvement in AD, and growth outcomes following formula modification in infants with AD and suspected non-IgE-mediated CMPA. Methods: This retrospective comparative cohort study included 107 infants aged ≤12 months with documented AD and suspected non-IgE-mediated CMPA evaluated at a tertiary academic center between January 2024 and December 2025. Infants were categorized according to initial management strategy: switch to extensively hydrolyzed formula (eHF; n = 63), switch to amino acid formula (AAF; n = 29), or continued standard cow’s milk-based formula (n = 15). The primary outcome was resolution of gastrointestinal symptoms within 2–4 weeks. Secondary outcomes included improvement in AD, weight gain, and need for further formula escalation. Multivariable logistic regression was performed to adjust for potential confounders. Results: Overall, gastrointestinal symptom resolution occurred in 74 of 107 infants (69.2%). Resolution rates were 71.4% in the eHF group, 79.3% in the AAF group, and 40% in the standard formula group (p = 0.01). In adjusted analysis, switching to eHF (aOR 2.8; 95% CI 1.1–7.3; p = 0.03) and AAF (aOR 4.1; 95% CI 1.3–12.5; p = 0.01) was independently associated with higher odds of symptom resolution compared with continued standard formula. Improvement in AD was observed in 57.9% of infants overall and differed significantly across groups (p = 0.04). Mean weight gain during follow-up did not differ significantly between groups (p = 0.63). Subsequent formula escalation was more frequent in the standard formula group (46.7%) compared with eHF (17.5%) and AAF (13.8%) groups (p = 0.004). Conclusions: In infants with AD and suspected non-IgE-mediated CMPA, substitution with extensively hydrolyzed or amino acid formula was independently associated with greater gastrointestinal symptom resolution and improvement in dermatitis compared with continued standard formula, without evidence of compromised growth. These findings provide supportive real-world evidence consistent with current international guidelines; however, given the observational design and potential for residual confounding, they should be interpreted as hypothesis-generating rather than confirmatory evidence of causal treatment effects. Full article

Introduction: Peanut oral immunotherapy (P-OIT) is an emerging treatment strategy for peanut allergy (PA). Although a standardized pharmaceutical product, Peanut (Arachis hypogaea) Allergen Powder-dnfp, has been approved in several countries, it is not universally available. In such contexts, real-world protocols using readily utilizable peanut products may represent an alternative approach. This study aimed to describe the feasibility, safety, and clinical outcomes of P-OIT using toasted peanuts in a real-world effort in a pediatric population. Methods: This single-center retrospective cohort study enrolled children who initiated P-OIT at our tertiary pediatric hospital Allergy Unit between April 2015 and December 2024. Demographic and clinical features, allergy test results, and information about P-OIT were recorded. Desensitization was defined as tolerance of 630 mg of peanut protein (PP). Results: Sixty patients (51.7% male; median age 8.2 years) were included. 22/60 (36.7%) achieved desensitization within a median time of 22.7 months. 21/60 (35%) were still undergoing P-OIT at a median tolerated dose of 100 mg of PP, and 17/60 (28.3%) discontinued treatment, most commonly due to loss to follow-up (44%). At least one adverse reaction occurred in 43/60 (71.7%) patients, predominantly mild and self-limiting (68.3% resolved spontaneously, 39.5% occurred at home). However, 11/60 (18.3%) showed anaphylaxis, and 3/60 (5%) received adrenaline. A reduction in Ara h 2 serum-specific IgE levels compared to the baseline was observed in patients completing escalation (p = 0.03). Conclusions: In this real-world single-center cohort, P-OIT using toasted peanuts was feasible in a subset of patients and was associated predominantly with mild adverse reactions, although systemic reactions were also recorded. Treatment discontinuation and adherence remain relevant challenges. These findings highlight the need for prospective, controlled studies to better define the role, safety profile, and patient selection criteria for food-based P-OIT protocols in settings where standardized products are not available. Full article

Sensitisation leading to food allergy may occur through the skin. Quantitative data on epidermal allergen penetration as a prerequisite for this remain limited. This study quantifies epidermal penetration of gluten and hydrolysed wheat protein (HWP) in 18 patients with challenge-confirmed WALDA (wheat allergy dependent on augmentation factors) and 12 healthy controls (HC). After 1 h of epicutaneous wheat application, 20 consecutive tape strips (TS) were collected, and wheat protein concentration was quantified by gliadin-specific ELISA. Skin barrier status was assessed by electrical impedance spectroscopy (EIS). Serum gliadin levels were measured before and 90 min after wheat application. Gliadin was detected across all TS layers for gluten and HWP. Penetration levels did not differ between patients and controls. Skin barrier status assessed by EIS did not differ significantly between individuals with and without a history of atopic dermatitis (p = 0.27). No correlation was observed between EIS-assessed skin barrier status and gliadin penetration. Serum gliadin was not increased after epicutaneous wheat application. This study using TS demonstrates for the first time that wheat allergens penetrated into the epidermis but could not be detected in the serum. Neither wheat allergy nor skin barrier status was associated with increased stratum corneum penetration. These findings suggest that epidermal uptake alone may not be sufficient to explain sensitisation. Full article

Background and Objectives: Patients with rheumatoid arthritis (RA) are found to have a higher risk of dental diseases. Although herbal medicines (HMs) have long been used to treat various conditions, few studies focus on its impact on dental diseases. In this longitudinal cohort study, we assessed the correlation between HM use and risk of dental diseases in RA groups. Materials and Methods: A total of 2359 persons with RA aged 20–80 who were free of dental diseases between 2001 and 2010 were retrospectively enrolled from nationwide register-based data. They were then classified into HMs and non-HMs groups based on whether they ever used combined HMs after RA onset. Incidence rate and hazard ratios (HRs) of dental diseases were estimated for both groups by the end of 2013 via fitting Cox proportional hazards model. Results: Incidence rate of dental disease was reported to be lower in the HMs group than in the non-HMs group (90.21 per 1000 person-years versus 106.94 per 1000 person-years, respectively). RA individuals treated with HMs showed a significantly lower risk of dental diseases, especially dental caries, pulpitis, periodontitis, and stomatitis. Among commonly prescribed formulas, eleven herbal products significantly associated with a lower risk of dental diseases, such as Hai-Piao-Xiao, Yan-Hu-Suo, Chuan-Niu-Xi, Mo-Yao, Olibanum, Bei-Mu, Mu-Gua, Gui-Zhi-Shao-Yao-Zhi-Mu-Tang, Shao-Yao-Gan-Cao-Tang, Xue-Fu-Zhu-Yu-Tang, and Ping-Wei-San. Conclusions: The addition of HMs treatment may have advantages to proactively prevent sequent risk of dental disorders for persons with rheumatic diseases. A deeper exploration focusing on pharmacological action is needed to provide more reliable evidence for the improvement of susceptible individuals’ oral hygiene. Full article

Hymenoptera venom allergy is a cause of anaphylaxis, which significantly affects patients’ daily lives due to the constant fear of accidental stings. Venom immunotherapy (VIT) is the only treatment capable of preventing severe systemic reactions (SSRs). Limited long-term real-life data are available, integrating both clinical and immunological outcomes. A five-year prospective observational study was conducted on 35 patients with a history of SSR who underwent VIT at a tertiary allergy center in Southern Italy; two of them had a diagnosis of systemic mastocytosis. Most patients were sensitized to Vespula, but others to Apis, Polistes dominula and Vespa crabro, reflecting the exposure pattern characteristic of Mediterranean regions. Clinical outcomes following accidental re-stings and serological trends, including total IgE, venom-specific IgE, and baseline serum tryptase, were assessed at treatment initiation and after five years of maintenance therapy. During the entire follow-up, all patients tolerated VIT. No SSRs occurred after accidental stings in 17/35 patients, confirming clinical protection achieved with VIT. Vespula serum-specific IgE presented a highly significant decrease; total IgE, tryptase and specific IgE for Apis, Polistes dominula and Vespa crabro showed a statistically significant decrease. Our findings reinforce the role of VIT as a well-tolerated, effective and disease-modifying treatment in a real-world setting. Full article

Background: Malaria parasites import essential nutrients from plasma into their host erythrocytes through the plasmodial surface anion channel (PSAC), a conserved ion and nutrient channel on the infected cell surface. A parasite-encoded ternary complex consisting of CLAG3, RhopH2, and RhopH3 determines PSAC activity, but the precise contributions of each member to formation of the nutrient uptake pore remains uncertain. Methods: Here, we devised a two-step CRIPSR transfection strategy to examine an amphipathic CLAG3 helix, termed α-helix 44 (α-H44), as a candidate pore-lining domain. Results: A CLAG3 truncation protein without α-H44 phenocopies a CLAG3 knockout line, suggesting a critical role of α-H44 in formation of the nutrient channel; CLAG3 restoration using a recodonized α-H44 restores PSAC activity fully. A saturation mutagenesis library that splits the helix into four sequential segments was devised and implemented. Two engineered mutants exhibit distinct PSAC phenotypes; their cultures failed to expand in a modified medium that approximates in vivo nutrient availability. Conclusions: These studies support a α-H44 role in channel permeation and block by a strain-specific inhibitor. Our strategy will enable saturation mutagenesis to determine how PSAC achieves its unique ion and nutrient selectivity and should help guide drug discovery against this antimalarial target. Full article

Background/Objectives: Neutrophil-to-lymphocyte ratio (NLR) may predict outcomes after organ transplantation. This study evaluated the peri-transplant prognostic value of NLR in lung transplantation (LTx). Methods: This retrospective study included 282 LTx recipients (2012–2020). NLR measured on PODs 1, 3, 7, and 28 predicted 6-month mortality. Generalized estimating equations analyzed serial trends. Multivariable regression and ROC analysis identified predictors for a composite model, assessing discrimination and calibration. Results: Among 282 recipients (mean age, 54.2 years; male, 65.2%; idiopathic pulmonary fibrosis, 54.3%), 24.1% died within 6 months, most commonly from infection. Median NLR increased sharply after LTx (pre-LTx, 5.4; POD 1, 23.1; POD 3, 31.2), then decreased (POD 7, 18.8; POD 28, 8.7). Non-survivors had significantly higher preoperative and postoperative NLRs, particularly on POD 28. POD 28 NLR independently predicted 6-month mortality (multivariable analysis: OR, 1.05 per unit; 95% CI, 1.02–1.07; p < 0.001), alongside age and donor lung PaO₂/FiO₂ (P/F) ratio. Notably, a composite model combining these variables demonstrated significantly superior discrimination (area under the curve [AUC], 0.742; p = 0.001) compared to the NLR-only model (AUC, 0.698; p < 0.05). GEE demonstrated significantly steeper post-transplant NLR decline among survivors than non-survivors after adjusting for age (p = 0.02). Patients with NLR > 9.20 at POD 28 (area under the curve, 0.698; 95% CI, 0.615–0.782; sensitivity, 71.4%; specificity, 59.8%)—showed significantly lower survival on Kaplan–Meier analysis (p < 0.001, log-rank). Conclusions: Persistent NLR elevation on POD 28 independently predicts early mortality post-LTx and may support routine post-transplant risk stratification. Full article

Background: Most penicillin allergy labels are documented in early childhood and result from events of low risk for allergy. In Germany, evidence-based strategies to evaluate the likelihood of a true penicillin allergy are still lacking. As general practitioner input is indispensable regarding required resources for the implementation of successful delabeling strategies in outpatient care, a mixed-methods study in Baden-Württemberg, Germany explored untapped delabeling potential and conditions for successful initiatives based on their experiences, to support preservation of penicillin as a treatment option and prevent resistance development. Methods: A cross-sectional convergent mixed-methods study was conducted with an online survey and semi-structured interviews. The survey link and invitation to participate in an interview was sent to randomly selected publicly available e-mail addresses. Survey data were analyzed descriptively. Qualitative data were analyzed inductively based on thematic analysis. Results: n = 101 survey questionnaires and n = 15 interviews were analyzed regarding relevance, experiences, framework conditions, and potential approaches to delabeling. All participants with limited recollection of the index reaction. Most participants considered delabeling a highly relevant topic in general practice. Delabeling efforts were discouraged by lack of time, expertise, and remuneration, and uncertainty due to missing guidelines. Taking a sufficient medical history and, if necessary, subsequent testing were seen as one approach to delabeling. For a standardized approach in primary care, patient and care provider education, precise guideline recommendations, and delabeling expert teams were suggested. Conclusions: The findings mirror aspects already identified in international research. A nationwide survey with general practitioners could confirm that addressing necessary resources and systemic adjustments would support effective penicillin allergy delabeling in outpatient care. Full article