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Urticaria is a debilitating skin condition affecting up to 20% of the global population, characterized by erythematous, maculopapular lesions and significant quality of life impairment. This study focused on the role of interleukin 33 (IL-33) and its polymorphisms, particularly SNP rs1929992, in chronic spontaneous urticaria (CSU). Using demographic, clinical, and laboratory data from CSU patients and controls, we estimated allele and genotype frequencies, Hardy–Weinberg equilibrium condition, and serum IL-33 levels, using unconditional binomial logistic regression for association analysis. Results revealed that CSU patients had significantly higher frequencies of the minor allele of IL-33 rs1929992 compared to controls (31.25% vs. 17.35%, p = 0.024), and carriers of the GA genotype exhibited increased odds of CSU (adjusted OR = 2.208, p ≤ 0.001). Additionally, serum IL-33 levels were markedly elevated in CSU patients, particularly those with the GA genotype. The findings suggest that the IL-33 SNP is associated with an increased susceptibility to CSU, emphasizing its potential as a diagnostic and therapeutic biomarker. This study underscores the genetic and immunological underpinnings of CSU, paving the way for personalized treatment approaches. [ABSTRACT FROM AUTHOR]

Rebinding CO2 in calcium silicate units through recarbonation Calcium silicate units (CSU) are manufactured using burnt lime. When installed in contact with air, CSU absorb more than 3 % of their own weight in CO2 from the air and store it permanently in the structure. An equal amount of CO2 was previously released during the production of burnt lime. This reabsorption is known as recarbonation. This article is based on the examination of around 2 t of masonry and documents this CO2 absorption. The data presented allows the conclusion that CSU usually recarbonate in contact with air within 50–60 years. As the service life of solid buildings generally exceeds 60 years by far, the simplified assumption of 95 % recarbonation at the end of the utilisation phase seems appropriate. The exact amount of CO2 reabsorption depends on the raw materials and the quantities used. It can therefore be taken into account directly in life cycle assessments. In EPD the amount of CO2 rebound for the use phase B1 is specified. Plasters, panels, coatings, etc. influence the recarbonation of wall‐building materials and must be taken into account in the LCA for constructions with CSU. [ABSTRACT FROM AUTHOR]

Backgrounds A large proportion of patients with chronic spontaneous urticaria (CSU) are resistant to a standard dose of antihistamine. Acknowledged biomarkers for identifying these patients have not been determined. The neutrophil/lymphocyte ratio (NLR) has been considered as an important indicator of inflammation in chronic diseases. Aims To explore whether NLR could serve as a biomarker for predicting the response to H1-antihistamine in patients with CSU. Methods This hospital-based, retrospective study included 109 patients with CSU diagnosed from 2017 to 2020 in our clinic and divided them into two groups by their responses to the 2-week antihistamine therapy of standard-dose: 69 with H1-antihistamine-refractory and 40 with non-H1-antihistamine-refractory CSU. The laboratory test results were collected from the hospital information system and integrated with SPSS software. Results Patients refractory to H1-antihistamine had significantly higher median NLR (P = 0.039), age (3 P = 0.021), complement C3 (P = 0.026), presence of elevated WBC (P = 0.026) and elevated monocytes (MONO) (P = 0.045) and significantly lower IgM (P = 0.022). The binary logistic regression model revealed that NLR was significantly associated with H1-antihistamine-refractory of CSU (odds ratio (OR) 1.717, 95% confidence interval (CI) 1.065–2.766, P = 0.026), which was consistent with that after adjusted for potential confounding factors including age, complement C3, presence of elevated WBC and MONO, and IgM (OR 1.681, 95% CI 1.019–2.773, P = 0.042). Conclusion Our results showed a strong and significant association between higher NLR and H1-antihistamine resistance in CSU, suggesting that NLR may be a potential biomarker for predicting the response to H1-antihistamine therapy in patients with CSU.

Introduction: In chronic spontaneous urticaria (CSU), interleukin (IL)-4 and IL-13 may promote mast cell activation directly via IL-4 receptor expression, or indirectly via upregulated immunoglobulin E (IgE) production. Dupilumab significantly improved CSU signs and symptoms in the phase 3, randomized, placebo-controlled LIBERTY-CSU CUPID Study A. This analysis explores the impact of dupilumab on CSU signs and symptoms and serum IgE levels in patients from LIBERTY-CSU CUPID Study A with serum total IgE above and below 100 IU/mL at baseline. Methods: Patients with H1-antihistamine-refractory CSU received dupilumab (n = 70) or placebo (n = 68) for 24 weeks. Efficacy endpoints were change from baseline to weeks 12 and 24 in serum total IgE levels, Itch Severity Score over 7 days (ISS7), Urticaria Activity Score over 7 days (UAS7), and Hives Severity Score over 7 days (HSS7) in dupilumab- or placebo-treated patients with serum total IgE above and below 100 IU/mL at baseline. Results: Dupilumab treatment significantly reduced median (interquartile range) IgE levels at week 12 [dupilumab: −31.9% (−41.9; −22.6); placebo: −6.3% (−21.3; 14.9)] and week 24 [dupilumab: −48.2% (−56.8; − 39.5); placebo: − 6.3% (−34.5; 14.8)]. Similar IgE reductions relative to baseline were observed in dupilumab-treated patients regardless of baseline IgE level. Dupilumab treatment improved ISS7, UAS7, and HSS7 over 12 and 24 weeks, regardless of baseline serum IgE level (interaction p ≥ 0.59 for all treatment by subgroup comparisons), with weak correlations (r < 0.2) observed between IgE level changes and ISS7, UAS7, and HSS7 outcomes. Conclusions: Dupilumab significantly improved CSU signs and symptoms and reduced serum IgE, regardless of baseline IgE levels. In the current analysis, baseline total IgE had no predictive value as a dupilumab treatment response biomarker in CSU. Downregulation of IgE, a key mediator of mast cell activation and histamine release, may at least partially explain the effectiveness of dupilumab in reducing CSU signs and symptoms. Trial Registration: ClinicalTrials.gov Identifier: NCT04180488. [ABSTRACT FROM AUTHOR]

Backgrounds: A large proportion of patients with chronic spontaneous urticaria (CSU) are resistant to a standard dose of antihistamine. Acknowledged biomarkers for identifying these patients have not been determined. The neutrophil/lymphocyte ratio (NLR) has been considered as an important indicator of inflammation in chronic diseases. Aims: To explore whether NLR could serve as a biomarker for predicting the response to H1-antihistamine in patients with CSU. Methods: This hospital-based, retrospective study included 109 patients with CSU diagnosed from 2017 to 2020 in our clinic and divided them into two groups by their responses to the 2-week antihistamine therapy of standard-dose: 69 with H1-antihistamine-refractory and 40 with non-H1-antihistamine-refractory CSU. The laboratory test results were collected from the hospital information system and integrated with SPSS software. Results: Patients refractory to H1-antihistamine had significantly higher median NLR (P = 0.039), age (3 P = 0.021), complement C3 (P = 0.026), presence of elevated WBC (P = 0.026) and elevated monocytes (MONO) (P = 0.045) and significantly lower IgM (P = 0.022). The binary logistic regression model revealed that NLR was significantly associated with H1-antihistamine-refractory of CSU (odds ratio (OR) 1.717, 95% confidence interval (CI) 1.065–2.766, P = 0.026), which was consistent with that after adjusted for potential confounding factors including age, complement C3, presence of elevated WBC and MONO, and IgM (OR 1.681, 95% CI 1.019–2.773, P = 0.042). Conclusion: Our results showed a strong and significant association between higher NLR and H1-antihistamine resistance in CSU, suggesting that NLR may be a potential biomarker for predicting the response to H1-antihistamine therapy in patients with CSU. [ABSTRACT FROM AUTHOR]

This article is dedicated to the examination of the diplomatic efforts undertaken by the USSR and the Federal Republic of Germany (FRG) to ensure military-political security during the period from 1987 to 1989. It explores the factors that contributed to changes in security policy. The analysis focuses on several under-researched aspects, including the strengthening of constructive forces within the federal government in 1987; the convergence of positions between the USSR and the FRG regarding disarmament and arms control; and the process of solidifying a positive trend in Soviet-West German political dialogue. Special attention is given to the role of the Free Democratic Party of Germany (FDP) in reorienting the governing coalition of the FRG from a policy of confrontation towards seeking compromises with the USSR in the realm of security. The evolution of Bonn’s official stance on the elimination of intermediate- and shorter-range missiles is also examined. It is demonstrated that, during 1988–1989, the course of the federal government became less dependent on the line of its key ally, the United States, thereby allowing for a consideration of the national interests of the FRG in addressing the issue of “nuclear rearmament”. The relevance of this study lies in its exploration of mechanisms through which the degradation of dialogue between the Russian Federation and Western collective countries in the sphere of security may be halted in contemporary times.

Background: The proximity of activated T cells and mast cells in the lesional skin of patients with chronic spontaneous urticaria (CSU) is held to contribute to the development of wheals and angioedema. In a previous study, we demonstrated that increased IL-17 expression in T cells and mast cells in skin lesions of patients with CSU is associated with T/mast cell proximity, but the mechanisms that drive T cell/mast cell co-localization remain unknown. Objectives: To assess if chemokines expressed in lesional CSU skin contribute to T cell/mast cell proximity. Patients and Methods: Biopsies from lesional CSU skin were compared to biopsies from healthy skin for expression of CCR5 and its ligand CCL3 by CD4+ T cells and mast cells, respectively. Results: Numbers of CCR5-positive CD4+ T cells in lesional CSU skin were significantly increased as compared to healthy normal skin (p < 0.0001). The number of mast cells expressing CCL3 (ligand for CCR5) in CSU skin was also increased (p < 0.0002) and significant association with T-cell close proximity (p < 0.0001) is noticed. Conclusions: The close proximity of T cells and mast cells in the skin of severe CSU may be driven, at least in part by increased CCR5 and CCL3 expression. Therapies that target CCL3 interaction with CCR5 should be assessed for their effects in CSU. [ABSTRACT FROM AUTHOR]

BackgroundOmalizumab (OMA) was the first FDA-approved biological drug for severe chronic spontaneous urticaria (CSU), and until today is the only beneficial and truly safe one. The objectives were: To assess the prevalence of CSU patients in whom OMA cannot be stopped over time. We also asked if biomarkers (e.g., anti-TPO antibodies and total IgE) could assist in anticipating this issue.MethodsWe used our prospective registry of 93 patients, which included CSU disease duration, the onset of OMA treatment, Urticaria Activity Score (UAS7) during follow-up, co-morbidities, serum IgE levels and the presence of anti-TPO antibodies. Finally, we assessed the response to OMA during a period of six years.ResultsOut of the 93 treated CSU patients, OMA was stopped in ten patients after six months being defined as failures. In another ten patients, OMA was discontinued after 2–4 years of therapy, achieving a remission. Seventy-three patients are still treated between 2 and 6 years, having different degrees of response. Of these, in thirty-eight (52%) patients, we could not stop OMA even after six years due to CSU relapses. The prevalence of lower serum IgE levels and anti-TPO antibody positivity was significantly higher in CSU patients in whom OMA could not be stopped.ConclusionThis is the first study where OMA-treated CSU patients were followed up to six years. In half of them, long-term therapy of six years is still required.

BackgroundThe proximity of activated T cells and mast cells in the lesional skin of patients with chronic spontaneous urticaria (CSU) is held to contribute to the development of wheals and angioedema. In a previous study, we demonstrated that increased IL-17 expression in T cells and mast cells in skin lesions of patients with CSU is associated with T/mast cell proximity, but the mechanisms that drive T cell/mast cell co-localization remain unknown.ObjectivesTo assess if chemokines expressed in lesional CSU skin contribute to T cell/mast cell proximity.Patients and methodsBiopsies from lesional CSU skin were compared to biopsies from healthy skin for expression of CCR5 and its ligand CCL3 by CD4+ T cells and mast cells, respectively.ResultsNumbers of CCR5-positive CD4+ T cells in lesional CSU skin were significantly increased as compared to healthy normal skin (p < 0.0001). The number of mast cells expressing CCL3 (ligand for CCR5) in CSU skin was also increased (p < 0.0002) and significant association with T-cell close proximity (p < 0.0001) is noticed.ConclusionsThe close proximity of T cells and mast cells in the skin of severe CSU may be driven, at least in part by increased CCR5 and CCL3 expression. Therapies that target CCL3 interaction with CCR5 should be assessed for their effects in CSU.

Background: Chronic spontaneous urticaria (CSU) is an immunologic condition with an estimated prevalence of 0.1%. For CSU that is poorly controlled despite the use of antihistamines, omalizumab is the only treatment approved and recommended by international guidelines. Objective: Our aim was to outline the impact of treatment accessibility on CSU outcomes in the real world. Methods: Serial data on adult patients with CSU receiving care for at least 6 months at a dedicated, immunologist-led urticaria clinic at Grantham Hospital in Hong Kong between 2018 and 2023 were analyzed. Patients’ clinicodemographic data, drug eligibility status (eligible for reimbursement or not), treatment step, and disease activity (weekly Urticaria Activity Score [UAS7]) were collected and compared according to drug eligibility status. Results: This study included 238 patients, 80 (33.6%) of whom were eligible for reimbursement and 158 of whom were not. No significant clinicodemographic differences, including disease activity, were found at baseline. At latest follow-up, significantly more patients in the eligible group were receiving omalizumab (28.7% vs 5.7% [P < .001]), which is equivalent to a multivariate odds ratio of 9.35 (95% CI = 3.689-23.703 [P < .001]). The discrepancy persisted even in patients with moderate-to-severe CSU whose UAS7 was 16 or higher (40.6% [13 of 32] vs 10.2% [6 of 59]; P < .001). In addition, there was significantly less dose reduction (

This study delves into the critical role of alarmins in chronic spontaneous urticaria (CSU), focusing on their impact on disease severity and the quality of life (QoL) of patients. We investigated the alterations in alarmin levels in CSU patients and their correlations with the Urticaria Activity Score (UAS7) and the Dermatology Life Quality Index (DLQI). We analyzed serum levels of interleukin-25 (IL-25), interleukin-33 (IL-33), and thymic stromal lymphopoietin (TSLP) in 50 CSU patients, comparing these to 38 healthy controls. The study examined the relationship between alarmin levels and clinical outcomes, including disease severity and QoL. Elevated levels of IL-33 and TSLP in CSU patients (p < 0.0001) highlight their potential role in CSU pathogenesis. Although IL-25 showed higher levels in CSU patients, this did not reach statistical significance (p = 0.0823). Crucially, IL-33's correlation with both UAS7 and DLQI scores underscores its potential as a biomarker for CSU diagnosis and severity assessment. Of the alarmins analyzed, IL-33 emerges as particularly significant for further exploration as a diagnostic and prognostic biomarker in CSU. Its substantial correlation with disease severity and impact on QoL makes it a compelling candidate for future research, potentially serving as a target for therapeutic interventions. Given these findings, IL-33 deserves additional investigation to confirm its role and effectiveness as a biomarker and therapeutic target in CSU. [ABSTRACT FROM AUTHOR]

Abstract Chronic spontaneous urticaria (CSU) is a condition in which wheals, angioedema, and pruritus occur spontaneously and recurrently for at least 6 weeks. The etiology of this disease is partially dependent on production of autoantibodies that activate and recruit inflammatory cells. Although the wheals can resolve within 24 h, symptoms have a significant detrimental impact on the quality of life of these patients. Standard therapy for CSU includes second-generation antihistamines and omalizumab. However, many patients tend to be refractory to these therapies. Available treatments such as cyclosporine, dapsone, dupilumab, and tumor necrosis factor alpha (TNFa) inhibitors have been used with success in some cases. Furthermore, various biologics and other novel drugs have emerged as potential treatments for this condition, and many more are currently under investigation in randomized clinical trials.

(1) Background: This study aimed to evaluate the implications of interleukin-31 (IL-31) in the pathogenesis of chronic spontaneous urticaria (CSU) and to assess the differences that occur between its serum values compared to controls. Additionally, the serum IL-31 levels were measured alongside other clinical and paraclinical parameters that were identified in the patients to understand its immunological importance in this skin disease and to determine if it could potentially serve as a therapeutic target in CSU in the future. (2) Methods: The serum levels of IL-31 were estimated in 50 patients diagnosed with CSU according to the accepted international guidelines. Additionally, 38 controls who had not experienced any episodes of urticaria during their lifetime were included. (3) Results: Significantly elevated serum IL-31 levels were observed in CSU patients compared to the controls (p < 0.0001). Although no direct correlations were found between IL-31 and inflammatory markers (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)), eosinophils, or total immunoglobulins E (IgE), significant differences in IL-31 levels were identified based on CSU severity, quality of life impact, itch intensity, and response to histamine H1 receptor antagonists (H1 antihistamines) (p < 0.05 for all). (4) Conclusions: Our findings underscore that IL-31 is not directly associated with general inflammation, eosinophilic response, or atopy in CSU. Nevertheless, its expression is influenced by key disease characteristics: severity, pruritus, and H1 antihistamine response. This investigation provides essential insights into CSU pathogenesis, potentially leading to novel therapeutic interventions. An enhanced understanding of these mechanisms is crucial due to the limitations of current treatment modalities in terms of fully managing CSU symptoms. [ABSTRACT FROM AUTHOR]

Rebounding of CO2 during service life and recycling in building materials reduces the CO2 content of the atmosphere. The CO2 was formerly released from limestone through deacidification during the production of cement and quicklime. Binder‐bound building materials later reabsorb this CO2 again. This process is called recarbonation. In contrast to concrete, detailed knowledge about the CO2 cycles of autoclaved aerated concrete (AAC) is missing. Standards concerning adequate sampling and measurement methods as well as suitable calculation methods are currently under development. According to the valid EN 15804:2012+A2:2019, life cycle assessments and environmental product declarations (EPDs) concern the entire product life cycle and thus also the CO2 reabsorption by building materials. For AAC, this amount can be calculated from the raw material input. The reduction bases on the active CaO contained in the AAC, is absolute and related to the binder mass used. Thus, it can be applied comprehensively and without the influence of the used database system of the background data in EPDs. Unfortunately, the amount of originally active CaO cannot be measured directly in AAC samples. As a first approximation, it was obvious to assume that all chemically determinable CaO in AAC was formerly active. However, this method underestimates the degree of recarbonation because the raw materials also contain non‐reactive CaO, for example, in the form of calcium silicates. Nevertheless, all diagrams concerning recarbonation of AAC are based on this assumption and the values are too low. In the presentation, we will introduce a new method to determine the degree of recarbonation of AAC—forced carbonation. Forced carbonation is carried out under defined temperature, humidity, and CO2 conditions in a climate chamber. The measurement is bases on the detection of CO2 in the sample and considers the proportion of non‐reactive CaO and thus leads to realistic degrees of recarbonation. [ABSTRACT FROM AUTHOR]

Abstract Background There is a paucity of studies reporting the presence of systemic symptoms and micronutrient deficiency in patients with chronic urticaria, and these data are lacking in a Canadian population. Objective To report the prevalence of gastrointestinal symptoms and vitamin B12 (cobalamin) deficiency in a Canadian patient population diagnosed with chronic urticaria. Methods A retrospective chart review of 100 adult patients with chronic urticaria was conducted. Demographic characteristics, medications, presence of gastrointestinal symptoms, and laboratory findings were abstracted from electronic medical records. Results Seventy percent of patients with chronic urticaria reported experiencing gastrointestinal symptoms. The most common symptom identified was gastroesophageal reflux (42%). Vitamin B12 (cobalamin) deficiency, defined as serum vitamin B12 level ≤ 250 pmol/L, was identified in 31.7% of the patients. Among those patients with urticaria and vitamin B12, 68% reported gastrointestinal symptoms. Conclusions This is the first study to provide data on the high prevalence of gastrointestinal symptoms and vitamin B12 (cobalamin) deficiency in a Canadian population diagnosed with chronic urticaria. Early recognition and management of systemic symptoms and micronutrient deficiency may lead to a more comprehensive approach to management of these patients. Trial registration Not applicable

Chronic spontaneous urticaria (CSU) is a condition in which wheals, angioedema, and pruritus occur spontaneously and recurrently for at least 6 weeks. The etiology of this disease is partially dependent on production of autoantibodies that activate and recruit inflammatory cells. Although the wheals can resolve within 24 h, symptoms have a significant detrimental impact on the quality of life of these patients. Standard therapy for CSU includes second-generation antihistamines and omalizumab. However, many patients tend to be refractory to these therapies. Available treatments such as cyclosporine, dapsone, dupilumab, and tumor necrosis factor alpha (TNFa) inhibitors have been used with success in some cases. Furthermore, various biologics and other novel drugs have emerged as potential treatments for this condition, and many more are currently under investigation in randomized clinical trials. [ABSTRACT FROM AUTHOR]