The Effect of Aspirin on Moderate to Severe Asthmatic Patients with Aspirin Hypersensitivity, Chronic Rhinosinusitis, and Nasal Polyposis

Asthmatic patients may have aspirin-exacerbated respiratory disease and experience acute dyspnea and nasal symptoms within 3 hours after the ingestion of aspirin. This study aimed to evaluate the effect and outcome of daily low-dose aspirin in the treatment of moderate to severe asthma in patients with concomitant aspirin hypersensitivity and chronic rhinosinusitis with nasal polyposis (CRSwNP). This clinical trial was conducted from February 2014 to February 2015 on 46 adult patients with moderate to severe asthma accompanied by CRSwNP. Patients with a positive aspirin challenge were blindly randomized in three groups receiving placebo/day (A); aspirin 100 mg/day (B); and aspirin 325mg/day (C), respectively. Clinical findings, FEV1 and ACT scores were recorded and compared before, during, and after treatment for 6 months. Of 46 participants at baseline, 30 patients completed this 6-month trial study. The level of asthma control was significant; based on Asthma Control Test (ACT) when comparing the results in groups A and C and also groups B and C, but it was not significant when comparing ACT scores between groups A and B. FEV1 before and after treatment was significant when comparing groups A and B, groups A and C, and groups B and C. To conclude, aspirin desensitization with a daily dose of 325 mg aspirin resulted in the improvement of long-term control of asthma. A daily aspirin dose of 100 mg was not associated with such an increase in ACT score

New Transition Wedge Design Composed by Prefabricated Reinforced Concrete Slabs

[EN] Important track degradation occurs in structure-embankment transitions, in which an abrupt change in track vertical stiffness arises, leading to a reduction in passengers comfort and safety. Although granular wedges are suggested by different railroad administrations as a solution to avoid these problems, they present some disadvantages which may affect track long-term performance. In this paper, a new solution designed with prefabricated reinforced concrete slabs is proposed. The aim of this solution is to guarantee a continuous and gradual track vertical stiffness transition in the vicinity of structures, overcoming granular wedges disadvantages. The aim of this study is to assess the performance of the novel wedge design by means of a 3-D FEM model and to compare it with the current solution.Real Herráiz, JI.; Zamorano-Martín, C.; Real-Herraiz, TP.; Morales-Ivorra, S. (2016). New Transition Wedge Design Composed by Prefabricated Reinforced Concrete Slabs. Latin American Journal of Solids and Structures. 13(8):1431-1449. doi:10.1590/1679-78252556S14311449138Gallego Giner, I., & López Pita, A. (2009). Numerical simulation of embankment—structure transition design. Proceedings of the Institution of Mechanical Engineers, Part F: Journal of Rail and Rapid Transit, 223(4), 331-343. doi:10.1243/09544097jrrt234Gallego, I., Muñoz, J., Rivas, A., & Sánchez-Cambronero, S. (2011). Vertical Track Stiffness as a New Parameter Involved in Designing High-Speed Railway Infrastructure. Journal of Transportation Engineering, 137(12), 971-979. doi:10.1061/(asce)te.1943-5436.0000288Insa, R., Salvador, P., Inarejos, J., & Roda, A. (2011). Analysis of the influence of under sleeper pads on the railway vehicle/track dynamic interaction in transition zones. Proceedings of the Institution of Mechanical Engineers, Part F: Journal of Rail and Rapid Transit, 226(4), 409-420. doi:10.1177/0954409711430174Li, D., & Davis, D. (2005). Transition of Railroad Bridge Approaches. Journal of Geotechnical and Geoenvironmental Engineering, 131(11), 1392-1398. doi:10.1061/(asce)1090-0241(2005)131:11(1392)Pita, A. L., Teixeira, P. F., & Robuste, F. (2004). High speed and track deterioration: The role of vertical stiffness of the track. Proceedings of the Institution of Mechanical Engineers, Part F: Journal of Rail and Rapid Transit, 218(1), 31-40. doi:10.1243/095440904322804411Molatefi, H., & Izadbakhsh, S. (2013). Continous rail absorber design using decay rate calculation in FEM. Structural Engineering and Mechanics, 48(4), 455-466. doi:10.12989/sem.2013.48.4.455Montalbán, L., Real, J., & Real, T. (2012). Mechanical characterization of railway structures based on vertical stiffness analysis and railway substructure stress state. Proceedings of the Institution of Mechanical Engineers, Part F: Journal of Rail and Rapid Transit, 227(1), 74-85. doi:10.1177/0954409712452348Montalbán Domingo, L., Real Herraiz, J. I., Zamorano, C., & Real Herraiz, T. (2014). Design of a new high lateral resistance sleeper and performance comparison with conventional sleepers in a curved railway track by means of finite element models. Latin American Journal of Solids and Structures, 11(7), 1238-1250. doi:10.1590/s1679-78252014000700009Montalbán Domingo, L., Zamorano Martín, C., Palenzuela Avilés, C., & Real Herráiz, J. I. (2014). Analysis of the Influence of Cracked Sleepers under Static Loading on Ballasted Railway Tracks. The Scientific World Journal, 2014, 1-10. doi:10.1155/2014/363547Real, J. I., Gómez, L., Montalbán, L., & Real, T. (2012). Study of the influence of geometrical and mechanical parameters on ballasted railway tracks design. Journal of Mechanical Science and Technology, 26(9), 2837-2844. doi:10.1007/s12206-012-0734-7Shan, Y., Albers, B., & Savidis, S. A. (2013). Influence of different transition zones on the dynamic response of track–subgrade systems. Computers and Geotechnics, 48, 21-28. doi:10.1016/j.compgeo.2012.09.006Shi, J., Burrow, M. P. N., Chan, A. H., & Wang, Y. J. (2012). Measurements and simulation of the dynamic responses of a bridge–embankment transition zone below a heavy haul railway line. Proceedings of the Institution of Mechanical Engineers, Part F: Journal of Rail and Rapid Transit, 227(3), 254-268. doi:10.1177/095440971246097

LPS-responsive beige-like anchor gene mutation associated with possible bronchiolitis obliterans organizing pneumonia associated with hypogammaglobulinemia and normal IgM phenotype and low number of B

LPS-Responsive Beige-like Anchor (LRBA) deficiency is a disease which has recently been described in a group of patients with common variable immunodeficiency (CVID) in association with autoimmunity and/or inflammatory bowel disease (IBD)-like phenotype. We here describe a 10-year-old boy who experienced recurrent infections, mainly in the respiratory system, associated with thrombocytopenia and anemia. Immunological workup showed low numbers of B cells and low IgG, but normal IgM levels. In spite of therapeutic doses of antibiotics, antivirals, and antifungal agents, in addition to immunoglobulin replacement therapy, he developed disseminated involvement of both lungs with peripheral nodules; transbronchial lung biopsy revealed possible bronchiolitis obliterans organizing pneumonia (BOOP). Combined homozygosity mapping and exome sequencing identified a homozygous LRBA mutation in this patient (p.Asp248Glufs * 2). Such clinical and immunological findings have not been described to date and illustrate the broad and variable clinical phenotype of human LRBA deficiency. © 2016 Tehran University of Medical Sciences. All rights reserved

Consensus Middle East and North Africa Registry on Inborn Errors of Immunity

Background: Inborn errors of immunity (IEIs) are a heterogeneous group of genetic defects of immunity, which cause high rates of morbidity and mortality mainly among children due to infectious and non-infectious complications. The IEI burden has been critically underestimated in countries from middle- and low-income regions and the majority of patients with IEI in these regions lack a molecular diagnosis. Methods: We analyzed the clinical, immunologic, and genetic data of IEI patients from 22 countries in the Middle East and North Africa (MENA) region. The data was collected from national registries and diverse databases such as the Asian Pacific Society for Immunodeficiencies (APSID) registry, African Society for Immunodeficiencies (ASID) registry, Jeffrey Modell Foundation (JMF) registry, J Project centers, and International Consortium on Immune Deficiency (ICID) centers. Results: We identified 17,120 patients with IEI, among which females represented 39.4%. Parental consanguinity was present in 60.5% of cases and 27.3% of the patients were from families with a confirmed previous family history of IEI. The median age of patients at the onset of disease was 36 months and the median delay in diagnosis was 41 months. The rate of registered IEI patients ranges between 0.02 and 7.58 per 100,000 population, and the lowest rates were in countries with the highest rates of disability-adjusted life years (DALY) and death rates for children. Predominantly antibody deficiencies were the most frequent IEI entities diagnosed in 41.2% of the cohort. Among 5871 patients genetically evaluated, the diagnostic yield was 83% with the majority (65.2%) having autosomal recessive defects. The mortality rate was the highest in patients with non-syndromic combined immunodeficiency (51.7%, median age: 3.5 years) and particularly in patients with mutations in specific genes associated with this phenotype (RFXANK, RAG1, and IL2RG). Conclusions: This comprehensive registry highlights the importance of a detailed investigation of IEI patients in the MENA region. The high yield of genetic diagnosis of IEI in this region has important implications for prevention, prognosis, treatment, and resource allocation

Impact of SARS-CoV-2 Pandemic on Patients with Primary Immunodeficiency

Although it is estimated that COVID-19 life-threatening conditions may be diagnosed in less than 1:1000 infected individuals below the age of 50, but the real impact of this pandemic on pediatric patients with different types of primary immunodeficiency (PID) is not elucidated. The current prospective study on a national registry of PID patients showed that with only 1.23 folds higher incidence of infections, these patients present a 10-folds higher mortality rate compared to population mainly in patients with combined immunodeficiency and immune dysregulation. Therefore, further management modalities against COVID-19 should be considered to improve the survival rate in these two PID entities using hematopoietic stem cell transplantation and immunomodulatory agents. © 2020, The Author(s)

Monogenic Primary Immunodeficiency Disorder Associated with Common Variable Immunodeficiency and Autoimmunity

Background: Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency disorder mainly characterized by recurrent bacterial infections besides other immunological defects including loss of or dysfunction of B cells and decreased immunoglobulin levels. In this study, our aim is to evaluate clinical, immunological, and molecular data of patients with a primary clinical diagnosis of CVID and autoimmune phenotype with a confirmed genetic diagnosis. Methods: Among 297 patients with CVID, who were registered in the Iranian Primary Immunodeficiency Registry at Children's Medical Center Hospital in Iran, 83 patients have been genetically examined and 27 patients with autoimmunity and confirmed genetic mutations were selected for analysis. Whole-exome sequencing and confirmatory Sanger sequencing methods were used for the study population. A questionnaire was retrospectively filled for all patients to evaluate demographic, laboratory, clinical, and genetic data. Results: In the 27 studied patients, 11 different genetic defects were identified, and the most common mutated gene was LRBA, reported in 17 (63.0) patients. Two patients (7.7) showed autoimmune complications as the first presentation of immunodeficiency. Eleven patients (40.7) developed one type of autoimmunity, and 16 patients (59.3) progressed to poly-autoimmunity. Most of the patients with mono-autoimmunity (n = 9, 90.0) primarily developed infectious complications, while in patients with poly-autoimmunity, the most common first presentation was enteropathy (n = 6, 37.6). In 13 patients (61.9), the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency. The most frequent autoimmune manifestations were hematologic (40.7), gastrointestinal (48.1), rheumatologic (25.9), and dermatologic (22.2) disorders. Patients with poly-autoimmunity had lower regulatory T cells than patients with mono-autoimmunity. Conclusion: In our cohort, the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency in most patients. This association highlights the fact that patients referring with autoimmune manifestations should be evaluated for humoral immunity. © 2020 Georg Thieme Verlag. All rights reserved

The evaluation of 25-hydroxy vitamin D, calcium, phosphate and alkaline phosphatase levels in epileptic children under antiepileptic medication

"n 800x600 Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 st1":*{behavior:url(#ieooui) } /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman","serif";} Background: Epilepsy is a common disease in the pediatric neurology. There are frequent anti-epileptic drugs which are used in management of epilepsy. Anti-epileptic drugs may have some complications on bone and vitamin-D metabolism. In this study we aimed to evaluate vitamin-D metabolism in epileptic children."n"nMethods: The study was a prospective and cross sectional one. A total 89 epileptic children who were taking anti-epileptic drugs for longer than six months with no underlying disorder in Imam Khomeini and Bahrami Hospitals in Tehran, Iran were enrolled in our study"n"nResults: Forty nine boys and 40 girls were enrolled in this study; mean age of the patients was 7.8±2.1 years. Mean duration of anti-epileptic drug therapy was 2.3 years (SD=0.4), 70 of patients were under monotherapy and 19 were under polytherapy. None of the patients had signs of rickets. Serum calcium and phosphor levels were within normal ranges. Serum alkaline phosphates levels were increased more than two times in 43%. 42% had vitamin-D deficiency (25-OH Vit D<10 ng/ml) and another 33% had vitamin-D insufficiency (10<25-oh Vit D<20 ng/ml). 29 patients (32%) were taking prophylactic supplemental Vit D (200-400 IU/day). There was significant difference between patients taking supplemental vitamin-D as prophylaxis and patients who did not (p=0.04). There was no significant difference in vitamin-D levels between patients according to age, gender or different drugs."n"nConclusion: Periodic measurement of 25-hydroxy vitamin-D is recommended in epileptic children taking anti-epileptic dugs. Supplemental vitamin-D administration in such patients may be helpful

Aspirin Sensitivity in Patients with Moderate to Severe Asthma

Asthma induced by ingestion of aspirin occurs when symptoms arise within 30 minutes to three hours after aspirin consumption. Previous data indicate that sensitivity to aspirin may be associated with poorly controlled asthma. This study aims to evaluate the frequency of aspirin sensitivity in patients with moderate to severe asthma receiving conventional asthma therapy. This clinical trial was conducted on 65 patients aged 18 to 65 years with moderate to severe asthma from February 2015 to February 2016 at the Allergy Department, Hazrat-e-Rasoul Hospital, Iran University of Medical Sciences, Tehran. To assess treatment responses in patients, forced expiratory volume in the first second (FEV1) and asthma control test (ACT) scores were measured at baseline and after 3 months. The results of the oral aspirin challenge revealed a prevalence of 35.38 for sensitivity to aspirin. Hypersensitivity reactions to aspirin were detected in 60.9 of the patients with moderate asthma and 39.1 of the patients with severe asthma. All patients with positive aspirin challenge tests suffered from rhinosinusitis and in 56.5 of cases, history of previous hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs) was detected. No meaningful differences were found between those patients with aspirin sensitivity and those with aspirin tolerance neither in mean prebronchodilator FEV1 nor in ACT scores pre- and post-treatment. To conclude, aspirin sensitivity was not found to have an association with an unfavorable response to conventional treatment in patients with uncontrolled asthma. Copyright © August 2020, Iran J Allergy Asthma Immunol. All rights reserved

Phenotyping and follow up of forty-seven Iranian patients with common variable immunodeficiency

Background: Common variable immune deficiency (CVID) is a heterogeneous syndrome with a wide variety of signs and symptoms. This study describes the phenotyping and survival of the CVID patients in the allergy and clinical immunology department of Rasol-E-Akram Hospital of Iran University of Medical Sciences in Tehran. Method: We retrospectively reviewed hospital files of CVID patients in our department until January 2014. All patients were diagnosed with standard diagnostic criteria of CVID, treated and visited monthly, during the follow-up period. We divided the patients into four phenotypes; infection only, cytopenia, polyclonal lymphocytic infiltration and unexplained enteropathy. The immunologic, demographic and clinical findings in different phenotypes were analysed. Results: The study included 47 CVID patients with mean age at onset of symptoms and diagnosis of 11.2 and 20.2 years, respectively. Phenotyping of our patients was: only infection (62), cytopenia (26) and PLI (19) and 94 of cases had only one phenotype. We did not find a significant relation between the clinical phenotypes and immunologic or demographic data. Rate of parental consanguinity in our cases was 47. Parental consanguinity was related to lower age at onset, lower age at diagnosis and higher baseline IgG levels. Patients with malignancy and autoimmunity had significantly higher age at onset. Our patients were followed-up for 6.9 years and the mortality rate during this time was 6. Conclusions: Parental consanguinity and age at onset of CVID symptoms may have important roles in CVID manifestations. © 2015 SEICAP

LPS-responsive beige-like anchor gene mutation associated with possible bronchiolitis obliterans organizing pneumonia associated with hypogammaglobulinemia and normal IgM phenotype and low number of B

LPS-Responsive Beige-like Anchor (LRBA) deficiency is a disease which has recently been described in a group of patients with common variable immunodeficiency (CVID) in association with autoimmunity and/or inflammatory bowel disease (IBD)-like phenotype. We here describe a 10-year-old boy who experienced recurrent infections, mainly in the respiratory system, associated with thrombocytopenia and anemia. Immunological workup showed low numbers of B cells and low IgG, but normal IgM levels. In spite of therapeutic doses of antibiotics, antivirals, and antifungal agents, in addition to immunoglobulin replacement therapy, he developed disseminated involvement of both lungs with peripheral nodules; transbronchial lung biopsy revealed possible bronchiolitis obliterans organizing pneumonia (BOOP). Combined homozygosity mapping and exome sequencing identified a homozygous LRBA mutation in this patient (p.Asp248Glufs * 2). Such clinical and immunological findings have not been described to date and illustrate the broad and variable clinical phenotype of human LRBA deficiency. © 2016 Tehran University of Medical Sciences. All rights reserved