Ингаляционные глюкокортикостероиды. Беклоджет — препарат с новой системой доставки действующего вещества

Beclojet is a dosed freon-free aerosol inhaler containing beclomethazone dipropionate and a jet delivery system. The aim of this study was to investigate clinical efficacy and safety of Beclojet in moderate to severe bronchial asthma patients who had been treated before with inhaled and/or systemic glucocorticodteroids (GCS).Forty patients aged 18 to 65 years have received Beclojet for 2 months in doses equal to those of previously given inhaled GCS or in combination with previously given systemic GCS without growing of their doses. The efficacy was evaluated before and after the therapy with Beclojet on the background of BA drug stability according to the need of β-agonists, daytime and nighttime BA symptoms, lung function parameters. The effectiveness of Beclojet was compared with the previous therapy with inhaled GCS.The Beclojet application in moderate to severe BA patients was quite effective at various clinical situations. There was not adverse events for the 2-month follow-up period. The drug was easy to use, economically reasonable (it was cheaper than other inhaled GCS). The results allow to recommend Beclojet for widespread application as the basic BA therapy.Беклоджет — бесфреоновый дозированный аэрозольный ингалятор, содержащий беклометазона дипропионат и оснащенный Je t-системой. Цель: изучение клинической эффективности и безопасности беклоджета у больных с бронхиальной астмой (БА) среднетяжелого и тяжелого течения, леченных ингаляционными и/или системными глюкокортикостероидами (ГКС).У 40 больных в возрасте от 18 до 65 лет в течение 2 мес проводили терапию беклоджетом, который назначался в дозах, эквивалентных предшествующей терапии ингаляционными ГКС (иГКС) или в комбинации с предшествующей терапией системными ГКС без увеличения дозы последних. Эффективность оценивалась до и после применения беклоджета на фоне медикаментозной ремиссии БА по потребности в β-агонистах, выраженности дневных и ночных симптомов БА, динамике показателей ФВД. Эффективность беклоджета сравнивалась с исходной базисной терапией и ГКС.Применение беклоджета у пациентов с БА среднетяжелого и тяжелого течения в различных клинических ситуациях показало хорошую эффективность, отсутствие нежелательных побочных эффектов (период наблюдения 2 мес), удобство применения, экономическую целесообразность (более низкая стоимость беклоджета по сравнению с другими иГКС). Полученные данные позволяют рекомендовать беклоджет для широкого применения в качестве базисной терапии БА

Features of high-dose intravenous immunotherapy administration in patients with reduced IgA level in neurological practice: literature review and description of a clinical case

Intravenous high-dose immunotherapy is one of the highly effective proven treatments for a number of autoimmune diseases of the nervous system. Nowadays there is enough knowledge about the spectrum of side effects and approaches to their prevention and monitoring. Most of them are leveled by improving the technology of the production process, but anaphylactic reactions remain one of the uncontrolled, albeit rare, undesirable reactions. The development of allergic reactions is associated with the presence of antibodies to immunoglobulin class A (IgA) in the patient, which is manifested by a decrease in the level of IgA during routine immunological examination. The article provides a review of the literature on the prevalence of IgA deficiency, its causes. A modern view of the need for routine testing of IgA level before the course of intravenous immunotherapy, approaches to reduce the risk of developing serious adverse reactions in such cases is described. A clinical case of treatment of a patient with chronic inflammatory demyelinating polyneuropathy and a reduced level of IgA is presented

Geographical Distribution, Incidence, Malignancies, and Outcome of 136 Eastern Slavic Patients With Nijmegen Breakage Syndrome and NBN Founder Variant c.657_661del5

Nijmegen breakage syndrome (NBS) is a DNA repair disorder characterized by combined immunodeficiency and a high predisposition to lymphoid malignancies. The majority of NBS patients are identified with a homozygous five base pair deletion in the Nibrin (NBN) gene (c.657_661del5, p.K219fsX19) with a founder effect observed in Caucasian European populations, especially of Slavic origin. We present here an analysis of a cohort of 136 NBS patients of Eastern Slav origin across Belarus, Ukraine, Russia, and Latvia with a focus on understanding the geographic distribution, incidence of malignancy, and treatment outcomes of this cohort. Our analysis shows that Belarus had the highest prevalence of NBS (2.3 per 1,000,000), followed by Ukraine (1.3 per 1,000,000), and Russia (0.7 per 1,000,000). Of note, the highest concentration of NBS cases was observed in the western regions of Belarus and Ukraine, where NBS prevalence exceeds 20 cases per 1,000,000 people, suggesting the presence of an “Eastern Slavic NBS hot spot.” The median age at diagnosis of this cohort ranged from 4 to 5 years, and delay in diagnosis was more pervasive in smaller cities and rural regions. A total of 62 (45%) patients developed malignancies, more commonly in males than females (55.2 vs. 34.2%; p=0.017). In 27 patients, NBS was diagnosed following the onset of malignancies (mean age: 8 years). Malignancies were mostly of lymphoid origin and predominantly non-Hodgkin lymphoma (NHL) (n=42, 68%); 38% of patients had diffuse large B-cell lymphoma. The 20-year overall survival rate of patients with malignancy was 24%. However, females with cancer experienced poorer event-free survival rates than males (16.6% vs. 46.8%, p=0.036). Of 136 NBS patients, 13 underwent hematopoietic stem cell transplantation (HSCT) with an overall survival of 3.5 years following treatment (range: 1 to 14 years). Indications for HSCT included malignancy (n=7) and immunodeficiency (n=6). Overall, 9% of patients in this cohort reached adulthood. Adult survivors reported diminished quality of life with significant physical and cognitive impairments. Our study highlights the need to improve timely diagnosis and clinical management of NBS among Eastern Slavs. Genetic counseling and screening should be offered to individuals with a family history of NBS, especially in hot spot regions. © Copyright © 2021 Sharapova, Pashchenko, Bondarenko, Vakhlyarskaya, Prokofjeva, Fedorova, Savchak, Mareika, Valiev, Popa, Tuzankina, Vlasova, Sakovich, Polyakova, Rumiantseva, Naumchik, Kulyova, Aleshkevich, Golovataya, Minakovskaya, Belevtsev, Latysheva, Latysheva, Beznoshchenko, Akopyan, Makukh, Kozlova, Varabyou, Ballow, Ong, Walter, Kondratenko, Kostyuchenko and Aleinikova.We thank all doctors for clinical help for patients. We also appreciate the support of patient and their parents for agreeing to take part in this study. TP thanks Sergey?Nikulshin, Marika Grutupa, and Zanna Kovalova. We thank Joseph Dasso for editing this manuscript, primarily for proper English

Patients with primary immunodeficiencies are a reservoir of poliovirus and a risk to polio eradication

ABSTARCT: Immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) have been isolated from primary immunodeficiency (PID) patients exposed to oral poliovirus vaccine (OPV). Patients may excrete poliovirus strains for months or years; the excreted viruses are frequently highly divergent from the parental OPV and have been shown to be as neurovirulent as wild virus. Thus, these patients represent a potential reservoir for transmission of neurovirulent polioviruses in the post-eradication era. In support of WHO recommendations to better estimate the prevalence of poliovirus excreters among PIDs and characterize genetic evolution of these strains, 635 patients including 570 with primary antibody deficiencies and 65 combined immunodeficiencies were studied from 13 OPV-using countries. Two stool samples were collected over 4 days, tested for enterovirus, and the poliovirus positive samples were sequenced. Thirteen patients (2%) excreted polioviruses, most for less than 2 months following identification of infection. Five (0.8%) were classified as iVDPVs (only in combined immunodeficiencies and mostly poliovirus serotype 2). Non-polio enteroviruses were detected in 30 patients (4.7%). Patients with combined immunodeficiencies had increased risk of delayed poliovirus clearance compared to primary antibody deficiencies. Usually, iVDPV was detected in subjects with combined immunodeficiencies in a short period of time after OPV exposure, most for less than 6 months. Surveillance for poliovirus excretion among PID patients should be reinforced until polio eradication is certified and the use of OPV is stopped. Survival rates among PID patients are improving in lower and middle income countries, and iVDPV excreters are identified more frequently. Antivirals or enhanced immunotherapies presently in development represent the only potential means to manage the treatment of prolonged excreters and the risk they present to the polio endgame. Keywords: Poliovirus eradication, Immunodeficiency-associated vaccine-derived polioviruses, Oral poliovirus vaccine, Humoral immunodeficiency, Combined immunodeficiency, Primary immunodeficienc

Особенности проведения высокодозной внутривенной иммунотерапии у пациентов со сниженным уровнем IgA в неврологической практике: обзор литературы и описание клинического случая

Intravenous high-dose immunotherapy is one of the highly effective proven treatments for a number of autoimmune diseases of the nervous system. Nowadays there is enough knowledge about the spectrum of side effects and approaches to their prevention and monitoring. Most of them are leveled by improving the technology of the production process, but anaphylactic reactions remain one of the uncontrolled, albeit rare, undesirable reactions. The development of allergic reactions is associated with the presence of antibodies to immunoglobulin class A (IgA) in the patient, which is manifested by a decrease in the level of IgA during routine immunological examination. The article provides a review of the literature on the prevalence of IgA deficiency, its causes. A modern view of the need for routine testing of IgA level before the course of intravenous immunotherapy, approaches to reduce the risk of developing serious adverse reactions in such cases is described. A clinical case of treatment of a patient with chronic inflammatory demyelinating polyneuropathy and a reduced level of IgA is presented.Внутривенная высокодозная иммунотерапия – один из высокоэффективных доказанных методов лечения ряда аутоиммунных заболеваний нервной системы. В настоящее время накоплено достаточно знаний о спектре побочных эффектов и подходах к их профилактике и мониторингу. Бόльшая часть из них нивелирована совершенствованием технологии процесса производства, однако анафилактические реакции остаются одной из неконтролируемых, хотя и редко встречающихся нежелательных реакций. Развитие аллергических реакций связывают с наличием у пациента антител к иммуноглобулину класса А (IgA), что проявляется снижением уровня IgA при рутинном иммунологическом исследовании. В статье представлен обзор литературы о распространенности дефицита IgA, его причинах. Описаны современный взгляд на необходимость рутинного исследования уровня IgA перед курсом внутривенной иммунотерапии, подходы к снижению риска развития серьезных нежелательных реакций в таких случаях. Представлен клинический случай лечения пациента с хронической воспалительной демиелинизирующей полинейропатией и сниженным уровнем IgA

One origin for metallo-β-lactamase activity, or two? An investigation assessing a diverse set of reconstructed ancestral sequences based on a sample of phylogenetic trees

This work was supported by BBSRC (grant BB/F016778/1)Bacteria use metallo-β-lactamase enzymes to hydrolyse lactam rings found in many antibiotics, rendering them ineffective. Metallo-β-lactamase activity is thought to be polyphyletic, having arisen on more than one occasion within a single functionally diverse homologous superfamily. Since discovery of multiple origins of enzymatic activity conferring antibiotic resistance has broad implications for the continued clinical use of antibiotics, we test the hypothesis of polyphyly further; if lactamase function has arisen twice independently, the most recent common ancestor (MRCA) is not expected to possess lactam-hydrolysing activity. Two major problems present themselves. Firstly, even with a perfectly known phylogeny, ancestral sequence reconstruction is error prone. Secondly, the phylogeny is not known, and in fact reconstructing a single, unambiguous phylogeny for the superfamily has proven impossible. To obtain a more statistical view of the strength of evidence for or against MRCA lactamase function, we reconstructed a sample of 98 MRCAs of the metallo-β-lactamases, each based on a different tree in a bootstrap sample of reconstructed phylogenies. InterPro sequence signatures and homology modelling were then used to assess our sample of MRCAs for lactamase functionality. Only 5 % of these models conform to our criteria for metallo-β-lactamase functionality, suggesting that the ancestor was unlikely to have been a metallo-β-lactamase. On the other hand, given that ancestral proteins may have had metallo-β-lactamase functionality with variation in sequence and structural properties compared with extant enzymes, our criteria are conservative, estimating a lower bound of evidence for metallo-β-lactamase functionality but not an upper bound.Publisher PDFPeer reviewe