Role of portocaval shunts in development of complications after liver transplantation

Rationale. Portal blood flow is a key component in the viability of the liver transplant. Portocaval shunts formed on the background of the liver cirrhosis before transplantation can cause portal vein steal syndrome, with subsequent development of ischemic necrosis of the graft. To date, the tactics of treating patients with portal vein steal syndrome during liver transplantation has not been sufficiently developed. This paper presents a literature review and our own experience on this important, but little-studied issue. Purpose. The purpose of this research is to study the role of portocaval shunts in the development of complications after liver transplantation, based on a retrospective analysis of clinical cases. Conclusions. In liver transplantation, portocaval shunts can cause the development of portal vein steal syndrome with subsequent development of liver failure. For the diagnosis of portal vein steal syndrome, it is important to use the data obtained at all stages of liver transplantation. Surgical correction of portal vein steal syndrome can be performed during liver transplantation and in the early postoperative period. © 2022 by the authors

СОВРЕМЕННОЕ СОСТОЯНИЕ ДОНОРСКОЙ СЛУЖБЫ В СВЕРДЛОВСКОЙ ОБЛАСТИ

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FEV1/FVC <0.70% — Is it the COPD absolute marker?

The article presents a discussion that unfolded around the post-bronchodilator indicator FEV1/FVC<0.7 as an indispensable criterion for the diagnosis of chronic obstructive pulmonary disease (COPD) in patients older than 40 and exposed to airborne pollutants. The indicator conditionality is presented: the lower age norm for people under 50–55 is higher than 0.7 and in older age groups (over 65) — lower than 0.7, which can cause both overdiagnosis and underdiagnosis of the disease. At the same time, an issue arose about the spirometric maneuver quality and determining fixed bronchial obstruction. This is crucial for diagnosing COPD. The prospective non-interventional study results based on the compilation and assessment of a patient register with chronic bronchial obstructive diseases in the Perm region are presented. A group of patients with typical COPD manifestations, but without reliable functional characteristic (FEV1 /FVC<0.7 was isolated. A discussion is presented on the isolating possibility of separate disease form, the distinctive features of which is the reduction in FEV1, without reducing FEV1 /FVC. The clinical features of this patient category are given. As a rule, they are distinguished by the following parameters: high frequency of cardiovascular diseases; emphysema minimal manifestations; diffuse peribronchial fibrosis pronounced manifestations (mainly in the upper and middle parts of the lungs); distinctness by bronchial and systemic inflammation signs. It is recommended to treat such patients in the same way as patients with COPD using the same drugs. The article shows the need for long-term dynamic monitoring of this patient category and the continuation of scientific research to answer the question: what is the disease natural development in such patients and will they progress towards COPD. To date, there is no more accessible and significant marker for the COPD diagnosis in real clinical practice as the post-bronchodilator ratio of FEV1 /FVC<0.7. Perhaps in the future, new, more sensitive and reliable criteria for COPD diagnosis will appear, especially at the early stages of its development.В статье представлена дискуссия, развернувшаяся вокруг постбронходилатационного показателя ОФВ1 /ФЖЕЛ <0.7 как обязательного критерия для постановки диагноза хронической обструктивной болезни легких (ХОБЛ) у пациентов старше 40 лет и подвергшихся действию аэрополлютантов. Показана условность этого показателя: нижняя возрастная норма у лиц моложе 50–55 лет бывает выше 0,7, а в старших возрастных группах (старше 65 лет) — ниже 0,7, что может служить причиной как гипердиагностики, так и гиподиагностики заболевания. Наряду с этим встал вопрос о качестве выполнения спирометрического маневра, определения фиксированной бронхиальной обструкции. Это имеет решающее значение для диагностики ХОБЛ. Представлены результаты проспективного неинтервенционного исследования, основанного на составлении и оценке регистра больных с хроническими бронхообструктивными заболеваниями в Пермском крае. Выделена группа больных с типичными проявлениями ХОБЛ, но не имеющими достоверной функциональной характеристики (ОФВ1 /ФЖЕЛ <0.7. В будущем, возможно, появятся новые, более чувствительные и надежные критерии диагностики ХОБЛ, особенно на ранних стадиях ее развития

Efficacy and safety of lebrikizumab in adult patients with mild-to-moderate asthma not receiving inhaled corticosteroids

Background: Asthma is a heterogeneous and complex disease in both its clinical course and response to treatment. IL-13 is central to Type 2 inflammation and contributes to many features of asthma. In a previous Phase 2 study, lebrikizumab, an anti-IL-13 monoclonal antibody, did not significantly improve FEV1 in mild-to-moderate asthma patients not receiving ICS therapy. This Phase 3 study was designed to further assess the efficacy and safety of lebrikizumab in adult patients with mild-to-moderate asthma treated with daily short-acting β2-agonist therapy alone. Methods: Adult patients with mild-to-moderate asthma were randomised to receive lebrikizumab 125 mg subcutaneously (SC), placebo SC, or montelukast 10 mg orally for 12 weeks, with an 8-week follow-up period. The primary efficacy endpoint was absolute change in pre-bronchodilator FEV1 from baseline at Week 12. Findings: A total of 310 patients were randomised and dosed in the study. The mean absolute change in FEV1 from baseline at Week 12 was higher in the lebrikizumab-treated arm compared with placebo (150 mL versus 67 mL); however, this improvement did not achieve statistical significance (overall adjusted difference of 83 mL [95% CI:-3, 170]; p = .06). Montelukast did not improve FEV1 as compared with placebo. Lebrikizumab was generally safe and well tolerated during the study. Interpretation: Lebrikizumab did not significantly improve FEV1 in mild-to-moderate asthma patients at a dose expected to inhibit the IL-13 pathway. Inhibiting IL-13 in this patient population was not sufficient to improve lung function. These data support the findings of a previous trial of lebrikizumab in patients not receiving ICS

Development of a technology for the preparation of a dry nutrient medium for anthrax vaccine production

Currently, submerged cultivation of the Bacillus anthracis STI-1 strain for live anthrax vaccine production requires liquid nutrient media, which have disadvantages of a short shelf life (no more than one month) and a narrow range of storage temperatures (2–8 °С). Dry media, in contrast, have a number of indisputable advantages: such media are transportable and easy to use, have a standard capability to retain properties, and can be stored without preservatives at 2–30 °С for 2–5 years. The aim of this work was to develop a technology for the preparation of a dry nutrient medium for anthrax vaccine production. Materials and methods: The study used the Bacillus anthracis STI-1 vaccine strain and a nutrient medium for its cultivation, containing a 70:30 mixture of an enzymatic digest of casein and a pre-processed corn extract solution. Drying of the nutrient medium was carried out on a spray-drying unit. The authors evaluated physicochemical parameters of experimental medium batches. The shelf life was determined by an accelerated stability study. The dry nutrient medium was used to produce a live anthrax vaccine. Quality attributes of the vaccine were assessed for compliance with regulatory requirements. Results: The authors developed the dry media production technology. According to it, the liquid nutrient medium is fed to the drying unit at a rate of 20–25 dm3/h. The spray air pressure is 0.02 MPa. Temperatures at the drying chamber inlet and outlet are 118–122 °С and 85–90 °С, respectively. The technology was used to obtain 3 experimental batches of the dry medium. The study results demonstrate that the technology is reproducible, and the tested quality attributes of experimental medium batches are consistent with the requirements. According to the accelerated stability study, the shelf life of the dry nutrient medium at 2–30 °С is at least 3 years. Experiments demonstrated the possibility of using the dry nutrient medium for live anthrax vaccine production. Critical quality attributes of the vaccine obtained with the medium met regulatory requirements. Conclusions: The developed technology allows for the production of a standard dry nutrient medium with a prolonged shelf life, which is convenient for live anthrax vaccine production

Национальные клинические рекомендации по диагностике и лечению хронической обструктивной болезни легких: алгоритм принятия клинических решений

Treatment of patients with chronic obstructive pulmonary disease (COPD) is one of the most important tasks of clinical medicine due to high prevalence of and high mortality from COPD. Treatment of COPD as a heterogeneous disease requires different approaches depending on the severity and the clinical course of COPD. Clinical guidelines have become the principal document that regulates different aspects of management of COPD patients. Algorithms of management and clinical decision making are the crucial part of guidelines because they help achieving a balance between making the decision in different clinical situations and simple graphics. The simplified approach is important for implementation the algorithm into clinical practice. Different evidence-based therapeutic schemes proposed by experts of Russian Respiratory Society and other countries have been enclosed into this article with discussion about their strengths and limitations and possibility of practical use. The Russian algorithm reflects a current view on differentiated management of COPD patients and fits the requirements of Healthcare Ministry of Russian Federation and needs of achieving the optimal balance between high informative significance and a simple graphics of the scheme. Терапия больных хронической обструктивной болезнью легких (ХОБЛ) – одна из наиболее важных проблем внутренней медицины вследствие высокой распространенности и смертности от этой патологии. При терапии ХОБЛ как гетерогенного заболевания требуются различные подходы в зависимости от тяжести и особенностей его течения. В последние десятилетия клинические рекомендации (руководства) стали основным документом, в котором определяются различные аспекты ведения больных ХОБЛ. Очень важным разделом клинических руководств являются алгоритмы ведения пациента и принятия клинических решений, основная проблема которых – достижение баланса между учетом различных вариантов течения заболевания, принятия клинических решений, с одной стороны, и простотой графического изображения – с другой. Важное условие применимости алгоритма в условиях реальной клинической практики – именно упрощенность подходов. В настоящей статье приводятся различные схемы терапии, предложенные экспертами разных стран и Российского респираторного общества, основанные на принципах доказательной медицины; описаны их достоинства и недостатки, а также пригодность для практического использования. Представленный отечественный алгоритм, отражающий сегодняшние взгляды на дифференцированные подходы к ведению больных ХОБЛ, составлен с учетом требований Министерства здравоохранения Российской Федерации к разработке алгоритмов действий врача и необходимости достижения оптимального баланса между максимальной информативностью схемы и простотой графического изображения. 

Strategies for Abatement of Contamination of Tableted Live Plague Vaccine at Different Stages of Manufacturing

Nowadays, problem of tableted drug form contamination with extraneous micro-flora is in the spotlight of scientists, as the specific share of these medical preparations in the world market amounts to more than 60 % and has a tendency to increase. Thus, objective of the study is to investigate the degree of contamination of the basic and auxiliary raw materials at different stages of live plague vaccine manufacturing, rapid dissolving tablets, and the ways to reduce it. Materials and methods. Utilized has been lyophilized Y. pestis live culture of the vaccine strain EV NIIEG, and the live plague vaccine, rapid dissolving tablets. Carried out has been assessment of “microbiological purity” at different stages of tableted live plague vaccine manufacturing: grinding, mixing, granulation, sublimation, and palletizing. Results and conclusions. Identified is the dynamic pattern of quantitative micro-flora composition of the mentioned above drug. Established is the alteration of microbial impurity at separate technological manufacturing steps. Specified is the technological stage with the most expressed contamination. Analysis of factors, which affect vaccine impurity, has revealed that finished dosage-form quality improvement is impossible without incoming control of stock and auxiliary materials, as well as enhancement of manufacturing procedure up to the level, complying with applicable pharmaceutical production standards. It is experimentally proved that series of tableted live plague vaccine, obtained using modernized technological equipment, provide for 3-fold reduction of contamination

РОССИЙСКОЕ РЕСПИРАТОРНОЕ ОБЩЕСТВО. ФЕДЕРАЛЬНЫЕ КЛИНИЧЕСКИЕ РЕКОМЕНДАЦИИ ПО ДИАГНОСТИКЕ И ЛЕЧЕНИЮ ХРОНИЧЕСКОЙ ОБСТРУКТИВНОЙ БОЛЕЗНИ ЛЕГКИХ

The guidelines have been developed by the Russian Respiratory Society (RRS) based on analysis of papers published during the last 5 years in MEDLINE and ENBASE databases and the Cochrane library. The results of the analysis were subsequently reviewed by independent experts with consideration of the opinion of physicians and general practitioners. A quality and a strength of the evidence were assessed using worldwide criteria. The guidelines are focused on epidemiology and social burden of chronic obstructive pulmonary disease (COPD), pathogenesis, clinical signs, characterization of phenotypes and severity, current diagnostic and differentiating methods and therapeutic approaches including long-tern oxygen therapyat home, long-term respiratory support at home, surgical treatment, pulmonary rehabilitation, treatment of complications and acute exacerbation of COPD.The guidelines are fully consistent with requirements of the Healthcare Ministry of Russia for federal guidelines on principal nosologies and treatmenttechniquesКлинические рекомендации составлены Российским респираторным обществом (РРО) на основании анализа данных, опубликованных за последние 5 лет в базах данных MEDLINE, ENBASE и Кокрановской библиотеке. Результаты анализа были рецензированы независимыми экспертами с учетом мнения практических врачей первичного звена. Качество и уровень выработанных доказательств и сила созданных на их основе рекомендаций оценены в соответствии с международными критериями. В данных клинических рекомендациях рассмотрены эпидемиология и социальная значимость, патогенез, клиническая картина, классификация по степени тяжести и фенотипам, современные методы диагностики и дифференциальной диагностики, а также подходы к медикаментозному и немедикаментозному лечению хронической обструктивной болезни легких (ХОБЛ), включая длительную кислородотерапию и неинвазивную вентиляцию легких на дому, хирургическое лечение, терапию осложнений и обострений ХОБЛ, методы легочной реабилитации.Настоящие клинические рекомендации соответствуют требованиям Министерства здравоохранения Российской Федерации к разработке Федеральных клинических рекомендаций по основным нозологическим формам и методам терапии