ADULT-ONSET STILL'S DISEASE: DIAGNOSIS AND TREATMENT

The paper describes adult-onset Still's disease (AOSD), a rare multisystemic disease of unknown etiology that is referred to as seronegative rheumatoid arthritis. It presents the major manifestations of AOSD: long-term fever, arthritis or persistent arthralgias, maculopapular eruption, seronegativity for rheumatoid factor, neutrophilic leukocytosis, and disease onset after 16 years of age, as well as additional signs: lymphadenopathy, hepatosplenomegaly, polyserositis, nasopharyngeal infection. It is noted that particular difficulties in the diagnosis of AOSD emerge when it is complicated by the hematophagocytic syndrome (HPS). The distinctive features of AOSD are the development of cutaneous and articular symptoms in practically 80% of patients and their absence in HPS. It is stated that of greater value in the diagnosis of HPS is examination of aspirate of the bone marrow than its biopsy. Most patients develop refractoriness to glucocorticoids and essential anti-inflammatory drugs. The positive results of using anakinra, rituximab, and tocilizumab are promising

Formation of the system of business processes at machine building enterprises

The article studies approaches to determination of totality of business processes of machine building enterprises of the RF within structural & functional and process-oriented model of management. It was found that in functional management, algorithm is limited by six steps, and totality of business processes is “tied” to technological productive processes; that in process management, there are ten steps of determination and development of business processes, and their totality is limited by flow of value creation or by quality loop (life cycle of production). The authors offer an algorithm of formation of the system of business processes of large industrial enterprises which issue a range of technologically complicated products and are on the stage of transition from linear & functional management to process management. At the stage of transition from one model to another, it is offered to found the algorithm on the functional model of management through determination of “basic element of management” with further transformations of the system. Methodology of formation of the system of business processes of enterprises is developed which – within the PLM concept – allows: structuring activities in the sphere of different business processes, designing product and processes simultaneously, and integrating systems of creation of product of enterprises-members into the system of business processes of final manufacturer. Targeted indicators of evaluation of efficiency of main business processes are offered, which are received as a result of implementation of methodology in view of separate production of machine building enterprise of the RF which stipulate determination of the list of top-level processes, reflecting interests of most of external members of the system and of those processes which do not have reserves for improvement and are subject to changes in future.peer-reviewe

Перспективы применения мелоксикама у больных старшей возрастной группы с ревматическими заболеваниями

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in complex therapy for pain syndrome in rheumatology. The paper describes the pathophysiological mechanisms responsible for the development of chronic and acute pain. It details the action of cyclooxygenase types 1 and 2 (COG 1 and COG 2), shows the key role of COG 2 in pain induction and transmission. The data of clinical trials of meloxicam that inhibits mainly COG 2 are given. The drug is highly effective in treating rheumatic diseases, particularly in old-age group patients with osteoporosis. The combined use of different meloxicam formulations makes it possible to choose adequate, maximally individualized treatment and to relieve the pain syndrome in the shortest possible time. Among NSAIDs, meloxicam shows an optimum efficacy-safety ratio.Нестероидные противовоспалительные препараты (НПВП) широко применяются в комплексной терапии болевого синдрома в ревматологии. В статье представлены патофизиологические механизмы развития острой и хронической боли. Подробно описаны функции циклооксигеназы 1-го и 2-го типов - ЦОГ 1 и ЦОГ 2, показана ключевая роль ЦОГ 2 в индукции и трансмиссии боли. Приведены данные клинических исследований мелоксикама - НПВП, ингибирующего преимущественно ЦОГ 2. Мелоксикам высокоэффективен в терапии ревматических болезней, особенно при остеоартрозе у больных старшей возрастной группы. Комбинированное использование различных лекарственных форм мелоксикама позволяет подобрать адекватное, максимально индивидуализированное лечение, и в кратчайшие сроки купировать болевой синдром. Среди НПВП мелоксикам выделяется оптимальным соотношением эффективности и безопасности

Spatial beam self-cleaning and supercontinuum generation with Yb-doped multimode graded-index fiber taper based on accelerating self-imaging and dissipative landscape

We experimentally demonstrate spatial beam self-cleaning and supercontinuum generation in a tapered Ytterbium-doped multimode optical fiber with parabolic core refractive index profile when 1064 nm pulsed beams propagate from wider (122 µm) into smaller (37 µm) diameter. In the passive mode, increasing the input beam peak power above 20 kW leads to a bell-shaped output beam profile. In the active configuration, gain from the pump laser diode permits to combine beam self-cleaning with supercontinuum generation between 520-2600 nm. By taper cut-back, we observed that the dissipative landscape, i.e., a non-monotonic variation of the average beam power along the MMF, leads to modal transitions of self-cleaned beams along the taper length

Коморбидность у больных лобулярным панникулитом-липодерматосклерозом

Lipodermatosclerosis (LDS) is one of the variants of lobular panniculitis. The onset of LDS falls on the age of 50–60 years, when many patients already have comorbid pathology requiring complex therapy, which affects the course, the choice of treatment and prognosis of LDS, as well as the quality of life.Objective: to study the structure and frequency of comorbid conditions in patients with LDS.Patients and methods. 53 patients (3 men and 50 women), 18–80 years old, with a verified diagnosis of LDS were included, all of them had an average follow up of 10 years (they were observed in the V.A. Nasonova Research Institute of Rheumatology). The duration of the disease ranged from 2 weeks to 20 years. During clinical examination, the localization, prevalence, color and number of affected skin areas and sub cutaneous fat were determined. The intensity of pain on palpation of the node was assessed using a visual analogue scale (VAS). Laboratory and instrumental research included: blood and urine tests, computed tomography of the chest and ultrasound Doppler of the lower extremities with registration of the linear blood flow velocity in the affected veins (femoral, popliteal, posterior tibial, foot veins). Clinical, laboratory and instrumental examination of patients was carried out 2 times a year. The CIRS and Charlson indices were used to assess the relationship between comorbid pathology and LDS.Results and discussion. Most patients (60.3%) were women with increased body weight (91.5±21.8 kg). Depending on the duration of the disease, the main variants of the LDS course were: acute (<3 months), subacute (3–6 months), and chronic (>6 months). Skin changes were associated with polyarthralgia (34%) and/or myalgia (22.6%), mainly on the side of the affected limb. In 16 patients, an increase in ESR, on average 23.8±7.8 mm per hour, was detected, in 7 patients, including 4 with an acute course of LDS, – more than a threefold increase in the level of CRP. No comorbid diseases had 17 patients, 64.7% of them were under 50 years and had an acute course of LDS (p=0.02). In 68% of patients, mainly with chronic LDS, the following concomitant diseases was recorded: chronic venous insufficiency (CVI; in 67.9%); exogenous constitutional obesity (in 60.3%); rheumatic diseases (45.2%), including osteoarthritis (75%), rheumatoid arthritis (17%), antiphospholipid syndrome (8%), and arterial hypertension (39.6%). Most patients had 1 concomitant disease, and almost one fifth of patients had 2 concomitant diseases. The proportion of patients with 3 comorbid pathologies was 11.1%, with 4 – 8.3% and with 5 – 5.5%. When assessing the Charlson index, a 10-year survival rate of >90% (index values from 0 to 2 points) was observed in 66% of patients, 53–77% (3–4 points) – in 26.4% and <21% (≥5 points) – in 7.5%. There was correlation between the comorbidity index and the age of patients (r=0.8, p<0.05); no association with the duration of LDS was found (r=0.3, p=0.2). Patients over 61 years had ≥1 comorbid disease. The average CIRS index for this group was 4.2±0.3 points (0–10), in most patients (45.2%) it was <5 points. Analysis of the Charlson and CIRS scales confirmed their statistically significant relationship (r=0.5, p=0.0000001).Conclusion. In patients with LDS, a high incidence of comorbid pathology was noted. Interdisciplinary approach with interaction between doctors of different specialties is required for treatment of these patients.Липодерматосклероз (ЛДС) – один из вариантов лобулярного панникулита. Дебют ЛДС приходится на возраст 50–60 лет, когда у многих пациентов уже имеется коморбидная патология, требующая комплексной терапии, что оказывает влияние на течение, выбор тактики лечения и прогноз ЛДС, а также на качество жизни.Цель исследования – изучение структуры и частоты коморбидных состояний у пациентов с ЛДС.Пациенты и методы. Обследовано 53 пациента (3 мужчин и 50 женщин) 18–80 лет с верифицированным диагнозом ЛДС, наблюдавшихся в ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой» в среднем 10 лет. Продолжительность заболевания варьировалась от 2 нед до 20 лет. При клиническом обследовании определяли локализацию, распространенность, окраску и количество пораженных участков кожи и подкожной жировой клетчатки. Интенсивность боли при пальпации узла оценивали по визуальной аналоговой шкале (ВАШ). Лабораторно-инструментальное исследование включало: анализы крови и мочи, компьютерную томографию органов грудной клетки и ультразвуковую допплерографию нижних конечностей с регистрацией линейной скорости кровотока в заинтересованных венах (бедренных, подколенных, задних большеберцовых, стопы). Клиническое, лабораторное и инструментальное обследование больных осуществляли 2 раза в год. Для оценки взаимосвязи коморбидной патологией с течением ЛДС использовали индексы CIRS и Charlson.Результаты и обсуждение. Среди пациентов преобладали женщины (60,3%) с повышенной массой тела (91,5±21,8 кг). В зависимости от длительности заболевания были выделены основные варианты течения ЛДС: острое (<3 мес), подострое (3–6 мес) и хроническое (>6 мес). Изменения кожи ассоциировалось с полиартралгиями (34%) и/или миалгиями (22,6%), преимущественно на стороне пораженной конечности. У 16 пациентов зарегистрировано повышение СОЭ в среднем до 23,8±7,8 мм/ч, у 7 больных в (том числе у 4 с острым течением ЛДС) – более чем трехкратное увеличение уровня СРБ. У 17 пациентов коморбидных заболеваний не выявлено, 64,7% из них были моложе 50 лет и имели острое течение ЛДС (р=0,02). У 68% больных, преимущественно с хроническим течением ЛДС, зафиксирована следующая сопутствующая патология: хроническая венозная недостаточность (ХВН; у 67,9%), экзогенно-конституциональное ожирение (у 60,3%); ревматические заболевания (у 45,2%), в том числе остеоартрит (у 75%), ревматоидный артрит (у 17%), антифосфолипидный синдром (у 8%), а также артериальная гипертензия (у 39,6%). У большинства пациентов имелось 1 сопутствующее заболевание, практически у пятой части – 2. Доля пациентов с 3 коморбидными патологиями составила 11,1%, с 4 – 8,3% и 5 – 5,5%. При оценке индекса Charlson показатель 10-летней выживаемости >90% (значения индекса от 0 до 2 баллов) отмечен у 66% больных, 53–77% (3–4 балла) – у 26,4% и <21% (≥5 баллов) – у 7,5%. Обнаружена взаимосвязь индекса коморбидности с возрастом пациентов (r=0,8, p<0,05), ассоциации с продолжительностью ЛДС не установлено (r=0,3, p=0,2). У больных старше 61 года зафиксировано ≥1 коморбидное состояние. Индекс CIRS для данной группы составлял в среднем 4,2±0,3 балла (0–10), у большинства больных (45,2%) он был <5 баллов. При анализе шкал Charlson и CIRS подтверждена их статистически значимая связь (r=0,5, р=0,0000001).Заключение. У больных ЛДС отмечена высокая частота коморбидной патологии. Курация больных требует междисциплинарного подхода и взаимодействия между врачами разных специальностей

Studying informativity of specific IgE levels to whole cow milk allergen and its components, as well as to soy and gluten in children

Successive development of immunological tolerance to cow’s milk proteins largely depends on the timeliness and validity of the elimination diet and is most difficult in IgE-mediated food allergy. From 2012 to 2017, when examining children aged 3 months to 10 years, we found some cases with high levels of specific IgE to beta-lactoglobulin that exceeded the levels of specific IgE to the whole cow’s milk allergen (the latter is often used as a screening allergen). The aim of this study was to assess the informativity of studying the levels of specific IgE to the whole cow’s milk allergens in blood serum of children at early, preschool and primary school age. We have also included gluten (gluten) and soy as possible components of early childhood nutrition into the list of allergens under study. The study involved 100 children aged 9 months to 12 years. Clinical selection criteria included presence of anamnestic data on exacerbation of atopic dermatitis, urticaria, exacerbation of rhinitis/asthma, diarrhea, constipation or abdominal pain in response to usage of cow’s milk and/or dairy products during the last 6 months. It is shown that extended study of specific IgE levels to whole cow’s milk allergen, its components, as well as to soy and gluten, increases the accuracy of laboratory diagnostics and differential diagnosis of IgEmediated form of food allergy to cow’s milk proteins, compared with determination of serum IgE to whole cow’s milk as a screening test. A detailed study of specific IgE to milk components allowed to confirm the presence of IgE-mediated form of allergy to cow’s milk in 7% of the examined children with signs of food allergy, but in absence of specific IgE to whole cow’s milk allergen. We have also shown that in 29% of cases, the level of specific IgE to milk components was higher than those to whole cow’s milk allergen. The results of this study may be of practical importance, since the form of food allergy, as well as intensity and dynamics of reduction of production of specific IgE, are accepted criteria to forecast development of tolerance to cow’s milk proteins. In addition, identification of specific allergen (including soy bean allergen) that causes the most intense production of specific IgE, may be importance for administration of a reasonable elimination diet. The most significant allergens for diagnosis and differential diagnostics of allergy to cow’s milk in children, in addition to the “whole cow’s milk, f2” preparation, are the following allergens: “whey, f236”, “beta-lactoglobulin, f77” and “soy, f14”

The effectiveness of combination of 7% hypertonic saline and 0.1% natrii hyaluronas in patients with chronic obstructive pulmonary disease who have suffered a new coronavirus infection

Introduction. New coronavirus infection (COVID-19) contributes to the aggravation of respiratory symptoms in patients with COPD, including affecting the intensity and nature of cough. Hypertonic solution (HS) has a positive effect on the rheological properties of sputum and mucociliary clearance. However, there are no studies in the available literature on the use of HS in patients who have undergone COVID-19.Goal. To evaluate the effect of the combination of 7% hypertonic saline and 0.1% natrii hyaluronas on the intensity and productive nature of cough in patients with COPD who have undergone a new coronavirus infection and the safety of its use in this cohort of patients.Materials and methods. 50 patients with severe COPD in remission who suffered a new coronavirus infection were examined. The rehabilitation stage of treatment was carried out in the conditions of the pulmonology department. From the moment of receiving the last negative PCR result for SARS-CoV-2 to admission to the hospital for rehabilitation, it took from 2 to 3 weeks. The duration of follow-up of patients was 10 days. The patients were divided into two groups: group 1 (n = 25) – patients who received combination of 7% hypertonic saline and 0.1% natrii hyaluronas 7% by inhalation through a nebulizer; group 2 (n = 25) – patients who did not receive combination of 7% hypertonic saline and 0.1% natrii hyaluronas. The severity of cough was assessed (cough severity scale; shortness of breath, cough and sputum scale), clinical and biochemical blood tests, ECG, spirometry.Results. In patients treated with combination of 7% hypertonic saline and 0.1% natrii hyaluronas, a significant decrease in the severity of cough, the amount of sputum was revealed. The tendency to reduce shortness of breath and improve the quality of life is determined. No serious adverse events were detected when using the drug.Conclusions. The use of the combination of 7% hypertonic saline and 0.1% natrii hyaluronas in patients with COPD who have suffered a new coronavirus infection at the rehabilitation stage leads to a decrease in the intensity of cough and improved sputum discharge, which helps to reduce the severity of shortness of breath and improve the quality of life. The use of the drug is safe and does not lead to clinically significant adverse events

Синдром Стилла у взрослых: диагностика и лечение

The paper describes adult-onset Still's disease (AOSD), a rare multisystemic disease of unknown etiology that is referred to as seronegative rheumatoid arthritis. It presents the major manifestations of AOSD: long-term fever, arthritis or persistent arthralgias, maculopapular eruption, seronegativity for rheumatoid factor, neutrophilic leukocytosis, and disease onset after 16 years of age, as well as additional signs: lymphadenopathy, hepatosplenomegaly, polyserositis, nasopharyngeal infection. It is noted that particular difficulties in the diagnosis of AOSD emerge when it is complicated by the hematophagocytic syndrome (HPS). The distinctive features of AOSD are the development of cutaneous and articular symptoms in practically 80% of patients and their absence in HPS. It is stated that of greater value in the diagnosis of HPS is examination of aspirate of the bone marrow than its biopsy. Most patients develop refractoriness to glucocorticoids and essential anti-inflammatory drugs. The positive results of using anakinra, rituximab, and tocilizumab are promising.Описан синдром Стилла у взрослых (ССВ) - редкое мультисистемное заболевание неизвестной этиологии, относящееся к сероне-гативному ревматоидному артриту. Приводятся основные проявления ССВ - длительная лихорадка, артрит или стойкие артралгии, макулопапулезная сыпь, серонегативность по ревматоидному фактору, нейтрофильный лейкоцитоз, развитие болезни после 16 лет, а также дополнительные признаки - лимфаденопатия, гепатоспленомегалия, полисерозит, носоглоточная инфекция. Отмечено, что особые трудности при диагностике ССВ возникают в случае его осложнения гематофагоцитарным синдромом (ГФС). Отличительными чертами ССВ являются развитие кожной и суставной симптоматики практически у 80% больных и отсутcтвие таковых при ГФС. Указано, что для диагностики ГФС большее значение имеет исследование аспирата костного мозга, чем его биопсия. У большинства пациентов развивается рефрактерность к глюкокортикоидам и базисным противовоспалительным препаратам. Надежду вселяют положительные результаты использования анакинры, ритуксимаба, тоцилизумаба

Панникулит: ревматологические аспекты

Different types of panniculitis (Pn) can be one of the symptoms of rheumatic diseases (RDs). Pn is a group of heterogeneous inflammatory diseases that are characterized by subcutaneous adipose tissue (SAT) lesion and often occur with musculoskeletal and visceral involvements. There is no single concept of the etiology and pathogenesis of Pn. Infections, injures, hormonal and immune disorders, drug intake, pancreatic disease, malignant neoplasms, etc. can play a role in the development of Pn. The latter is associated with RDs in a fairly large group of patients. There have recently been reports of about 200 and 50 cases of only idiopathic lobular Pn in the world and Russian literature, respectively. There have also been publications on other types of Pn, such as erythema nodosum, eosinophilic fasciitis, superficial migratory thrombophlebitis, lupus Pn, dermatomyositis Pn, scleroderma systematica, gout, psoriatic arthritis, etc. There is now a need to study skin changes and SAT lesions in the context of RDs, which will be able to estimate the true clinical and prognostic value of Pn in RDs. Based on recent literature data, this review characterizes the main types of Pn, their clinical and histological signs, and diagnostic methods.У пациентов с ревматическими заболеваниями (РЗ) в качестве одного из симптомов могут выступать разные формы панникулита (Пн). Пн – группа гетерогенных воспалительных заболеваний, характеризующихся поражением подкожной жировой клетчатки (ПЖК) и нередко протекающих с вовлечением в процесс опорно-двигательного аппарата и внутренних органов. Единая концепция этиологии и патогенеза Пн отсутствует. В развитии Пн могут играть роль инфекции, травмы, гормональные и иммунные нарушения, прием лекарственных препаратов, заболевания поджелудочной железы, злокачественные новообразования и др. У довольно многочисленной группы пациентов Пн ассоциируется с ревматическими заболеваниями (РЗ). За последние годы в мировой литературе описано около 200, а в отечественной литературе – 50 случаев только идиопатического лобулярного Пн. Опубликованы и работы, посвященные другим формам Пн, таким как узловатая эритема, эозинофильный фасциит, поверхностный мигрирующий тромбофлебит, люпус-Пн, Пн при дерматомиозите, системной склеродермии, подагре, псориатическом артрите и др. В настоящее время ощущается необходимость изучения кожных изменений и поражения ПЖК с позиций РЗ, что позволит оценить истинное клиническое и прогностическое значение Пн при РЗ.На основании данных литературы последних лет в обзоре охарактеризованы основные формы Пн, их клинические и гистологические признаки, методы диагностики.

Мезентериальный панникулит в практике ревматолога

Mesenteric panniculitis (MPn) is a rare form of adipose tissue inflammation, mainly of the intestinal mesentery, less often of the omentum, preand retroperitoneal tissue. There are not many descriptions of MPn in rheumatic diseases in the literature: in systemic lupus erythematosus, systemic sclerosis, Sjogren's syndrome, rheumatoid arthritis (RA), ankylosing spondylitis, mesenteric form (MF) of idiopathic lobular panniculitis (ILPn) and IgG4-related disease (IgG4-RD). Given the polymorphism of clinical manifestations, including systemic ones, it is of interest to look at the problem of MPn from the perspective of a rheumatologist.Objective: to evaluate the clinical and laboratory features of MPn in modern rheumatological practice.Material and methods. The study included 64 patients (19 men and 45 women aged 19 to 76 years, median disease duration 28.6 [0.3; 243] months). Laboratory and instrumental studies were carried out according to a single algorithm, which included standard clinical, immunological methods, as well as the determination of fecal calprotectin and tumor markers, ultrasound of the skin and subcutaneous adipose tissue (SAT), computed tomography of the chest and abdominal organs, abdominal positron emission tomography, pathomorphological examination of biopsies of the skin, pancreas and mesentery.Results and discussion. 89% of patients had abdominal pain, 48.4% had nausea, 53.1% had weakness, 44% had subfebrile fever, 32.8% had articular syndrome, and 29.6% – skin and pancreas involvement. Median ESR was 34 [11; 52] mm/h, CRP level – 14 [2; 72] mg/l. Most of the immunological parameters remained within the normal range, but in some cases there was an increase in the concentration of rheumatoid factor, antibodies to the cyclic citrullinated peptide, IgG4. The level of tumor markers CA 125, CEA, CA 19–9 and TumorM2-PK was increased 2 times or more in 5 patients. In our study, all radiological signs and all degrees of severity of MPn were observed. An additional examination confirmed the presence of MF ILPn, RA, IgG4-RD, gastrointestinal, malignant, hematological and other diseases, which made it possible to identify five diagnostic blocks.Conclusion. Early diagnosis and correct interpretation of the described changes require a lot of work-up and a multidisciplinary approach, which contributes to accurate and timely recognition of the disease.Mesenteric panniculitis (MPn) is a rare form of adipose tissue inflammation, mainly of the intestinal mesentery, less often of the omentum, preand retroperitoneal tissue. There are not many descriptions of MPn in rheumatic diseases in the literature: in systemic lupus erythematosus, systemic sclerosis, Sjogren's syndrome, rheumatoid arthritis (RA), ankylosing spondylitis, mesenteric form (MF) of idiopathic lobular panniculitis (ILPn) and IgG4-related disease (IgG4-RD). Given the polymorphism of clinical manifestations, including systemic ones, it is of interest to look at the problem of MPn from the perspective of a rheumatologist.Objective: to evaluate the clinical and laboratory features of MPn in modern rheumatological practice.Material and methods. The study included 64 patients (19 men and 45 women aged 19 to 76 years, median disease duration 28.6 [0.3; 243] months). Laboratory and instrumental studies were carried out according to a single algorithm, which included standard clinical, immunological methods, as well as the determination of fecal calprotectin and tumor markers, ultrasound of the skin and subcutaneous adipose tissue (SAT), computed tomography of the chest and abdominal organs, abdominal positron emission tomography, pathomorphological examination of biopsies of the skin, pancreas and mesentery.Results and discussion. 89% of patients had abdominal pain, 48.4% had nausea, 53.1% had weakness, 44% had subfebrile fever, 32.8% had articular syndrome, and 29.6% – skin and pancreas involvement. Median ESR was 34 [11; 52] mm/h, CRP level – 14 [2; 72] mg/l. Most of the immunological parameters remained within the normal range, but in some cases there was an increase in the concentration of rheumatoid factor, antibodies to the cyclic citrullinated peptide, IgG4. The level of tumor markers CA 125, CEA, CA 19–9 and TumorM2-PK was increased 2 times or more in 5 patients. In our study, all radiological signs and all degrees of severity of MPn were observed. An additional examination confirmed the presence of MF ILPn, RA, IgG4-RD, gastrointestinal, malignant, hematological and other diseases, which made it possible to identify five diagnostic blocks.Conclusion. Early diagnosis and correct interpretation of the described changes require a lot of work-up and a multidisciplinary approach, which contributes to accurate and timely recognition of the disease