The added value of a European Reference Network on rare and complex connective tissue and musculoskeletal diseases : insights after the first 5 years of the ERN ReCONNET

Funding Information: I. Bulina has received honoraria from Abbvie, Boehringer Ingelheim, Janssen and Pfizer. N. Costedoat-Chalumeau has received grants from UCB for a clinical research study. M. Matucci-Ce rinic has received grants from Janssen and MSD, and he is a member of speak ers bureau for Janssen, Sandoz, Bio gen, BI, Lilly and MSD. A. Meyer re ceived honoraria (<10,000 euros) from Lilly, LFB, Pfizer, Boehringer, Sanofi and research grants/support from CSL Behring, LFB, Sanofi, Fresenius Kabi and BMS. L. Mouthon received a grant from LFB. J.M. van Laar has received honoraria from Abbvie, Boehringer In-gelheim, Celltrion, Galapagos, Magenta, Roche, and grants from Astra Zeneca, Boehringer Ingelheim, Roche and Thermofischer. J.K. de Vries-Bouwstra received consulting fees from Abbvie, Janssen and Boehringer Ingelheim, and research grants from Roche, Galapagos and Janssen. The other authors have declared no competing interests. Publisher Copyright: © Copyright CliniCal and ExpErimEntal rhEumatology 2022.In order to address the main challenges related to the rare diseases (RDs) the European Commission launched the European Reference Networks (ERNs), virtual networks involving healthcare providers (HCPs) across Europe. The mission of the ERNs is to tackle low prevalence and RDs that require highly specialised treatment and a concentration of knowledge and resources. In fact, ERNs offer the potential to give patients and healthcare professionals across the EU access to the best expertise and timely exchange of lifesaving knowledge, trying to make the knowledge travelling more than patients. For this reason, ERNs were established as concrete European infrastructures, and this is particularly crucial in the framework of rare and complex diseases in which no country alone has the whole knowledge and capacity to treat all types of patients. It has been five years since their kick-off launch in Vilnius in 2017. The 24 ERNs have been intensively working on different transversal areas, including patient management, education, clinical practice guidelines, patients' care pathways and many other fundamental topics. The present work is therefore aimed not only at reporting a summary of the main activities and milestones reached so far, but also at celebrating the first 5 years of the ERN on Rare and Complex Connective Tissue and Musculo-skeletal Diseases (ReCONNET), in which the members of the network built together one of the 24 infrastructures that are hopefully going to change the scenario of rare diseases across the EU.publishersversionPeer reviewe

TUMOUR NECROSIS FACTOR alpha IN RHEUMATOID ARTHRITIS AND OSTEOARTHRITIS PATIENTS IN BLOOD SERUM AND SYNOVIAL FLUID

publishersversionPeer reviewe

Formation of TiC-Cu nanocomposites by a reaction between Ti25Cu75 melt-spun alloy and carbon

In this work, Ti25Cu75 melt-spun partially amorphous alloy was used as a source of Ti and Cu to synthesize in-situ TiC-Cu nanocomposites. The reaction between the alloy and carbon started during ball milling and continued during Spark Plasma Sintering. At the same time, during ball milling, the alloy experienced phase transformations: crystallization of the amorphous phase was followed by decomposition of TiCu3. Copper crystallites formed during the alloy transformations were the reason for the presence of copper regions 0.5–1 µm in size free from TiC nanoparticles in the sintered composites. The Ti-Cu intermetallics transformed into non-agglomerated TiC 10–20 nm in size distributed in the copper matrix. The hardness of the synthesized TiC-Cu nanocomposites exceeded that of composites obtained by conventional sintering of ball-milled Ti-C-Cu powders

Crystallization of Ti33Cu67 metallic glass under high-current density electrical pulses

We have studied the phase and structure evolution of the Ti33Cu67 amorphous alloy subjected to electrical pulses of high current density. By varying the pulse parameters, different stages of crystallization could be observed in the samples. Partial polymorphic nanocrystallization resulting in the formation of 5- to 8-nm crystallites of the TiCu2 intermetallic in the residual amorphous matrix occurred when the maximum current density reached 9.7·108 A m-2 and the pulse duration was 140 μs, though the calculated temperature increase due to Joule heating was not enough to reach the crystallization temperature of the alloy. Samples subjected to higher current densities and higher values of the evolved Joule heat per unit mass fully crystallized and contained the Ti2Cu3 and TiCu3 phases. A common feature of the crystallized ribbons was their non-uniform microstructure with regions that experienced local melting and rapid solidification

Оценка своевременности вакцинации против коклюша детей первого года жизни и причин нарушения графика прививок

The maximum incidence of pertussis in young children confirms the importance of their timely immunization.The goal is – to study the timeliness of vaccination against whooping cough, causes of violation of the vaccination schedule in young children, the effect of recombinant interferon-a on the post-vaccination period.Materials and methods: the vaccination history and data on the course of the post-vaccination period after immunization with DPT and DaPT vaccines of 469 children at the age of 3–24 months were studied.Results. The analysis showed that 14,9% of the observed children were not vaccinated against whooping cough in a timely manner. Of these: 34,3% had a written refusal to vaccinate (5.1% of the total number of observed children), in 32,8% of cases, the vaccination schedule was violated due to late arrival of parents, 32,9% of children by the start of immunization had medical challenges, and only half of them had justified contraindications. Non-serious side effects associated with immunization were observed in 11.3% of cases, statistically more often with DTP (22,0%) compared with DaPT (5.,5%). General and local reactions, in general, were recorded on DPT (6,9% and 15,1%, respectively) and less often developed with the use of DaPT (1,0% and 4,5%, respectively). Within 1 month after immunization, 16,2% of the observed children had an acute respiratory viral infection of varying severity. Those who did not receive antiviral therapy more often carried the disease in a moderate and severe form, which in all cases led to the postponement of the administration of the second and third doses of the vaccine.Conclusion. To increase the timeliness of vaccination of children against whooping cough, medical professionals should persistently remind parents about the timing of turnout for the next vaccination, when making medical withdrawals, be guided by modern methodological documents and instructions for vaccines. The use of antiviral and immunomodulatory effects of IFN-alpha drugs allows us to comply with the recommended schedule for vaccination of children with a high risk of SARS in the post-vaccination period.Максимальная заболеваемость коклюшем детей раннего возраста подтверждает важность их своевременной иммунизации.Цель: изучить своевременность вакцинации против коклюша, причины нарушения графика прививок у детей раннего возраста, влияние препаратов рекомбинантного интерферона-aльфа на течение поствакцинального периода.Материалы и методы: изучен прививочный анамнез и данные о течении поствакцинального периода после иммунизации вакцинами АКДС и препаратами с бесклеточным коклюшным компонентом 469 детей в возрасте от 3 мес. до 24 мес.Результаты. Анализ показал, что 14,9% наблюдаемых детей оказались своевременно не привиты против коклюша, из них: у 34,3% оформлен письменный отказ от прививки (5,1% от общего числа наблюдаемых детей), в 32,8% случаев график вакцинации был нарушен из-за несвоевременной явки родителей, 32,9% детей к началу иммунизации имели медицинские отводы, причем только у половины противопоказания были обоснованные. Несерьезные побочные проявления, связанные с иммунизацией, наблюдались в 11,3% случаев, статистически чаще при введении АКДС (22,0%) по сравнению с бесклеточными коклюшными вакцинами (5,5%). Общие и местные реакции, в основном, регистрировались на АКДС (6,9% и 15,1% соответственно) и реже развивались при использовании препаратов с бесклеточным коклюшным компонентом (1,0% и 4,5% соответственно). В течение 1 месяца после иммунизации 73 ребенка (16,2%) перенесли острую респираторную вирусную инфекцию различной степени тяжести. Не получавшие противовирусную терапию чаще переносили заболевание в среднетяжелой и тяжелой форме, что во всех случаях привело к переносу срока введения второй и третьей дозы вакцины.Заключение. Для увеличения своевременности вакцинации детей против коклюша медицинские работники должны настойчиво напоминать родителям о сроках явки на очередную вакцинацию, при оформлении медицинских отводов, руководствоваться современными методическими документами и инструкциями к вакцинам. Использование противовирусного и иммуномодулирующего эффекта препаратов интерферон-альфа позволяет соблюсти рекомендованный график при вакцинации детей с высоким риском заболеваемости острой респираторной вирусной инфекцией в поствакцнальном периоде.

Early experience of COVID-19 vaccination in adults with systemic rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance Vaccine Survey.

Background: We describe the early experiences of adults with systemic rheumatic disease who received the COVID-19 vaccine. Methods: From 2 April to 30 April 2021, we conducted an online, international survey of adults with systemic rheumatic disease who received COVID-19 vaccination. We collected patient-reported data on clinician communication, beliefs and intent about discontinuing disease-modifying antirheumatic drugs (DMARDs) around the time of vaccination, and patient-reported adverse events after vaccination. Results: We analysed 2860 adults with systemic rheumatic diseases who received COVID-19 vaccination (mean age 55.3 years, 86.7% female, 86.3% white). Types of COVID-19 vaccines were Pfizer-BioNTech (53.2%), Oxford/AstraZeneca (22.6%), Moderna (21.3%), Janssen/Johnson & Johnson (1.7%) and others (1.2%). The most common rheumatic disease was rheumatoid arthritis (42.3%), and 81.2% of respondents were on a DMARD. The majority (81.9%) reported communicating with clinicians about vaccination. Most (66.9%) were willing to temporarily discontinue DMARDs to improve vaccine efficacy, although many (44.3%) were concerned about rheumatic disease flares. After vaccination, the most reported patient-reported adverse events were fatigue/somnolence (33.4%), headache (27.7%), muscle/joint pains (22.8%) and fever/chills (19.9%). Rheumatic disease flares that required medication changes occurred in 4.6%. Conclusion: Among adults with systemic rheumatic disease who received COVID-19 vaccination, patient-reported adverse events were typical of those reported in the general population. Most patients were willing to temporarily discontinue DMARDs to improve vaccine efficacy. The relatively low frequency of rheumatic disease flare requiring medications was reassuring

ПАНДЕМИЧЕСКИЙ ГРИПП A (H1N1) PDM 09 В ЭПИДСЕЗОН 2015/2016 ГГ.: АНАЛИЗ ЛЕТАЛЬНЫХ ИСХОДОВ У ДЕТЕЙ

The analysis of the characteristics of the current influenza A(H1N1) pdm 09 at 624 children in the 2015/2016 season. For severe illness (5%) characterized by short incubation period, lack of initial period, acute or acute onset with rapid development of multiorgan failure, prolonged febrile body temperature (up to 5—6 days or more) in the absence of complications, a prolonged severe intoxication (4—5 days or more), a significant frequency of diarrhea syndrome (10,2%), hemorrhagic syndrome (5.3%), exacerbation of comorbidity (20%), combined  with other viral infections  — herpes, rotavirus, enterovirus and others (33%).In the clinical analysis of blood — leukopenia (33.9%), leukocytosis (14.5%) with neutrophilic  shift (11.3%), neutrophilia (51.6%), monocytosis (45.2%), lymphocytosis (9.7%), thrombocytopenia, anemia, accelerated erythrocyte sedimentation rate moderately; in the biochemical analysis of blood, hypernatremia, increase in the concentration of lactate, hyperfermentemia (ALT, AST, ALP, LDH, CPK), hypoproteinemia, dysproteinemia, increased CRP, increased creatinine and urea, increase of procalcitonin (PCT). In the structure of complications of pneumonia was 6%, stenosing laryngotracheitis — 9.8%, obstructive bronchitis — 14.5%. Two unvaccinated against influenza in infants who become ill during the epidemic period for influenza and SARS from homes with a typical clinical picture, died from severe (toxic) form of pandemic influenza. Pandemic influenza occurred at the background of severe immunosuppression (atrophy of the thymus, depletion  of follicles of peripheral organs of immunogenesis — spleen, lymph nodes, tonsils). The main cause of death was the development of multiple organ failure with rapid progressive lesion of the vital organs. Проведен анализ особенностей течения гриппа A (H1N1) pdm 09 у 624 детей в эпидсезон 2015/2016 гг. При тяжелой форме болезни (5%) отмечаются: короткий инкубационный период, отсутствие начального периода, острое или острейшее начало с быстрым развитием полиорганной недостаточности, длительная фебрильная температура тела (до 5—6 суток и более) при отсутствии осложнений,  выраженная длительная интоксикация (4—5 суток и более), значительная частота синдрома диареи (10,2%), развитие геморрагического синдрома (5,3%), обострение сопутствующей патологии (20%), сочетание с другими вирусными инфекциями — герпесвирусной, ротавирусной, энтеровирусной и др. (33%).В клиническом  анализе крови отмечаются лейкопения (33,9%), лейкоцитоз (14,5%) с нейтрофильным сдвигом (11,3%), нейтрофилез (51,6%), моноцитоз (45,2%), лимфоцитоз (9,7%), тромбоцитопения, анемия, умеренно ускоренная СОЭ; в биохимическом анализе крови  — гипернатриемия, нарастание концентрации лактата, гиперферментемия (АЛТ, АСТ, ЩФ, ЛДГ, КФК), гипопротеинемия, диспротеинемия, повышение СРБ, повышение креатинина и мочевины, увеличение прокальцитонина (ПКТ). В структуре  осложнений  пневмонии  составили 6%, стенозирующие ларинготрахеиты  —  9,8%, обструктивные   бронхиты  — 14,5%. Двое непривитых против гриппа детей раннего возраста, заболевшие в эпидемический период по гриппу, из семейных очагов ОРВИ, с типичной клинической картиной, умерли от тяжелой (токсической) формы пандемического гриппа. Пандемический грипп протекал на фоне выраженной иммуносупрессии (атрофия тимуса, истощение фолликулов периферических органов иммуногенеза — селезенки, лимфатических узлов, миндалин). Основной причиной смерти явилось развитие полиорганной недостаточности с быстрым прогрессирующим поражением жизненно важных органов

Геморрагическая лихорадка с почечным синдромом у ребенка раннего возраста

In Russia, Hemorrhagic Fever with Renal Syndrome (HFRS) takes the leading place among all natural focal infections, the incidence rate in 2018 was 3,99 per 100 thousand population. In the Northwestern Federal District of the Russian Federation, HFRS occurs much less frequently – 1,46 cases per 100 thousand population. The disease is more susceptible to men aged 16–50 years, children rarely get sick. In 2019, 73 cases of HFRS (1,36 per 100 thousand population) were registered in St. Petersburg, among them only 2 episodes – in children under 18 years of age. A clinical case of HFRS in a child aged 1 year and 8 months is presented. The diagnosis was established on the basis of clinical and epidemiological data (acute onset of the disease, the presence of fever, thrombohemorrhagic syndrome, oliguria, anuria, information on cases of HFRS at the place of residence of the child) and laboratory data (detection of specific IgM antibodies to the Hantaan virus) in the later stages of the disease. The described case should alert pediatricians regarding possible natural focal diseases, including HFRS. A thorough analysis of the anamnestic, epidemiological and clinical data of the patient will help in the early stages of the disease to suggest a diagnosis, conduct laboratory diagnostics and prescribe appropriate therapy.В России геморрагическая лихорадка с почечным синдромом (ГЛПС) занимает ведущее место среди всех природно-очаговых инфекций, показатель заболеваемости в 2018 г. составил 3,99 на 100 тыс. населения. В СевероЗападном федеральном округе Российской Федерации ГЛПС встречается значительно реже – 1,46 случаев на 100 тыс. населения. Заболеванию больше подвержены мужчины в возрасте 16–50 лет, дети болеют редко. В Санкт-Петербурге в 2019 г. зарегистрировано 73 случая ГЛПС (1,36 на 100 тыс. населения), среди них только 2 эпизода у детей до 18 лет. Представлен клинический случай геморрагической лихорадки с почечным синдромом у ребенка в возрасте 1год 8 мес. Диагноз установлен на основании клинико-эпидемиологических (острое начало заболевания, наличие лихорадки, тромбогеморрагического синдрома, олигурии, анурии, сведений о случаях ГЛПС по месту жительства ребенка) и лабораторных (обнаружение специфических IgM-антител к Hantaanвирусу) данных в поздние сроки болезни. Описанный случай должен насторожить врачей-педиатров в отношении возможных природно-очаговых заболеваний, в том числе ГЛПС. Тщательный анализ анамнестических, эпидемиологических и клинических данных больного поможет в ранние сроки болезни предположить диагноз, провести лабораторную диагностику и назначить соответствующую терапию

Влияние пандемии COVID-19 на инфекционную заболеваемость у детей в условиях мегаполиса

In the work, based on a retrospective analysis of the medical documentation of a children's clinic for 2017—2022. the impact of the COVID-19 pandemic on in- fectious morbidity in children was assessed. The data obtained indicate that in the children's population of St. Petersburg, as well as throughout the world, along with low involvement in the epidemic process of a new coronavirus infection, the incidence of seasonal acute respiratory and intestinal infections, chicken pox, scarlet fever, and whooping cough has significantly decreased. The COVID-19 pandemic did not have a significant impact on the structure and seasonality of in- fectious diseases in children. The phased exit from the lockdown did not lead to the predicted explosive growth of seasonal infections — as restrictions were eased, the incidence of acute respiratory and intestinal infections over the past two years has smoothly returned to pre-pandemic levels.В работе на основе ретроспективного анализа медицинской документации детской поликлиники за 2017—2022 гг. проведена оценка влияния пандемии COVID-19 на инфекционную заболеваемость у детей. Полученные данные свидетельствуют о том, что в детской популяции Санкт-Петербурга, как и во всем мире, наряду с низкой вовлеченностью в эпидемический процесс по новой коронавирусной инфекции, значительно снизилась заболеваемость сезонными острыми респираторными и кишечными инфекциями, ветряной оспой, скарлатиной, коклюшем. Пандемия COVID-19 не оказала существенного влияния на структуру и сезонность инфекционных заболеваний у детей. Поэтапный выход из локдауна не привел к прогнозируемому взрывному росту сезонных инфекций — по мере смягчения ограничений заболеваемость острыми респираторными и кишечными инфекциями в течение двух последних лет плавно вернулась к допандемическому уровню

Особенности новой коронавирусной инфекции у детей разного возраста

The new coronavirus infection (COVID-1 9) is a socially significant problem around the world. According to available statistics, complications are less common among children, asymptomatic or mild forms of the disease prevail more often.This article presents the features of the viral landscape of the upper respiratory tract in children with ARVI in a pandemic, the clinical and laboratory features of the course of COVID-1 9 in children of different ages.It was found that SARS-CoV-2 is detected only in a third (32.9%) of hospitalized patients with respiratory symptoms, in 4.3% of cases — in combination with seasonal CoV-OC43 / CoV-229E, in 1 1.6% — with other respiratory viruses. The most frequent source of infection with the SARS-Cov-2 were family members. Children with a moderate form of the disease predominated among the patients. The leading symptoms of COVID-19 were fever, catarrhal symptoms, as well as gastrointestinal manifestations and anosmia. A feature of the new coronavirus infection in newborns and children of the first month of life was the absence of fever and intoxication, the lack of expression of catarrhal manifestations when the colon is involved in the pathological process (colitis, rarely — hemocolitis). In the compete blood test in children under the age of one year, monocytosis prevailed, in children over 7 years old — leukopenia and accelerated ESR. Among the changes in the biochemical analysis of blood, the most common was an increased C-reactive protein.Новая коронавирусная инфекция (COVID-19) является социально-значимой проблемой во всем мире. По имеющейся статистике, среди детей реже встречаются осложнения и чаще преобладают бессимптомные или легкие формы заболевания.В данной статье представлены особенности вирусного пейзажа верхних дыхательных путей у детей с ОРВИ в условиях пандемии, клинико-лабораторные особенности течения COVID-19 у детей разного возраста.Установлено, что SARS-CoV-2 обнаруживается только у трети (32,9%) госпитализированных пациентов с респираторными симптомами, в 4,3% случаях — в сочетании с сезонными CoV-OC43/CoV-229E, в 11,6% — с другими респираторными вирусами. Источником заражения SARS-Cov-2 чаще являлись члены семьи. Среди пациентов преобладали дети со среднетяжелой формой заболевания. Ведущими симптомами COVID-19 являлись лихорадка, катаральные симптомы, а также гастроинтестинальные проявления и аносмия. Особенностью новой коронавирусной инфекции у новорожденных и детей первого месяца жизни являлось отсутствие лихорадки и интоксикации, невыраженность катаральных проявлений при вовлечении в патологический процесс толстой кишки (колит, редко — гемоколит). В гемограмме у детей в возрасте до года преобладал моноцитоз, у детей старше 7 лет — лейкопения и ускорение СОЭ. Среди изменений в биохимическом анализе крови наиболее часто встречалось повышение С-реактивного белка