Warning signs of primary immunodeficiencies: is there any benefits?

Primary immunodeficiencies is a group of diseases resulting from a variety of genetic defects. At the moment, more than 300 immunodeficiencies are known, most of which negatively affect the quality and duration of life, leading to deaths in the first year of a child's life. The most severe and at the same time quite frequent are defects in cellular immunity. It is currently known that the incidence of clinically significant T lymphopenias is 1: 4000 live newborns, and the incidence of clinically significant cellular primary immunodeficiencies is 1: 10000 live newborns. Despite the extensive treatment options for these diseases, patient survival is low. This is a consequence of the delayed setting of the correct diagnosis and, accordingly, the beginning of adequate therapy. Early detection of primary immunodeficiencies is a key factor in the successful treatment of patients with these diseases. Despite the fact that clinical warning signs were formulated more than 25 years ago, and their promotion is incredibly successful, the correct diagnosis is delayed for most immunodeficient patients by years. This situation is a consequence of an extremely wide range of clinical manifestations of immunodeficiencies. At the moment, there are several lists of warning signs. There is also an approach in which alarming clinical signs are formulated separately for different specialists. All of these lists are the result of attempts to increase the sensitivity and specificity of this instrument. These attempts each time turned out to be unsuccessful, since they slightly increased its effectiveness. The work of immunologists from Great Britain, Germany, Egypt, USA showed that it is almost impossible to formulate a list of warning signs from only clinical and anamnestic indicators. Apparently, it is necessary to add screening laboratory techniques

TREC and KREC Levels as a Predictors of Lymphocyte Subpopulations Measured by Flow Cytometry

Primary immunodeficiency diseases (PID) is a heterogeneous group of disorders caused by genetic defects of the immune system, which manifests clinically as recurrent infections, autoimmune diseases, or malignancies. Early detection of other PID remains a challenge, particularly in older children due to milder and less specific symptoms, a low level of clinician PID awareness and poor provision of hospital laboratories with appropriate devices. T-cell recombination excision circles (TREC) and kappa-deleting element recombination circle (KREC) in a dried blood spot and in peripheral blood using real-time polymerase chain reaction (PCR) are used as a tool for severe combined immune deficiency but not in PID. They represent an attractive and cheap target for a more extensive use in clinical practice. This study aimed to assess TREC/KREC correspondence with lymphocyte subpopulations, measured by flow cytometry and evaluate correlations between TREC/KREC, lymphocyte subpopulations and immunoglobulins. We carried out analysis of data from children assessed by clinical immunologists at Speransky Children’s Hospital, Moscow, Russia with suspected immunodeficiencies between May 2013 and August 2016. Peripheral blood samples were sent for TREC/KREC, flow cytometry (CD3, CD4, CD8, and CD19), IgA, IgM, and IgG analysis. A total of 839 samples were analyzed for using TREC assay and flow cytometry and 931 KREC/flow cytometry. TREC demonstrated an AUC of 0.73 (95% CI 0.70–0.76) for CD3, 0.74 (95% CI 0.71–0.77) for CD4 and 0.67 (95% CI 0.63–0.70) for CD8, respectively, while KREC demonstrated an AUC of 0.72 (95% CI 0.69–0.76) for CD19. Moderate correlation was found between the levels of TREC and CD4 (r = 0.55, p < 0.01) and KREC with CD19 (r = 0.56, p < 0.01). In this study, promising prediction models were tested. We found that TREC and KREC are able to moderately detect abnormal levels of individual lymphocyte subpopulations. Future research should assess associations between TREC/KREC and other lymphocyte subpopulations and approach TREC/KREC use in PID diagnosis

TREC and KREC Levels as a Predictors of Lymphocyte Subpopulations Measured by Flow Cytometry

Primary immunodeficiency diseases (PID) is a heterogeneous group of disorders caused by genetic defects of the immune system, which manifests clinically as recurrent infections, autoimmune diseases, or malignancies. Early detection of other PID remains a challenge, particularly in older children due to milder and less specific symptoms, a low level of clinician PID awareness and poor provision of hospital laboratories with appropriate devices. T-cell recombination excision circles (TREC) and kappadeleting element recombination circle (KREC) in a dried blood spot and in peripheral blood using real-time polymerase chain reaction (PCR) are used as a tool for severe combined immune deficiency but not in PID. They represent an attractive and cheap target for a more extensive use in clinical practice. This study aimed to assess TREC/KREC correspondence with lymphocyte subpopulations, measured by flow cytometry and evaluate correlations between TREC/KREC, lymphocyte subpopulations and immunoglobulins. We carried out analysis of data from children assessed by clinical immunologists at Speransky Children’s Hospital, Moscow, Russia with suspected immunodeficiencies between May 2013 and August 2016. Peripheral blood samples were sent for TREC/KREC, flow cytometry (CD3, CD4, CD8, and CD19), IgA, IgM, and IgG analysis. A total of 839 samples were analyzed for using TREC assay and flow cytometry and 931 KREC/flow cytometry. TREC demonstrated an AUC of 0.73 (95% CI 0.70–0.76) for CD3, 0.74 (95% CI 0.71–0.77) for CD4 and 0.67 (95% CI 0.63–0.70) for CD8, respectively, while KREC demonstrated an AUC of 0.72 (95% CI 0.69–0.76) for CD19. Moderate correlation was found between the levels of TREC and CD4 (r = 0.55, p < 0.01) and KREC with CD19 (r = 0.56, p < 0.01). In this study, promising prediction models were tested. We found that TREC and KREC are able to moderately detect abnormal levels of individual lymphocyte subpopulations. Future research should assess associations between TREC/KREC and other lymphocyte subpopulations and approach TREC/KREC use in PID diagnosis

Applying Design-Thinking In Didactic ActivitieS (ADIDAS)

Background: Although didactic lectures are a common medical education teaching method, data suggest long term retention is minimal. Objective: Design thinking as a potential means to improve a didactic session on operating room (OR) equipment and safety is explored here. Methods: During a 2021 didactic session for five CA-1 residents, a faculty member structured a design activity on OR equipment and safety. The residents were asked to build an OR rapid prototype using office supplies. They were given ten minutes to brainstorm, followed by thirty minutes to build. Results: General feedback from residents (60% response rate) was positive, reporting increased knowledge and engagement. Conclusions: This activity required the residents to think critically about the functions of anesthesia machines from multiple perspectives, including patient safety and clinician needs. The design thinking process may help the residents better retain information, understand, and engage with the purpose of each item in the OR. Efficacy in future iterations will be through resident ITE score gaps in this topic. Future studies should ascertain the applicability of this learning format to specific didactic lectures

Детская инфекционная заболеваемость в Москве: проблемы и их решение

Based on statistical data, a comparative analysis of infectious morbidity and mortality in Moscow in 2015 and 2014 revealed a whole, the decline in these indicators. Made significant progress in reducing infectious morbidity in Moscow due to the vaccination of children, including — increased regional calendar of preventive vaccinations. However, analysis of the work of medical institutions indicates the feasibility of the development and introduction of technologies of management of patients with post-infectious syndromes, as well as improving the health care system for children with infectious diseases based on a multidisciplinary approach in close cooperation infectious disease and pediatricians of different specialties. To solve these problems is proposed a plan to improve the effectiveness of children's infectious diseases services relating to the reorganization of hospital beds and outpatient care, ensure the continuity of the different health facilities, implementation of modern methods of etiological diagnosis of infections, the organization of continuous vocational training of paediatricians in Moscow on a specialty «Infectious diseases».На основе статистических данных проведен сравнительный анализ инфекционной заболеваемости и летальности в Москве за 2015 и 2014 гг., выявивший, в целом, тенденцию к сокращению этих показателей. Достигнуты существенные успехи в снижении инфекционной заболеваемости у детей Москвы за счет вакцинопрофилактики, в том числе — расширения регионального календаря профилактических прививок. Вместе с тем, анализ работы медицинских учреждений указывает на целесообразность разработки и внедрения технологий ведения больных с постинфекционными синдромами, а также совершенствования системы оказания медицинской помощи детям с инфекционными заболеваниями на основе междисциплинарного подхода при тесном взаимодействии инфекционистов и педиатров различных специальностей. Для решения этих задач предложен план повышения эффективности детской инфекционной службы, касающийся реорганизации коечного фонда и амбулаторной помощи, обеспечения преемственности разных ЛПУ, внедрения современных методов этиологической диагностики инфекций, организации непрерывного профессионального образования врачей-педиатров Москвы по специальности «Инфекционные болезни»

Ульцерогландулярная форма туляремии

The article provides a brief literature review on tularemia, shows the current epidemic situation of tularemia in Russia and analyzes the characteristic clinical picture of the ulceroglandular form of tularemia. A clinical example of an ulceroglandular form of tularemia in a child.В статье представлен краткий обзор литературы, посвященный туляремии, показана текущая эпидемическая ситуация по туляремии в России и разобрана характерная клиническая картина ульцерогландулярной формы туляремии. Приводится клинический пример ульцерогландулярной формы туляремии у ребенка

Бактериальные диареи у госпитализированных детей

Objective: to study the clinical and laboratory manifestations of acute intestinal infections of bacterial etiology in hospitalized children, depending on the etiology, age, topic of the lesion, and complications.A cohort clinical study of 570 children hospitalized from January to October 2019 in the infectious wards of Children's Clinical Hospital No.9 in Moscow was conducted. Studies included routine laboratory methods, bacteriological analysis of feces, Latex test, ELISA, PCR to detect pathogens, serological reactions to detect specific antibodies in blood serum. Two groups of patients were specially formed to compare the features of the course of bacterial diarrhea without hemorrhagic colitis (n = 111) and with hemorrhagic colitis (n = 125).Among 33.2% of cases of deciphered etiology of bacterial diarrhea, Salmonella was isolated in 14.6%, Campylobacter — in 4.7%, Shigella — in 3%, in other cases — conditionally pathogenic flora. Salmonellosis and Сampylobacteriosis with the same frequency are recorded in children in the age groups of 1—3 and 3—7 years, in half of the patients proceed as enterocolitis (58 and 52%, respectively). Shigellosis is diagnosed in children older than 1 year of life with the same frequency in age groups 1—3, 3—7 and older than 7 years, a third of patients (35%) develop severe forms.In most cases (83.2%), a complicated course of bacterial diarrhea was detected, more often dehydration 1 and 2 degrees (36.5%), acute respiratory viral infections (19.6%), mesadenitis (11.2%), community-acquired pneumonia (4.6%).Enterocolitis is the topic of lesion in half of the children, and every 5th patient develops hemorrhagic colitis (21.9%). In 44% of cases of established etiology of hemorrhagic colitis, Salmonella was confirmed. Hemocolitis also develops more often with shigellosis, campylobacteriosis and clostridiosis. In the group of bacterial diarrhea with hemorrhagic colitis, significant differences were revealed compared with the group without hemocolitis: by the frequency of development in children under 3 years of age; by the duration of treatment in a hospital; by the frequency of mesadenitis; by the content of stab neutrophils in the hemogram, reflecting a more pronounced inflammation in hemorrhagic colitis.Thus, bacterial diarrhea in children remains relevant due to the severity of inflammation, the incidence of complicated course and hemorrhagic colitis, which requires hospitalization.Цель: изучение клинико-лабораторных проявлений острых кишечных инфекций (ОКИ) бактериальной этиологии у госпитализированных детей в зависимости от этиологии, возраста, топики поражения, осложнений.Проводилось когортное клиническое исследование 570 детей, госпитализированных с января по октябрь 2019 г. в инфекционные отделения ДГКБ № 9 им. Г.Н. Сперанского ДЗ г. Москвы, включающее рутинные лабораторные методы, для верификации возбудителей — бактериологический анализ кала, Latex-тест, ИФА, ПЦР, для выявления специфических антител в сыворотке крови — серологические реакции (РНГА). Были специально сформированы две группы больных для сравнения особенностей течения бактериальных диарей без геморрагического колита (n = 111) и с гемоколитом (n = 125).Среди 33,2% случаев расшифрованной этиологии бактериальных диарей в 14,6% выделена Salmonella, в 4,7% — Campylobacter, в 3% — Shigella, в остальных — УПФ. Сальмонеллез и кампилобактериоз одинаково часто выявляются у детей в возрастных группах 1—3 и 3—7 лет и в половине случаев протекают по типу энтероколита (58 и 52% соответственно). Шигеллез диагностируется у детей старше 1 года жизни с одинаковой частотой во всех возрастных группах (1—3, 3—7 и старше 7 лет), у трети больных (35%) протекает в тяжелых формах.В большинстве случаев (83,2%) выявлено осложненное течение бактериальных диарей, чаще регистрировался эксикоз 1 и 2 степени (36,5%), ОРВИ (19,6%), мезаденит (11,2%), внебольничная пневмония (4,6%).Топикой поражения в половине случаев является энтероколит, а у каждого 5-го больного развивается геморрагический колит (21,9%). В 44% случаев установленной этиологии гемоколита подтверждена Salmonella. Также значительно чаще гемоколит развивается при шигеллезе, кампилобактериозе и клостридиозе. В группе бактериальных диарей с гемоколитом выявлены достоверные различия по сравнению с группой без гемоколита: по частоте развития у детей в возрасте до 3 лет жизни; по длительности пребывания в стационаре; по частоте возникновения мезаденита; по содержанию палочкоядерных нейтрофилов в гемограмме, т.е. более выраженному воспалению при гемоколитах.Таким образом, бактериальные диареи у детей сохраняют свою актуальность ввиду выраженности воспаления, частоты развития осложненного течения и геморрагических колитов, что требует госпитализации

Легионеллезная пневмония с формированием множественных абсцессов легких

A case of bilateral polysegmental destructive legionella pneumonia with the formation of multiple lung abscesses in an immunocompetent boy aged 15 years is presented.The child had symptoms of intoxication with febrile fever, myalgia, unproductive cough, respiratory failure, dull percussion sound and weakening of breathing on both sides in the lower sections. A computed tomography of the chest revealed multiple bilateral multifocal foci of pulmonary tissue with destruction. The diagnosis of legionella pneumonia was made on the basis of detection of IgM antibodies to L. pneumophila with an increase in titer in the dynamics and exclusion of other causes of lung damage. Levofloxacin turned out to be an effective antibacterial drug.It is necessary to take into account the ability of microorganisms of the genus Legionella to cause multiple abscess formation of lung tissue.Представлен случай двусторонней полисегментарной  деструктивной легионеллезной  пневмонии с формированием множественных абсцессов легких у иммунокомпетного мальчика в возрасте 15 лет.У ребенка отмечались  симптомы интоксикации с фебрильной лихорадкой, миалгии, малопродуктивный кашель, дыхательная недостаточность, притупление перкуторного звука и ослабление дыхания с обеих сторон в нижних отделах. При компьютерной томографии грудной клетки были выявлены множественные  билатеральные мультифокальные очаги уплотнения легочной ткани с деструкцией. Диагноз легионеллезной  пневмонии был поставлен на основании обнаружения антител класса IgМ к L. pneumophila с нарастанием титра в динамике и исключении других причин поражения легких. Эффективными антибактериальным препаратом оказался левофлоксацин.Таким образом, необходимо принимать во внимание способность микроорганизмов рода Legionella вызывать множественное абсцедирование легочной ткани