Popliteal Cysts in Paediatric Patients: Clinical Characteristics and Imaging Features on Ultrasound and MRI

Popliteal cysts, or Baker cysts, are considered rare in children and may exhibit particular features, as compared with adults. We studied data from 80 paediatric patients with 55 Baker cysts, examined over a period of 7 years, and correlated clinical presentation with findings on ultrasonography and MRI. Prevalence of popliteal cysts was 57% in arthritic knees, 58% with hypermobility syndrome, and 28% without risk factors. Only one patient had a trauma history and showed an ipsilateral cyst. Mean cyst volume was 3.4 mL; cysts were larger in boys. Patients with arthritis had echogenic cysts in 53%. Cyst communication with the joint space was seen in 64% on ultrasonography and 86% on MRI. In conclusion, Baker cysts are a common finding in a clinically preselected paediatric population. Children with Baker cysts should be assessed for underlying arthritis and inherited joint hypermobility, while sporadic Baker cysts appear to be common, as well

Severe immune dysregulation with neurological impairment and minor bone changes in a child with spondyloenchondrodysplasia due to two novel mutations in the ACP5 gene

Spondyloenchondrodysplasia (SPENCD) is a rare skeletal dysplasia, characterized by metaphyseal lesions, neurological impairment and immune dysregulation associated with lupus-like features. SPENCD is caused by biallelic mutations in the ACP5 gene encoding tartrate-resistant phosphatase. We report on a child, who presented with spasticity, multisystem inflammation, autoimmunity and immunodeficiency with minimal metaphyseal changes due to compound heterozygosity for two novel ACP5 mutations. These findings extend the phenotypic spectrum of SPENCD and indicate that ACP5 mutations can cause severe immune dysregulation and neurological impairment even in the absence of metaphyseal dysplasia

Immunization of preterm infants: current evidence and future strategies to individualized approaches

Preterm infants are at particularly high risk for infectious diseases. As this vulnerability extends beyond the neonatal period into childhood and adolescence, preterm infants beneft greatly from infection-preventive measures such as immunizations. However, there is an ongoing discussion about vaccine safety and efcacy due to preterm infants’ distinct immunological features. A signifcant proportion of infants remains un- or under-immunized when discharged from primary hospital stay. Educating health care professionals and parents, promoting maternal immunization and evaluating the potential of new vaccination tools are important means to reduce the overall burden from infectious diseases in preterm infants. In this narrative review, we summarize the current knowledge about vaccinations in premature infants. We discuss the specifcities of early life immunity and memory function, including the role of polyreactive B cells, restricted B cell receptor diversity and heterologous immunity mediated by a cross-reactive T cell repertoire. Recently, mechanistic studies indicated that tissue-resident memory (Trm) cell populations including T cells, B cells and macrophages are already established in the fetus. Their role in human early life immunity, however, is not yet understood. Tissue-resident memory T cells, for example, are diminished in airway tissues in neonates as compared to older children or adults. Hence, the ability to make specifc recall responses after secondary infectious stimulus is hampered, a phenomenon that is transcriptionally regulated by enhanced expression of T-bet. Furthermore, the microbiome establishment is a dominant factor to shape resident immunity at mucosal surfaces, but it is often disturbed in the context of preterm birth. The proposed function of Trm T cells to remember benign interactions with the microbiome might therefore be reduced which would contribute to an increased risk for sustained infammation. An improved understanding of Trm interactions may determine novel targets of vaccination, e.g., modulation of T-bet responses and facilitate more individualized approaches to protect preterm babies in the future

New Insights into Adult and Paediatric Chronic Non-bacterial Osteomyelitis CNO

Purpose of Review To describe in detail the clinical synopsis and pathophysiology of chronic non-bacterial osteomyelitis and SAPHO syndrome. Recent Findings Chronic non-bacterial osteomyelitis (CNO) has been identified as a disease entity for almost 50 years. This inflammatory bone disorder is characterized by osteolytic as well as hyperostotic/osteosclerotic lesions. It is chronic in nature, but it can present with episodic flairs and phases of remission, which have led to the denomination “chronic recurrent osteomyelitis”, with its severe multifocal form “chronic recurrent multifocal osteomyelitis” (CRMO). For almost three decades, an infectious aetiology had been considered, since especially Propionibacterium acnes had been isolated from bone lesions of individual patients. However, this concept has been challenged since long-term antibiotic therapy did not alter the course of disease and modern microbiological techniques (including PCR) failed to confirm bone infection as an underlying cause. Over recent years, a profound dysregulation of cytokine expression profiles has been demonstrated in innate immune cells of CNO patients. A hallmark of monocytes from CNO patients is the failure to produce immune regulatory cytokines interleukin-10 (IL-10) and IL-19, which have been linked with genetic and epigenetic alterations. Subsequently, a significant upregulation of pro-inflammatory, NLRP3 inflammasome-dependent cytokines (IL-1β and TNF-α), has been demonstrated. Summary The current knowledge on CNO, the underlying molecular pathophysiology, and modern imaging strategies are summarized; differential diagnoses, treatment options, outcome measures, as well as quality of life studies are discussed

Chronic nonbacterial osteomyelitis in childhood: prospective follow-up during the first year of anti-inflammatory treatment

Introduction: Chronic nonbacterial osteomyelitis (CNO) is an inflammatory disorder of unknown etiology. In children and adolescents CNO predominantly affects the metaphyses of the long bones, but lesions can occur at any site of the skeleton. Prospectively followed cohorts using a standardized protocol in diagnosis and treatment have rarely been reported. Methods: Thirty-seven children diagnosed with CNO were treated with naproxen continuously for the first 6 months. If assessment at that time revealed progressive disease or no further improvement, sulfasalazine and short-term corticosteroids were added. The aims of our short-term follow-up study were to describe treatment response in detail and to identify potential risk factors for an unfavorable outcome. Results: Naproxen treatment was highly effective in general, inducing a symptom-free status in 43% of our patients after 6 months. However, four nonsteroidal anti-inflammatory drug (NSAID) partial-responders were additionally treated with sulfasalazine and short-term corticosteroids. The total number of clinical detectable lesions was significantly reduced. Mean disease activity estimated by the patient/physician and the physical aspect of health-related quality of life including functional ability (global assessment/childhood health assessment questionnaire and childhood health assessment questionnaire) and pain improved significantly. Forty-one percent of our patients showed radiological relapses, but 67% of them were clinically silent. Conclusions: Most children show a favorable clinical course in the first year of anti-inflammatory treatment with NSAIDs. Relapses and new radiological lesions can occur at any time and at any site in the skeleton but may not be clinically symptomatic. Whole-body magnetic resonance imaging proved to be very sensitive for initial and follow-up diagnostics

Hemorrhagic Bullous Henoch-Schönlein Purpura: Case Report and Review of the Literature

Henoch-Schönlein Purpura (HSP) or IgA vasculitis is the most common systemic vasculitis of childhood and may affect skin, joints, gastrointestinal tract, and kidneys. Skin manifestations of HSP are characteristic and include a non-thrombocytopenic palpable purpura of the lower extremities and buttocks. Rarely, HSP may initially present as or evolve into hemorrhagic vesicles and bullae. We present an otherwise healthy 5-year-old boy with an acute papulovesicular rash of both legs and intermittent abdominal pain. After a few days the skin lesions rapidly evolved into palpable purpura and hemorrhagic bullous lesions of variable size and severe hemorrhagic HSP was suspected. A histological examination of a skin biopsy showed signs of a small vessel leukocytoclastic vasculitis limited to the upper dermis and direct immunofluorescence analysis revealed IgA deposits in vessel walls, compatible with HSP. To further characterize the clinical picture and treatment options of bullous HSP we performed an extensive literature research and identified 41 additional pediatric patients with bullous HSP. Two thirds of the reported patients were treated with systemic corticosteroids, however, up to 25% of the reported patients developed skin sequelae such as hyperpigmentation and/or scarring. The early use of systemic corticosteroids has been discussed controversially and suggested in some case series to be beneficial by reducing the extent of lesions and minimizing sequelae of disease. Our patient was treated with systemic corticosteroids tapered over 5 weeks. Fading of inflammation resulted in healing of most erosions, however, a deep necrosis developing from a large blister at the dorsum of the right foot persisted so that autologous skin transplantation was performed. Re-examination 11 months after disease onset showed complete clinical remission with re-epithelialization but also scarring of some affected areas

IgD shapes the pre-immune naïve B cell compartment in humans

B cell maturation and immunoglobulin (Ig) repertoire selection are governed by expression of a functional B cell receptor (BCR). Naïve B cells co-express their BCR as IgM and IgD isotype. However, the role of the additionally expressed IgD on naïve B cells is not known. Here we assessed the impact of IgD on naïve B cell maturation and Ig repertoire selection in 8 individuals from 3 different families with heterozygous loss-of-function or loss-of expression mutations in IGHD. Although naïve B cells from these individuals expressed IgM on their surface, the IGHD variant in heterozygous state entailed a chimeric situation by allelic exclusion with almost half of the naïve B cell population lacking surface IgD expression. Flow cytometric analyses revealed a distinct phenotype of IgD-negative naïve B cells with decreased expression of CD19, CD20 and CD21 as well as lower BAFF-R and integrin-β7 expression. IgD-negative B cells were less responsive in vitro after engaging the IgM-BCR, TLR7/9 or CD40 pathway. Additionally, a selective disadvantage of IgD-negative B cells within the T2 transitional and mature naïve B cell compartment as well as reduced frequencies of IgMlo/- B cells within the mature naïve B cell compartment lacking IgD were evident. RNA-Ig-seq of bulk sorted B cell populations showed an altered selection of distinct VH segments in the IgD-negative mature naïve B cell population. We conclude that IgD expression on human naïve B cells is redundant for generation of naïve B cells in general, but further shapes the naive B cell compartment starting from T2 transitional B cells. Our observations suggest an unexpected role of IgD expression to be critical for selection of distinct Ig VH segments into the pre-immune Ig repertoire and for the survival of IgMlo/- naïve B cells known to be enriched in poly-/autoreactive B cell clones

Управление качеством российского инженерного образования

В данном исследовании предложена модель управления качеством образования, методика проведения занятия, в которой используется компетентностная модель, основанная на проектно-ориентированном, сетецентрическом (кибефизическом) подходе.This study proposes a model for managing the quality of education, a methodology for conducting a lesson, which uses a competency model based on a project-oriented, network-centric (cybephysical) approach

280 lentiviral mediated gene therapy restores b cell homeostasis and tolerance in wiskott aldrich syndrome patients

Wiskott-Aldrich Syndrome (WAS) is a severe X-linked primary immunodeficiency characterized by micro-thrombocytopenia, eczema and increased risk of infections, autoimmunity and tumors. Allogeneic hematopoietic stem cell (HSC) transplantation is a recognized curative treatment for WAS, but when a matched donor is not available, administration of WAS gene-corrected autologous HSCs represents a valid alternative therapeutic approach. Since alterations of WAS protein (WASp)-deficient B lymphocytes contribute to immunodeficiency and autoimmunity in WAS, we followed the B cell reconstitution in 4 WAS patients treated by lentiviral vector-gene therapy (GT) after a reduced-intensity conditioning regimen combined with anti-CD20 administration. We analyzed the B cell subset distribution in the bone marrow and peripheral blood by flow cytometry and the autoantibody profile by a high-throughput autoantigen microarray platform before and after GT. Lentiviral vector-transduced progenitor cells were able to repopulate the B cell compartment with a normal distribution of transitional, naive and memory B cells. The reduction in the proportion of autoimmune-associated CD21low B cells and in the plasma levels of B cell-activating factor was associated with the decreased autoantibody production in WAS patients after GT. Then, we evaluated the functionality of B cell tolerance checkpoints by testing the reactivity of recombinant antibodies isolated from single B cells. Before GT, we found a decreased frequency of autoreactive new emigrant/transitional B cells in WAS patients, suggesting a hyperfunctional central B cell checkpoint in the absence of WASp. In contrast, high frequency of polyreactive and Hep2 reactive clones were found in mature naive B cells of WAS patients, indicating a defective peripheral B cell checkpoint. Both central and peripheral B cell tolerance checkpoints were restored after GT, further supporting the qualitative efficacy of this treatment. In conclusion, WASp plays an important role in the regulation of B cell homeostasis and in the establishment of B cell tolerance in humans and lentiviral-mediated GT is able to ameliorate the functionality of B cell compartment contributing to the clinical and immunological improvement in WAS patients