Pediatric Immunology Research Articles

Using immature platelet fraction as a factor in deciding on the need for platelet transfusions

Our study aimed to assess the prognostic significance of immature platelet fraction (IPF) and its role in deciding whether to transfuse platelets. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. We monitored this hematologic parameter in 6 patients before and after hematopoietic stem cell transplantation (HSCT). For the study, we used whole blood collected in K EDTA tubes. IPF levels were measured by flow cytometry on the automated hematology analyzer SYSMEX XE-2100 (Sysmex, Kobe, Japan). The presence of platelet antibodies was detected using Capture-P Ready-Screen solid phase system for the detection of antibodies to platelets and the NEO Blood Bank Analyzer by Immucor, Inc. It was shown that the use of IPF enabled an early establishment of platelet engraftment and helped to make more a reasoned decision regarding the transfusion of platelets. It was established that if a rise in IPF > 6% was not accompanied by an increase in platelet count, serum platelet antibody testing was needed. IPF can help diagnose platelet engraftment failure following HSCT and thus eliminate the need for bone marrow aspiration. IPF is of great clinical importance; if adopted as a routine hematologic parameter, it can serve as an additional factor in deciding on the need for platelet transfusions and platelet antibody testing and subsequent personalized selection of platelets.

The prophylaxis of severe hemophilia A with inhibitors in children in the Republic of Belarus: a 12-year experience

The development of inhibitory antibodies against FVIII is the most serious complication associated with the use of FVIII concentrates in hemophilia A patients. There is a need for more research on measures that could reduce the risk of inhibitor formation in previously untreated patients (PUPs) with severe hemophilia A. The purpose of this study was to determine the effectiveness of the prevention of clotting inhibitor development in PUPs (or minimally treated patients) with severe hemophilia A by administering plasma-derived factor VIII concentrate (pdFVIII) at a dose of 25 IU/kg once a week for a year. The study was approved by the Independent Ethics Committee and the Scientific Council of the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology (the Republic of Belarus). Between 2010 and 2022, 56 boys were newly diagnosed with severe hemophilia A. Twenty-one of them received pdFVIII as on-demand treatment to stop bleeding (Group 1). Thirty-five boys received pdFVIII at a dose of 25 IU/kg body weight once a week during the first 50 weeks of treatment for the prevention of inhibitor development (Group 2). The administration of pdFVIII at a dose of 25 IU/kg once a week in the PUPs (or minimally treated patients) contributed to a decrease in the cumulative incidence of inhibitors to 15.9 ± 7.7% (4 out of the 35 patients who had been treated prophylactically) compared with 43.7 ± 11.8% (8 out of the 21 patients who had received hemostatic therapy to stop bleeding) (log-rank test, p = 0.041). Thus, the administration of pdFVIII concentrate at a dose of 25 IU/kg once a week for the first 50 weeks of treatment lead to a decrease (p = 0.009) in the cumulative incidence of inhibitors against the administered coagulation factor VIII to 15.9 ± 7.7%.

Molecular genetic diagnosis in the group of hemophilia A patients in Belarus: 12 new allelic variants in the <i>F8</i> gene

Hemophilia A is the most common severe bleeding disorder caused by various genetic changes in the F8 gene, leading to coagulation factor VIII deficiency. Hemophilia A is characterized by high heterogeneity of genetic defects. The severity of hemophilia A varies depending on the type of genetic defects in the F8 gene. More than 3000 unique variants of the F8 gene are associated with the hemophilia A. Approximately 30% of genetic defects occur de novo. The aim of this study is to determine the spectrum of genetic defects in the F8 gene in children with hemophilia A in Belarus. The study was approved by the Independent Ethics Committee and the Scientific Council of the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology (the Republic of Belarus). The study included 98 patients with hemophilia A, who had been treated or followed up at the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology (the Republic of Belarus). Patients were categorized into 3 groups based on the severity of their disease: severe (n = 82), moderate (n = 3), and mild (n = 13). Twenty (20.4%) patients had a history of inhibitors to factor VIII. For our study, we used venous blood samples. Genomic DNA was isolated from leukocyte suspension (obtained from the whole blood samples) using phenol-chloroform extraction. All severe hemophilia A patients were prescreened for intron 22 and 1 inversions in the F8 gene using inverse and multiplex polymerase chain reaction assays, respectively. Sequencing of F8 coding regions was carried out by next generation sequencing. All clinically relevant variants were confirmed by Sanger sequencing. Genetic testing revealed that 99% of the patients with hemophilia A (n = 97) had pathogenic variants in the F8 gene. Intron 22 and intron 1 inversion mutations within the F8 gene were detected in 45.1% (n = 37) and 1.2% (n = 1) patients with severe hemophilia A, respectively. Two patients had an abnormal pattern of intron 1 inversion, not previously described in the literature. A total of 48 different variants in the F8 gene were detected in 57 patients using next generation sequencing. Eleven of the 48 genetic variants identified have not been previously reported.

The efficacy of the TRK inhibitor entrectinib in patients with extracranial <i>NTRK</i> fusion-positive tumors

Somatic translocations involving the NTRK genes occur in 0.34–2.2% of all malignant neoplasms in children. TRK inhibitors whose efficacy has been demonstrated in prospective clinical studies expand treatment options for patients with solid tumors harboring NTRK gene rearrangements. The aim of our study was to summarize the first Russian experience with the use of the TRK inhibitor entrectinib in patients with extracranial NTRK fusion-positive solid tumors included in the compassionate use program. This study was approved by the Independent Ethics Committee and the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The study included 8 patients who had been treated at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology and the N.N. Blokhin National Medical Research Center of Oncology. The main criteria for inclusion in the compassionate use program were a confirmed rearrangement of either NTRK1/2/3 genes in a solid tumor in patients with unresectable disease for whom no effective standard systemic therapy was available, progressive or recurrent disease during therapy prescribed according to the established diagnosis, risk group and risk stratification criteria, and the infeasibility of non-mutilating radical surgery. The median age at diagnosis was 4.3 months (range 1.2–83.6). The male to female ratio was 1:1. The primary site distribution was as follows: head and neck (n = 6; 75%), chest wall (n = 1; 12.5%), pelvis (n = 1; 12.5%). None of the patients had regional lymph node involvement or distant metastases at diagnosis. The distribution by histology (according to histopathology reports) was as follows: infantile fibrosarcoma (n = 4; 50%), undifferentiated round cell sarcoma, low-grade (n = 1; 12.5%), undifferentiated spindle cell sarcoma, high-grade (n = 1; 12.5%), NTRK-rearranged spindle cell sarcoma, low-grade (n = 1; 12.5%), spindle cell tumor associated with an NTRK rearrangement (n = 1; 12.5%). Immunohistochemistry (IHC) with a pan-Trk monoclonal antibody was performed in 7/8 (87.5%) patients. Pan-Trk IHC was positive in 4/7 (57%) patients. Rearrangements in the NTRK1 and NTRK3 genes were confirmed in all the patients. The final methods used for the detection of fusion transcripts were as follows: reverse transcription polymerase chain reaction (n = 4; 50%) and RNA-based next-generation sequencing (n = 4; 50%). NTRK1 and NTRK3 gene translocations were detected in 3/8 (37.5%) and 5/8 (62.5%) patients, respectively. The following fusion transcripts were identified: ETV6::NTRK3 (n = 4), DIP2C::NTRK3 (n = 1), TPR::NTRK1 (n = 1), TPM3::NTRK1 (n = 1), MYH10::NTRK1 (n = 1). One (12.5%) patient received entrectinib as first-line therapy, other patients (7/8, 87.5%) received entrectinib as secondor subsequent-line therapy. Three (37.5%) patients had undergone surgery before treatment with entrectinib: 2 had R2 resection, 1 had R0/R1 resection (resection margins were not evaluated). None of the patients received radiation therapy. The median duration of entrectinib therapy at the time of analysis was 11.8 months (range 2.3–20.1). Delayed surgery was performed in 2/8 patients; according to the histopathology reports, they achieved grade IV pathomorphosis. Three patients experienced adverse events during treatment with entrectinib. The median time to adverse events was 0.23 months (range 0.2–7.96). Three patients required temporary interruption in treatment to relieve symptoms, a subsequent dose reduction by one dose level was necessary when resuming therapy in two patients. The median follow-up since diagnosis was 19.5 months (range 14.9–75.0). All the patients included in our analysis were alive, three of them had no radiologic evidence of disease. Fifty percent of the patients completed targeted therapy, another 50% of the patients continued treatment with entrectinib. Complete and very good partial response was achieved in 3/8 and 2/8 patients, respectively. Partial response, minor partial response and stable disease were observed in one patient each. These results indicate high efficacy and safety of entrectinib in pediatric patients with extracranial NTRK fusion-positive solid tumors. Further studies are needed to determine the therapeutic potential of TRK inhibitors in the treatment of different solid malignant neoplasms in children and to assess long-term treatment results.

Risk factors for coagulation inhibitor development in children with severe hemophilia A

Aim of the study: to examine the role of potential risk factors in inhibitor development in previously untreated patients (PUPs) (or minimally treated patients) with severe hemophilia A. The study was approved by the Independent Ethics Committee and the Scientific Council of the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology (the Republic of Belarus). The study included 89 boys who underwent regular follow-up for severe hemophilia A at the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology (the Republic of Belarus) from 1998 to 2022. The median age (10th–90th percentile) at diagnosis of hemophilia was 8.0 (1.0–21.0) months, the baseline factor VIII activity was 0.7% (0.4–0.95%). Age at first exposure to factor VIII concentrate was 11.0 (1.0–31.0) months. Out of 89 patients, 23 children had severe hemophilia A with inhibitors. The cumulative incidence of inhibitors in the whole group of PUPs was 31.0 ± 5.6%. The cumulative incidence of hemophilia A with inhibitors was higher in the patients with null mutations (37.0 ± 6.9%) than in the patients with non-null mutations (6.5 ± 6.0%) (the log-rank test, p = 0.041). The use of plasma-derived FVIII concentrate (approved for use in neonates and for prophylaxis) from one manufacturer was associated (c2 = 8.53; p = 0.004) with a lower incidence of factor VIII inhibitors (up to 21.3 ± 8.5%) compared with the incidence in the group of patients treated with FVIII concentrates from different manufacturers (45.2 ± 7.8%). Age (> 1 year old or < 1 year old) at first exposure to FVIII had no effect on the formation of inhibitors (the log-rank test, p = 0.746). Such factors as age at diagnosis of hemophilia (odds ratio (OR) 0.99; 95% confidence interval (CI) 0.93–1.024; p = 0.991) and baseline factor VIII activity (OR 0.99; 95% CI 0.8–1.06; p = 0.09) were not associated with inhibitor development. The first measurements of activated partial thromboplastin time (APTT) ratio (patient APTT value over the APTT reference value) (OR 1.89; 95% CI 0.72–5.09; p = 0.21) and FVIII recovery in vivo (OR 0.74; 95% CI 0.27–2.01; p = 0.55) were not associated with inhibitor development either. We have confirmed that one of the main risk factors for FVIII inhibitor development is F8 gene mutations. The incidence of inhibitors among the patients who received plasma-derived FVIII concentrates (recommended for use in PUPs in the neonatal period) from one manufacturer was lower than among those who received FVIII from different manufacturers.

The results of therapy with venetoclax, daratumumab and plerixafor as part of the conditioning regimen in chemotherapy-refractory acute leukemia in children

The main outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) in chemotherapy-refractory acute leukemia remain suboptimal due to a high relapse rate. The incorporation of targeted anti-leukemia agents into the conditioning regimens is a potential approach to improve the efficacy of HSCT. We assessed the safety and potential efficacy of the addition of venetoclax, daratumumab, and plerixafor to the conditioning regimens in children with chemotherapy-refractory acute leukemias who received allogeneic TCRab/CD19-depleted HSCT. We used data from a pilot study, as well as the data of patients from a retrospective cohort who received similar therapy according to the individual indications. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. All 43 patients (33 acute myeloid leukemias (AML), 8 T-cell acute lymphoblastic leukemias (T-ALL) and 2 acute leukemias of ambiguous lineage) had active disease status at the time of transplantation. The preparative regimen included myeloablative conditioning based on either total body irradiation or treosulfan or melphalan. A haploidentical related donor was used as a graft source in 38 cases, while a fully matched related or unrelated donor was used in 5 cases. The engraftment was observed in 93% of cases, no excessive toxicity was noted. MRD-negative complete remission was achieved in 37 patients (86%). The cumulative incidence of grade II–IV acute graft-versus-host disease (GvHD) was 10%, and the cumulative incidence of chronic GvHD was 5%. At 2 years, transplant-related mortality was 7%, relapse incidence was 52%, event-free survival was 41%, and overall survival was 51%. The overall survival rate for the AML group was 58% and 25% for the T-ALL group. Our data show that the addition of targeted agents to the conditioning regimens is safe, however, does not significantly improve the results of HSCT in the study cohort of patients.

The use of next generation sequencing technologies for the diagnosis of inborn errors of immunity

Primary immunodeficiencies are congenital genetically determined immune disorders. Recent advances in molecular genetic technologies have enabled a simultaneous analysis of a large number of genes in a patient. The purpose of this study was to analyze the mutational spectrum in DNA samples collected from patients with various types of primary immunodeficiencies. In this study, we applied next-generation sequencing technology using a panel developed at the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology and consisting of 290 genes that are associated with primary immunodeficiencies according to the existing literature. The testing was carried out in 96 patients with a clinical history suggesting a primary immunological defect. As a result, 37.5% of cases (36/96 patients) were found to harbor genetic defects that lead to disorders of the immune system.

Quantitative bone marrow magnetic resonance imaging in children with lymphoblastic leukaemia

The aim of the study was to evaluate fat fraction (FF) changes in patients diagnosed with acute lymphoblastic leukaemia (ALL) in comparison with children without haematological disorders. All the patients or their legal representatives gave their informed consent to magnetic resonance imaging (MRI). The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology and was conducted in line with the Ethical Principles of the World Health Organization (the Declaration of Helsinki) for Medical Research Involving Human Subjects. The study included 33 healthy volunteers aged 13.4 ± 2.8 years (the control group) and 34 patients with acute phase ALL whose mean age was 12.2 ± 3.6 years (the group of interest). Imaging of the pelvic bones and lumbar vertebrae was performed on a Philips Achieva 3T scanner using the mDixon-quant sequence, with a subsequent construction of FF maps. The Mann–Whitney U-test was used to compare the FF data of the cases with each other and with the controls. Four regions of interest were selected, 100 mm2 each: in the bodies of the right and the left iliac bones as well as in the bodies of the L4 and L5 vertebras. For each group of subjects and each region of interest, mean FF was calculated. In the group of the patients with acute phase ALL, FF was the lowest: 3.53 ± 2.75% and 3,72 ± 3.09% in the bodies of the left and right iliac bones respectively, and 2.62 ± 1.86% and 2.47 ± 2.17% in the L4 and L5 vertebras respectively. In the control group, FF in the respective regions of interest was 51.3 ± 9.5%; 49.9 ± 11.0%; 31.3 ± 8.73% and 32.4 ± 10.3%. It is obvious that bone marrow FF in the patients with ALL differs significantly from the control group. Quantitative MRI can become a new method for the assessment of changes in the bone marrow of children with leukaemias.

IgE-Mediated and Non-IgE-Mediated Fish Allergy in Pediatric Age: A Holistic Approach-A Consensus by Diagnostic Commission of the Italian Society of Pediatric Allergy and Immunology.

Fish is one of the "big nine" foods triggering allergic reactions. For this reason, fish allergens must be accurately specified on food labels. Fish allergy affects less than 1% of the world population, but a higher prevalence is observed in pediatric cohorts, up to 7%. Parvalbumin is the main fish allergen found in the muscles. In childhood, sensitization to fish allergens occurs most frequently through the ingestion of fish, rarely transcutaneously or by inhalation. Fish allergy symptoms usually appear within two hours of the allergen contact. The diagnosis begins with the collection of the history. If it is suggestive of fish allergy, prick tests or the measurement of serum-specific IgE should be performed to confirm the suspicion. The oral food challenge is the gold standard for the diagnosis. It is not recommended in case of a severe allergic reaction. It is important to make a differential diagnosis with anisakiasis or scombroid poisoning, which have overlapping clinical features but differ in pathogenesis. Traditionally, managing fish allergy involves avoiding the triggering species (sometimes all bony fish species) and requires an action plan for accidental exposures. The present review will analyze IgE- and non-IgE-mediated fish allergy in children from epidemiology, pathogenesis to clinical features. Moreover, clinical management will be addressed with a particular focus on potential nutritional deficiencies.

What is the tolerance age of patients with cow's milk protein allergy? What are the parameters that can predict its persistence?

Objective: Cow’s milk allergy (CMA) is one of the most common food allergies in infants. The natural history of CMA indicates that resolution is common. Some studies suggest that food allergies are now being resolved at an older age. The aim of this study was to investigate the tolerance and persistence characteristics, as well as the timing of tolerance, in our own CMA patients. Material and Methods: Patients who were diagnosed with CMA and followed up in our pediatric immunology and allergy outpatient clinic between 2016-2021 years were evaluated retrospectively. Patients’ demographic characteristics, laboratory results, and tolerance time were recorded. Results: The 632 patients’ files were reviewed. 192 (30%) of the patients were followed for more than two years. The tolerance to baked products was observed with a median of 14 months, while the tolerance to fermented products was observed with a median of 17 months. Full tolerance was observed with a median of 25 months. The number of patients older than 2 years of age who could not consume any milk protein-containing product was 72 (11.4%) and 56 (77.7%) of them were IgE mediated CMA. The rate of girls with tolerance (43.5%) was found to be significantly higher than nontolerant girls (25%) (p=0.001). The mean skin test diameter of the tolerant group was significantly higher than the mean of the non-tolerant group (p=0.022). The percentage of eosinophils (p=0.003) and total IgE level (p=0.004) in the tolerant group were significantly lower compared to the intolerant group. There was no significant difference between the presence of tolerance in terms of allergy number, eosinophil count and specific IgE count (p>0.05). Conclusion: Identifying the factors influencing tolerance can lead to changes in the management of the disease. We observed that 88.6% of patients older than 2 years were tolerant to milk proteins, and all patients with non-IgE mediated CMA achieved tolerance by 2 years of age. The ratio of total IgE to specific IgE, age, total IgE and specific IgE levels, presence of non-IgE or IgE mediated allergy, and gender were factors that influenced the development of tolerance in our study. Age at diagnosis and having a single or multiple food allergies did not impact the tolerance status. The prognosis for CMA remains favorable. The use of the milk ladder in managing CMA is an important approach for promoting early tolerance.

Sensitization to Rice in Allergic Children Pediatric Allergy and Immunology Unit, Children's Hospital, Ain Shams University

Background The prevalence of food allergy among Egyptian children is largely unknown, more so for the different food allergens. Although there are several studies reporting on the common food allergens, yet none was done to explore the allergy to rice, a food allergen that is much less recognized both by pediatricians and allergic patients. Objectives To estimate the frequency of sensitization to rice in pediatric allergic patients in Egypt. Patients and Methods This analytical cross-sectional study was carried out in the period from April 2019 to September 2020. The study included 150 physician-diagnosed allergic patients aged 6 months to 18 years, enrolled consecutively from the Pediatric Allergy and Immunology Unit, Children's Hospital, Ain Shams university. They were 90 (60%) males and 60 (40%) females. SPT was done using a commercial rice allergen extract, Prick-to-prick test with cooked rice. Patients with clinical and /or SPT results suggestive of rice allergy were subjected to oral challenge test under medical supervision in hospital. Results None of the screened allergic children (n = 150) gave a self/parentally reported history of allergy to rice, nor after inquiry by the investigator. SPT using commercial rice extract revealed that only 8 reacted positively (>3mm) and were considered sensitized. PPT was done to all patients using a home prepared cooked rice extract and the test was positive in 5 patients; 2 of these were positive also by SPT. A total of 11 patients (7.3%) were considered sensitized and were subjected to OCT and none had a positive test. There was statistically significant difference in age between rice sensitized and non sensitized, being higher in rice-sensitized patients, with p-value = 0.043. Conclusion Our study is a pilot research which draws the attention to the existence of sensitization to rice in allergic children. PPT is a useful test with a reliable specificity which when positive, would aid in diagnosing rice allergy in settings with limited resources and unavailability of rice protein extracts.

Screening of Strawberry Allergy in Egyptian Atopic Children

Background Strawberries are included in the list of allergenic foods. However, definite figures in many countries including Egypt are lacking. Children with food allergy are 2 to 4 times more likely to have asthma, eczema, and allergic rhinitis than their non-allergic peers. We therefore sought to investigate IgE-mediated strawberry sensitization among a group of atopic children and correlate it to their clinical and laboratory parameters. Patients and Methods This study comprised 256 children, 1 to 18 years old, with physician-diagnosed bronchial asthma (98 patients), allergic rhinitis (28 patients), atopic dermatitis (53 patients), food allergy (10 patients) and combined allergies (67 patients). They were enrolled consecutively from the Pediatric Allergy, Immunology and Rheumatology Unit, Children's Hospital, Ain Shams University, Cairo. Sensitization to strawberry was assessed using prick-prick test (PPT). Results Strawberry sensitization was observed in 7.8% of the studied children. Confirmed strawberry allergy was elicited in 2% of them. Strawberry sensitization was more prevalent in patients with food allergy followed by those with atopic dermatitis. Severity of allergic disease, frequency of flare ups and response to treatment did not influence the rate of strawberry sensitization in our series. Conclusion Strawberry allergy is not as common as claimed to be among Egyptian children with allergic disorders. Sensitization to strawberry did not impact the severity of allergy or response to treatment. The findings are limited by the sample size.

Safety of Intravenous Immunoglobulin Replacement Therapy in a Group of Patients with Primary Immune Deficiency

Background Intravenous immunoglobulin (IVIG) has been used as antibody replacement therapy in primary immunodeficiency diseases for more than 50 years. Most routinely, IVIG is used in patients with predominantly antibody deficiency and combined immunodeficiency. Aim To evaluate the safety of regular intravenous immunoglobulin (IVIG) among patients with primary immunodeficiency diseases who receive IVIG as a replacement treatment. Methods Our study included 40 patients with primary immunodeficiency following up regularly in the Pediatric Allergy and Immunology Unit, Children’s Hospital, Ain Shams University, These patients were followed up for one year in order to evaluate the incidence of occurrence of adverse reactions among the patients who received IVIG monthly, Once patients with adverse reactions have been identified, the following data were taken and reviewed : a specific type of adverse reaction to IVIG; the time interval between onset of adverse reaction and beginning of IVIG infusion; IVIG preparation, dose and infusion rate; medical management done during side effects . Statistics were used to analyze and interpret the data. Results This study included 40 PID patients. They were 31 males (77.5%) and 9 females 22.5% with a male to female ratio of 3.4:1. At time of enrolment in the study, the median age was 73.5 months (14 – 218 months). In our studied population the median age of symptoms onset was 23 months (1 – 187 months), and age at diagnosis was 25 months (2-192 months). This made the diagnostic lag to have a median of 9 months (0-56 months). From our studied population only one patient (2.5%) out of the study groups developed anaphylaxis and was shifted to another brand. Conclusion IVIG is a safe drug for patients with primary antibody deficiency with minimal reported side effects.

The Multifaceted Syndromic Primary Immunodeficiencies in Children.

Disorders of immunity are poorly recognised in some rare multisystem genetic conditions. We aim to describe syndromic features and immunological defects in children with syndromic primary immunodeficiencies (sPIDs). This is a retrospective descriptive study of children aged 0-18 years with sPIDs under the care of the paediatric immunology service at the Bristol Royal Hospital for Children, United Kingdom, from January 2006 to September 2021. sPIDs were identified in 36 patients. Genetic diagnoses which are not commonly associated with PIDs and not included in the International Union of Immunological Societies classification were present in 7/36 (19%): Trisomy 22, Arboleda-Tham syndrome, 2p16.3 deletion syndrome, supernumerary ring chromosome 20 syndrome, Myhre syndrome, Noonan syndrome, and trichothiodystrophy/Cockayne syndrome complex. Recurrent and/or severe infections were the most common clinical features (n = 33, 92%). Approximately half had combined immunodeficiency or antibody deficiency. The most common extra-immunological manifestations include dysmorphism (72%), disorders of nervous (78%), musculoskeletal (69%), haematology/lymphatic (58%), and gastrointestinal, hepatic/pancreatic (58%) systems. Patients with sPIDs often have multiorgan involvement and some are non-immunologically mediated. There should be a low threshold to clinically assess and investigate for disorders of immunity in any patients with syndromic features especially when they present with recurrent/severe/opportunistic infections, features of immune dysregulation, autoinflammation or lymphoproliferation.

WINTER SPECIALIZED IMMUNOLOGY SCHOOL, “INBORN ERRORS OF IMMUNITY”

On December 15–17, 2022, the Winter Specialized Immunology School, “Inborn Errors of Immunity,” was held in Uzhgorod of Zakarpattia Region with the support of Danylo Halytsky Lviv National Medical University, the International Interdisciplinary Association of Medical Professionals, the All-Ukrainian Association of Pediatric Immunology NGO, and the International European University. This school aims to analyze new approaches to the early diagnosis of primary/congenital disorders of the immune response in the context of the multidisciplinary approach, as well as to discuss the strategy of therapeutic tactics of such patients. The scientific event was held in the case marathon and direct communication formats. At the beginning of the event, a round table was held with the participation of regional experts in pediatric and adult immunology from different parts of Ukraine. More active cooperation with European colleagues and the creation of a national registry of immunodeficient patients with impaired antibody synthesis were noted. More than 20 speeches by clinical immunologists/pediatric immunologists were presented during two days of intensive work. During this school, results of Biopharma activities, a domestic producer of immunoglobulins, and plans for the future were presented in the field of domestic immunology development and diagnosis of patients with inborn errors of immunity. Discussions during the Winter School revealed the need to actively protect persons with congenital disorders of the immune system against infections by means of timely systematic seasonal vaccination, replacement immunoglobulin therapy, prophylactic antimicrobial therapy, and coordinated activities of specialists from various fields to provide immunological aid to patients in war conditions. At the end of the “Inborn Errors of Immunity” Winter School, organizers expressed confidence that most efforts and ideas highlighted during the professional meeting will be successfully implemented.

БОЛЬШИЕ ДАННЫЕ И ВИЗУАЛЬНАЯ АНАЛИТИКА В ДЕТСКОЙ ОНКОЛОГИИ И ГЕМАТОЛОГИИ

The potential of big data in healthcare relies on the ability to detect patterns and turn high volumes of data into actionable knowledge for precision medicine and decision makers. Due to constantly increasing amount of data, healthcare systems around the world are facing challenges associated with data processing and analysis while keeping costs under control. There is a number of examples where the use of big data in healthcare already provides solutions that optimize patient care and generate value for healthcare institutions. However, a further increase in the amount and variety of dynamically changing data in healthcare systems requires that all the relevant stakeholders collaborate and adapt the design and performance of their systems. To this end, it is necessary both to invest in the human capital and to build the technological infrastructure to house and converge a huge volume of healthcare data. It is also important to provide a set of tools that can improve data analytics by creating interactive visual interfaces to help analysts navigate and make sense of massive datasets. Here we provide an overview of international advanced initiatives related to big data analytics in various sectors of public healthcare that are aimed at obtaining new knowledge, improving clinical care and rationalizing epidemiological surveillance. Here we also share our own experience of applying visual analytics tools in the "Electronic Passport of Pediatric Oncology and Hematology Service." This passport was created by specialists from the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of Russia in order to improve the quality of specialized care in the Russian regions. This software solution is based on data from checklists and questionnaires (baseline assessment) completed during an outreach event and its preparation as well as from correspondence regarding the implemented corrective measures (baseline and follow-up assessments). This system is an important tool that helps improve the quality of monitoring of the pediatric oncology and hematology service. The structured electronic database allows the user to rank the Russian regions based on a whole range of parameters as well as to generate recommendations for process optimization in regional institutions. In such a complex information system, a user-friendly interface for the processing of large volumes of heterogeneous dynamic data is crucially important.

ШЕЙНАЯ ЭКТОПИЯ ТИМУСА У ДЕТЕЙ

Thymus ectopia is a rare solid neck lesion in children. The location of the formation along the path of thymus migration (thymopharyngeal duct), the echo pattern and the intensity of the MR signal, which is identical to the normally developed thymus, help in making a confident diagnosis. Materials and methods of the research: 14 pediatric patients were treated against the cervical thymus ectopia in 2018-2022 in the Russian Children's Clinical Hospital with the Pirogov Russian National Research Medical University of the Ministry of Healthcare of Russia and the National Scientific and Practical Center for Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev (both located in Moscow, Russia). The diagnosis was set only after the histological examination results in all cases. A differential diagnosis was made with other cystic and solid formations, taking into account its location and distribution according to ultrasound, computed tomography, and magnetic resonance imaging in each case. Results: stable, relapse-free treatment result was achieved after more than a year of follow-up in all cases. The correct diagnosis wasn’t set in every case until the biopsy results due to the rarity and diverse clinical and radiological picture of the disease. Conclusion: cervical thymus ectopia is a benign and relatively rare condition in children that is rarely diagnosed preoperatively by the visualization only. The conservative management may be appropriate in some cases when the thymus is in the chest cavity only, but surgical correction is more often needed in cases with the neck deforming formations.

ФИЗИЧЕСКОЕ И ДВИГАТЕЛЬНОЕ РАЗВИТИЕ ДЕТЕЙ, ЛЕЧИВШИХСЯ ОТ ОНКОЛОГИЧЕСКИХ ЗАБОЛЕВАНИЙ, КАК ФАКТОР, ВЛИЯЮЩИЙ НА СВЯЗАННОЕ СО ЗДОРОВЬЕМ КАЧЕСТВО ЖИЗНИ

Article represents the results of the research undertaken to prove the relationship between the physical conditions of patients treated for oncological diseases (OD) and the decrease in their health-related quality of life (HRQOL). Materials and methods used: 1564 children aged 6 to 18 y/o who have undergone rehabilitation at the “Russkoye pole” Clinical Rehabilitation Research Center for patients in remission with the National Scientific and Practical Center for Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev located in Grishenki village, Chekhovsky District, Moscow Oblast, Russia, after the complex treatment for OD from 2018 to 2021 participated in the research, of which 864 boys and 700 girls. The average age of the patients was 10.6+/-3.4 y/o, the average remission period was 5.4+/-2.7 years. The comparison group consisted of healthy siblings aged 6 to 18 y/o who stayed at the same facility and during the same period, a total of 238, of which 111 boys and 127 girls. The average age of the examined siblings was 10.2+/-2.4 y/o. The indicators of physical condition were tested as follows: anthropometry, strength endurance of muscles, tolerance to physical loads, development of motor skills. The PedsQL questionnaire was used for the HRQOL assessment. In order to build the mathematical models and to evaluate the statistically significant influence of factors, the classical linear regression models were used. The analysis of the relationship between groups of variables was carried out with the canonical correlation analysis. Comparison of children treated for OD and healthy children was carried out using the Welch's t-test. Results: all of the HRQOL indicators in all gender and age subgroups in children with OD were statistically significantly lower compared to healthy siblings. The most significant differences were obtained in the scale of physical functioning (p=0.001). A direct moderate relationship was found between HRQOL and a factor indicator for the physical condition (rcc=0.53), a direct moderate-weak relationship with a generalized measure of strength endurance (rcc=0.315) and a direct moderate relationship with motor skills (rcc=0.5). It was also found that a lag in the formation of basic motor skills had the greatest negative impact on the HRQOL of children treated for OD. Conclusion: the results of the research do confirm the role of physical condition in improving the patients’ quality of life. Continued research would allow developing a new tool for assessment of the effectiveness of physical rehabilitation for patients in this category.

Editorial introductions.

Editorial introductions.

Allergic Contact Dermatitis and Orthodontics.

Pediatric Allergy, Immunology, and PulmonologyVol. 36, No. 2 Expert CommentaryAllergic Contact Dermatitis and OrthodonticsErin BantaErin BantaAddress correspondence to: Erin Banta, MD, Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, NYU Langone Hospital-Long Island, NYU Langone Health, 120 Mineola Blvd, Suite 410, Mineola, NY 11501, USA E-mail Address: erin.banta@nyulangone.orgDivision of Rheumatology, Allergy and Immunology, Department of Internal Medicine, NYU Langone Hospital-Long Island, NYU Langone Health, Mineola, New York, USA.Search for more papers by this authorPublished Online:16 Jun 2023https://doi.org/10.1089/ped.2023.0050AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Allergic Contact Dermatitis and Orthodontics." Pediatric Allergy, Immunology, and Pulmonology, 36(2), pp. 50–51FiguresReferencesRelatedDetails Volume 36Issue 2Jun 2023 InformationCopyright 2023, Mary Ann Liebert, Inc., publishersTo cite this article:Erin Banta.Allergic Contact Dermatitis and Orthodontics.Pediatric Allergy, Immunology, and Pulmonology.Jun 2023.50-51.http://doi.org/10.1089/ped.2023.0050Published in Volume: 36 Issue 2: June 16, 2023Online Ahead of Print:May 30, 2023PDF download