Immunology Center Research Articles

Chronic urticaria in children - New insights from a large cohort.

Chronic spontaneous urticaria is well-described in adults, but less so in children. The aim of this study is to describe the demographics, clinical characteristics, comorbidities, and outcomes of children with chronic, spontaneous urticaria. This retrospective study followed children up to 18years old, diagnosed with chronic spontaneous urticaria, between the years 2002-2018, and treated in a tertiary referral allergy and clinical immunology center. Data including demographics, clinical characteristics, comorbidities, treatments, and outcomes were extracted from electronic medical records. Records of 380 children coded to have chronic urticaria were reviewed, of which 250 (65.8%) fulfilled the diagnostic criteria for chronic spontaneous urticaria. There were 136 females (54.4%). Mean age at diagnosis was 11.4years, and 122 (48%) were adolescents. The average duration of chronic spontaneous urticaria was 12.25±15.2months. The urticaria in 208 children )83.2%) resolved within 24months. Eighty-seven patients (34.8%) had at least one atopic disease. Atopic comorbidities included atopic dermatitis in 17.2%, allergic rhinitis in 16%, asthma in 13.2%, and food allergy in 3.2%. Eighteen patients (7.2%) had a concomitant autoimmune disease. Nine (3.6%) had thyroid disease. Chronic spontaneous urticaria in children is a self-limited disease with favorable prognosis. Atopic diseases are more prevalent in children with chronic spontaneous urticaria than in the general pediatric population, increasing the possibility of a special subgroup of TH2-related chronic urticaria in children.

First case series of clozapine induced hypogammaglobulinaemia in England

Evidence is emerging that clozapine can adversely affect immunoglobulin levels. We present a case series of 17 clozapine-treated patients referred to clinical immunology centres in the north west of England with otherwise-unexplained hypogammaglobulinaemia. This adds to existing evidence and suggests that clozapine can cause clinically significant antibody deficiency that will sometimes require specialist intervention. We speculate that this putative drug toxicity could be mediated via interaction with PI3K (phosphatidylinositol-3-kinase) signalling pathways involved in the development and homeostasis of B cells. It may be advisable to monitor immunoglobulin levels in patients being treated with clozapine.

Clinical, Immunological, and Molecular Features of Severe Combined Immune Deficiency: A Multi-Institutional Experience From India.

BackgroundSevere Combined Immune Deficiency (SCID) is an inherited defect in lymphocyte development and function that results in life-threatening opportunistic infections in early infancy. Data on SCID from developing countries are scarce.ObjectiveTo describe clinical and laboratory features of SCID diagnosed at immunology centers across India.MethodsA detailed case proforma in an Excel format was prepared by one of the authors (PV) and was sent to centers in India that care for patients with primary immunodeficiency diseases. We collated clinical, laboratory, and molecular details of patients with clinical profile suggestive of SCID and their outcomes. Twelve (12) centers provided necessary details which were then compiled and analyzed. Diagnosis of SCID/combined immune deficiency (CID) was based on 2018 European Society for Immunodeficiencies working definition for SCID.ResultsWe obtained data on 277 children; 254 were categorized as SCID and 23 as CID. Male-female ratio was 196:81. Median (inter-quartile range) age of onset of clinical symptoms and diagnosis was 2.5 months (1, 5) and 5 months (3.5, 8), respectively. Molecular diagnosis was obtained in 162 patients - IL2RG (36), RAG1 (26), ADA (19), RAG2 (17), JAK3 (15), DCLRE1C (13), IL7RA (9), PNP (3), RFXAP (3), CIITA (2), RFXANK (2), NHEJ1 (2), CD3E (2), CD3D (2), RFX5 (2), ZAP70 (2), STK4 (1), CORO1A (1), STIM1 (1), PRKDC (1), AK2 (1), DOCK2 (1), and SP100 (1). Only 23 children (8.3%) received hematopoietic stem cell transplantation (HSCT). Of these, 11 are doing well post-HSCT. Mortality was recorded in 210 children (75.8%).ConclusionWe document an exponential rise in number of cases diagnosed to have SCID over the last 10 years, probably as a result of increasing awareness and improvement in diagnostic facilities at various centers in India. We suspect that these numbers are just the tip of the iceberg. Majority of patients with SCID in India are probably not being recognized and diagnosed at present. Newborn screening for SCID is the need of the hour. Easy access to pediatric HSCT services would ensure that these patients are offered HSCT at an early age.

Infections and associated diseases in patients with mannose-binding lectin deficiency, presenting to a tertiary care immunology clinic

Clinical significance of mannose-binding lectin MBL deficiency (MBLd) has been argued. The role of mannose-binding lectin (MBL) as a disease modifier, causing other diseases to present with a more severe phenotype, has been suggested. We conducted a retrospective chart review of patients presenting to a tertiary immunology center with recurrent and/or severe infections. All patients underwent immune evaluation and were found to have undetectable MBL levels (<70ng/ml). Types of infections and associated diseases were recorded. 53 patients with MBLd were identified. Most (47/53) had sinopulmonary infections (47/53) including sinusitis (40/53), viral upper respiratory infections (25/53), bronchitis (19/53), pneumonia (15/53), Streptococcal pharyngitis (9/53), otitis media (9/53). Other infections were skin infections (6/53), sepsis (2/53), meningitis (2/53). Among 33 patients with chronic sinusitis, 15/33 had chronic rhinosinusitis without polyps, 10/33 had aspirin exacerbated respiratory disease (AERD), 7/33 chronic rhinosinusitis with polyps (non AERD), 2/33 had allergic fungal sinusitis. Many were atopic (44/53) with allergic rhinitis (30/44), asthma (25/44), atopic dermatitis (7/44), and food allergy (7/44). Associated immunodeficiencies were (13/53) were with common variable immunodeficiency (7/13), IgG subclass deficiency (2/13), isolated IgM deficiency (2/13), other hypogammaglobulinemia (1/13), specific antibody deficiency (1/13), transient T cell lymphopenia of infancy (1/13). Rheumatologic disease was seen in 14/53 patients, hematologic disease in 8/53 and inflammatory bowel disease in 5/53. Other disease findings included bronchiectasis (8/53). Even in the absence of other immunodeficiency, people with MBLd have recurrent infections, most commonly sinopulmonary. Further research, comparing infections, severity and associated illnesses in those with patients with different MBL levels is warranted to define its clinical significance.

The efficacy and safety of romiplostim in the treatment of thrombocytopenia in pediatric patients with Wiskott–Aldrich syndrome: the results of a retrospective study

Reduction of haemorrhage and improving the quality of life for patients with Wiskott–Aldrich syndrome (WAS) before hematopoietic stem cell transplantation (HSCT) are the most important goals. We aimed to investigate the efficacy and safety of thrombopoietin receptor agonist (TPO-RA) in children with WAS. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. 67 patients with genetically confirmed WAS treated with subcutaneous romiplostim at the dose of 9 µg/kg weekly between 2012 and 2019 in Dmitry Rogachev National Center of Pediatric Hematology, Oncology, and Immunology were enrolled. The median treatment duration was 8 months (range, 1‒12). Overall, 22 patients (33%) achieved complete response and 18 (27%) partial. There were no apparent severe adverse effects associated with romiplostim administration. The only notable and possibly not related to the treatment was arterial thrombosis in one patient who had ongoing systemic vasculitis and a history of aortic aneurysm formation. The results of our study demonstrated that use of romiplostim was safe and effective in managing of thrombocytopenia and bleeding in most WAS patients.

Non-infectious complications in the group of pediatric patients with chronic granulomatous disease

Chronic granulomatous disease (CGD) is a primary immunodeficiency (PID), characterized by a defective production of reactive oxygen species by phagocytes. Infectious diseases are a classic manifestation of this form of PID; however, many patients present with a variety of inflammatory and immune non-infectious complications. We analyzed non-infectious complications in a group of 60 patients with CGD, who were treated in Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology (Moscow, Russia) since 2012 to February 2020. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Non-infectious manifestations were recorded in 53/60 patients, the most frequent of which were granulomatous complications (81.7% (49/60) of cases) in the following organs - the gastrointestinal tract, lungs, liver and lymph nodes. The median age of granulomas presentation was 3 years, and 45.8% of patients had a combined granulomatous lesion of several organs. Hepatomegaly (40%), splenomegaly (31.7%), dermatitis (21.7%) and chorioretinal lesions (11.3%) were other non-infectious complications. Hematological features outside acute infectious episodes included monocytosis (26.7%), eosinophilia (20%), neutrophilia (13.3%). 96.7% of patients had anemia with a decrease level of serum iron (65%), 31.7% - with signs of hemolysis. Autoimmune manifestations included arthritis, thyroiditis, immune thrombocytopenia or immune neutropenia. Non-infectious complications comprise a significant part of the CGD manifestations and often are the first symptoms of the disease. Awareness of this fact is very important for multidisciplinary approach in treatment of CGD. Delayed diagnosis and immunosuppressive therapy of non-infectious complications without prophylactic antimicrobial therapy can be life-threatening for patients with CGD.

Characteristics of a group of patients with WHIM syndrome

WHIM syndrome (warts, hypogammaglobulinemia, infections, myelokathexis) is a rare combined primary immunodeficiency. Here we describe 10 Russian patients with WHIM syndrome that were followed in the Dmitry Rogachev National Medical Research Center оf Pediatric Hematology, Oncology and Immunology. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Neutropenia and lymphopenia were observed in all 10 patients, hypogammaglobulinemia – in 7/10 patients. In all cases bone marrow analysis demonstrated myelokathexis features (cytoplasmic vacuolization in neutrophils and eosinophils, hyperlobulated pyknotic nuclear lobes connected by long thin strands, hypogranular and hypersegmented neutrophils). All patients were treated with granulocyte colony-stimulating factor and intravenous immunoglobulin. In 3/10 poor disease control was an indication to perform HSCT. In 2 of 3 patients HSTC was successful and all symptoms of the disease resolved. In conclusion, the diagnosis of WHIM syndrome must be considered in patients with early onset of neutro- and lymphopenia in conjunction with morphological features of myelokathexis. Treatment of this disease is still a challenging problem.

Chronic nonbacterial osteomyelitis: single center experience

Chronic nonbacterial osteomyelitis (CNO) is a rare autoinflammatory disease from the group of multifactorial diseases. It is characterized by non-infectious recurrent bone lesions, usually manifesting in childhood. The aim of this study was to analyze the clinical, laboratory, radiological and histological data of 33 patients (12 boys, 21 girls) with a diagnosis of chronic nonbacterial osteomyelitis. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. 25/33 patients were hospitalized to the Center with suspected neoplastic disease bone. The median age of CNO manifestation was 9.6 years. 24/33 had a multi-focal form of the disease. 5 patients had fever. Nonsteroidal anti-inflammatory drugs were the first therapy for all patients, achieving clinical remission in 4 cases. Zoledronic acid were used in 29 patients with remission in 19, adalimumab in 10 patient with remission in 9. In one patient stabilization was achieved only with the combination of methotrexate and canakinumab therapy.

Influence of clinical and immunophenotypic variants of severe combined immunodeficiency on severity and outcomes of opportunistic infections

Severe combined immunodeficiency (SCID) is a primary immunodeficiency that presents with life-threating symptoms in early infancy and has poor prognosis if not promptly treated. Here we present an analysis of infectious presentation and its course depending on clinical and immunophenotypic form of SCID. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. 54 patients were diagnosed with SCID in our center from 2012 to June 2020 and included to this study. The median age at diagnosis was 5.8 months. All patients were divided into 3 groups: classic SCID ( n = 31); Omenn syndrome ( n = 11); SCID with maternal fetal engraftment ( n = 12). To determine opportunistic infections severity, based on a number of infected organs at disease presentation, 3 groups were formed: with no infections or 1 infected organ, n=15; with 2 infected organs ( n = 15); with 3 and more infected organs ( n = 22). 22 of 46 BCG vaccinated patients (48%) developed BCG-infection: 16 local and 6 disseminated. There was no difference in severity of infections between 3 groups of SCID ( p = 0.22), with more severe infections found in patients older than 6 months of age at diagnosis. T- and NK-cell numbers lower than median level predisposed to severer infections in Omenn syndrome patients ( p = 0.041). There was a higher risk of BCG infections in classic SCID with low levels of NK-cells ( p = 0.009). 45 patients received allogeneic hematopoietic stem cell transplantation (HSCT). 9 patients died before HSCT and 21 after HSCT of infections and infections-related inflammatory syndromes. Though Т- and NKcells might have a role in protecting from severe infections, the early diagnosis is the most important factor of better prognosis of SCID patients.

Chromosomal aberrations as the cause of a complex phenotype in children with primary immunodeficiencies

Most of known primary immunodeficiencies (PID) are monogenic diseases, mainly due to the point defects in the immune system genes. However, in some rare cases the immunodeficiency is caused by various chromosomal aberrations. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. A retrospective analysis was performed on a group of 15 patients with clinical and laboratory signs of immunodeficiency, whose chromosomal aberrations were detected by various methods. In six patients from four different families, microdeletions with inclusion of a gene ( CTLA4 , NFKB1 ) or a part of a known PID gene ( NBAS , DCLRE1C ) were detected. Four patients had a complex phenotype, where a mutation in the known PID genes ( BTK , CYBB , STAT1 GOF , ATM ) was combined with a chromosomal defect. In one case, a homozygous damage in the USB1 gene was confirmed by detection of dysomy chromosome 16 from the father`s side. Two patients were diagnosed with known chromosomal defects – DiGeorge2 and Jacobsen syndrome. Two other patients had various chromosome abnormalities not previously described in PID`s patients. 12/15 (80%) patients had syndromic features – various skeletal dysmorphisms, malformations, and developmental delay. Immunodeficiency genes can be damaged within the chromosomal aberrations. The combination of the various methods of genetic testing is important for patients with PID. Even in PID patients without syndromic features the chromosomal analysis methods or PID diagnosis are necessary.

Immunoglobulin replacement therapy in patients with primary immunodeficiency diseases in Russia

According to the data from Russian primary immunodeficiencies (PID) registry 71% of registered patients were treated with immunoglobulins (IG). Regular immunoglobulin substitutions were reported in 90% of patients with primary antibody deficiencies (PAD), 86% - with syndromic PID and 91% of patients with combined T and B cell defects. The study was supported by Academic Council of Dmitry Rogachev National Medical Center of Pediatric Hematology, Oncology and Immunology and approved by Local Ethical Committee within the Russian PID registry. Regular IG substitution was analyzed in the representative cohort of 235 PID patients from 12 Russian regions. Of these 121 were children, 114 – adults. In 78% cases IG treatment has been started during the first 10 years of life. 80% patients were treated with highly safe products (Octagam 5% and 10%, Privigen, IG VENA, Gamunex) reaching therapeutic median pre-infusion level of serum IgG of 7 g/l. Significantly lower levels of pre-infusion serum IgG were observed in patients treated with Gabreglobin-IgG. Irregular treatment was observed in 61% of patients mainly due to the poor drug supply (lack of medication in the health care centers). Infections were reported in 90% percent of patients with irregular treatment. Unscheduled hospitalizations were two times more frequent in the group of patients with irregular IVIG treatment. Additionally, we assessed quality of life of patients with regular IVIG treatment, which significantly improved in comparison with the pretreatment period and became comparable to the group of healthy controls.

Hepatitis C in immunocompromised pediatric patients: an epidemiological analysis of data from a center of pediatric hematology, oncology and immunology

Objective. To analyze the incidence of HCV in patients of the «Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology» (Center), to compare with the overall population incidence of HCV, to identify risk factors and risk groups of HCV infection in the Center’s patients. Materials and Methods. A retrospective analysis of the HCV incidence of HCV patients of the Center who were admitted to the Center between 01.07.2014 and 31.12.2020 was carried out. The study included patients aged 0 to 18 years, from all regions of the country, who had previously received therapy at their place of residence. Patient profile: hematological, oncological, immunological and surgical. The indications for testing for HCV were: hospitalization at the Center, stay at the center for 4–6 months, clinical indications. To assess risk factors and identify risk groups for HCV incidence, the main epidemiological aspects (age, sex, disease characteristics, geographical prevalence) were analyzed. Results. The incidence of HCV in the Center’s patients was 1.7%, which is 5 times higher than the incidence of the entire population of the country, and 50 times higher than that of the pediatric population. The highest incidence rate was observed in children aged 1 to 2 years – 2.8%. When comparing the risks of infection of the Center’s patients with the children’s population of the country in age groups under 1 year, from 1 to 14 years, and from 14 to 19 years, an excess of 29, 24 and 9 times was revealed, respectively. When analyzing nosological forms, it was found that the highest HCV incidence was in patients with primary immunodeficiencies – 3.2%, while in patients with malignant neoplasms – 1.8%. The region with the highest prevalence of HCV in our study was the Far Eastern Federal District (9%), namely the Amur Region (14%). Conclusions. Thus, the morbidity of patients with oncological and hematological profiles and patients with primary immunodeficiencies clearly demonstrates the problem of implementing the artificial mechanism of HCV transmission, which requires taking measures regarding the safety of invasive manipulations.

Antibody Development and Disease Severity of Covid-19 in Non-Immunized Patients with Rheumatic Immune-Mediated Inflammatory Diseases: Data from a Prospective Cohort Study

Background: Research on the disease severity of COVID-19 in patients with rheumatic immune-mediated inflammatory diseases (IMIDs) has been inconclusive, and long-term prospective data on the development of SARS-CoV-2 antibodies in these patients are lacking. We conducted an investigator-driven prospective cohort study to compare the disease severity of COVID-19, and the development of SARS-CoV-2 antibodies over time between patients with rheumatic IMIDs and healthy controls.Methods: Adult patients with rheumatic IMIDs from the Amsterdam Rheumatology & immunology Center, Amsterdam were invited to participate. All patients were asked to recruit their own sex- and age-matched control subject. We developed a new platform for collecting clinical data in large patient groups with online questionnaires (at baseline, and after 1-4 and 5-9 months of follow-up). Serum samples were collected two times during follow-up; after completing the follow-up questionnaires and prior to COVID-19 vaccination. All serum samples were analyzed for the presence of SARS-CoV-2 specific antibodies with a total-antibody bridging ELISA. IgG titers were quantified in samples with a positive test result in the bridging assay. Logistic regression analyses, and linear and logistic mixed model analyses were used to compare COVID-19 related hospitalization rates, proportions of SARS-CoV-2 seropositivity and IgG antibody titers between patients and controls, and between patients stratified for major immunosuppressive drug categories (i.e. biological [b] or conventional synthetic [cs] disease modifying anti-rheumatic drugs [DMARDs]).Findings: In total, 3080 consecutive patients and 1102 healthy controls with comparable age and sex distribution were included for analyses. The incidence of COVID-19 was slightly lower in patients compared to controls (14.7% vs. 16.0% had detectable SARS-CoV-2 antibodies), but patients were more frequently hospitalized compared to controls; 23 of 347 (7%) patients vs. 1 of 134 (0.7%) controls (adjusted OR: 7.33, 95% CI: 0.96 – 55.77, P 0.055). Three (13%) of 23 patients were admitted to the intensive care unit (ICU), and one of these died. Only treatment with B-cell targeting therapy was independently associated with an increased risk of COVID-19 related hospitalization (adjusted OR: 14.62, 95% CI: 2.31 – 92.39, P 0.004). Proportions of SARS-CoV-2 seropositivity in participants with a PCR confirmed COVID-19 diagnosis were similar for patients and controls ( P 0.73), and did not significantly decrease during the first twelve months after infection ( P 0.10). IgG antibody titers were higher in hospitalized patients compared to non-hospitalized patients, and slowly declined with time (rate per month: 0.86, 95% CI: 0.81 – 0.91, P Interpretation: We observed that patients with rheumatic IMIDs, especially those treated with B-cell targeting therapy, were more likely to be hospitalized when infected with SARS-CoV-2, although subsequent ICU admissions and/or death were infrequent. In addition, treatment with cs- or bDMARDs other than B-cell targeting agents is unlikely to have negative effects on the development of long-lasting humoral immunity against SARS-CoV-2.Funding Information: ZonMw and Reade Foundation.Declaration of Interests: None to declare. Ethics Approval Statement: The research protocol was approved by the medical ethical committee of the VU University medical center (registration number 2020.169). All participants gave written informed consent.

Helping asthmatic children through bonding therapy

Abstract: Disruptions in maternal-infant bonding are shown to be the mediating variable between maternal distress and the subsequent expression of childhood asthma. When bonding is repaired, it seems that children's asthmatic symptoms diminish or remit. This study evaluated 16 asthmatic children before and after their mothers were treated with bonding therapy. Fourteen improved on 11 measures, including reduction in STEP classification system and medication use. Thirteen children were able to stop all medications. The links between bonding disruptions, stress, and airway inflammation are discussed. Keywords iBonding Therapy, Childhood Asthma, Bonding Disruption, Asthma Treatment Introduction Asthma affects more children's lives than any other chronic illness (Lara et al., 2002). In 2008, just over 10 million children within the U. S were reported as ever having had a diagnosis of asthma (Akinbami, Moorman, Garbe, & Sondik, 2009). It is the third-ranking cause of hospital admissions in children under 15 (DeFrances, Cullen, & Kozak, 2007). The financial cost in America in 2007 was $56 billion in health costs, lost school and work days, and early deaths (Center for Disease Control and Prevention, 2011). Asthma is responsible for 14 million missed school days annually (Martin, 2004) - more than any other chronic illness. Since childhood asthma has reached epidemic proportions and has major public health and financial impacts, researchers have been attempting to identify risk factors for the development of this disease. For several years a significant focus of attention has revolved around the connection between maternal distress and the subsequent development of asthma children. Mrazek, Klinnert, Mrazek, and Macey (1991), at the National Jewish Center for Immunology and Respiratory Medicine in Denver, studied 150 children whose mothers were asthmatic. They found a link between early problems in coping/parenting and the subsequent expression of asthma. Klinnert et al. (2001), surprised by this finding, noted that this link between parental stress in care-giving and the subsequent development of asthma was the first documented report of such a connection. Maternal stress is known to be caused by many factors: Cesarean section deliveries, maternal health issues, psychological problems, maternal despondency, to list a few. Cesarean section deliveries and emergency cesarean sections have been linked to childhood asthma. A Finnish study of 60,000 births found that mothers who delivered by cesarean sections were 50% more likely to have a child who later developed asthma (Kero et al., 2002). Emergency cesarean section deliveries (even more stressful) predictably raised the asthma rate up to 60%. This finding was replicated by Roduit et al. (2009) who studied 2,917 children. Annesi-Maesano, Moreau, and Strachan (2001), using a British cohort of 2,583 mothers, investigated whether in utero and perinatal influences contribute to the development and severity of asthma in childhood. Childhood asthma was more frequently reported by mothers when there had been health complications during pregnancy, labor, or delivery, or when the child was ill during the first week of life. She concluded that there is evidence that in utero and perinatal factors may increase the risk of developing asthma. Similarly, a Norwegian study of over 1.5 million mothers and 5,938 asthmatic children found that many types of pregnancy complications represented a risk factor for the development of asthma in the offspring (Nafstad, Samuelsen, Irgens, & Bjerkedal, 2003). Kozyrskyj et al. (2008) studied healthcare records of 13,907 children and their mothers from Manitoba databases. Healthcare or prescription medication for depression or anxiety was used to define maternal distress, and asthma status was determined from the children's asthma prescription records. They found that risk for childhood asthma was increased among children who were exposed to continued maternal distress from birth until age 7 years. …

Attitudes toward a mindfulness-based intervention from African American women living with HIV: A qualitative study.

Introduction:Mindfulness-based interventions train participants to pay attention to their own emotions in the current moment without judging themselves. This study aims to assess the attitudes toward a mindfulness-based stress reduction intervention among African American women living with HIV.Methods:We collected qualitative data from three focus group discussions with 18 African American women living with HIV who were purposely recruited from the Palmetto Health-USC Immunology Center in South Carolina, United States. The participants discussed how they coped with stress, and then were given a presentation on mindfulness-based stress reduction and a sample mindfulness-based stress reduction mini workshop with follow-up discussion about their thoughts and opinions on the information presented to them.Results:Participants said that mindfulness could be a useful technique and they were interested in participating in a mindfulness-based stress reduction program. Their main concerns included physical ability to perform some of the mindfulness techniques (e.g. yoga) and logistic barriers, such as schedule constraints. They also provided some suggestions to further tailor the mindfulness-based stress reduction, such as modifying yoga, using familiar terms, and combining both in-person and online components. These results suggest that African American women living with HIV showed strong interest in mindfulness-based stress reduction and a high level of willingness to participate in mindfulness-based stress reduction, but the existing mindfulness-based stress reduction program needs to be tailored to address challenges and barriers these women may face for attendance and completion.Conclusion:The next step is to further test the feasibility, acceptability, and efficacy through a pilot study for African American women living with HIV to practice a tailored mindfulness-based stress reduction for this group.

Клинико-лабораторные особенности COVID-19

The problem of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) remains highly relevant. Objective. To analyze clinical and laboratory characteristics of patients with moderate COVID-19. Materials and methods. This retrospective study included 132 patients with moderate COVID-19 treated in the Republican Immunological Center of the Republic of Dagestan between July and December 2020. The sample included 69 males and 63 females with a mean age of 52.4 ± 5.9 years. Results. The most common clinical manifestations included fever, fatigue, dry cough, and headache. Many participants had increased erythrocyte sedimentation rate (ESR); some patients had leukopenia, lymphopenia, and thrombocytopenia. Biochemical testing demonstrated mild alterations in the levels of C-reactive protein (CRP), ferritin, glucose, activity of liver enzymes (alanine aminotransferase, as-partate aminotransferase), fibrinogen, and D-dimer. These alterations were primarily observed in COVID-19 patients with CT-2 changes in their lung tissue. One-third of participant had lesions in lungs upon discharge. ECG changes (rhythm and conduction abnormalities) were detected in 15.9% of patients with concomitant cardiovascular diseases. Conclusion. COVID-19 patients with persistent clinical, laboratory, or radiological changes upon their discharge from hospital, as well patients with changes on ECG, require careful follow-up to assess their long-term outcomes. Key words: COVID-19, SARS-CoV-2, coronavirus, clinical and laboratory parameters, coagulogram, ECG changes, radiological changes

1013. Enhanced Oral Health Care Services for PLWHA - Midlands Region, South Carolina

BackgroundAn estimated 58- 64 % of people living with HIV/AIDS (PLWHA) do not receive regular dental care and this gap may be attributed to barriers related to cost, access to dental care, logistical issues, indifference to or fear of dental care.1,2 The Immunology Center at Prisma- University of South Carolina, School of Medicine is a Ryan White funded Part B Program that provides care to > 2400 PLWHA. Based on the perceived barriers, an enhanced oral health care program was implemented in 2018, wherein patients in need of dental care and meeting inclusion criteria are referred to contracted local general dentistry and specialty practices.EnhancementsDedicated Dental Services Coordinator (DSC)Facilitated transport to and from the dental clinicAnnual budget of $2700 per patientAccess to dental specialties (oral and maxillofacial surgery)Restorative services (crowns, dentures and root canals)Program GoalsThe ultimate goal of the oral health care program is to provide biannual dental prophylaxis and expanded restorative services to PLWHA.Inclusion criteria for referrals1 Virological suppression over 6 months. (HIV Viral Load < 200 c/mL)2 Adherence with HIV clinic appointments.Midlands Region, South Carolina MethodsThe DSC completes the following: monitoring of referrals, patient compliance to program inclusion criteria, linkage to dental care, payments for dental services, and coordination with case management.ResultsBetween 2018 and 2019, 535 patients were referred to the oral health care program. Almost 75% 399 completed at least one dental clinic visit. The average number of visits for patients from their enrollment date (2018-2019 to December 2019 was 1.56, with an average of 8.08 services, and 1.13 prophylaxis visits with their oral health care provider. Patients were predominantly African American and male but were spread across a wide age spectrum and 8 counties. Nearly 94% of patients remained virologically suppressed during their oral health care treatment.Table 1: 2018-2019 Program Summary of Oral Health Care Table 2 & Figure 1: Oral Health Care Patients by Age Group, Figure 2: Oral Health Care Patient by Gender Table 3 & Figure 3: Oral Health Care Patients by Race and Ethnicity, Table 4 & Figure 4: Oral Health Care Patient by County ConclusionPLWHA have high rates of unmet oral health care needs and low utilization of oral health services. Adequate resources and coordination of care with local dentists can overcome traditional barriers and improve access to dental care. References Disclosures: All Authors: No reported disclosures

1012. Efficacy, safety and tolerability of switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in HIV-1 infected virologically-suppressed older adults in a real-world setting

BackgroundApproximately 50% of people living with HIV (PLWH) in the United States are ≥50 years old. Efforts are ongoing to identify antiretrovirals associated with fewer drug-drug interactions (DDIs) and long-term side effects in this group. Clinical trials of B/F/TAF demonstrated favorable efficacy and safety in older adults, however, data from real-word settings are needed to validate these results.MethodsThis retrospective analysis evaluated records from PLWH aged ≥ 50 years at the Orlando Immunology Center who were switched to B/F/TAF between 2/7/2018 and 5/31/2019. Eligible patients had baseline HIV-1 RNA< 50 copies/mL and were followed for 48 weeks post-switch. The primary endpoint was maintenance of HIV-1 RNA< 50 copies/mL at week 48. The impact of switching to B/F/TAF on DDIs, adverse events (AEs) and safety parameters were analyzed throughout the study.Results306 patients met inclusion criteria. 62 (20%) were female, 126 (41%) were non-white, median age was 58 years (range [r] 50-81), median duration of HIV infection was 19.5 years (r 2-40), median number of chronic co-morbid conditions was 5 (r 0-20), and median number of baseline concomitant medications was 4 (r 0-23). 159 (52%) patients were switched from regimens containing ritonavir or cobicistat. The most commonly documented reason for switch was simplification (Table 1). At Week 48, 287 (94%) patients maintained an HIV-1 RNA< 50 copies/ml and 19 (6%) had an HIV-1 RNA between 50-200 copies/mL (Figure 1). 1 patient discontinued due to lack of efficacy. A total of 123 potential DDIs were identified in 104 (34%) patients taking a boosting agent or rilpivirine at baseline (Table 2). At Week 48, there was a significant median decline in total cholesterol (15.5 mg/dL, 95% confidence interval [CI]: 9.5; 21.5), LDL cholesterol (9.5 mg/dL, 95% CI: 4; 15.5) and triglycerides (20 mg/dL, 95% CI: 9.5; 32.5), and median weight increased by 2.5 pounds (95% CI: 1.5; 3.5). Treatment-related AEs occurred in 33 (11%) patients (all Grade 1-2) and led to 7 (2%) discontinuations.Table 1-Baseline demographic and clinical characteristics Table 2-Avoidance of Drug-Drug Interactions (DDIs) following switch to B/F/TAF Figure 1-Subgroup analysis of virologic outcomes at Week 48 ConclusionIn this real-world cohort, switching to B/F/TAF was associated with maintenance of virologic control, improvement in lipid parameters, and avoidance of DDIs in a large proportion of patients. These data support use of B/F/TAF as a treatment option in older PLWH.Disclosures Charlotte-Paige M. Rolle, MD MPH, Gilead Sciences (Grant/Research Support, Scientific Research Study Investigator, Speaker’s Bureau)Janssen Infectious Disease (Grant/Research Support)ViiV Healthcare (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau) Kiran Patel, PharmD, Gilead Sciences (Employee) Federico Hinestrosa, MD, AbbVie (Speaker’s Bureau)Gilead Sciences (Speaker’s Bureau)Merck (Speaker’s Bureau)Theratechnologies (Speaker’s Bureau) Edwin DeJesus, MD, Gilead Sciences (Advisor or Review Panel member)

Bilateral adrenal neuroblastoma: clinical presentation, diagnostic and therapeutic approaches, treatment results

Bilateral adrenal neuroblastoma (BANB) is a very rare entity. It is more common in young children and has certain clinical features. Patients with BANB have a more favorable prognosis than patients with unilateral adrenal neuroblastoma (NB). The article presents an analysis of 29 cases of BANB in children who underwent treatment at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. The analysis was performed for the period from April 2012 to December 2018. Bilateral adrenal involvement was diagnosed on the basis of analysis/assessment of the results of all relevant imaging and instrumental tests. Additionally, we performed a retrospective analysis of the findings of computed tomography, magnetic resonance imagining, and scintigraphy with 123I-metaiodobenzylguanidine (123I-MIBG). In view of 123I-MIBG scintigraphy sensitivity threshold, and in order to confirm the diagnosis, imaging findings were reviewed by an experienced radiologist. The patients received therapy in accordance with the risk-adapted NB-2004 protocol. Here, we analyzed the details of clinical presentation of the disease, age at the time of diagnosis, time from the disease onset to diagnosis, the presence or absence of life-threatening symptoms (LTS) and adrenal insufficiency, the aspects of patient management (including special aspects of surgical treatment), and treatment results. The median age at the time of diagnosis was 1.9 months. The patients were divided into 3 groups: children with localized BANB; children with true stage 4 disease; children with stage 4S disease. Most patients had metastatic NB, whereby stage 4S cases prevailed (55%, n = 16). Given the low sensitivity of MIBG scintigraphy for the detection of small tumours (less than 2 cm), one should use a comprehensive approach to the assessment of the results of imaging and instrumental tests in patients with BANB in order to confirm bilateral involvement. At diagnosis, about half of the patients with BANB (48%) had clinical symptoms associated with the presence of a retroperitoneal tumour mass and massive hepatomegaly because of liver metastases. Thirty-four percent of patients developed LTS. One of the typical features of BANB was the frequent development of adrenal insufficiency (in 41% of cases) caused by bilateral adrenal involvement, and this should be taken into account when performing diagnostic investigations and providing treatment to patients. Since bilateral radical resection is associated with the inevitable development of adrenal insufficiency, surgical treatment should be determined on an individual basis. Bilateral adrenalectomy is not generally recommended and can be undertaken after an interdisciplinary discussion in case of unfavourable course of the disease (e.g. in case of recurrence). Even if patients with BANB develop certain complications or events (progression) their prognosis is still good. The three- and five-year event-free survival rates in patients with BANB were 86 ± 6.4%. The three- and five-year overall survival rates were 100%. The analysis of patients with BANB showed that they have a more favourable course of the disease, and this may serve as grounds for assigning such patients into a special group. In view of the degree of tumour extension, the specifics of staging, and frequent development of adrenal insufficiency, standard check-ups should be complemented by endocrine monitoring, and surgical approaches should be chosen on an individual basis.

Pharmacokinetics of 13-cis-Retinoic acid in high-risk neuroblastoma patients

13-cis-Retinoic acid is a differentiation agent for neuroblastoma cells and is a part of post-consolidation therapy for high-risk patients. The effectiveness of this therapeutic approach is currently under study. 26 patients with high-risk neuroblastoma treated at Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology were included in the study of 13-cis-Retinoic acid pharmacokinetics by high-performance liquid chromatography assay with ultraviolet detector depending on the method of administration of drug (swallowed capsules or opened capsules before administration). This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The current study showed that the therapeutic concentration of &gt; 2 μM when taking 13-cis-Retinoic acid at a dose of 160 mg/m2/day was achieved in two groups, regardless of the method of drug administration. However, plasma concentrations of 13-cis-Retinoic acid at 4 hours after administration on the 14th day of therapy were higher in the group of patients who swallowed the capsules (4.1 ± 1.8 μM), compared to those who could not do it (1.9 ± 1.5 μM) (p = 0.022). The introduction into the clinical practice of therapeutic drug monitoring of 13-cis-retinoic acid in high-risk neuroblastoma patients with an assessment of peak concentration and dose adjustment of the following courses may be an important point in the attempt to optimize postconsolidation therapy and improve prognosis.