Development and preliminary validation of a new screening questionnaire for identifying atopic children

Background: Allergic diseases represent a frequent and increasing condition affecting children. A screening questionnaire allowing an easy identification of children with symptoms of allergic diseases may improve management and clinical outcome. The aim of this study was to develop and validate an easy-to-use screening questionnaire to detect children requiring further allergological evaluations. Methods: A 10-item questionnaire, evaluating the presence and the history of the most frequent allergic conditions affecting children, including allergic asthma, allergic rhinitis and conjunctivitis, food allergy, and atopic dermatitis, was developed and administered to 214 parents of children from 5 to 10 years of age (163 with allergic disease and 51 healthy, nonallergic children). Validation was performed by Pearson's correlation between the clinical diagnosis and the responses to the questionnaire. Internal consistency was computed by Cronbach's alpha correlation coefficient. Sensitivity and specificity of the novel questionnaire were assessed by the receiver operating characteristic (ROC) curve. Results: Validation analysis of the new children atopy (ChAt) questionnaire showed good internal consistency with a Cronbach's alpha of 0.757. Responses to the items evaluating the presence of individual allergic conditions significantly correlated with the clinical diagnosis (p<0.001). The ROC curve showed an area of 0.956 and identified a cutoff value >2 of the ChAt questionnaire total score for detection of allergy (sensitivity =0.92 and specificity =0.902). Conclusion: The novel ChAt questionnaire represents a simple tool able to detect the presence of all major allergic diseases in a pediatric population allowing an early identification of allergic multimorbidity and potentially facilitating clinical management

One step closer to influenza vaccine inclusiveness

Flu virus infection is a common cause of acute respiratory illness, with the major incidence in pediatric age, high morbidity, and mortality. The flu vaccine is recommended for all people aged ≥6 months, unless specific contraindications are present. Younger and older age, pregnancy, chronic diseases like asthma, and immunodeficiency are risk factors for severe complications following flu infection. Thus, these categories represent the target for flu vaccine strategies in most countries. Inactivated influenza vaccine (IIV), recombinant influenza vaccine (RIV) or live‐attenuated influenza virus (LAIV) are currently available, with specific precautions and contraindications. We aim to resume the current indications for vaccines in the vulnerable populations to support flu vaccination inclusiveness, in anticipation of a “universal vaccine” strategy

Novel artful applications of vaccines at the horizon

Some live vaccines, particularly Bacillus Calmette-Guerin (BCG), oral polio vaccine (OPV), and measles vaccine, can reduce the incidence of all-cause mortality by outreaching the mere control of specific infections and exerting off-target effects. Asides from the prevention of viral infection, some other vaccines, such as those against flu or rotavirus, could reduce the risk of developing autoimmunity. The nonspecific effects of vaccines are mediated by the innate immune system, mainly through the so-called trained innate immunity. These observations paved the way for developing tolerogenic and trained immunity-based vaccines with substantial implications for more effective use of vaccines and combat vaccine hesitancy

Biweekly Hizentra® in Primary Immunodeficiency: a Multicenter, Observational Cohort Study (IBIS)

Immunoglobulin G (IgG) replacement therapy is a standard treatment for patients with primary immunodeficiency diseases (PIDs). Hizentra®, a 20% human subcutaneous IgG (SCIG), is approved for biweekly administration for PIDs. The aim of the multicenter IBIS study was to prospectively investigate the efficacy of biweekly Hizentra® compared with previous IVIG or SCIG treatment regimens in patients with PIDs. The study consisted of a 12-month retrospective period followed by 12-month prospective observational period. The main endpoints included pre-infusion IgG concentrations, proportion of patients with serious bacterial infections (SBIs), other infections, hospitalizations due to PID-related illnesses, and days with antibiotics during the study periods. Of the 36 patients enrolled in the study, 35 patients continued the study (mean age 26.1 ± 14.4 years; 68.6% male). The mean pre-infusion IgG levels for prior immunoglobulin regimens during the retrospective period (7.84 ± 2.09 g/L) and the prospective period (8.55 ± 1.76 g/L) did not show any significant variations (p = 0.4964). The mean annual rate of SBIs/patient was 0.063 ± 0.246 for both prospective and retrospective periods. No hospitalizations related to PIDs were reported during the prospective period versus one in the retrospective period. All patients were either very (76.5%) or quite (23.5%) satisfied with biweekly Hizentra® at the end of the study. In conclusion, the IBIS study provided real-world evidence on the efficacy of biweekly Hizentra® in patients with PIDs, thus verifying the data generated by the pharmacometric modeling and simulation study in a normal clinical setting

Penile metastasis from primary cholangiocarcinoma: the first case report

BACKGROUND: Metastatic penile carcinoma derived from cholangiocarcinoma (CCA) has not been previously reported in the literature. Common metastatic sites for CCA include the regional lymph nodes and adjacent organs. CCAs are not highly vascularised tumours, making hematogenous metastases uncommon. Hematogenous CCA metastases commonly occur at distant organs such as the lungs, adrenal glands, and bones. Median survival for patients with metastatic disease is generally less than 1 year. CASE PRESENTATION: A 74-year-old Caucasian man consulted us after having undergone penile ultrasonography for pain and increased thickness at the base of the penis after self-examination. The patient presented with a history of hepatitis C-related cirrhosis and intrahepatic CCA, diagnosed 3 years previously. A biopsy of the corpora cavernosa on both sides revealed a carcinoma harbouring the same histological and immunophenotypical features as the primary hepatic lesion. CONCLUSIONS: To date, there is no case of penile or urogenital system metastasis from CCA described in the literature. Therefore, this article represents the first case report of penile metastasis from CCA

Consensus statement of the Italian society of pediatric allergy and immunology for the pragmatic management of children and adolescents with allergic or immunological diseases during the COVID-19 pandemic

The COVID-19 pandemic has surprised the entire population. The world has had to face an unprecedented pandemic. Only, Spanish flu had similar disastrous consequences. As a result, drastic measures (lockdown) have been adopted worldwide. Healthcare service has been overwhelmed by the extraordinary influx of patients, often requiring high intensity of care. Mortality has been associated with severe comorbidities, including chronic diseases. Patients with frailty were, therefore, the victim of the SARS-COV-2 infection. Allergy and asthma are the most prevalent chronic disorders in children and adolescents, so they need careful attention and, if necessary, an adaptation of their regular treatment plans. Fortunately, at present, young people are less suffering from COVID-19, both as incidence and severity. However, any age, including infancy, could be affected by the pandemic.Based on this background, the Italian Society of Pediatric Allergy and Immunology has felt it necessary to provide a Consensus Statement. This expert panel consensus document offers a rationale to help guide decision-making in the management of children and adolescents with allergic or immunologic diseases

Rituximab Unveils Hypogammaglobulinemia and Immunodeficiency in Children with Autoimmune Cytopenia

BACKGROUND: Rituximab (RTX; anti-CD20 mAb) is a treatment option in children with refractory immune thrombocytopenia, autoimmune hemolytic anemia (AHA), and Evans syndrome (ES). Prevalence and clinical course of RTX-induced hypogammaglobulinemia in these patients are poorly known. OBJECTIVE: To evaluate the prevalence and risk factors for persistent hypogammaglobulinemia (PH) after RTX use. METHODS: Clinical and immunologic data from children treated with RTX for immune thrombocytopenia, AHA, and ES were collected from 16 Italian centers and 1 UK center at pre-RTX time point (0), +6 months, and yearly, up to 4 years post-RTX. Patients with previously diagnosed malignancy or primary immune deficiency (PID) were excluded. RESULTS: We analyzed 53 children treated with RTX for immune thrombocytopenia (n = 36), AHA (n = 13), and ES (n = 4). Median follow-up was 30 months (range, 12-48). Thirty-two percent of patients (17 of 53) experienced PH, defined as IgG levels less than 2 SD for age at last follow-up (>12 months after RTX). Significantly delayed B-cell recovery was observed in children experiencing PH (hazard ratio, 0.55; P < .05), and 6 of 17 (35%) patients had unresolved B-cell lymphopenia at last follow-up. PH was associated with IgA and IgM deficiency, younger age at RTX use (51 vs 116 months; P < .01), a diagnosis of AHA/ES, and better response to RTX. Nine patients with PH (9 of 17 [53%]) were eventually diagnosed with a PID. CONCLUSIONS: Post-RTX PH is a frequent condition in children with autoimmune cytopenia; a sizable proportion of patients with post-RTX PH were eventually diagnosed with a PID. In-depth investigation for PID is therefore recommended in these patients

Vaccine hesitancy and knowledge regarding maternal immunization among reproductive age women in central Italy: a cross sectional study

BackgroundVaccination in pregnancy offers protection to the mother and the newborn. In Italy, influenza, pertussis, and COVID-19 vaccinations are recommended in pregnancy, but vaccination coverage is still far from the National Immunization Plan goals. We aimed to assess knowledge and attitude on maternal immunization in two groups of Italian women, in pregnancy and in reproductive age (non pregnant).MethodsA cross sectional study on Italian childbearing age women gathering information on their knowledge on maternal immunization and attitudes to receiving influenza and pertussis vaccines in pregnancy was carried out at the University of Rome Tor Vergata, between September 2019 and February 2020. Logistic and multinomial regressions were chosen as statistical tests for our analysis.Results1,031 women participated in the survey by answering the questionnaire. Out of these, 553 (53.6%) women were pregnant, and 478 (46.4%) were in the reproductive age. 37% (204/553) of pregnant women and 41% (198/476) of non pregnant women are aware of the existence of an immunization plan for pregnant women in Italy. The group with age between 20 and 30, for both pregnant women and women in the reproductive age, has a better knowledge of vaccination in pregnancy. Working status is a variable associated with more awareness about vaccination during pregnancy only for pregnant women (OR = 2.34, p &lt; 0.00001). Educational status, trimester of pregnancy and knowledge on the topic are associated with vaccine hesitancy in our multivariate analysis for pregnant women. In the reproductive age group women who had a previous pregnancy are more likely to be hesitant towards vaccination in pregnancy, on the other hand the one with a higher knowledge and educational status are more likely to get vaccinated.ConclusionsThe study highlights the persistent vaccine hesitancy among Italian women of reproductive age and pregnant women. Despite healthcare providers being identified as a reliable source of information, their recommendations alone are insufficient to overcome vaccine hesitancy. Factors such as employment status, educational level, pregnancy trimester, and knowledge about vaccinations during pregnancy influence vaccine hesitancy. Tailored educational interventions and communication campaigns targeting these areas can help reduce vaccine hesitancy and promote maternal immunization

The Interplay between CD27dull and CD27bright B Cells Ensures the Flexibility, Stability, and Resilience of Human B Cell Memory

Summary: Memory B cells (MBCs) epitomize the adaptation of the immune system to the environment. We identify two MBC subsets in peripheral blood, CD27dull and CD27bright MBCs, whose frequency changes with age. Heavy chain variable region (VH) usage, somatic mutation frequency replacement-to-silent ratio, and CDR3 property changes, reflecting consecutive selection of highly antigen-specific, low cross-reactive antibody variants, all demonstrate that CD27dull and CD27bright MBCs represent sequential MBC developmental stages, and stringent antigen-driven pressure selects CD27dull into the CD27bright MBC pool. Dynamics of human MBCs are exploited in pregnancy, when 50% of maternal MBCs are lost and CD27dull MBCs transit to the more differentiated CD27bright stage. In the postpartum period, the maternal MBC pool is replenished by the expansion of persistent CD27dull clones. Thus, the stability and flexibility of human B cell memory is ensured by CD27dull MBCs that expand and differentiate in response to change. : Grimsholm et al. show that CD27dull and CD27bright represent sequential MBC developmental stages. T cell- and germinal center (GC)-independent CD27dull MBCs are the plastic source of strongly selected and GC-dependent CD27bright MBCs. CD27dull MBCs, able to expand and differentiate in response to change, ensure stability and flexibility of human B cell memory. Keywords: memory B cells, pregnancy, immunological memory, CD27, VH repertoire, immunodeficiency, aging, spleen, vaccine, germinal cente