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Kabuki Syndrome (KS) is a multisystemic genetic disorder. A portion of patients has immunological manifestations characterized by increased susceptibility to infections and autoimmunity. Aiming to describe the clinical and laboratory immunological aspects of KS, we conducted a retrospective multicenter observational study on patients with KS treated in centers affiliated to the Italian Primary Immunodeficiency Network.Thirty-nine patients were enrolled, with a median age at evaluation of 10 years (range: 3 m-21y). All individuals had organ malformations of variable severity. Congenital heart defect (CHD) was present in 19/39 patients (49%) and required surgical correction in 9/39 (23%), with associated thymectomy in 7/39 (18%). Autoimmune cytopenia occurred in 6/39 patients (15%) and was significantly correlated with thymectomy (p < 0.002), but not CHD. Individuals with cytopenia treated with mycophenolate as long-term immunomodulatory treatment (n = 4) showed complete response. Increased susceptibility to infections was observed in 22/32 patients (69%). IgG, IgA, and IgM were low in 13/29 (45%), 13/30 (43%) and 4/29 (14%) patients, respectively. Immunoglobulin substitution was required in three patients. Lymphocyte subsets were normal in all patients except for reduced naïve T-cells in 3/15 patients (20%) and reduced memory switched B-cells in 3/17 patients (18%). Elevated CD3 + TCRαβ + CD4-CD8-T-cells were present in 5/17 individuals (23%) and were correlated with hematological and overall autoimmunity (p < 0.05).In conclusion, immunological manifestations of KS in our cohort include susceptibility to infections, antibody deficiency, and autoimmunity. Autoimmune cytopenia is correlated with thymectomy and elevated CD3 + TCRαβ + CD4-CD8-T-cells, and benefits from treatment with mycophenolate., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Children and young adult with high grade gliomas (HGG) have dismal prognoses and treatment options remain limited. We present 19 patients diagnosed with anaplastic astrocytoma (AA) or glioblastoma (GBM) treated with concomitant and adjuvant 20-30 mg/m 2 /dose of vinorelbine and 30 mg/kg/day valproic acid (VA) in combination to consolidated TMZ and focal RT after maximal surgery. We evaluated the feasibility of treating children diagnosed with HGG. The median follow-up time was 51.4 months (range, 6.2-106.6 months). The 5-year OS was 57.9% (CI 95%, 33.2-76.3) and the 5-year PFS was 57.9% (CI 95%, 33.2-76.3). Eight patients (42.1%) have progressed so far, with a median time to progression of 9 months from diagnosis (range, 4.6-34.7 months). All of them died for disease progression. At time of analysis, 11 patients were still alive with no evidence of disease. It is notable that all events occurred within 35 months from the start of therapy. All 19 treated patients reported low-grade drug-related adverse events (AEs). The treatment was well tolerated in our limited cohort of patients without significant toxicity. Further studies of the efficacy and safety of combination of vinorelbine/VA to consolidated RT/TMZ therapy in children with HGG are underway in a clinical trial setting., Competing Interests: None., (AJCR Copyright © 2023.)

Objective: Many very preterm infants are treated with phototherapy (PT) for hyperbilirubinemia and it has been reported that PT can negatively affect gut perfusion. Thus, our aim was to evaluate the occurrence of feeding intolerance in the course of PT in these patients., Methods: We retrospectively studied infants born at 25 +0 -31 +6  weeks from November 2017 to April 2020 who required PT during the first two weeks of life. Patients were used as their own controls recording for each one the occurrence of feeding intolerance after starting PT and the resumption of feeding tolerance after its termination., Results: We studied 125 preterm infants of whom 58 (46%) developed a feeding intolerance which disappeared in 47 (81%) of them at the end of PT. Regression analysis showed a trend toward a not significant decrease of risk of feeding intolerance in infants with higher birth weight and age at the start of the first course of PT., Conclusion: We found that about half of our patients developed a transient feeding intolerance during PT that ceased in the vast majority of them after termination of the therapy. Further studies are necessary to confirm the correlation between PT and feeding intolerance.

Inborn errors of immunity (IEI) are genetic disorders characterized by a wide spectrum of clinical manifestations, ranging from increased susceptibility to infections to significant immune dysregulation. Among these, primary immune regulatory disorders (PIRDs) are mainly presenting with autoimmune manifestations, and autoimmune cytopenias (AICs) can be the first clinical sign. Significantly, AICs in patients with IEI often fail to respond to first-line therapy. In pediatric patients, autoimmune cytopenias can be red flags for IEI. However, for these cases precise indicators or parameters useful to suspect and screen for a hidden congenital immune defect are lacking. Therefore, we focused on chronic/refractory AIC patients to perform an extensive clinical evaluation and multiparametric flow cytometry analysis to select patients in whom PIRD was strongly suspected as candidates for genetic analysis. Key IEI-associated alterations causative of STAT3 GOF disease, IKAROS haploinsufficiency, activated PI3Kδ syndrome (APDS), Kabuki syndrome and autoimmune lymphoproliferative syndrome (ALPS) were identified. In this scenario, a dysregulated immunophenotype acted as a potential screening tool for an early IEI diagnosis, pivotal for appropriate clinical management and for the identification of new therapeutic targets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Schiavo, Martini, Attardi, Consonni, Ciullini Mannurita, Coniglio, Tellini, Chiocca, Fotzi, Luti, D’Alba, Veltroni, Favre and Gambineri.)

Background: To evaluate the ability of Weighted-Incidence Syndromic Combination Antibiograms (WISCA) to inform the selection of empirical antibiotic regimens for suspected paediatric community-acquired urinary tract infections., Methods: Data were collected from outpatients (< 15 years) accessing the emergency rooms of Padua University-Hospital and Mestre Dell' Angelo-Hospital (Venice) between January 1st, 2016, and December 31st, 2018. WISCAs were developed by estimating the coverage of eight regimens using a Bayesian hierarchical model adjusted for age, sex, and previous antibiotic treatment or renal/urological comorbidities., Results: 385 of 620 urine culture requests were included in the model analysis. The most frequently observed bacterium was E. coli (85% and 87%, Centre A and B). No centre effect on coverage estimates was found, and data were successfully pooled together. Coverage ranged from 77.8% (Co-trimoxazole) to 97.6% (Carbapenems). Complex cases and males had significantly lower odds of being covered by a regimen than non-complex cases and females (odds ratio (OR) 0.49 [95% HDI, 0.38-0.65], and OR: 0.73 [95% HDIs, 0.56-0.96] respectively). Children aged 3-5 years had lower odds of being covered by a regimen than other age groups, except for neonates., Conclusions: The developed WISCAs provide highly informative estimates on coverage patterns overcoming the limitation of combination antibiograms and expanding the framework of previous Bayesian WISCA algorithm.

The main factors studied were the overall energy output and, in particular, the effects on the respiratory, cardiac and circulatory systems. The basic result was to demonstrate that while driving there occur more or less marked physiological modifications to these systems, which can be determined as to quantity; it seems clear that during particularly difficult conditions at the wheel or in subjects whose health is less than perfect, this can go as far as pathological situations. The values of catecholamines and their metabolites in the blood and urine were chosen as evaluation parameters. Catecholamines--that is, adrenaline, noradrenaline and dopamine--are substances produced by the adrenal glands; they play an essential part in the "functioning" of the sympathetic nervous system (which has important tasks, such as that of regulating the organism's equilibrium especially in reactions to sudden events or emergency situations) and are a reliable indication of effort and stress. Their action is seen in stimulation of the nervous system, cardiac agitation, an increase in blood pressure and in the production of lactic acid, increases in the basal metabolism, and so on. An excessive amount of these substances in the blood can cause real damage, above all to the heart and brain, especially in organs already affected in some way. The subjects studied were healthy volunteers, ranging in age between 20 and 35 and of comparable height and weight. A sort of "cross-over" experiment was carried out, so that the same subject was first studied driving with one type of gear change and then, two days later, was studied in the same experimental conditions but driving a vehicle with the other type of gear change. Analysis of the blood and urine sample was carried out in "single blind-test" conditions, in the sense that the research worker did not know where the samples came from. The biochemical analyses of the blood were: 1) Gas-analysis; 2) Hemochrome; 3)LDH-SGOT-Alkaline phosphatase; 4)Noradrenaline; 5)Cortisol. The following urine analyses were made: 1)Total catecholamines; 2)Vanillylmandelic acid. Clinical tests included: 1. Measurement of arterial pressure, at the beginning, at the end and during the driving period at the 30th and 90th minute. 2. Measurement of cardiac frequency,at the beginning, at the end and during the driving period at the same times. Blood pressure was measured by the auscultatory method, using an armband apparatus with aneroid capsule; cardiac frequency was measured at the wrist using the simple palpatory method, per 60 seconds.