Search

Objectives: Kawasaki disease (KD) is the most frequent cause of acquired heart disease in children in high-income countries because of coronary artery involvement. Risk factors for coronary lesions can vary in consideration of different genetic background and environmental factors. Methods: Multicenter retrospective and prospective study including 372 consecutive children (58% boys; mean age 34.3 ± 30.3 months, Caucasian 85%) was diagnosed with KD. We divided the cohort into 2 groups according to the presence of coronary anomalies (CAA) and aneurysms. We compared the groups and studied the risk factors for CAA and for aneurysms, the most severe lesions. Results: Children with CAA were 91/372 (24.46%, aneurysms 20/372, 5.37%). Children with CAA were more likely to have a longer duration of fever (p < 0.001), later day of treatment (p < 0.001), to be IVIG non-responders and late treated (p < 0.001), while age, clinical presentation, and seasonality were not different. They also had significantly higher WBC and neutrophils, lower lymphocytes, Hb and Na during the acute stage, and slower resolution of inflammation. Age, IVIG unresponsiveness, and presence of non-coronary cardiac findings were independent risk factors for CAA and for aneurysms, while neutrophils just for CAA. Age under 6 months was a risk factor for the aneurysm. Aneurysms occurred more frequently in the first quartile of the age of KD onset (under 14 months). Conclusion: Very young children with non-coronary cardiac findings are at increased risk for a more severe form of KD with aneurysms. These children could benefit from adjunctive therapy beside IVIG, especially if they have higher markers of inflammation, particularly neutrophils.Key points• Risk factors for coronary lesions can vary in consideration of different genetic background and environmental factors.• Risk factors for coronary involvement have been extensively studied in the Asian population, and others have been validated in cohorts with mixed ethnicities.• In our predominantly Caucasian population, non-coronary cardiac findings, age younger than 6 months, and IVIG unresponsiveness are independent risk factors for a more severe form of KD with aneurysms.

The recent lockdown, resulting from the SARS-CoV-2 pandemic, has had a strong social and psychological impact on the most fragile individuals and family structures. In the present work we investigated the experience of families without specific elements of social or health vulnerability during the quarantine period that occurred in the spring of 2020.Between May and July 2020, 22 primary care pediatricians belonging to AUSL Romagna administered to a number of families a questionnaire to detect changes that occurred, during the lockdown, in family environment, school attendance and personal attitudes.A total of 721 questionnaires were collected, analyzing the associations between variables relating to home environment, daily rhythms, school and warning signs in relation to the age of children. As a result of the lockdown, family habits changed in 31% of cases, with a greater presence of the reference figure in 68% of these. Three out of four families reported they had sufficient domestic spaces, and nine out of ten had access to an outdoor, private or condominium space. Daily rhythms were preserved in 56.7% of cases; mood disorders appeared in 30% of adolescent children, followed by sleep, appetite and psychosomatic disorders. One in three children has made progress in terms of evolution and behavior, and one in 5 children has seen their relationships improve. The overall resilience of families during the lockdown period was considered good in 66.3%, sufficient in 31.3% and not satisfactory in only 2.4% of cases.Our data show that, in the interviewed families, the simultaneous presence of adults and children at home has generally intensified. Families refer, on the whole, a positive and resilient behavior in the lockdown period, even if initial emotional problems are reported in one out of three children-adolescents. The ability to maintain a family organized structure seems to be partially compromised. Forced cohabitation leads to competition for the same resources of time and space and affects the entire family unit. The school institution emerges as a protective factor for children, young people and also for the well-being of families themselves.

Background Very few studies describe factors associated with COVID-19 diagnosis in children. Aim We here describe characteristics and risk factors for COVID-19 diagnosis in children tested in 20 paediatric centres across Italy. Methods We included cases aged 0–18 years tested between 23 February and 24 May 2020. Our primary analysis focused on children tested because of symptoms/signs suggestive of COVID-19. Results Among 2,494 children tested, 2,148 (86.1%) had symptoms suggestive of COVID-19. Clinical presentation of confirmed COVID-19 cases included besides fever (82.4%) and respiratory signs or symptoms (60.4%) also gastrointestinal (18.2%), neurological (18.9%), cutaneous (3.8%) and other unspecific influenza-like presentations (17.8%). In multivariate analysis, factors significantly associated with SARS-CoV-2 positivity were: exposure history (adjusted odds ratio (AOR): 39.83; 95% confidence interval (CI): 17.52–90.55; p Conclusion Recommendations for SARS-CoV-2 testing in children should consider the evidence of broader clinical features. Exposure history, fever and anosmia/ageusia are strong risk factors in children for positive SARS-CoV-2 testing, while other symptoms did not help discriminate positive from negative individuals. This study confirms that COVID-19 was a mild disease in the general paediatric population in Italy. Further studies are needed to understand risk, clinical spectrum and outcomes of COVID-19 in children with pre-existing conditions.

Since resistance to intravenous immunoglobulin (IVIG) is associated with coronary lesions (CALs) in Kawasaki disease (KD), it is crucial to identify patients at risk to protect them from coronary involvement. The available risk scores to predict IVIG resistance were developed in Asian populations in whom their effectiveness has been proven, but data on non-Asian children are limited. The aim of this study is to evaluate the ability of the Kobayashi, Egami, and Formosa risk scores to predict IVIG resistance and CALs in Italian patients with KD. A multicenter retrospective analysis involving children with KD diagnosed between 2000 and 2015 was carried out: 257 patients were enrolled (57.9% boys, 89.9% Caucasian); 43 patients were IVIG resistant (16.7%). The scores have low sensitivity and specificity in predicting IVIG resistance: respectively, KS 64% and 62.5%, ES 41.4% and 77.4%, and FS 70.8% and 44.9%. The predictive value of the 3 scores for predicting CALs was also poor.Conclusion: Kobayashi, Egami, and Formosa Scores are ineffective in predicting IVIG resistance and coronary involvement in a predominantly Caucasian cohort. A specific score system for mostly Caucasian children with KD is needed enable the early identification of those at risk for CALs who could benefit from intensified treatment. What is Known: • There are several risk scores developed in the Asian population to early identify patients with KD at risk for immunoglobulin-resistance and thus for coronary lesions. • Data are scarce on their effectiveness in non-Asian children. What is New: • We present a comprehensive analysis of the ability of 3 Asian risk scores in a cohort of mostly Caucasian children to predict immunoglobulin resistance and coronary involvement. • Low sensitivity and specificity of the Asian scores for immunoglobulin-resistance and coronary lesions suggest the need for criteria specific for different ethnicities.

Background Kawasaki disease (KD) is a febrile systemic vasculitis of unknown etiology and the main cause of acquired heart disease among children in the developed world. To date, abdominal involvement at presentation is not recognized as a risk factor for a more severe form of the disease. Objective To evaluate whether presenting abdominal manifestations identify a group at major risk for Intravenous immunoglobulin (IVIG)-resistance and coronary lesions. Methods Retrospective study of KD patients diagnosed between 2000 and 2015 in 13 pediatric units in Italy. Patients were divided into 2 groups according to the presence or absence of abdominal manifestations at onset. We compared their demographic and clinical data, IVIG-responsiveness, coronary ectasia/aneurysms, laboratory findings from the acute and subacute phases. Results 302 patients (181 boys) were enrolled: 106 patients with, and 196 patients without presenting abdominal features. Seasonality was different between the groups (p = 0.034). Patients with abdominal manifestations were younger (p = 0.006) and more frequently underwent delayed treatment (p = 0.014). In the acute phase, patients with abdominal presentation had higher platelet counts (PLT) (p = 0.042) and lower albuminemia (p = 0.009), while, in the subacute phase, they had higher white blood cell counts (WBC) and PLT (p = 0.002 and p < 0.005, respectively) and lower red blood cell counts (RBC) and hemoglobin (Hb) (p = 0.031 and p 0.009). Moreover, the above mentioned group was more likely to be IVIG-resistant (p < 0.005) and have coronary aneurysms (p = 0.007). In the multivariate analysis, presenting abdominal manifestations, age younger than 6 months, IVIG- resistance, delayed treatment and albumin concentration in the acute phase were independent risk factors for coronary aneurysms (respectively p

A defective production of protective levels of antibodies to Hepatitis B (HB) vaccine is reported to occur in 4-10% of healthy subjects and a correlation with the presence of specific human leukocyte antigen (HLA) molecules, including DQ2, which also confers genetic predisposition to celiac disease (CD) and type I diabetes mellitus (T1DM), has been suggested. The aim of this study was to analyze the serological response to HB vaccine and measles-containing vaccines in 69 diabetic patients (T1DM), 42 patients with celiac disease (CD) and 79 healthy control subjects (CT). The median interval between the third dose of HB vaccine and serum collection was 6.8, 3.5, and 4.7 years for T1DM, CD and CT groups, respectively. 50/69 (72%) T1DM patients, 32/42 (76%) CD patients and 61/79 (77%) CT subjects showed protective anti-HBs antibodies after vaccination, with no statistically significant difference. On the contrary, a lower statistically significant difference was found in the mean HBsAb level of T1DM subjects when compared with the other two groups. No correlation between HLA DQ2 expression in T1DM and vaccine response was detected. The comparison of serological response to measles after vaccination also showed no statistically significant differences in the three groups. Contrasting results between these data and those reported in the literature might be due to differences in the time intervals between vaccination and testing. Prospective studies in pathological and healthy groups with the same age at HBV vaccination and with the same time interval for blood sample collection to determine antibody titers are necessary in order to provide more conclusive data.

Celiac disease (CD) is an autoimmune disorder of the small intestine triggered by environmental factors in genetically predisposed individuals. A strong association between type 1 diabetes (T1DM) and CD has been reported. We have previously shown that rotavirus infection may be involved in the pathogenesis of CD through a mechanism of molecular mimicry. Indeed, we identified a subset of anti-transglutaminase IgA antibodies that recognize the rotavirus viral protein VP7. In this study, we aimed at evaluating whether such antibodies may predict the onset of CD in children affected by T1DM. Moreover, to further analyze the link between rotavirus infection and pathogenesis of CD, we analyzed the effect of anti-rotavirus VP7 antibodies on T84 intestinal epithelial cells using the gene-array technique, complemented by the analysis of molecules secreted in the supernatant of stimulated cells. We found that anti-rotavirus VP7 antibodies are present in the vast majority (81%) of T1DM-CD tested sera, but are detectable also in a fraction (27%) of T1DM children without CD. Moreover, we found that anti-rotavirus VP7 antibodies are present before the CD onset, preceding the detection of anti-tTG and anti-endomysium antibodies. The gene-array analysis showed that purified anti-rotavirus VP7 antibodies modulate genes that are involved in apoptosis, inflammation, and alteration of the epithelial barrier integrity in intestinal epithelial cells, all typical features of CD. Taken together, these new data further support the involvement of rotavirus infection in the pathogenesis of CD and suggest a predictive role of anti-rotavirus VP7 antibodies.

Background. Early pathogenetic events of gluten intolerance may be overlooked in patients with serologic markers of celiac disease and normal intestinal mucosa by both conventional histology and immunohistochemistry. Aims. To investigate if a submicroscopical damage of the absorptive cell surface was associated with developing gluten sensitivity. Patients and methods. Duodenal biopsies of seven subjects with positive anti-endomysial antibodies and normal histology underwent ultrastructural evaluation of the epithelial surface by means of both scanning and transmission electron microscopy. Specimens of intestinal mucosa of 14 children with non-celiac conditions were used as controls. Results. In four patients, electron microscopy revealed alterations of the enterocyte brush border with a significant reduction of the height of microvilli. After several months, three of them had a second biopsy that eventually showed histological modifications suggestive of celiac disease. In the other three patients, no significant alteration of enterocyte ultrastructure was observed. One of them, rebiopsied after 12 months, still showed a normal duodenal histology. Conclusions. Gluten sensitivity can be associated with ‘minimal’ mucosal changes not detectable with conventional light microscopy. Such lesions, which primarily involve microvillous structure, may imply a reduction of intestinal absorptive surface already in the latent stage of the disease.

Sensitivity of forced expiratory flow between 25% and 75% of the vital capacity (FEF25-75) in detecting airway obstruction was investigated in 14 children with mild-moderate asthma, allergic to house dust mites, while at high altitude (1756 m). Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), FEF25-75, and peak expiratory flow (PEF) were measured every 2 weeks for 12 weeks (total, 84 measurements). The presence or absence of wheezing at the chest auscultation was ascertained before each test. During the study period, a significant improvement of both mean (SD) FEF25-75 [61 (12)% vs. 68 (11)% of the predicted value, p = 0.005] and PEF [95 (16)% vs. 103 (13)%, p = 0.002] was observed. FEV1 changed only marginally [82 (7)% vs. 86 (6)%, p = 0.05]. Wheezing was present on 12/84 occasions. Wheezing was associated with abnormal FEF25-75 values on most occasions but not with abnormal FEV1 or PEF. FEF25-75 was decreased on 51% of days in which wheezing was absent. FEV1 and PEF were, respectively, normal in 69% (p < 0.0001) and 92% (p < 0.0001) of measurements in which FEF25-75 was abnormal. These results suggest that FEF25-75 may be considered a good indicator of airflow obstruction and a sensitive marker of respiratory improvement in asthmatic children during reduced antigen exposure.

Massive hemoptysis and/or recurrent expectoration of measurable amounts of blood are common complications of chronic bronchopulmonary infections in cystic fibrosis (CF). When conservative treatment fails to control bleeding, surgery or bronchial artery embolization (BAE) is frequently considered. We present our experience and long-term follow up of BAE in 14 CF patients (age range 15–39 years) with massive (6 subjects) and/or recurrent (8 subjects) hemoptysis not responsive to medical treatment. Seven had chronic hypercapnic respiratory failure. After angiographic evaluation, polyvinyl alcohol particles (halon) were injected to embolize obviously enlarged bronchial arteries. Seventeen procedures were performed in 14 patients and 36 bronchial arteries were embolized. All the patients stopped bleeding immediately upon BAE. Most of the patients had postembolization fever, dysphagia, and transient chest pain which were managed symptomatically. After median follow-up period of 10.5 months (range 0.5–38 months), no recurrence of hemoptysis was observed in 8 patients who are still alive. In 3 patients hemoptysis recurred and they underwent reembolization after 3,22, and 25 months, respectively. Three subjects died of respiratory failure within 5 months from BAE. Presently, 50% of patients studied had a ≥ 1 year interval free of major hemoptysis after the first BAE. Our experience indicates that massive and/or recurrent hemoptysis in C:F patients can be safety and effectively managed by BAE if the procedure is performed by skilled practitioner. The procedure was well tolerated and resulted in prolonged and satisfactory bleeding control in most patients. © 1995 Wiley-Liss, Inc.

Background Vomiting in children with acute gastroenteritis (AG) is not only a direct cause of fluid loss but it is also a major factor of failure of oral rehydration therapy (ORT). Physicians who provide care to paediatric patients in the emergency department (ED) usually prescribe intravenous fluid therapy (IVT) for mild or moderate dehydration when vomiting is the major symptom. Thus, effective symptomatic treatment of vomiting would lead to an important reduction in the use of IVT and, consequently, of the duration of hospital stay and of frequency of hospital admission. Available evidence on symptomatic treatment of vomiting shows the efficacy of the most recently registered molecule (ondansetron) but a proper evaluation of antiemetics drugs largely used in clinical practice, such as domperidone, is lacking. Objectives To compare the efficacy of ondansetron and domperidone for the symptomatic treatment of vomiting in children with AG who have failed ORT. Methods/Design Multicentre, double-blind randomized controlled trial conducted in paediatric EDs. Children aged from 1 to 6 years who vomiting, with a presumptive clinical diagnosis of AG, and without severe dehydration will be included. After the failure of a initial ORS administration in ED, eligible children will be randomized to receive: 1) ondansetron syrup (0,15 mg/Kg of body weight); 2) domperidone syrup (0,5 mg/Kg of body weight); 3) placebo. The main study outcome will be the percentage of patients needing nasogastric or IVT after symptomatic oral treatment failure, defined as vomiting or fluid refusal after a second attempt of ORT. Data relative to study outcomes will be collected at 30 minute intervals for a minimum of 6 hours. A telephone follow up call will be made 48 hours after discharge. A total number of 540 children (i.e. 180 patients in each arm) will be enrolled. Discussion The trial results would provide evidence on the efficacy of domperidone, which is largely used in clinical practice despite the lack of proper evaluation and a controversial safety profile, as compared to ondansetron, which is not yet authorized in Italy despite evidence supporting its efficacy in treating vomiting. The trial results would contribute to a reduction in the use of IVT and, consequently, in hospital admissions in children with AG. The design of this RCT, which closely reflect current clinical practice in EDs, will allow immediate transferability of results. Trial Registration ClinicalTrials.gov: NCT01257672

An objective approach for monitoring the treatment of acute pulmonary exacerbation in cystic fibrosis was evaluated. Eleven biochemical markers of inflammation (erythrocyte sedimentation rate, neutrophil count, C-reactive protein, alpha-1 antitrypsin, haptoglobin, ceruloplasmin, fibronectin, alpha-1 glycoprotein, alpha-2 macroglobulin, C3, granulocyte elastase and anti-Pseudomonas IgG) were measured in blood serum and plasma from 46 cystic fibrosis patients with chronic Pseudomonas aeruginosa colonization before and after treatment. The overall outcome in each patient was evaluated by means of a pondered sum of clinical, chest X-ray and lung function scores. Biochemical markers were related to the overall clinical improvement: haptoglobin, ceruloplasmin, fibronectin and alpha-1 glycoprotein showed a good sensitivity (64-70%), specificity (60-70%) and positive predictive value (86-89%). Granulocyte elastase showed a similar sensitivity (67%) and positive predictive value (85%) but a lower specificity (33%). The negative predictive value was generally poor (32-39%). Our data suggest that the combined measurement of some markers of inflammation and of conventional clinical parameters, may help in evaluating the efficacy of anti-infective treatment in cystic fibrosis.

Aim: To determine the contribution of HLA-DQA1* and HLA-DQB1* genes to the risk of coeliac disease (CD) in a cohort of children with type 1 diabetes mellitus (T1DM) from northern Italy. Methods: Three hundred and fifty-seven children with T1DM, attending the Childhood Diabetes Unit of the University of Verona, have been regularly tested for serum IgA endomysial antibodies (EMA). All patients with positive EMA underwent small bowel biopsy to confirm the diagnosis of CD. HLA typing was performed in subjects with T1DM and CD, and in a control group of 79 EMA-negative patients with T1DM. Results: Of the 357 patients tested, 25 (7%) had CD. The frequency of HLA- DQA1*0501-DQB1*0201 (T1DM + CD 68% vs T1DM 62%) and of DQA1*0301-DQB1*0302 (T1DM + CD 40% vs T1DM 35%) haplotypes, between T1DM patients with and without CD, was statistically comparable. A trend towards a reduction of the risk of CD (p= 0.055, OR: 0.22, CI 0.05: 1.04) was observed in patients with T1DM (28% vs T1DM + CD 2%) who did not carry either the HLA-DQA1*0501-DQB1*0201 or the DQA1*0301-DQB1*0302 haplotype. Conclusion: A high prevalence of HLA-DQA1* and -DQB1* susceptibility haplotypes for CD was observed both in EMA-negative diabetics and in those with associated CD. The implementation of screening programmes of CD in a T1DM population, based on the identification of HLA susceptibility haplotypes, seems to be of limited usefulness. Serial serologic screening of diabetic patients remains the advisable strategy.

Changes of diurnal variation of peak expiratory flow rate (%PEF variation) and their relationship with bronchial hyperresponsiveness (BHR) to methacholine (PC20) were evaluated in 12 children with mild-to-moderate asthma and house-dust mite allergy, during successive periods of stay in a mite-free environment at high altitude (1756 m) and at their home at sea level. The children remained at the high altitude from October until the end of December; then they spent a 3-week period at home and returned to high altitude residence in January. PEF was measured daily, in the morning and in the evening, during the 3 months' stay at high altitude and them for 10 days after the return in January. PC20 was assessed in 8/12 children, once a month from October to December, and at the return in January. Mean absolute PEF values did not change significantly throughout the study. From October to December, patients showed a significant decrease of mean %PEF variation (P = 0.04), while PC20 showed an increase (P = 0.05). After the 3 weeks at home, both %PEF variation (P = 0.03) and PC20 (P = 0.05) significantly worsened. The correlation between PC20 values and mean %PEF variation in the 2 days before and after each methacholine test was r = -0.63 (P = 0.001). Our data suggest that there is a beneficial effect of a prolonged stay in a mite-free environment, on both PEF variability and BHR, also in asthmatic children with good pulmonary function. PEF variability and bronchial responsiveness to methacholine were significantly correlated also for small changes of the two variables.

Plasma fibronectin (FN) concentrations were measured by an immunonephelometric method in cord blood from 76 healthy newborns (45 full term and 31 preterm), in 181 healthy children, from 1 month-15 years old, divided by age into seven groups and in 81 control adults. FN levels in newborns were 35% of those of adults. There was no difference between plasma FN in term and preterm (gestational age greater than 30 weeks) infants. Preterm newborns below the gestational age of 30 weeks showed particularly low FN levels. No clear correlation was seen with birth weight. In the child population, a strong increase in FN values was noted in the first 6 months of life, rising to 65% of the normal adult values. No further increase occurred until puberty.