Outcomes of MIS-C patients treated with anakinra: a retrospective multicenter national study.

Background: The treatment of multisystem inflammatory syndrome in children unresponsive to first-line therapies (IVIG and/or steroids) is challenging. The effectiveness of IL-1 receptor antagonist, anakinra, is debated. Patients and methods: We conducted an anonymous retrospective multicenter study on MIS-C patients treated with anakinra in Italy from January 2020 to February 2021. Our study outcomes included the percentage of patients who required further therapeutic step-up, the percentage of patients who experienced fever resolution within 24 h and a reduction of CRP by half within 48 h, and the percentage of patients who developed Coronary Artery Anomalies (CAA) during follow-up. Results: 35 cases of MIS-C were treated in 10 hospitals. Of these, 13 patients started anakinra while in the ICU, and 22 patients started anakinra in other wards. 25 patients (71.4%) were treated with corticosteroids at a starting dose 2-30 mg/Kg/day plus IVIG (2 g/Kg), 10 patients (28.6%) received only corticosteroids without IVIG. Anakinra was administered intravenously to all patients in Group A (mean dose 8 mg/Kg/day), and subcutaneously in Group B (mean dose 4 mg/Kg/day). Only two patients required further treatment step-up and no patients developed CAA after receiving anakinra. The most commonly observed side effect was an increase in ALT, occurring in 17.1% of patients. Conclusions: In this retrospective cohort of severe MIS-C patients treated with anakinra we report favorable clinical outcomes with a low incidence of side effects. The simultaneous use of steroids ± IVIG in these patients hinders definitive conclusions regarding the need of IL-1 inhibition in MIS-C treatment.

COVID-19 in Infants Less than 3 Months: Severe or Not Severe Disease?

Compared to adults, severe or fatal COVID-19 disease is much less common in children. However, a higher risk for progression has been reported in infants. Different pediatric COVID-19 severity scores are reported in the literature. Methods: Subjects under 90 days of age admitted to 35 Italian institutions for COVID-19 were included. The severity of COVID-19 was scored as mild/moderate or severe/critical following the classification reported in the literature by Venturini, Dong, Kanburoglu, and Gale. To assess the diagnostic accuracy of each classification system, we stratified all enrolled patients developing a posteriori severity score based on clinical presentation and outcomes and then compared all different scores analyzed. Results: We included 216 infants below 90 days of age. The most common symptom was fever, followed by coryza, poor feeding, cough, and gastrointestinal manifestations. According to Venturini, Dong, Kanburoglu, and Gale's severity scores, 18%, 6%, 4.2%, and 29.6% of infants presented with severe/critical disease, respectively. A correlation analysis between these four scores and the a posteriori severity score assigned to all enrolled subjects was performed, and a crescent strength of correlation from Gale (R = 0.355, p < 0.001) to Venturini (R = 0.425, p < 0.001), Dong (R = 0.734, p < 0.001), and Kanburoglu (R = 0.859, p < 0.001) was observed. Conclusions: The percentage of infants with severe COVID-19 varies widely according to the score systems. A unique clinical score should be designed for neonates and infants with COVID-19.

A neonatal cluster of novel coronavirus disease 2019: clinical management and considerations.

BACKGROUND: Lately, one of the major clinical and public health issues has been represented by Coronavirus disease of 2019 (COVID-19) during pregnancy and the risk of transmission of the infection from mother to child. Debate on perinatal management and postnatal care is still ongoing, principally questioning the option of the joint management of mother and child after birth and the safety of breastfeeding. According to the available reports, neonatal COVID-19 appears to have a horizontal transmission and seems to be paucisymptomatic or asymptomatic, compared to older age groups. The aim of this work is to describe a cluster of neonatal COVID-19 and discuss our experience, with reference to current evidence on postnatal care and perinatal management. METHODS: This is a retrospective observational case series of five mother-child dyads, who attended the Labor and Delivery Unit of a first-level hospital in Italy, in March 2020. Descriptive statistics for continuous variables consisted of number of observations, mean and the range of the minimum and maximum values. RESULTS: Five women and four neonates tested positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). In one case, the mother-child dyad was separated and the neonate remained negative on two consecutive tests. Two positive neonates developed symptoms, with a predominant involvement of the gastrointestinal tract. Blood tests were unremarkable, except for a single patient who developed mild neutropenia. No complications occurred. CONCLUSIONS: We agree that the decision on whether or not to separate a positive/suspected mother from her child should be made on an individual basis, taking into account the parent's will, clinical condition, hospital logistics and the local epidemiological situation. In conformity with literature, in our study, affected neonates were asymptomatic or paucisymptomatic. Despite these reassuring findings, a few cases of severe presentation in the neonatal population have been reported. Therefore, we agree on encouraging clinicians to monitor the neonates with a suspected or confirmed infection.

Differences in morbidity and mortality in Down syndrome are related to the type of congenital heart defect.

Morbidity and mortality in Down syndrome (DS) are mainly related to congenital heart defects (CHDs). While CHDs with high prevalence in DS (typical CHDs), such as endocardial cushion defects, have been extensively described, little is known about the impact of less common CHDs (atypical CHDs), such as aortic coarctation and univentricular hearts. In our single-center study, we analyzed, in observational, retrospective manner, data regarding cardiac features, surgical management, and outcomes of a cohort of DS patients. Literature review was performed to investigate previously reported studies on atypical CHDs in DS. Patients with CHDs were subclassified as having typical or atypical CHDs. Statistical analysis was performed for comparison between the groups. The study population encompassed 859 DS patients, 72.2% with CHDs, of which 4.7% were atypical. Statistical analysis showed a significant excess in multiple surgeries, all-cause mortality and cardiac mortality in patients with atypical CHDs (p = .0067, p = .0038, p = .0001, respectively). According to the Kaplan-Meier method, survival at 10 and 40 years was significantly higher in typical CHDs (99 and 98% vs. 91 and 84%, log rank <0.05). Among atypical CHDs, it seems that particularly multiple complex defects in univentricular physiology associate with a worse outcome. This may be due to the surgical difficulty in managing univentricular hearts with multiple defects concurring to the clinical picture or to the severity of associated defects themselves. Further studies need to address this specific issue, also considering the higher pulmonary pressures, infective complications, and potential comorbidities in DS patients.

SOS1 mutations in Noonan syndrome: Cardiomyopathies and not only congenital heart defects! Report of six patients including two novel variants and literature review.

Noonan syndrome (NS) is caused by mutations in more than 10 genes, mainly PTPN11, SOS1, RAF1, and RIT1. Congenital heart defects and cardiomyopathy (CMP) are associated with significant morbidity and mortality in NS. Although hypertrophic CMP has "classically" been reported in association to RAF1, RIT1, and PTPN11 variants, SOS1 appears to be poorly related to CMP. Patients with NS attending our Center from January 2013 to June 2018 were eligible for inclusion if they carried SOS1 variants and presented with-or developed-CMP. Literature review describing the co-existence of SOS1 mutation and CMP was also performed. We identified six patients with SOS1 variants and CMP (male to female ratio 2:1) including two novel variants. CMP spectrum encompassed: (a) dilated CMP, (b) nonobstructive hypertrophic CMPs, and (c) obstructive hypertrophic CMPs. Survival is 100%. Literature review included 16 SOS1 mutated in CMP. CMP, mainly hypertrophic, has been often reported in association to RAF1, RIT1, and PTPN11 variants. Differently from previous reports, due to the frequent association of SOS1 variants and CMP in our single center experience, we suggest potential underestimated proportion of SOS1 in pediatric CMPs.

Evaluation of thermal comfort and carbon dioxide levels during ventricular-assist-device implant. / Valutazione del benessere termico e dei livelli di anidride carbonica durante l'impianto di in dispositivo di assistenza ventricolare.

BACKGROUND: Environmental measurements were performed in an operating theatre within a pediatric cardiac department, during a surgical operation involving the use of carbon dioxide for the implantation of a ventricular system (VAD). OBJECTIVES: After some reports from the staff, who were complaining about low temperatures in the operating room, it was decided to check carbon dioxide levels, the conditions of thermal comfort and the presence of draughts. METHODS: Microclimatic parameters and carbon dioxide concentration were performed with a microclimatic unit Delta OHM model HD 32.1. RESULTS: The carbon dioxide concentration values measured during the operation were below the levels at which the working environment was not comfortable, as expressed by both the ASHRAE (American Society of Heating, Refrigeration and Air Conditioning Engineers) and the ACGIH (American Conference of Government Industrial Hygienists) standards. PMV (Predicted Mean Vote) and PPD (Preticted Pencentage of Dissatisfied) values obtained indicate a thermal discomfort tendency to cold perception, perceived in particular by the anesthesiologist, circulating nurse and cardiovascular perfusionist. Airflow discomforts occurred at different stages of the operation. CONCLUSIONS: Acting on the air conditioning system, decreasing air velocity, while guaranteeing the minimum number of air recirculation prescribed by the regulations, appears to be the best prevention measure. Changing the mode of laminar air inlet above the cot may, however, affect the "wash" effect of the operating range. Otherwise, a "protective" measure could concern staff clothes, providing them with garments with better insulation, in order to protect the neck area, which is affected by the effects of draughts.

Congenital primary adrenal insufficiency and selective aldosterone defects presenting as salt-wasting in infancy: a single center 10-year experience.

BACKGROUND: Salt-wasting represents a relatively common cause of emergency admission in infants and may result in life-threatening complications. Neonatal kidneys show low glomerular filtration rate and immaturity of the distal nephron leading to reduced ability to concentrate urine. METHODS: A retrospective chart review was conducted for infants hospitalized in a single Institution from 1(st) January 2006 to 31(st) December 2015. The selection criterion was represented by the referral to the Endocrinology Unit for hyponatremia (serum sodium <130 mEq/L) of suspected endocrine origin at admission. RESULTS: Fifty-one infants were identified. In nine infants (17.6 %) hyponatremia was related to unrecognized chronic gastrointestinal or renal salt losses or reduced sodium intake. In 10 infants (19.6 %) hyponatremia was related to central nervous system diseases. In 19 patients (37.3 %) the final diagnosis was congenital adrenal hyperplasia (CAH). CAH was related to 21-hydroxylase deficiency in 18 patients, and to 3ß-Hydroxysteroid dehydrogenase (3ßHSD) deficiency in one patient. Thirteen patients (25.5 %) were affected by different non-CAH salt-wasting forms of adrenal origin. Four familial cases of X-linked adrenal hypoplasia congenita due to NROB1 gene mutation were identified. Two unrelated girls showed aldosterone synthase deficiency due to mutation of the CYP11B2 gene. Two unrelated infants were affected by familial glucocorticoid deficiency due to MC2R gene mutations. One girl showed pseudohypoaldosteronism related to mutations of the SCNN1G gene encoding for the epithelial sodium channel. Transient pseudohypoaldosteronism was identified in two patients with renal malformations. In two infants the genetic aetiology was not identified. CONCLUSIONS: Emergency management of infants presenting with salt wasting requires correction of water losses and treatment of electrolyte imbalances. Nevertheless, the differential diagnosis may be difficult in emergency settings, and sometimes hospitalized infants presenting with salt-wasting are immediately started on steroid therapy to avoid life-threatening complications, before the correct diagnosis is reached. Physicians involved in the management of infants with salt-wasting of suspected hormonal origin should remember that, whenever practicable, a blood sample for the essential hormonal investigations should be collected before starting steroid therapy, to guide the subsequent diagnostic procedures and in particular to address the analysis of candidate genes.

Effectiveness of an App for Reducing Preoperative Anxiety in Children: A Randomized Clinical Trial.

IMPORTANCE: Effective methods to reduce children's preoperative anxiety (such as giving information beforehand, organizing a tour of the operating room [OR] before the intervention, and incorporating clown physicians) may be difficult to implement for some hospitals, as they are time-consuming and expensive and require hospital staff to be performed. OBJECTIVE: To test the effectiveness of Clickamico, an app that shows clown physicians giving a comical and informative tour of the OR, for reducing preoperative anxiety in children. DESIGN, SETTING, AND PARTICIPANTS: This unblinded randomized clinical trial included 40 children aged 6 to 11 years undergoing a planned surgical intervention at a third-level Italian pediatric hospital from December 2013 to September 2014 randomized into experimental (n = 20) and control (n = 20) groups. INTERVENTIONS: The experimental intervention was a 6-minute video showing 2 clown physicians visiting the OR and explaining to each other what is in the OR in a joking way. The video was shown on a tablet to children in the experimental group the afternoon preceding a planned surgical procedure. The control intervention was the standard informative intervention regarding the surgical procedure the next day. MAIN OUTCOMES AND MEASURES: The main outcome was preoperative anxiety. Preoperative anxiety was measured before the experimental and control interventions and immediately before entering the OR using the modified Yale Preoperative Anxiety Scale (m-YPAS). RESULTS: The experimental and control groups were homogeneous with regard to age (mean [SD] age, 8.8 [2.5] vs 8.6 [2.2] years), sex (female, 11 [55.0%] vs 9 [45.0%]), parents' age (mean [SD] age, 41.8 [6.2] vs 41.3 [5.0] years), and previous surgical procedures (already underwent surgical procedure, 9 [45.0%] vs 10 [50.0%]). The initial mean (SD) m-YPAS scores were 37.3 (21.7) and 37.1 (13.8) for the experimental and control groups, respectively; the mean (SD) m-YPAS scores when entering the OR were 33.0 (18.4) and 48.6 (15.9), respectively (P = .009). The mean (SD) difference between the m-YPAS score at the first and second measurements of each participant was -2.8 (7.2) in the experimental group and 10.7 (10.8) in the control group. The 13.5-point difference between these averages was statistically significant (P = .003). CONCLUSIONS AND RELEVANCE: The app was effective in reducing preoperative anxiety in Italian children admitted to an Italian National Health System pediatric hospital and may act as a substitute for staff-provided interventions, allowing possible reductions of hospital costs. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01688115.

Actual implementation of sick children's rights in Italian pediatric units: a descriptive study based on nurses' perceptions.

BACKGROUND: Several charters of rights have been issued in Europe to solemnly proclaim the rights of children during their hospital stay. However, notwithstanding such general declarations, the actual implementation of hospitalized children's rights is unclear. The purpose of this study was to understand to which extent such rights, as established by the two main existing charters of rights, are actually implemented and respected in Italian pediatric hospitals and the pediatric units of Italian general hospitals, as perceived by the nurses working in them. METHODS: Cross-sectional study. A 12-item online questionnaire was set up and an invitation was sent by email to Italian pediatric nurses using professional mailing lists and social networks. Responders were asked to score to what extent each right is respected in their hospital using a numeric scale from 1 (never) to 5 (always). RESULTS: 536 questionnaires were returned. The best implemented right is the right of children to have their mothers with them (mean score 4.47). The least respected one is the right of children to express their opinion about care (mean 3.01). Other rights considered were the right to play (4.29), the right to be informed (3.95), the right to the respect of privacy (3.75), the right to be hospitalized with peers (3.39), the right not to experience pain ever (3.41), and the right to school (3.07). According to the majority of nurses, the most important is the right to pain relief. Significant differences in the implementation of rights were found between areas of Italy and between pediatric hospitals and pediatric units of general hospitals. CONCLUSION: According to the perception of pediatric nurses, the implementation of the rights of hospitalized children in Italian pediatrics units is still limited.

Perception of venipuncture pain in children suffering from chronic diseases.

BACKGROUND: Venipuncture pain in children results from a variety of co-factors which increase the intensity of the nociceptive stimulus. Among them, anticipatory anxiety plays an important role. Children with chronic diseases undergo invasive procedures and venipuncture more often than other children. Some healthcare professionals still believe that children who are repeatedly exposed to painful procedures, such as children with chronic diseases, gradually increase their pain tolerance and that, as a result, they have a higher pain threshold than children with no chronic diseases. The purpose of this study was to assess whether a difference exists in the perception of venipuncture pain between children with chronic diseases and children with no previous health problems nor experience of venipuncture. METHODS: A cross-sectional study was carried out using the Wong and numeric pain scales and the Observational Scale of Behavioral Distress (OSBD) for the assessment of behavioral distress. A group of children with chronic diseases and a group of children with no previous health problems nor experience of venipuncture, aged 4 to 12 years, both boys and girls, were observed during a standardized venipuncture procedure. RESULTS: The study included 230 children in total: 82 of them suffered from chronic diseases and had already experienced venipuncture at least once, while the remaining 148 children had no previous experience of venipuncture. The children with chronic diseases reported more pain (median pain score of 8 on the Wong or numeric scales,) and showed more signs of behavioral distress (median score of 27 on the OSBD) than non-chronic children (median pain score of 2 on the Wong/numeric scales, p = 0.00001; median OSBD score 5, p = 0.00001). CONCLUSIONS: Our study suggests that children with chronic diseases have a lower pain threshold than children of the same sex and age who experience venipuncture for the first time.

Cross-sectional study on differences in pain perception and behavioral distress during venipuncture between italian and chinese children.

Venipuncture is perhaps the scariest aspect of hospitalization for children as it causes pain and high levels of behavioral distress. Pain is a complex experience which is also influenced by social factors such as cultural attitudes, beliefs and traditions. Studies focusing on ethnic/cultural differences in pain perception and behavioral distress show controversial results, in particular with regards to children. The aim of this paper is to evaluate differences in pain perception and behavioral manifestations between Italian and Chinese children undergoing a venipuncture, through a cross-sectional study. Behavioral distress and self-reported pain were measured in Chinese and Italian outpatient children during a standardized blood-drawing procedure, using the Observational Scale of Behavioral Distress (OSBD) and pain scales. We observed 332 children: 93 Chinese and 239 Italian. Chinese children scored higher than Italians on pain scales - mean scores 5.3 (95%CI 4.78-5.81) vs. 3.2 (95%CI 2.86-3.53) - but lower mean OSBD scores - mean 4.1 (95%CI 3.04-5.15) vs. 8.1 (95%CI 7.06-9.14). Our data suggest that Chinese children experience higher levels of pain than their Italian peers, although they show more self-control in their behavioral reaction to pain when experiencing venipuncture.