Antibiotic Prophylaxis in Infants with Grade III, IV, or V Vesicoureteral Reflux.

BACKGROUND: The efficacy of continuous antibiotic prophylaxis in preventing urinary tract infection (UTI) in infants with grade III, IV, or V vesicoureteral reflux is controversial. METHODS: In this investigator-initiated, randomized, open-label trial performed in 39 European centers, we randomly assigned infants 1 to 5 months of age with grade III, IV, or V vesicoureteral reflux and no previous UTIs to receive continuous antibiotic prophylaxis (prophylaxis group) or no treatment (untreated group) for 24 months. The primary outcome was the occurrence of the first UTI during the trial period. Secondary outcomes included new kidney scarring and the estimated glomerular filtration rate (GFR) at 24 months. RESULTS: A total of 292 participants underwent randomization (146 per group). Approximately 75% of the participants were male; the median age was 3 months, and 235 participants (80.5%) had grade IV or V vesicoureteral reflux. In the intention-to-treat analysis, a first UTI occurred in 31 participants (21.2%) in the prophylaxis group and in 52 participants (35.6%) in the untreated group (hazard ratio, 0.55; 95% confidence interval [CI], 0.35 to 0.86; P = 0.008); the number needed to treat for 2 years to prevent one UTI was 7 children (95% CI, 4 to 29). Among untreated participants, 64.4% had no UTI during the trial. The incidence of new kidney scars and the estimated GFR at 24 months did not differ substantially between the two groups. Pseudomonas species, other non-Escherichia coli organisms, and antibiotic resistance were more common in UTI isolates obtained from participants in the prophylaxis group than in isolates obtained from those in the untreated group. Serious adverse events were similar in the two groups. CONCLUSIONS: In infants with grade III, IV, or V vesicoureteral reflux and no previous UTIs, continuous antibiotic prophylaxis provided a small but significant benefit in preventing a first UTI despite an increased occurrence of non-E. coli organisms and antibiotic resistance. (Funded by the Italian Ministry of Health and others; PREDICT ClinicalTrials.gov number, NCT02021006; EudraCT number, 2013-000309-21.).

Nonpharmacological treatment of rumination syndrome in childhood: A systematic review of the literature.

Rumination syndrome (RS) is a complex functional disorder characterized by recurrent, repetitive regurgitation of recently swallowed food. RS may have medical and psychosocial implications, compromising the quality of life and causing high rates of school absenteeism. Pediatric RS has been poorly studied and little evidence regarding its treatment is available. This systematic review aims to evaluate the literature on the nonpharmacological treatment of RS in childhood. A systematic literature search was conducted on MEDLINE/PubMed, CINAHL, Cochrane Library, PsycINFO, and PEDro, from 2000 to 2023. The methodological quality of the publications was assessed by applying the guidelines proposed by the Equator network, according to the different designs of study, and the risk of bias was evaluated with the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I). Five hundred ninety-six studies were screened, and 7 studies were included in the review. Diaphragmatic breathing was the most used nonpharmacological treatment, and it was always combined with other therapeutic strategies. The vast heterogeneity of the physical or mental comorbidities and the methodology adopted in the publications did not allow a comparative analysis of the different treatments. Regardless of the type of treatment, high-intensity therapeutic programs and specific operators' training emerged as the most influencing factors for patients' outcomes. According to the available evidence, there is not enough high-quality evidence to suggest a defined therapeutic strategy. Large observational studies on selected patients accounting for possible confounders, with adequate follow-up times, and with clearly defined treatment regimens are needed to identify the best therapeutic approach.

Effectiveness of bismuth subgallate for preventing bleeding following adenotonsillectomy: A multicentre study.

BACKGROUND: Tonsillectomy and adenotonsillectomy are surgical procedures routinely performed worldwide, with various complications, including postoperative bleeding (PTH). Among haemostatic agents, bismuth subgallate (BS) has been employed in the past decades, but its use is controversial in children. OBJECTIVE: This retrospective, multicentre study aims to evaluate the effectiveness and safety of BS in preventing PTH following tonsillectomy and adenotonsillectomy. MATERIALS AND METHODS: Two cohorts of children between 0 and 18 years of age were compared in two different hospitals. The first (active) group of patients included children who underwent tonsillectomy/adenotonsillectomy performed using BS added to gauze swabs, whereas this agent was not administered to the second (control) group. The following variables were analysed: age, gender, degree of tonsillar hyperplasia, length of hospital stay, acute complications (including bleeding and infection), further admissions to the Paediatric Emergency Department (PED), and further hospital admissions in the 30 days postoperatively. RESULTS: Four-thousand- seven hundred forty-four children were included in the study, 2598 in the active group and 2146 in the control group. The cases included in the active treatment group displayed a significantly reduced PTH prevalence, 1.4 versus 2.6 % (p < 0.05). No cases of neurological complications or aspiration pneumonia were detected. CONCLUSIONS: This study supports BS as a safe and reliable option for preventing severe PTH following tonsillectomy/adenotonsillectomy.

Decrease in Mycophenolate Mofetil Plasma Concentration in the Presence of Antibiotics: A Case Report in a Cystic Fibrosis Patient with Lung Transplant.

Immunosuppression management in transplant recipients is a critical component of pharmacotherapy. This becomes particularly crucial when patients are exposed to multiple medications that may lead to pharmacological interactions, potentially compromising the effectiveness of immunosuppression. We present the case of a 46-year-old patient diagnosed with cystic fibrosis in childhood at our hospital, who underwent bilateral lung transplantation and is undergoing immunosuppressive therapy. The patient was hospitalized due to an acute pulmonary exacerbation. During the hospitalization, the patient was administered various classes of antibiotics while continuing the standard antirejection regimen of everolimus and mycophenolate. Plasma concentrations of immunosuppressants, measured after antibiotic therapy, revealed significantly lower levels than the therapeutic thresholds, providing the basis for formulating the hypothesis of a drug-drug interaction phenomenon. This hypothesis is supported by the rationale of antibiotic-induced disruption of the intestinal flora, which directly affects the kinetics of mycophenolate. These levels increased after discontinuation of the antimicrobials. Patients with CF undergoing lung transplantation, especially prone to pulmonary infections due to their medical condition, considering the enterohepatic circulation of mycophenolate mediated by intestinal bacteria, necessitate routine monitoring of mycophenolate concentrations during and immediately following the cessation of antibiotic therapies, that could potentially result in insufficient immunosuppression.

Celiac Disease Frequency Is Increased in IgE-Mediated Food Allergy and Could Affect Allergy Severity and Resolution.

OBJECTIVES: An increased frequency of celiac disease (CeD) has been reported in severe Immunoglobulin E (IgE) -mediated food allergy (FA). This observation requires confirmation, and whether CeD affects FA severity and resolution is unknown. The study aims to estimate the prevalence of CeD in patients with FA and to investigate whether CeD affects FA severity and oral tolerance. METHODS: Consecutive patients with FA referred for allergen reintroduction, either to evaluate allergy resolution or to start oral immunotherapy (OIT), were evaluated for CeD and for FA severity. The primary outcome was the prevalence of CeD. Secondary outcomes were the frequency of severe FA and the level of clinical tolerance at study entry and at last follow-up in patients with isolated FA versus patients with FA + CeD. RESULTS: Two hundred twenty-eight patients were included. CeD was confirmed in 15 patients (6.6%) of whom, 8 patients had a previously established diagnosis of CeD and were on a gluten-free diet. Severe FA was observed in 12 patients with FA + CeD (80%) versus 88 patients with FA (42%) ( P = 0.006). At baseline, patients with FA + CeD had significantly higher median allergen-specific IgE levels [61.8 kU/L; interquartile range (IQR) 11.6-279.0] compared to patients with FA (20.3 kU/L; IQR 2.9-72.7) ( P < 0.001). Complete clinical tolerance was observed in 1 of 15 patients (7%) with FA + CeD versus 98 of 205 patients (48%) with FA ( P = 0.002). CONCLUSIONS: CeD is highly prevalent in patients with FA and could affect FA severity and response to OIT. CeD screening should be considered in patients with severe or persistent FA.

Oral ibuprofen versus oral ketorolac for children with moderate and severe acute traumatic pain: a randomized comparative study.

This study is to compare ibuprofen and ketorolac for children with trauma-related acute pain. We conducted a multicentre randomized, double-blind, controlled trial in the Paediatric Emergency Department setting. We enrolled patients aged 8 to 17 who accessed the emergency department for pain related to a limb trauma that occurred in the previous 48 h. At the admission, patients were classified based on numeric rating scale-11 (NRS-11) in moderate (NRS 4-6) and severe (NRS 7-10) pain groups. Each patient was randomized to receive either ibuprofen (10 mg/kg) or ketorolac (0.5 mg/kg) and the placebo of the not given drug in a double dummies design. NRS-11 was asked every 30 min until 2 h after drug and placebo administration. The primary outcome was NRS-11 reduction at 60 min. Among 125 patients with severe pain, NRS-11 reduction after 60 min from drug administration was 2.0 (IQR 1.0-4.0) for ibuprofen and 1.0 (IQR 1.0-3.0) for ketorolac (p = 0.36). Ibuprofen was significantly better, considering secondary outcomes, at 90 min with a lower median of NRS-11 (p 0.008), more patients with NRS-11 less than 4 (p 0.01) and a reduction of pain score of more than 3 NRS-11 points (p 0.01). Among 87 patients with moderate pain, the NRS-11 reduction after 60 min from drug administration was 1.63 (± 1.8) for ibuprofen and 1.8 (± 1.6) for ketorolac, with no statistically significant difference.Conclusions: Oral ibuprofen and ketorolac are similarly effective in children and adolescents with acute traumatic musculoskeletal pain.Trial registration: ClinicalTrial.gov registration number: NCT04133623.

Active production of music as distraction for venipuncture in children and adolescents: a randomized clinical trial.

More than 50% of children report considerable pain during venipuncture or intravenous cannulation. Despite the tools and techniques may be employed to reduce pain and distress in everyday clinical practice, the care offered is frequently insufficient. Music's potential effect in healthcare settings has received increasing attention. This study aimed to verify if the active production of music with a Leap Motion Controller could help decreasing pain and distress during venipuncture in children and adolescents. We conducted an open-label randomized controlled clinical trial with parallel arms. Children aged 8 to 17 were enrolled at the blood-drawing center of the Institute for Maternal and Child Health IRCCS Burlo Garofolo of Trieste, Italy. We hypothesized that in order to demonstrate an adequate improvement in the pain score in the intervention group, at least 200 children, 100 in each group, were needed, with alpha 5% and 1-beta 80%. Differences between the groups were evaluated with the nonparametric Mann-Whitney U-test. The subjects were randomly assigned either to the active production of music group or to the standard of care group. The primary outcome was the median self-reported procedural pain score between experimental and standard of care group. Secondary outcomes were: the median pain and distress scores according to parental judgment and operators' judgment between the experimental and control group. Three hundred subjects entered the study and were randomized, 150 in the active production of music group and 150 in the standard of care group. Median self-reported pain scores were 1 (0-2) in the active production of music group and 2 (1-2) in the standard of care group and this difference was statistically significant (p = 0.0016). Median procedural distress was 1 (0-3) in the active production of music group and 3 (1-6) in the standard of care group, according to parental judgment, and this difference was statistically significant (p = 0.0000016). CONCLUSION: This research showed that the active production of music is a valuable distraction technique to decrease venipuncture related pain and distress in children and adolescents. TRIAL REGISTRATION: The study protocol was registered with ClinicalTrial.gov (June 28[th] 2022, NCT05441241) before the start of the subjects' enrolment. WHAT IS KNOWN: • The benefits of music on pain and anxiety are well known and have been tested during different painful procedures. • The effect of active production of music has never been tested in children during venipuncture. WHAT IS NEW: • In our study median self-reported pain scores and median procedural distress, according to parental judgment, were lower in the active production of music group than in the standard of care group and these differences were statistically significant.

Impact of compounded drugs on the caregivers' burden of home therapy management in pediatric palliative care: A descriptive study.

BACKGROUND: Children with medical complexity need complex assistance, that considerably affects caregivers' quality of life. They often need multiple medications, with a consequent relevant risk of errors or poor compliance. Galenic (or compounded) drugs are blended in the pharmacy's laboratory worldwide according to different rules and tailoring the patient's needs. While their use may sometimes simplify these therapies, little is known about parents' attitude about this issue. AIM: This study aimed at investigating the complexity of the daily therapy management and exploring the parents' opinions about galenic compounds. DESIGN: Parents were interviewed by using a structured questionnaire. SETTING: Children followed by the Pediatric Palliative Care Network in Friuli Venezia Giulia, Italy, were included from November 2021 to April 2022. Those diagnosed with malignancies were excluded, since therapies are mainly administered through a central venous catheter. RESULTS: Thirty-four parents were interviewed. Fourteen patients took drugs orally, one via nasogastric tube (NGT), 18 via gastrostomy, and one orally + NGT. The mean number of drugs taken every day was six (2-14), in mean 10 (3-18) administrations, that overall required a mean of 44 (8-180) minutes to be delivered. Twenty-eight parents used galenic compounds, and 24 reported relevant advantages, because of a ready-to-use and safe formulation. CONCLUSIONS: The therapy management of children with medical complexity relies on parents. Galenic compounds may improve both patients' and caregivers' quality of life, either in terms of shorter time of administration or smaller risk of errors. Therefore, their use should be encouraged worldwide, according to the different reference rules.

Children with mild hyponatremia at the emergency department are at higher risk of hospitalization.

BACKGROUND: Mild hyponatremia is frequently encountered in the pediatric emergency department (PED). Although usually of little clinical concern, its prognostic meaning as a possible marker of more severe disease has not yet been well established. METHODS: We retrospectively analyzed data from children and adolescents who performed a blood sample with plasmatic sodium measurement on admission to the PED of IRCCS "Burlo Garofolo" Pediatric Hospital in Trieste, Italy, in 2019. We compared the rate, length of admissions and laboratory characteristics of patients with hyponatremia to those with normal sodium. RESULTS: Among 807 subjects, hyponatremia (sodium < 135 mEq/L) was present in 17.6%, being mild (between 130 and 134 mEq/L) in 16.5%. Hyponatremic patients were younger, more frequently males, with an infection diagnosis, mainly of the respiratory tract and viral aetiology. They presented higher C-reactive protein (CRP) levels and erythrocyte sedimentation rates (ESR). Compared to normonatremic individuals, hyponatremic patients presented a higher risk of underlying infection (aOR 2.02; 95%CI 1.33-3.08), hospital admission (aOR 1.72; 95%CI 1.06-2.48), and a hospital stay of > 5 days (aOR 1.99; 95%CI 1.03-3.85). When considering only subjects with mild hyponatremia, we found similar results. CONCLUSION: Hyponatremia and mild hyponatremia in the PED are associated with an increased admission rate and extended hospital stays. Mild hyponatremia should be considered a warning sign for a possibly more serious condition.

A Short-Duration Gonadotropin-Releasing Hormone Stimulation Test for the Diagnosis of Central Precocious Puberty.

Background and Objectives: The gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard method for diagnosing central precocious puberty (CPP), although it requires multiple blood samplings over 120 min. This study aimed to evaluate if a shorter test may have an equivalent diagnostic accuracy. Materials and Methods: We retrospectively reviewed the GnRH tests of 188 consecutive pediatric patients (169 females) referred for signs of early pubertal development. The diagnostic accuracy of the hormonal levels was evaluated at different time points (15, 0, 60, 90, and 120 min after the GnRH stimulus). Results: A diagnosis of CPP was made in 130 cases (69%), with 111 (85%) being female. Sensitivity and specificity ratings higher than 99% for the diagnosis of CPP were achieved for LH levels ≥4.7 mU/mL at 30 and 60 min after the stimulus (area under the ROC curve (AUC) = 1), with no further increase in the diagnostic accuracy in the remaining time points. No sex differences in diagnostic accuracy were found. The LH/FSH ratio at 30 min showed a sensitivity of 94.9%, with an AUC of 0.997 and a value ≥0.76. Conclusions: A short-duration GnRH test of 60 min provided optimal results for the diagnosis of CPP. Extending the test for an extra hour is therefore unnecessary and inadvisable.

Pediatric males receiving hematopoietic stem cell transplant lose their male disadvantage in disease risk after the procedure: A retrospective observational study.

Sex differences play a relevant role in cancer susceptibility, incidence and survival. Exploring such differences is difficult because of the close interplay of genetic, epigenetic and hormonal factors. However, a better understanding of the role of such disparities in cancer mechanisms could improve its prevention and therapy. Our study explores how sex differences in pediatric outcomes vary after undergoing first and advanced-line therapy for hematological malignancies. The primary goal was to evaluate if sex differences in pediatric outcomes after first-line therapy persist after allogeneic hematopoietic stem cell transplantation (HSCT). The secondary goal was to analyze sex differences in disease risk at onset and pediatric outcomes after first-line therapy to compare our results with the literature's reported results. Among a total of 485 patients (280 males, 205 females) admitted for hematological malignancies, disease risk at the onset was significantly higher in males (P < .05). One hundred and seventy-four patients (111 males and 63 females) had a high-risk disease requiring HSCT. Before HSCT, all patients underwent myeloablative conditioning, which substantially impaired gonadal function. Although the number of boys undergoing HSCT was almost double that of girls, there were no sex-related differences in overall survival, cancer relapse and complications after HSCT exposure (P > .05). These findings suggest that the existing sex differences in cancer risk ab initio can be somehow flattened by a conditioning regimen, shedding new light on the role of hormonal factors in cancer mechanism and management.

Dietary Beliefs in Children and Adolescents with Inflammatory Bowel Disease and their Parents.

OBJECTIVES: Patients with inflammatory bowel disease (IBD) may have diet-related beliefs that lead to restrictive dietary behaviours. This study aimed to evaluate dietary beliefs in young patients with IBD and their parents and the presence of restrictive behaviours. METHODS: A questionnaire regarding dietary beliefs was administered to IBD patients aged 8-17 years and their parents. A Food Frequency Questionnaire was administered to patients with IBD and a peer control group. RESULTS: Seventy-five patients and 105 parents were interviewed. Twenty-seven (36%) patients and 39 (37.1%) parents believed that dietary modifications could control the IBD course.Twenty-five (33.0%) patients and 33 (33.0%) parents believe that some dietary components can prevent relapse or improve symptoms (mainly abdominal pain and diarrhoea), while 36 (48%) patients and 60 (60.0%) parents believe that some foods can induce or worsen symptoms during an IBD flare.Patients believe that milk, dairy, fried and spicy foods, sweets and carbonated drinks could have a negative effect on IBD while fruits, vegetables and rice could have a positive impact. Parents believe that fruits and vegetables have a negative effect.Responses did not differ among patients classified according to IBD phenotype, activity status, or current therapies.Compared to controls, young patients with IBD have reduced daily consumption of milk, lunch meat, raw and cooked vegetables. CONCLUSIONS: About one-third of paediatric patients with IBD and their parents have dietary beliefs that lead to restrictive dietary behaviours.

Prevalence of children witnessed violence in a pediatric emergency department.

Witnessed violence is a form of child abuse with detrimental effects on child wellbeing and development, whose recognition relies on the assessment of their mother exposure to intimate partner violence (IPV). The aim of this study was to assess the frequency of witnessed violence in a population of children attending a pediatric emergency department (ED) in Italy, by searching for IPV in their mother, and to define the characteristics of the mother-child dyads. An observational cross-sectional study was conducted from February 2020 to January 2021. Participating mothers were provided a questionnaire, which included the Woman Abuse Screening Tool (WAST) and additional questions about their baseline data and health. Descriptive analysis was reported as frequency and percentage for the categorical variables and median and interquartile range (IQR) for quantitative variables. Mothers and children screened positive and negative for IPV and witnessed violence, respectively, were compared by the chi-square test or the exact Fisher test for categorical variables, and by the Wilcoxon-Mann-Whitney test for continuous variables. Out of 212 participating mothers, ninety-three (43.9%) displayed a positive WAST. Mothers tested positive were mainly Italian (71%, p 0.003), had a lower level of education (median age at school dropout 19, p 0.0002), and a higher frequency of unemployment (p 0.001) and poor personal health status (8.6%, p 0.001). The children of mothers tested positive showed a higher occurrence of abnormal psychological-emotional state (38.7%, p 0.002) and sleep disturbances (26.9%, p 0.04). CONCLUSION: IPV was common in a population of mothers seeking care for their children in a pediatric ED. WHAT IS KNOWN: • Witnessed violence is a form of child abuse, usually inferred by their mothers' exposure to IPV. The latter is suffered by one in three women worldwide. WHAT IS NEW: • This study shows a 43.9% prevalence of IPV among mothers attending an Italian pediatric ED. • Positive mother-child dyads displayed a higher frequency of poor mothers' health status and children's abnormal emotional state and sleep disturbances.

Adolescents' pain and distress during peripheral intravenous cannulation in a paediatric emergency setting.

The objective of the study is to investigate pain and distress experienced by a group of adolescents and children during peripheral intravenous cannulation in a paediatric emergency department. This cross-sectional study was performed between November 2019 and June 2020 at the paediatric emergency department of the Institute for Maternal and Child Health of Trieste, Italy. Eligible subjects were patients between 4 and 17 years old undergoing intravenous cannulation, split into three groups based on their age: adolescents (13-17 years), older children (8-12 years), and younger children (4-7 years). Procedural distress and pain scores were recorded through validated scales. Data on the use of topical anaesthesia, distraction techniques, and physical or verbal comfort during procedures were also collected. We recruited 136 patients: 63 adolescents, 48 older children, and 25 younger children. There was no statistically significant difference in the median self-reported procedural pain found in adolescents (4; IQR = 2-6) versus older and younger children (5; IQR = 2-8 and 6; IQR = 2-8, respectively). Furthermore, no significant difference was observed in the rate of distress between adolescents (79.4%), older (89.6%), and younger (92.0%) children. Adolescents received significantly fewer pain relief techniques.Conclusion: This study shows that adolescents experience similar pain and pre-procedural distress as younger children during peripheral intravenous cannulation. What is Known: • Topical and local anaesthesia, physical and verbal comfort, and distraction are useful interventions for pain and anxiety management during intravenous cannulation in paediatric settings. • No data is available on pain and distress experienced by adolescents in the specific setting of the emergency department. What is New: • Adolescents experienced high levels of pre-procedural distress in most cases and similar levels of pain and distress when compared to younger patients • The number of pain relief techniques employed during procedures was inversely proportional to patient's age, topical or local anaesthesia were rarely used.

Increased use of high-flow nasal cannulas after the pandemic in bronchiolitis: a more severe disease or a changed physician's attitude?

After the SARS-CoV-2 pandemic, we noticed a marked increase in high-flow nasal cannula use for bronchiolitis. This study aims to report the percentage of children treated with high-flow nasal cannula (HFNC) in various seasons. The secondary outcomes were admissions for bronchiolitis, virological results, hospital burden, and NICU/PICU need. We conducted a retrospective study in four Italian hospitals, examining the medical records of all infants (< 12 months) hospitalized for bronchiolitis in the last four winter seasons (1 September-31 March 2018-2022). In the 2021-2022 winter season, 66% of admitted children received HFNC versus 23%, 38%, and 35% in the previous 3 years. A total of 876 patients were hospitalized in the study periods. In 2021-2022, 300 infants were hospitalized for bronchiolitis, 22 in 2020-2021, 259 in 2019-2020, and 295 in 2018-2019. The percentage of patients needing intensive care varied from 28.7% to 18%, 22%, and 15% in each of the four considered periods (p < 0.05). Seventy-seven percent of children received oxygen in the 2021-2022 winter; vs 50%, 63%, and 55% (p < 0.01) in the previous 3 years. NIV/CPAP was used in 23%, 9%, 16%, and 12%, respectively. In 2021-2020, 2% of patients were intubated; 0 in 2020-2021, 3% in 2019-2020, and 1% in 2018-2019. CONCLUSION: This study shows a marked increase in respiratory support and intensive care admissions this last winter. While these severity indexes were all driven by medical choices, more reliable indexes such as intubation rate and length of stay did not change. Therefore, we suggest that there is a more aggressive treatment attitude rather than a more severe disease. WHAT IS KNOWN: • COVID-19 pandemic deeply impacted bronchiolitis epidemiology, reducing hospitalizations to onetenth. In the 2021-2022 winter, bronchiolitis resurged to pre-pandemic numbers in Europe. WHAT IS NEW: • Bronchiolitis hospitalization rose much faster in the 2021-2022 winter period, peaking at a higher level. Respiratory supports and high-flow nasal cannula increased significantly compared to the pre-pandemic era.

New insights on Noonan syndrome's clinical phenotype: a single center retrospective study.

BACKGROUND: Noonan syndrome (NS) is a clinically and genetically heterogeneous disorder. Since its clinical phenotype is often mild and difficult to differentiate from other syndromes, its diagnosis can be challenging and its prevalence in the pediatric population is most certainly underestimated. The difficulty in identifying Noonan syndrome is also increased by the fact that genetic tests are currently not able to detect an underlying mutation in around 10% of the cases. METHODS: This is a retrospective, observational study conducted at the Institute for Maternal and Child "Burlo Garofolo" in Trieste, Italy. We recruited all the patients with clinical and/or genetic diagnosis of NS who were evaluated at the Department of Pediatrics between October 2015 and October 2020. Statistical analyses were performed with IBM SPSS Statistics software. The association between discrete variables has been evaluated through chi-squared test, indicating statistically significant p with Pearson test or Fischer test for variables less than 5. RESULTS: We recruited a total of 35 patients affected by Noonan syndrome. In 24 patients (75%) we identified an underlying genetic substrate: 17 patients had a mutation on PTPN11 (61%), 2 in SOS1, KRAS and SHOC2 (7% each) and only 1 in RAF1 (4%). 25% of the subjects did not receive a genetic confirm. As for the phenotype of the syndrome, our study identified the presence of some clinical features which were previously unrelated or poorly related to NS. For example, renal and central nervous system abnormalities were found at a higher rate compared to the current literature. On the contrary, some features that are considered very suggestive of NS (such as lymphatic abnormalities and the classical facial features) were not frequently found in our population. CONCLUSIONS: In our analysis, we focused on the main phenotypic features of NS, identifying various clinical manifestation that were not associated with this genetic condition before. This could be helpful in raising the knowledge of NS's clinical spectrum, facilitating its diagnosis.

A toddler with an unusually severe polyarticular arthritis and a lung involvement: a case report.

BACKGROUND: COPA syndrome is a rare hereditary inflammatory disease caused by mutations in the gene encoding the coatomer protein subunit alpha, causing excessive production of type I interferon. This case is a reminder for the general paediatrician, highlighting the relevance of the association between arthritis and lung involvement in toddlers. CASE PRESENTATION: We report the case of a 2-year-old girl with intermittent limping and joint pain. Her family history was relevant for a Still disease with lung involvement in the mother. Physical examination showed moderate wrist swelling. Laboratory findings on admission showed an increase in inflammatory markers, positive rheumatoid factor, antibodies antinuclear antibody (ANA) and cyclic citrullinated peptide (anti-CCP). Wrists' ultrasound documented synovial thickening, and chest X-rays showed an unexpected severe interstitial pneumopathy. Genetic testing confirmed the diagnosis of a heterozygous mutation of the COPA gene in c.841C > T (p.R281W). Janus kinase treatment was started (baricitinib, 4 mg daily per os) with a remarkable improvement in limping and joint pain after two weeks. CONCLUSIONS: In cases of recurrent arthritis with family history and multiple involvement organs, a genetic disorder should be suspected and genetic testing should be performed. Furthermore, this case suggests that therapy with jak inhibitors may be effective and safe in interferonopathies.

The first winter of social distancing improved most of the health indexes in a paediatric emergency department.

AIM: We compared visits to a tertiary level paediatric emergency department (PED) in Italy, during winter 2020-2021, when COVID-19 social distancing measures were in place, with winter 2019-2020. METHODS: This was a retrospective analysis of an electronic database. We obtained the number of visits and the ages, main complaints, triage codes, discharge diagnoses and outcomes of patients who accessed the PED from the 1 October 2020 to 28 February 2021. These were compared to the same period in 2019-2021. RESULTS: Visits fell by 52%, from 10982 in 2019-2020 to 5317 in 2020-2021 (p < 0.0001). The reductions were 52% in neonates, 58% in infants, 53% in toddlers, 61% in preschool children, 48% in school children and 46% in adolescents. Non-urgent and urgent triage codes declined. Respiratory and gastrointestinal infections fell by 72% and 71% respectively. Injuries declined by 42%, mainly among adolescents. Accidental intoxication, psychiatric symptoms and substance or alcohol abuse declined by 24%, 33% and 64%. Hospital admissions reduced by 8% and admissions to intensive care fell by 29%. CONCLUSION: During the first winter of pandemic social distancing visits to an Italian PED fell by 52%, with higher reductions in younger children and infants, and hospital admissions fell by 8%.

Anomalous aortic origin of coronary artery: For a challenging diagnosis, a transthoracic echocardiogram is recommended.

Anomalous aortic origin of a coronary artery (AAOCA), especially the interarterial course of the right or left coronary artery, predisposes paediatric patients to myocardial ischaemia. This rare condition is a leading cause of sudden cardiac death. General paediatricians face challenges when diagnosing this anomaly, and they should pay particular attention to the recurrence of exercise-related syncope without prodromal symptoms, chest pain and dyspnoea. An accurate transthoracic echocardiogram with Doppler colour flow mapping is the best method to use to identify AAOCA. CONCLUSION: Identifying an AAOCA is challenging, and we provide advice on clinical red flags and diagnostic approaches for general paediatricians.

SBI is uncommon in the absence of paediatricians' gut feeling and abnormal respiratory pattern.

AIM: According to the Italian national statistical institute, severe bacterial infections (SBI) in Italy are responsible for 1.7% of mortality under 5 years of age and their recognition is often challenging, especially in the first stages of the disease. We tried to estimate the prevalence of SBI in our target population and to identify signs and symptoms that could guide in the initial evaluation of a child with a possible SBI. METHODS: We designed a prospective, multicentre study and enrolled patients aged 0-14 years at the first evaluation to the emergency department with an acute illness lasting a maximum of 5 days. The presence of variables suggestive of SBI was collected for every enrolled patient. One week after the enrolment, every patient was followed up by telephone. RESULTS: SBI is more likely to be detected with the 'gut feeling' in both univariate and multivariate models (univariate OR: 7.16, 95% CI: 4.08-12.56; multivariate OR: 5.34, 95% CI: 2.78-10.25), while abnormal breathing pattern resulted significative only in univariate model (OR 3.83, 95% CI: 1.98-7.40). Nevertheless, their associated sensitivity is low. CONCLUSION: SBI is uncommon in the absence of paediatricians' gut feeling and abnormal respiratory pattern.