Ten years of a neonatal screening program for hemoglobinopathies in Friuli-Venezia Giulia: first regional experience in Italy.

BACKGROUND: Hemoglobinopathies are the commonest genetic defect worldwide (7% of the world's population has at least one hemoglobin mutation). Although prenatal screening for hemoglobinopathies is not obligatory during pregnancy in Italy, it is offered to women by the Italian National Health Service in the pre-conception phase. The screening of newborns is a valid alternative, and has been adopted in various European countries, albeit in a piecemeal fashion. Neonatal screening has the advantage of providing early diagnosis of a hemoglobinopathy. Here we report the findings from the experience with neonatal screening in Friuli-Venezia Giulia since 2010. MATERIALS AND METHODS: The hemoglobinopathy screening project in Friuli-Venezia Giulia, a Region in north Italy, began in November 2010. High-performance liquid chromatography was performed on dried blood spot samples collected by obstetric nurses from neonates within 5-8 days after birth. RESULTS: From 2010 to 2019, 11,956 newborns were screened, and abnormal hemoglobin was found in 519 of them (4.34%): the variants identified included HbS, HbC, HbD, HbE and HbX. More specifically, the HbS variant was observed in 347 (2.9%) newborns and the homozygous pattern was identified in 24 (0.2%) cases. The screening also detected two cases of ß-thalassemia major. DISCUSSION: We report our experience of 10 years of screening newborns for hemoglobinopathies in the Region of Friuli-Venezia Giulia, in which 7.7% of people come from malaria-endemic areas. Increased mobility and migratory flows bringing in hemoglobinopathy carriers from endemic areas have led to an increase in mutations in non-malarial countries, with a current incidence of around 4% in the newborns we tested. This means that hemoglobinopathies can be described as a rare condition. Our data show that incidence rates are comparable to those of other inherited disorders such as phenylketonuria, thereby justifying the inclusion of the test for hemoglobinopathies into screening programs for rare diseases.

How Covid-19 changed the epidemiology of febrile urinary tract infections in children in the emergency department during the first outbreak.

BACKGROUND: The first Covid-19 pandemic affected the epidemiology of several diseases. A general reduction in the emergency department (ED) accesses was observed during this period, both in adult and pediatric contexts. METHODS: This retrospective study was conducted on the behalf of the Italian Society of Pediatric Nephrology (SINePe) in 17 Italian pediatric EDs in March and April 2020, comparing them with data from the same periods in 2018 and 2019. The total number of pediatric (age 0-18 years) ED visits, the number of febrile urinary tract infection (UTI) diagnoses, and clinical and laboratory parameters were retrospectively collected. RESULTS: The total number of febrile UTI diagnoses was 339 (73 in 2020, 140 in 2019, and 126 in 2018). During the first Covid-19 pandemic, the total number of ED visits decreased by 75.1%, the total number of febrile UTI diagnoses by 45.1%, with an increase in the UTI diagnosis rate (+ 121.7%). The data collected revealed an increased rate of patients with two or more days of fever before admission (p = 0.02), a significant increase in hospitalization rate (+ 17.5%, p = 0.008) and also in values of C reactive protein (CRP) (p = 0.006). In 2020, intravenous antibiotics use was significantly higher than in 2018 and 2019 (+ 15%, p = 0.025). Urine cultures showed higher Pseudomonas aeruginosa and Enterococcus faecalis percentages and lower rates of Escherichia coli (p = 0.02). CONCLUSIONS: The first wave of the Covid-19 pandemic had an essential impact on managing febrile UTIs in the ED, causing an absolute reduction of cases referring to the ED but with higher clinical severity. Children with febrile UTI were more severely ill than the previous two years, probably due to delayed access caused by the fear of potential hospital-acquired Sars-Cov-2 infection. The possible increase in consequent kidney scarring in this population should be considered.

Oral steroids for reducing kidney scarring in young children with febrile urinary tract infections: the contribution of Bayesian analysis to a randomized trial not reaching its intended sample size.

BACKGROUND: This study aimed to evaluate the effect of oral dexamethasone in reducing kidney scars in infants with a first febrile urinary tract infection (UTI). METHODS: Children aged between 2 and 24 months with their first presumed UTI, at high risk for kidney scarring based on procalcitonin levels (≥1 ng/mL), were randomly assigned to receive dexamethasone in addition to routine care or routine care only. Kidney scars were identified by kidney scan at 6 months after initial UTI. Projections of enrollment and follow-up completion showed that the intended sample size could not be reached before funding and time to complete the study ran out. An amendment to the protocol was approved to conduct a Bayesian analysis. RESULTS: We randomized 48 children, of whom 42 had a UTI and 18 had outcome kidney scans (instead of 128 planned). Kidney scars were found in 0/7 and 2/11 patients in the treatment and control groups respectively. The probability that dexamethasone could prevent kidney scarring was 99% in the setting of an informative prior probability distribution (which fully incorporated in the final inference the information on treatment effect provided by previous studies) and 98% in the low-informative scenario (which discounted the prior literature information by 50%). The probabilities that dexamethasone could reduce kidney scar formation by up to 20% were 61% and 53% in the informative and low-informative scenario, respectively. CONCLUSIONS: Dexamethasone is highly likely to reduce kidney scarring, with a more than 50% probability to reduce kidney scars by up to 20%. TRIAL REGISTRATION NUMBER: EudraCT number: 2013-000388-10; registered in 2013 (prospectively registered) A higher resolution version of the Graphical abstract is available as Supplementary information.

Characteristics and risk factors for SARS-CoV-2 in children tested in the early phase of the pandemic: a cross-sectional study, Italy, 23 February to 24 May 2020.

BackgroundVery few studies describe factors associated with COVID-19 diagnosis in children.AimWe here describe characteristics and risk factors for COVID-19 diagnosis in children tested in 20 paediatric centres across Italy.MethodsWe 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.ResultsAmong 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 < 0.0001), cardiac disease (AOR: 3.10; 95% CI: 1.19-5.02; p < 0.0001), fever (AOR: 3.05%; 95% CI: 1.67-5.58; p = 0.0003) and anosmia/ageusia (AOR: 4.08; 95% CI: 1.69-9.84; p = 0.002). Among 190 (7.6%) children positive for SARS-CoV-2, only four (2.1%) required respiratory support and two (1.1%) were admitted to intensive care; all recovered.ConclusionRecommendations 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.

Characteristic of COVID-19 infection in pediatric patients: early findings from two Italian Pediatric Research Networks.

Detailed data on clinical presentations and outcomes of children with COVID-19 in Europe are still lacking. In this descriptive study, we report on 130 children with confirmed COVID-19 diagnosed by 28 centers (mostly hospitals), in 10 regions in Italy, during the first months of the pandemic. Among these, 67 (51.5%) had a relative with COVID-19 while 34 (26.2%) had comorbidities, with the most frequent being respiratory, cardiac, or neuromuscular chronic diseases. Overall, 98 (75.4%) had an asymptomatic or mild disease, 11 (8.5%) had moderate disease, 11 (8.5%) had a severe disease, and 9 (6.9%) had a critical presentation with infants below 6 months having significantly increased risk of critical disease severity (OR 5.6, 95% CI 1.3 to 29.1). Seventy-five (57.7%) children were hospitalized, 15 (11.5%) needed some respiratory support, and nine (6.9%) were treated in an intensive care unit. All recovered.Conclusion:This descriptive case series of children with COVID-19, mostly encompassing of cases enrolled at hospital level, suggest that COVID-19 may have a non-negligible rate of severe presentations in selected pediatric populations with a relatively high rates of comorbidities. More studies are needed to further understand the presentation and outcomes of children with COVID-19 in children with special needs. What is Known: • There is limited evidence on the clinical presentation and outcomes of children with COVID-19 in Europe, and almost no evidence on characteristics and risk factors of severe cases. What is New: • Among a case series of 130 children, mostly diagnosed at hospital level, and with a relatively high rate (26.2%) of comorbidities, about three-quarter had an asymptomatic or mild disease. • However, 57.7% were hospitalized, 11.5% needed some respiratory support, and 6.9% were treated in an intensive care unit.

Ogilvie syndrome in a 8 year old girl after laparoscopic appendectomy.

BACKGROUND: Ogilvie's syndrome is described in the adult population, but rarely seen in children. CASE PRESENTATION: We present a case of a girl who suffered acute colonic pseudo-obstruction after laparoscopic appendectomy. CONCLUSIONS: Ogilvie's syndrome, although rare in the pediatric population, should be considered as possible diagnosis after a surgical procedure in presence of persisting subocclusive symptoms and radiological signs of massive colonic dilatation without mechanical obstruction.

Measuring empathy in pediatrics: validation of the Visual CARE measure.

BACKGROUND: Empathy is a key element of "Patient and Family Centered Care", a clinical approach recommended by the American Academy of Pediatrics. However, there is a lack of validated tools to evaluate paediatrician empathy. This study aimed to validate the Visual CARE Measure, a patient rated questionnaire measuring physician empathy, in the setting of a Pediatric Emergency Department (ED). METHODS: The empathy of physicians working in the Pediatric ED of the University Hospital of Udine, Italy, was assessed using an Italian translation of the Visual Care Measure. This test has three versions suited to different age groups: the 5Q questionnaire was administered to children aged 7-11, the 10Q version to those older than 11, and the 10Q-Parent questionnaire to parents of children younger than 7. The internal reliability, homogeneity and construct validity of the 5Q and 10Q/10Q-Parent versions of the Visual Care Measure, were separately assessed. The influence of family background on the rating of physician empathy and satisfaction with the clinical encounter was also evaluated. RESULTS: Seven physicians and 416 children and their parents were included in the study. Internal consistency measured by Cronbach's alpha was 0.95 for the 10Q/10Q-Parent versions and 0.88 for the 5Q version. The item-total correlation was > 0.75 for each item. An exploratory factor analysis showed that all the items load onto the first factor. Physicians' empathy scores correlated with patients' satisfaction for both the 10Q and 10Q-Parent questionnaires (Spearman's rho = 0.7189; p < 0.001) and for the 5Q questionnaire (Spearman's rho = 0.5968; p < 0,001). Trust in the consulting physician was lower among immigrant parents (OR 0.43. 95% CI 0.20-0.93). CONCLUSIONS: The Visual Care Measure is a reliable second-person test of physician empathy in the setting of a Pediatric Emergency Room. More studies are needed to evaluate the reliability of this instrument in other pediatric settings distinct from the Emergency Room and to further evaluate its utility in measuring the impact of communication and empathy training programmes for healthcare professionals working in pediatrics.

Usefulness of 99mTc-dimercaptosuccinic acid renal scan in the diagnosis and follow-up of acute tubulointerstitial nephritis in children.

BACKGROUND: Symptoms and signs of acute tubulointerstitial nephritis (ATIN) are nonspecific; therefore, renal biopsy is often necessary to clarify the diagnosis. The aim of this study was to evaluate the use of 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy in the diagnosis and follow-up of ATIN. METHODS: We retrospectively reviewed the charts of five patients (nine renal units) with a median age of 14 years who underwent DMSA scan after a clinical and/or biopsy-proven diagnosis of ATIN. The exam was performed within 1 month after disease onset and repeated at a median time of 12 months after the acute phase. RESULTS: DMSA renal scans performed during the acute phase allowed the discovery of suggestive findings, including diffuse reduction of the renal uptake of radionuclide and presence of multiple 'cold' focal lesions in a corticomedullary distribution. The follow-up scintigraphy resulted normal in two patients who were treated with steroids and in one patient who presented a mild renal dysfunction in the acute phase. By contrast, the control scan showed persistent renal damage in one patient who was further readmitted because of hypertension and in one renal transplanted patient who presented a Stage 3 acute kidney injury in the acute phase. CONCLUSIONS: DMSA renal scan might be a reliable tool for an early non-invasive diagnosis of ATIN in children and might be particularly useful in those patients who are not candidates for a kidney biopsy. Moreover, DMSA scan gives accurate follow-up evaluation, as it allows monitoring of the evolution of acute renal parenchymal inflammation with potential risk of renal scar formation. Due to the small sample size, our findings warrant further validation in a larger study.

Age-related renal parenchymal lesions in children with first febrile urinary tract infections.

OBJECTIVE: The aim of this study was to define the association between age and the occurrence of acute pyelonephritis and renal scars. METHODS: Between 1999 and 2002, all children 0 to 14 years of age consecutively seen with a first febrile urinary tract infection were enrolled in the study. (99m)Tc-Dimercaptosuccinic acid renal scintigraphy was performed within 5 days after admission for the detection of renal parenchymal involvement. The presence of vesicoureteral reflux was assessed by using cystography performed 1 month after the infection. If the acute scan results were abnormal, then follow-up (99m)Tc-dimercaptosuccinic acid scanning was performed after 6 months, to assess the frequency of scars. RESULTS: A total of 316 children were enrolled in the study (190 children <1 year, 99 children 1-4 years, and 27 children 5-14 years of age). (99m)Tc-Dimercaptosuccinic acid scintigraphy revealed that 59% of the children had renal involvement in the acute phase of infection. The frequency of kidney involvement in infants <1 year of age (49%) was significantly lower than that in children 1 to 4 years of age (73%) and >5 years of age (81%). Of the 187 children with positive acute (99m)Tc-dimercaptosuccinic acid scan results, 123 underwent repeat scintigraphy after 6 months. Renal scars were found for 28% of children <1 year, 37% of children 1 to 4 years, and 53% of children 5 to 14 years of age. No significant differences in the frequency of scars and the presence or absence of vesicoureteral reflux were noted. CONCLUSIONS: Our findings confirm that acute pyelonephritis and subsequent renal scarring occur only in some children with first febrile urinary tract infections. Children <1 year of age with febrile urinary tract infections have a lower risk of parenchymal localization of infection and renal scarring.

Procalcitonin: a marker of severity of acute pyelonephritis among children.

OBJECTIVE: Febrile urinary tract infection (UTI) is a common problem among children. The diagnosis and management of acute pyelonephritis is a challenge, particularly during infancy. The distinction between acute pyelonephritis and UTI without renal involvement is very important, because renal infection may cause parenchymal scarring and thus requires more aggressive investigation and follow-up monitoring. However, this distinction is not easy among children, because common clinical findings and laboratory parameters are nonspecific, especially among young children. In an attempt to differentiate acute pyelonephritis from febrile UTI without renal lesions in a group of 100 children, we measured serum levels of procalcitonin (PCT), a new marker of infection. The objective of the study was to determine the accuracy of PCT measurements, compared with C-reactive protein (CRP) measurements, in diagnosing acute renal involvement during febrile UTI and in predicting subsequent scars, as assessed with 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy. DESIGN: Serum CRP levels, erythrocyte sedimentation rates, leukocyte counts, and PCT levels were measured for 100 children, 1 month to 13 years of age, admitted for suspected febrile UTI (first episode). Renal parenchymal involvement was evaluated with DMSA scintigraphy within 5 days after admission. The DMSA study was repeated 6 months later if the initial results were abnormal. RESULTS: The mean PCT level was significantly higher in acute pyelonephritis than in UTI without renal lesions (4.48 +/- 5.84 ng/mL vs 0.44 +/- 0.30 ng/mL). In these 2 groups, the mean CRP levels were 106 +/- 68.8 mg/L and 36.4 +/- 26 mg/L, mean erythrocyte sedimentation rates were 79.1 +/- 33 mm/hour and 58.5 +/- 33 mm/hour, and leukocyte counts were 18 492 +/- 6839 cells/mm3 and 16 741 +/- 5302 cells/mm3, respectively. For the prediction of acute pyelonephritis, the sensitivity and specificity of PCT measurements were 83.3% and 93.6%, respectively; CRP measurements had a sensitivity of 94.4% but a specificity of only 31.9%. Positive and negative predictive values for prediction of renal involvement with PCT measurements were 93.7% and 83% and those with CRP measurements were 61.4% and 83.3%, respectively. When inflammatory markers were correlated with the severity of the renal lesions, as assessed with DMSA scintigraphy, a highly significant correlation with both PCT and CRP levels was found. However, when the 2 parameters were correlated with renal scarring in follow-up scans, a significant positive association was found only for PCT levels. CONCLUSIONS: Serum PCT levels may be a sensitive and specific measure for early diagnosis of acute pyelonephritis and determination of the severity of renal parenchymal involvement. Therefore, this measurement could be useful for the treatment of children with febrile UTIs, allowing prediction of patients at risk of permanent parenchymal renal lesions.