Recurrent upper respiratory tract infections in early childhood: a newly defined clinical condition.

BACKGROUND: Recurrent Upper Respiratory Tract Infections (R-URTIs) pose a significant challenge in pediatric healthcare, affecting both children and their families. This study aimed to investigate the prevalence, risk factors, and clinical implications of R-URTI in children aged 0-5 years. METHODS: This observational study involved a sample of 483 children aged 0-5 years, focusing on establishing a practical and dynamic definition of R-URTI. Family pediatricians prospectively collected socio-demographic information, medical history, and recorded the occurrence of URTI episodes. Children were followed from recruitment until March 2021, predating the COVID-19 outbreak. RESULTS: A substantial prevalence of R-URTIs was found, estimating it at 5-10% among this age group. To define R-URTI, a practical and dynamic criterion was proposed: children experiencing a minimum of four URTI episodes, each lasting four days or more, within a six-month period, with intervals of well-being in between. CONCLUSIONS: The study highlighted that specific risk factors for R-URTI were elusive, suggesting that this condition may affect children regardless of their family or clinical history. Moreover, the study's stratification by age group and times of observation facilitated patient-specific clinical decision-making. The proposed definition may represent a valuable tool for clinicians in diagnosing and addressing R-URTI cases.

Leading reasons for antibiotic prescriptions in pediatric respiratory infections: influence of fever in a primary care setting.

BACKGROUND: Antibiotic overuse in children is a significant public health concern, as it can lead to the emergence and spread of antibiotic-resistant bacteria. Although respiratory infections account for most antibiotic prescriptions in children, many of these infections are viral and do not require antibiotics. In this study, we aimed to investigate the use of antibiotics in children with respiratory infections in a primary care setting and to explore the possible role of fever on antibiotic prescription. METHODS: We conducted a prospective observational study that evaluated preschool children aged 0-5 years who were assessed by their primary care pediatricians for respiratory infectious diseases between October 2019 and March 2021. The study involved 69 public primary care pediatricians and a total of 678 pediatric episodes for respiratory infections. RESULTS: Amoxicillin/clavulanate was the most frequently prescribed drug. Bronchitis accounted for most of inappropriate antibiotic prescriptions (73%). Furthermore, the presence of fever was associated with a ~ 300% increase in the likelihood of prescribing antibiotics for respiratory infections that do not typically require antibiotics. CONCLUSION: Our findings emphasize the need for adherence to international guidelines and recommendations in the primary care of children to reduce unnecessary antibiotic use and prevent the development of antibiotic resistance. This study also underscores the potential relevance of new studies to evaluate antibiotic prescription attitudes in other clinical settings and geographical areas.

The Role of Bronchoscopy in the Management of Children With Cystic Fibrosis.

BACKGROUND: Currently, no consensus guidelines recommend routine bronchoscopy procedure in cystic fibrosis (CF), as no evidence is available concerning its use as either a diagnostic or therapeutic tool. Its efficacy is controversial, and no randomized controlled prospective trials are available to check its effectiveness. The aims of the present study were to evaluate the effectiveness of bronchoscopy as a diagnostic/therapeutic tool in CF children and adolescents; and to verify the effect of serial bronchoscopy on lung disease progression in subjects with CF not responding to a single procedure. METHODS: Data of patients who received bronchoscopy at 2 Italian CF centers were collected. Bronchoalveolar lavage was performed during the procedure including airway clearance with mucolytics, inhaled antibiotics, and/or surfactant instillation. RESULTS: A total of 16 patients in center 1 and 17 in center 2 underwent, respectively, 28 and 23 bronchoscopic procedure in the study period. Five patients in each center underwent >1 procedure. All procedures were generally well tolerated. No patient required admission to the pediatric intensive therapy unit. In 19.6% of bronchoalveolar lavages, growth of Aspergillus fumigatus was evident, although not detected by sputum analyses. After the procedure, an increase in mean percent predicted forced expiratory volume in the 1 second >10% was observed, and a significant decrease in pulmonary exacerbations yearly was evident. CONCLUSION: Based on the results, we suggest bronchoscopy is not to be considered an obsolete tool, and it remains useful in CF management, although in selected cases. We encourage to support longitudinal observational studies to standardize the procedure, focusing on the choice of drugs to be instilled, modalities and timing of serial bronchoscopy and subsequent follow-up in selected severe clinical conditions.

Incidence of acute respiratory infections in preschool children in an outpatient setting before and during Covid-19 pandemic in Lombardy Region, Italy.

INTRODUCTION: The incidence of acute respiratory tract infections (ARTIs) in children is difficult to estimate because they are typically treated in outpatient settings and the majority of epidemiological data originate from hospital settings and refer to the most severe illnesses. Therefore, the incidence of ARTIs in a real-world setting remains largely unexplored. Therefore, this study aims to estimate the incidence of ARTIs, upper respiratory tract infections (URTIs), and lower respiratory tract infections (LRTIs) in children aged 0-5 years in an outpatient setting. METHODS: This prospective cohort study was conducted in Lombardy, Italy, from October 1st, 2019, to March 31st, 2021, before and during the COVID-19 pandemic that began in March 2020. Caucasian healthy children aged 0-5 years were recruited from 69 Family Pediatricians (FP) and followed-up in an outpatient setting. Data were collected whenever a child was referred to FP and ARTI was diagnosed (Covid-19 related ARTI were excluded). The primary outcome was an estimate of the incidence of ARTIs. The incidence of ARTIs in different age groups and the effect of the COVID-19 pandemic on the incidence of ARTIs were secondary outcomes. RESULTS: We enrolled 484 children, 249 male (51.8%), mean age of 2.39 ± 1.68 years. The mean estimated incidence of ARTIs was 12.1/100 children × 30 days (95% CIs: 9.5-12.9), with the highest value observed in infants aged 1-12 months (24.9/100 children × 30 days; 95% CIs: 17.6-28.9). The mean estimated incidence of URTIs was higher than that of LRTIs (8.3 - CIs: 7.6-8.9 vs 3.8/100 children × 30 days - CIs: 6.4-4.3, respectively). The comparison of ARTIs, which occurred in the pre-pandemic winter, to those measured during the COVID-19 pandemic, revealed an impressive 82.1% drop in the incidence rate (CIs: 77.8-85.7). CONCLUSIONS: This study showed that infants aged 1-12 months are more likely to develop ARTIs than older children and that COVID-19 pandemic has dramatically altered the epidemiology of ARTIs in children aged 0-5 years.

Clinical, anamnestic, and sociodemographic predictors of positive SARS-CoV-2 testing in children: A cross sectional study in a tertiary hospital in Italy.

OBJECTIVES: We aimed to identify clinical, anamnestic, and sociodemographic characteristics associated with a positive swab for SARS-CoV2, and to provide a predictive score to identify at risk population in children aged 2-14 years attending school and tested for clinical symptoms of COVID-19. DESIGN: Cross sectional study. SETTING: Outpatient clinic of the IRCCS Burlo Garofolo, a maternal and child health tertiary care hospital and research centre in Italy. DATA COLLECTION AND ANALYSIS: Data were collected through a predefined form, filled out by parents, and gathered information on sociodemographic characteristics, and specific symptoms, which were analysed to determine their association with a positive SARS-CoV-2 swab. The regression coefficients of the variables included in the multivariate analysis were further used in the calculation of a predictive score of the positive or negative test. RESULTS: Between September 20th and December 23rd 2020, from 1484 children included in the study, 127 (8.6%) tested positive. In the multivariate analysis, the variables retained by the model were the presence of contact with a cohabiting, non-cohabiting or unspecified symptomatic case (respectively OR 37.2, 95% CI 20.1-68.7; 5.1, 95% CI 2.7-9.6; 15.6, 95% CI 7.3-33.2); female sex (OR 1.49, 95% CI 1.0-2.3); age (6-10 years old: OR 3.2, 95% CI 1.7-6.1 p<0.001; >10 years old: OR 4.8, 95% CI 2.7-8.8 p<0.001); fever (OR 3.9, 95% CI 2.3-6.4); chills (OR 1.9, 95% CI 1.1-3.3); headache (OR 1.45, 95% CI 0.9-2.4); ageusia (OR 1.3, 95% CI 0.5-4.0); sore throat (OR 0.48, 95% CI 0.3-0.8); earache (OR 0.4, 95% CI 0.1-1.3); rhinorrhoea (OR 0.8, 95% CI 0.5-1.3); and diarrhoea (OR 0.52, 95% CI 0.2-1.1). The predictive score based on these variables generated 93% sensitivity and 99% negative predictive value. CONCLUSIONS: The timely identification of SARS-CoV2 cases among children is useful to reduce the dissemination of the disease and its related burden. The predictive score may be adopted in a public health perspective to rapidly identify at risk children.

Fluid intake and blood pressure in children: the Salus per Aquam project.

BACKGROUND: Sodium intake is known to contribute to the development of hypertension, thus intake reduction is a cornerstone in the prevention and management of hypertension. The increase in renal sodium excretion might represent a further potential preventive and/or therapeutic opportunity. OBJECTIVE: To explore the working hypothesis that an increased fluid intake can improve renal sodium handling towards a decrease in blood pressure. METHODS: The SPA Project is a multicenter, observational, cross-sectional, cohort study investigating healthy children, aged 5-8 years as to sodium and fluid intake by means of urinary sodium and creatinine from multiple samples taken in different days in order to characterize them in lower/higher sodium and lower/higher fluid intake. Both SBP and DBP (by multiple office blood pressure measurements) were used as outcome measures. RESULTS: Three hundred and thirty-nine healthy, nonoverweight children (51.6% boys) with a median age of 5.7 years old (IQR: 5.3-6.2) participated in the study but only 223 could be analyzed. Among children with higher sodium intake, those introducing more fluids, showed a significantly lower blood pressure (both systolic and diastolic) compared with those with lower fluid intake: systolic 86.0 ±â€Š8.5 vs. 90.0 ±â€Š8.1 mmHg; P = 0.014 and diastolic: 53.8 ±â€Š4.9 vs. 58.6 ±â€Š6.6 mmHg; P < 0.0001. CONCLUSION: An increased fluid intake is associated with a reduced blood pressure possibly by increasing renal sodium excretion. We speculate that this simple, highly acceptable, inexpensive, and harmless measure might have a role in preventing and/or minimizing the epidemics of hypertension and of its related morbidities both in children and in adults.

Multiple, random spot urine sampling for estimating urinary sodium excretion.

The measurement of sodium intake may be important for the management of hypertension. Dietary surveys and 24-h urinary collection are often unreliable and/or impractical. We hypothesized that urinary sodium excretion can be accurately estimated through multiple spot urine samples from different days. All enrolled subjects were children of the coauthors of the study. Fifty-two 24-h urinary collections (4 per subject) for measuring sodium excretion and the 297 related urinary samples (1 per voiding) were collected for calculating the urinary sodium/urinary creatinine ratio in 13 children. The mean of 4 measured sodium excretions served as the individual "gold standard". Twenty-four urinary collections were used to generate the equation predicting the mean measured sodium excretion from the mean of 4 urinary sodium/urinary creatinine [= 0.016 × urinary sodium (mmol/L) / urinary creatinine (mmol/L) ratio + 3.3)]; the remaining 28 urinary collections and 153 urinary samples were used for the external validation. All subjects underwent an additional validation procedure involving 12 urinary samples randomly collected on different days 6 months apart. The performance of sodium excretion calculated from a total of over 22,000 possible means of 4 out of all the available urinary samples, randomly taken on different days, was analyzed as to precision (by means of the coefficient of variation) and as to accuracy (by means of the P30). The coefficients of variations of measured vs. calculated sodium excretion were 25.3% vs. 25.8%, and the P30 of calculated sodium excretion was 100%. The excellent performance of calculated sodium excretion was confirmed both by external validation and by samples collected 6 months apart with mean P30s, all between 86 and 100%.Conclusion: In the described experimental conditions, urinary sodium excretion was estimated with equal precision and more accurately (and practically) by the mean of 4 urinary sodium/urinary creatinine ratios from random samples from different days than by a single urinary collection. In real life, with several errors systematically affecting urinary collection, the superiority of calculated sodium excretion is likely to be even greater. What is Known: • The measurement of sodium intake with the current standards of care (dietary survey or 24-h urinary collection) is laborious and can be inaccurate. What is New: • The study provides evidence that sodium intake can be estimated equally precisely, more accurately and more practically with the urinary sodium-to-urinary creatinine ratio from 4 urine samples taken on different days than with a single urinary collection.

A rapid and feasible tool for clinical decision making in community-dwelling patients with COVID-19 and those admitted to emergency departments: the Braden-LDH-HorowITZ Assessment-BLITZ.

There is no univocal standardized strategy to predict outcomes and stratify risk of SARS-CoV-2 infected patients, notably in emergency departments. Our aim is to develop an accurate indicator of adverse outcomes based on a retrospective analysis of a COVID-19 database established at the Emergency Department (ED) of a North-Italian hospital during the first wave of SARS-CoV-2 infection. Laboratory, clinical, psychosocial and functional characteristics including those obtained from the Braden Scale-a standardized scale to quantify the risk of pressure sores which takes into account aspects of sensory perception, activity, mobility and nutrition-from the records of 117 consecutive patients with swab-positive COVID-19 disease admitted to the Emergency Medicine ward between March 1, 2020 and April 15, 2020 were included in the analysis. Adverse outcomes included admission to the Intensive Care Unit (ICU) and in-hospital death. Among the parameters collected, the highest cutoff sensitivity and specificity scores to best predict adverse outcomes were displayed by lactate dehydrogenase (LDH) blood value at admission > 439 U/L, Horowitz Index (P/F Ratio) < 257 and Braden score < 18. The estimation power reached 93.6%. We named the assessment BLITZ (Braden-LDH-HorowITZ). Despite the retrospective and preliminary nature of the data, a multidimensional tool to assess overall functions, not chronological age, produced the highest prediction power for poor outcomes in relation to SARS-CoV-2 infection. Further analyses are now needed to establish meaningful correlations between ventilation therapies and multidimensional frailty as assessed by ad-hoc validated and standardized tools.

Non-invasive tools for detection of liver disease in children and adolescents with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a multi-organ genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene which encodes the CFTR protein. CF-associated liver disease (CFLD) is a common complication; diagnosis is based on clinical, laboratory findings and abdominal imaging. However, non-invasive diagnostic approaches are needed to early detect CFLD, its progression and severity. Recent studies demonstrate a possible role of point shear wave elastography (p-SWE) with liver stiffness measurement (LSM) as a tool for CFLD diagnosis also in children. This non-invasive technique measures liver stiffness to assess liver fibrosis and is suggested to be less operator-dependent compared to ultrasonography. Aim of our prospective observational study is to investigate the role of p-SWE with LSM for CFLD diagnosis in children and adolescents with CF and to compare this finding with aspartate aminotransferase to platelet ratio index (APRI), fibrosis index based on four factors (FIB-4) and gamma-glutamyl-transpeptidase to platelet ratio (GPR) indices. METHODS: Fifty-nine children with CF, who had routinely undergone abdominal imaging, were consecutively enrolled. Laboratory findings and clinical data were recorded, as abdominal ultrasound and shear wave elastography at baseline. The cases were divided into two groups based on collected data and classified as CFLD and CFnoLD (without liver disease) according to Debray criteria. APRI, FIB-4 and GPR fibrosis indices were also evaluated. RESULTS: Twenty-four/59 (40.7%) were defined as CFLD. LSM test is superior to the APRI (P<0.001), the FIB-4 test (P=0.001) and the GPR test for early detection of liver fibrosis. LSM had an area under receiver operating characteristic (ROC) curve =0.818 (95% CI: 0.702-0.934) compared with APRI (0.571, 95% CI: 0.421-0.722), FIB-4 (0.656, 95% CI: 0.511-0.801) and GPR (0.632, 95% CI: 0.485-0.779). At a cut-off of ≥6.2 LSM show a sensitivity of 75.0% and a specificity of 88.6%. CONCLUSIONS: LSM by transient p-SWE is a non-invasive, highly accessible, reliable, and reproducible test that can be used to assess early detection of liver fibrosis and its severity in children and adolescents with CF, limiting the use of liver biopsy. These preliminary observations point to the need of larger study population to confirm our data.

Do the opinions of pediatricians influence their recommendations on complementary feeding? Preliminary results.

Complementary feeding practices are debated among pediatricians, primarily regarding whether nutritional needs or developmental readiness should be prioritized in recommendations for starting complementary feeding. The aim of the present study was to analyze the timing of the start of complementary feeding and the related motivations with an 8-item online survey administered to active members of the Italian Society of Primary Care Pediatricians. The participation rate was 43.3% (350 of 808), and 213 (60.9%) and 137 (39.1%) of the participants chose items related to developmental readiness and nutritional needs, respectively, as the criteria for starting complementary feeding. Approximately 74% of the participants reported that they recommended starting complementary feeding between 5 and 6 months of age, 17% recommended starting before 5 months, and 8% recommended starting after 6 months. Predefined schemes were proposed by 38% of the participants, and a responsive feeding modality was proposed by 13%, while the majority (49%) recommended both modalities depending on family characteristics. Regarding recommendations based on nutritional needs, 89% of pediatricians reported providing indications concerning the quantity of meat consumed during the first year of life, and 91% reported recommending introducing added salt only after 12 months of age. Compared with pediatricians who emphasized developmental readiness, those who prioritized nutritional needs suggested earlier complementary feeding start and a higher use of predefined schemes and were more likely to make recommendations regarding meat quantity and added salt (p < 0.0001).Conclusions: Pediatricians who used a developmental readiness criterion for starting complementary feeding may less frequently provide nutritional advice to parents, even if a trend to harmonize the different positions regarding complementary feeding start time is emerging.What is Known:• Pediatricians make suggestions for introducing complementary feeding based on scientific evidence, local traditions, and personal beliefs.• Either infants' nutritional needs or their developmental readiness currently is used as determinant for the timing of complementary feeding.What is New:• More than 60% of Italian pediatricians consider developmental readiness a priority for introducing complementary feeding.• Pediatricians following the criterion of developmental readiness may less frequently give detailed nutritional advice.

Cystic fibrosis screen positive inconclusive diagnosis (CFSPID): Experience in Tuscany, Italy.

OBJECTIVE: The implementation of cystic fibrosis (CF) newborn screening (NBS) has led to identification of infants with a positive NBS test but inconclusive diagnosis classified as "CF screen positive, inconclusive diagnosis" (CFSPID). We retrospectively evaluated the prevalence and clinical outcome of CFSPID infants diagnosed by 2 NBS algorithms in the period from 2011 to 2016 in the Tuscany region of Italy. METHODS: In 2011-2016, we assessed the diagnostic impact of DNA analysis on the NBS 4-tier algorithm [immunoreactive trypsin (IRT) - meconium lactase - IRT2 - sweat chloride (SC)]. All CFSPID patients repeated SC testing every 6 months, and CFTR gene analysis was performed (detection rate 98%). We reclassified children as: CF diagnosis in presence of at least 2 pathological SC results; healthy carrier or healthy in presence of at least 2 normal SC results for age and either 1 or 0 CF-causing mutations, respectively. RESULTS: We identified 32 CF and 50 CFSPID cases: 20/50 (40%) were diagnosed only by the IRT-DNA-SC algorithm and 16/50 (32%) only by IRT-meconium lactase-IRT2-SC. Both protocols identified the remaining 14 cases (28%). Thirty-seven of 50 (74%) CFSPID patients had a conclusive diagnosis on December 31, 2017:5 (10%) CF, 17 (34%) healthy and 15 (30%) healthy carriers; 13/50 (26%) cases were asymptomatic with persistent intermediate SC and followed as CFSPID (CF:CFSPID ratio 2.85:1). CONCLUSIONS: In 6 years, the CF:CFSPID ratio modified from 0.64:1 to 2.85:1, and 10% of CFSPID cases progressed to CF. Genetic analysis improved positive predictive value and identified a higher number of CFSPID infants progressing to CF.

Sleep and new media usage in toddlers.

Several studies over the years have demonstrated the association between lack of sleep in children and certain physical, psychological, and behavioral disorders. The aim of this study was to disentangle the association between new screen-based electronic devices and sleep problems in toddlers, adjusting for other covariates already known to be associated with sleep quality. We conducted a cross-sectional study with the aid of a national sample of 1117 toddlers. Parents reported children's sleeping habits such as total sleep time and sleep onset latency, recreational activities, bedtime routines, and temperament. An ordered logistic regression was run to assess the associations between new media exposure and two sleep outcomes (total sleep time and sleep onset latency). Everyday use of a tablet or smartphone raised the odds of a shorter total sleep time (OR 1.95 [1.00-3.79], p < 0.05) and a longer sleep onset latency (OR 2.44 [1.26-4.73] p < 0.05) irrespective of other factors, such as temperament (restlessness, sociability), or traditional screen exposure (watching TV or playing videogames).Conclusion: New media usage is a factor associated in toddlers with sleeping fewer hours and taking longer to fall asleep, irrespective of other confounding factors. What is known • Studies have found an association between sleep behavior and the use of computers and video games in early childhood. • The blue light emitted from TV screens suppresses endogenous melatonin. What is new • The study found an association between daily new media (tablet and smartphone) usage and sleep quality in toddlers • New media usage exposes toddlers to the risk of fewer hours of sleep and taking longer to fall asleep, irrespective of other factors.

Patients with cystic fibrosis having a residual function mutation: Data from the Italian registry.

BACKGROUND: CFTR mutations permitting residual function (RF) of the CFTR protein are disease-causing. These mutations are associated with a pneumopathy that is delayed in onset and is slower in progression than are more common forms of cystic fibrosis (CF), although the disease may become severe in some patients. RF mutations are among the most frequent in Italy, thus encouraging investigation of their prevalence and associated phenotypes. METHODS: Data from the Italian Registry were used to compare patients with at least one RF mutation with those homozygous for F508del. RESULTS: A total of 806 patients bearing at least one RF mutation were identified among 5204 registered patients (15.5%). The RF patients were older than the F508del homozygotes (median age 26.0 years vs 19.8 years, respectively), with a higher median age at diagnosis (6.3 years vs 0.2 years, respectively) and a lower median sweat chloride value (76.0 mmol/L vs 100.0 mmol/L, respectively). In the RF group, lung infections and comorbidities were less prevalent than those in the F508del homozygotes, while better FEV1 and nutritional status were observed at all ages. Within the RF group, RF/F508del subjects showed more severe pneumopathy than did patients with RF/other mutations. In particular, the 3849 + 10kbC → T/F508del subjects had worse FEV1 and a higher prevalence of lung infections than did patients with other genotypes. CONCLUSIONS: Patients with RF mutations are numerous in Italy and have a milder disease phenotype than do F508del homozygotes. Inside the RF group, F508del heterozygotes and, in particular, 3849 + 10kbC → T/F508del patients showed more severe pneumopathy.

Defining research priorities in cystic fibrosis. Can existing knowledge and training in biomedical research affect the choice?

The aim of this report is to assess whether the research issues priorities are perceived differently according to the Stakeholders (SH)'s individual knowledge of research topics and degree of training in biomedical research. Four groups of SH were enrolled in this study: 1. Skilled SH, specifically trained in biomedicine; 2. Unskilled untrained SH who responded to a written questionnaire in 2015; 3. SH who were trained for one year in a course delivered by professionals; 4. Untrained SH who responded to an online questionnaire in 2017. The large ranking order variability observed among groups addresses the question that the choices are markedly influenced by the SH's backgrounds. Such results emphasize the need to consider the education level and the delivery of ad hoc training activities by professionals to broaden the base of SH who may be considered qualified to transfer the Patient Centered Outcome Research principles into practice.

Clinical expression of cystic fibrosis in a large cohort of Italian siblings.

BACKGROUND: A clinical heterogeneity was reported in patients with Cystic Fibrosis (CF) with the same CFTR genotype and between siblings with CF. METHODS: We investigated all clinical aspects in a cohort of 101 pairs of siblings with CF (including 6 triplets) followed since diagnosis. RESULTS: Severe lung disease had a 22.2% concordance in sib-pairs, occurred early and the FEV1% at 12 years was predictive of the severity of lung disease in the adulthood. Similarly, CF liver disease occurred early (median: 15 years) and showed a concordance of 27.8% in sib-pairs suggesting a scarce contribution of genetic factors; in fact, only 2/15 patients with liver disease in discordant sib-pairs had a deficiency of alpha-1-antitrypsin (a known modifier gene of CF liver phenotype). CF related diabetes was found in 22 pairs (in 6 in both the siblings). It occurred later (median: 32.5 years) and is strongly associated with liver disease. Colonization by P. aeruginosa and nasal polyposis that required surgery had a concordance > 50% in sib-pairs and were poorly correlated to other clinical parameters. The pancreatic status was highly concordant in pairs of siblings (i.e., 95.1%) but a different pancreatic status was observed in patients with the same CFTR mutations. This suggests a close relationship of the pancreatic status with the "whole" CFTR genotype, including mutations in regulatory regions that may modulate the levels of CFTR expression. Finally, a severe course of CF was evident in a number of patients with pancreatic sufficiency. CONCLUSIONS: Physicians involved in care of patients with CF and in genetic counseling must be aware of the clinical heterogeneity of CF even in sib-pairs that, at the state of the art, is difficult to explain.

Intra-individual biological variation in sweat chloride concentrations in CF, CFTR dysfunction, and healthy pediatric subjects.

BACKGROUND: The sweat test is one of the main diagnostic tools used in newborn screening programs and as a confirmatory test, in case of suspect of Cystic Fibrosis (CF). Since sweat chloride (Cl) concentration is also considered an appropriate parameter to explore the efficacy of CFTR modulators in clinical trials, it is crucial to evaluate the biological variability of this test in healthy and pathological conditions. The aim of this pilot study was to determine the intra-individual biological variability of sweat Cl, both in healthy individuals and CF patients and to assess its correlation with diet, season, and menstrual cycle. METHODS: Thirty-five out of 36 selected subjects (6-18 years) were enrolled by 2 CF care centers and assigned to 3 cohorts: CF, CFTR-related disorder (CFTR-RD) and healthy volunteers. Each participant was subjected to eight sweat tests in different conditions and time of the year. Data were analyzed using linear mixed effects models for repeated measures, taking also into account intra-individual correlations. RESULTS: We observed a high intra-individual variability of sweat Cl, with the lowest mean CV% values among CF patients (20.21 in CF, 29.74 in CFTR-RD, and 31.15 in healthy subjects). Gender and diet had no influence on sweat Cl variability, nor had pubertal age and menstrual phase. CONCLUSION: Results of this pilot study confirmed that sweat Cl variability is high in CF patients, although non-CF individuals displayed even higher mean CV% values. Season significantly influenced sweat test values only in CF patients, likely due to changes in their hydration status.

Accuracy of serum procalcitonin for the diagnosis of sepsis in neonates and children with systemic inflammatory syndrome: a meta-analysis.

BACKGROUND: A number of biomarkers have been studied for the diagnosis of sepsis in paediatrics, but no gold standard has been identified. Procalcitonin (PCT) was demonstrated to be an accurate biomarker for the diagnosis of sepsis in adults and showed to be promising in paediatrics. Our study reviewed the diagnostic accuracy of PCT as an early biomarker of sepsis in neonates and children with suspected sepsis. METHODS: A comprehensive literature search was carried out in Medline/Pubmed, Embase, ISI Web of Science, CINAHL and Cochrane Library, for studies assessing PCT accuracy in the diagnosis of sepsis in children and neonates with suspected sepsis. Studies in which the presence of infection had been confirmed microbiologically or classified as "probable" by chart review were included. Studies comparing patients to healthy subjects were excluded. We analysed data on neonates and children separately. Our primary outcome was the diagnostic accuracy of PCT at the cut-off of 2-2.5 ng/ml, while as secondary outcomes we analysed PCT cut-offs <2 ng/ml and >2.5 ng/ml. Pooled sensitivities and specificities were calculated by a bivariate meta-analysis and heterogeneity was graphically evaluated. RESULTS: We included 17 studies, with a total of 1408 patients (1086 neonates and 322 children). Studies on neonates with early onset sepsis (EOS) and late onset sepsis (LOS) were grouped together. In the neonatal group, we calculated a sensitivity of 0.85, confidence interval (CI) (0.76; 0.90) and specificity of 0.54, CI (0.38; 0.70) at the PCT cut-off of 2.0-2.5 ng/ml. In the paediatric group it was not possible to undertake a pooled analysis at the PCT cut-off of 2.0-2.5 ng/ml, due to the paucity of the studies. CONCLUSIONS: PCT shows a moderate accuracy for the diagnosis of sepsis in neonates with suspected sepsis at the cut-off of 2.0-2.5 ng/ml. More studies with high methodological quality are warranted, particularly in neonates, studies considering EOS and LOS separately are needed to improve specificity. TRIAL REGISTRATION: PROSPERO Identifier: CRD42016033809 . Registered 30 Jan 2016.

Update of literature from cystic fibrosis registries 2012-2015. Part 6: Epidemiology, nutrition and complications.

Patient registries provide useful information to afford more knowledge on rare diseases like Cystic Fibrosis (CF). Twenty-two studies originating from national CF registries, focusing on demographics, survival, genetics, nutritional status, and non-pulmonary complications, were published between December 2011 and March 2015. The purpose of this review article is to examine these reports, aiming attention to the clinical characteristics of CF patients included in the registries, current, and estimated future epidemiological data, the role of gender gap, the increasing survival in different countries. Some studies offer insights into pubertal growth and non-pulmonary complications, such as liver disease, nephropathy, and cancer. Pediatr Pulmonol. 2017;52:390-398. © 2016 Wiley Periodicals, Inc.