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Background and Objective: This retrospective study aims to disclose further early parameters of COVID-19 morbidity and mortality. Methods: Three hundred and eighty-two COVID-19 patients, recruited between March and April 2020, were divided into three groups according to their outcome: (1) hospital ward group (patients who entered the hospital wards and survived); (2) intensive care unit (ICU) group (patients who attended the ICU and survived); (3) the deceased group (patients admitted to ICU with a fatal outcome). We investigated routine laboratory parameters such as albumin, glycemia, hemoglobin amylase, lipase, AST, ALT, GGT, LDH, CK, MGB, TnT-hs, IL-6, ferritin, CRP, PCT, WBC, RBC, PLT, PT, INR, APTT, FBG, and D-dimer. Blood withdrawal was carried out at the beginning of the hospitalization period. Results: ANOVA and ROC data evidenced that the concomitant presence of alterations in albumin, lipase, AST, ALT, LDH, MGB, CK, IL-6, ferritin in women, CRP and D-dimer is an early sign of fatal outcomes. method: 382 COVID-19 patients, recruited between March and April 2020, were divided into three groups according to their outcome: (1) hospital ward group (patients who entered the hospital wards and survived); (2) intensive care unit (ICU) group (patients who attended the ICU and survived); (3) the deceased group (patients admitted to ICU with a fatal outcome). We investigated routine laboratory parameters such as albumin, glycemia, amylase, lipase, AST, ALT, GGT, LDH, CK, MGB, TnT-hs, IL-6, ferritin, CRP, PCT, WBC, PLT, PT, INR, APTT, FBG, and D-dimer. Blood withdrawal was carried out at the beginning of the hospitalization period. Conclusion: The present study confirms and extends the validity of routine laboratory biomarkers (i.e., lipase, AST, ALT, LDH, CK, IL-6, ferritin in women, CRP and D-dimer) as indicators of COVID-19 morbidity and mortality. Furthermore, the investigation suggests that both gross changes in albumin and MGB, markers of liver and heart damage, may early disclose COVID-19 fatal outcomes. result: ANOVA and ROC data evidenced that the concomitant presence of alterations in albumin, lipase, AST, ALT, LDH, MGB, CK, IL-6, ferritin in women, CRP and D-dimer is an early sign of fatal outcomes. other:

Type 1 diabetes (T1D) represents a risk factor for bone loss and impaired bone quality.We conducted an exploratory retrospective cross-sectional study involving youths with new-onset T1D, to investigate the relationship between lumbar spine dual-energy X-ray absorptiometry (DXA) and phalangeal quantitative ultrasound (QUS) measurements, along with their correlation with markers of bone turnover, glucose homeostasis, and residual β-cell function.17 children and adolescents (8 females) with recent-onset T1D were enrolled into this study. Lumbar spine areal bone mineral density (aBMD) and age-adjusted amplitude-dependent speed of sound (AD-SoS) Z-scores were indicative of low BMD status (≤ -2.0 SD) in 11.7% and 17.6% of participants, respectively. Spearman's correlation analysis revealed significant inverse correlations between AD-SoS values and circulating levels of β-CrossLaps, alkaline phosphatase, and osteocalcin, along with a significant positive correlation between bone transmission time (BTT) values and fasting plasma C-peptide (FCP) levels. There was no statistically significant correlation between DXA-QUS parameters, fasting plasma glucose (FPG), and glycated haemoglobin (HbA1c). Finally, there was a significant positive correlation between lumbar spine aBMD and BTT values.Our study suggests that DXA and/or QUS parameters may be altered in a small proportion of T1D children and adolescents at the disease onset. Additionally, residual β-cell function may represent a protective factor against T1D-related detrimental skeletal changes. Large and long-term prospective studies are needed to confirm these preliminary findings since the present study is limited by the retrospective cross-sectional design and by its small sample size.

AIM To determine the prevalence rate of cancer diagnoses by an emergency route, the related risk factors and whether the emergency diagnosis was associated with poorer outcome. METHODS Retrospective observational study with identification of patients diagnosed at the Pediatric Oncology Unit of "Sapienza" University between 2008 and 2018. The percentage of patients who received a first-time diagnosis after an emergency presentation was determined. Two-year survival and clinical factors, such as sex, age and histology, associated to emergency presentation were evaluated. RESULTS Of 207 patients (109 girls and 98 boys; median age, 120 months), with a first-time diagnosis of solid tumor, 5.8% were diagnosed during an emergency admission after a median latency time of 2.5 days. Cases with an emergency diagnosis were younger compared with those who were diagnosed electively (median age, 30 months vs 120 months, P < 0.005). Higher prevalence rate of emergency presentation was detected in patients with lymphoma compared with those with no lymphoma disease (28.6% vs 4.1%; P < 0.0001). All patients were managed to overcome their emergency presentation, 33.3% of these died later. No statistically significant difference for 2-year overall survival was found between patients with an emergency diagnosis and those with elective diagnosis (66.7% vs 81.0%; odds ratio, 2.1; confidence interval, 0.6-7.5; P = 0.22). CONCLUSIONS A minor but not negligible number of pediatric patients come to a first-time diagnosis of cancer as result of a life-threatening event; risk factors were younger age and lymphoma disease. The emergency event can be successfully treated, and it was not related to a poorer survival.

Background Cystic fibrosis (CF) is one of the most frequent genetic diseases and the median survival of these patients has improved in the last few decades, therefore it becomes necessary to evaluate the long-term complications as renal and cardiovascular risk factors. Aim of the study To evaluate the incidence, the manifestations of renal disease and the possible association with metabolic and endothelial dysfunction markers in the CF population. Materials and methods We performed a cross-sectional, observational study on 226 CF patients. Clinical and laboratory instrumental parameters (metabolic, inflammatory and endothelial dysfunction markers) were evaluated. Results We showed 65 patients with chronic kidney disease (CKD) and 158 patients with a reduced value of forced expiratory volume in 1 s (FEV1), of which 58 patients with a severe reduction of FEV1. Moreover 28 patients had undergone lung transplantation and them had a significant lower estimated Glomerular Filtration Rate (eGFR) with respect to the non-transplanted patients (p Conclusions Our study showed a high prevalence of CKD in CF patients. Moreover we showed an increase of endothelial dysfunction and metabolic indexes in patients with reduced renal function, as SUA, serum triglycerides and LDL, suggesting the need for an early and complete screening of the main metabolic indexes to reduce cardiovascular risk and progression of renal damage, in particular in patients with lung transplant.

Objectives Lung transplantation is currently the only treatment for end-stage respiratory failure in patients with cystic fibrosis (CF). In this study we retrospectively analyzed our experience since the start of the transplantation program in 1996 with focus on survival analysis. Methods All patients with CF who underwent lung transplant at our center were included (1996–2016). Survival analysis after lung transplant was performed using the Kaplan-Meier estimate, comparing by sex and by 4 eras (1996–2000, 2001–2005, 2006–2010, and 2011–2016). Results In a 20-year period, 243 patients with CF were listed for lung transplant; 123 patients (61 male, 62 female) underwent transplant, and 85 died while waiting for donor organs. The mean (SD) and median age at transplant was 27.7 (8.7) years and 26.9 years (range, 9.1 – 52.1 years), respectively. Mean (SD) forced expiratory volume in the first second was 27.6 (9.7)% predicted; 115 patients (92.0%) were pancreatic insufficient, and 43 patients (34.0%) had CF-related diabetes. Removing patients with CF who died within the first 3 postoperative months, the mean (SD) and median survival after transplant were 8.2 (5.7) years and 7.5 years (range, 3 months-20 years), respectively. Overall post–lung transplant 1-year survival was 93.6%, 5-year survival was 71.4%, 10-year survival was 53.6%, 15-year survival was 36.7%, and 20-year survival was 31.6%. We found no difference in survival between sex (P = .22) and among the 4 eras (P = .56). Conclusions Survival after lung transplant in our single center is similar to international data.

Background. Cystic fibrosis (CF) is one of the most frequent genetic diseases. The discovery and implementation of new therapies prolonged the survival of CF patients in the last years. Evaluation of long-term complications could be useful to improve the outcome of these patients. Aim of the Study. To evaluate renal function, metabolic, nutritional, and inflammatory status in CF patients on cystic fibrosis transmembrane regulator (CFTR) modulators therapy as well as lung transplant recipients (LRs) and patients on conservative therapy (control group). Materials and Methods. We performed a prospective, longitudinal study on 69 CF patients. Clinical and laboratory parameters (metabolic and nutritional indices and inflammatory markers) were evaluated in all patients before starting CFTR therapy or transplant (T0) and after 3 years (T1). Results. We enrolled 69 CF patients (42 males). Patients were distributed into three groups. The average age was 35.01 ± 10.57 years for the control group (group 0), 32.47 ± 9.40 years for patients on CFTR modulators therapy (group 1), and 38.93 ± 7.14 years for LRs (group 2). At T1, we showed a significant difference among the three groups in terms of renal function indices: creatinine, eGFR, serum nitrogen as well as serum uric acid, sodium, and potassium ( p < 0.001 , p < 0.001 , p < 0.001 , p < 0.001 , p < 0.001 , and p < 0.001 , respectively), particularly in LRs patients. Significant differences were found in nutritional status parameters among the three groups: total protein, serum albumin, serum fibrinogen, serum transferrin, and white blood cell counts ( p < 0.001 , p = 0.037 , p = 0.04 , p = 0.003 , and p = 0.007 , respectively), particularly in LRs compared with other groups. Moreover, we found significant differences in metabolic profile (HbA1c, p = 0.026 ) and inflammatory status, with a significant difference in C-reactive protein values, neutrophil counts, and neutrophil-lymphocyte ratio (NLR) among the three groups ( p < 0.001 , p = 0.005 , and p = 0.026 , respectively). Conclusions. Our study showed a reduced renal function and poor nutritional status in LRs, along with worse metabolic control. Moreover, we showed a lower inflammatory status in patients on CFTR modulators therapy. Therefore, we suggest early and careful monitoring of renal function, metabolic, and nutritional parameters in CF patients, whether they are on conservative therapy, CFTR modulators therapy, and LRs patients.

In morbid obesity nonalcoholic fatty liver disease (NAFLD) is endemic. Aim of this study is to evaluate the diagnostic accuracy of the most common noninvasive methods for identify NAFLD and fibrosis in a cohort of morbid obese population. Ninety morbid obese patients undergoing bariatric surgery (BS) and intraoperative liver biopsy were evaluated preoperatively with Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and serum biomarkers for steatosis and fibrosis and liver stiffness measurement (LSM) using acoustic radiation force impulse (ARFI) elastography. All nondiabetic patient (n = 77) underwent OGTT and calculation of Oral Glucose Insulin Sensitivity index (OGIS). In the entire cohort prevalence of NAFLD was 77%, NASH 24%, moderate/severe steatosis 50%, and significant fibrosis 14%. New cut-offs were evaluated for all steatosis score assessed in this population. In all patients with moderate/severe steatosis HOMA IR was significantly greater than 3.5. ALT, GGT, Triglycerides, HOMA IR, and ARFI increased with fibrosis grade (p 0.03, p 0.008, p 0.04, p 0.05, respectively) and AST to Platelet ratio (APRI) was the only noninvasive fibrosis score significantly increased in significant fibrosis (p 0.04). A combination of 1/OGIS and VAI was able to discriminate NASH from simple steatosis (NAFL) (p 0.02). In morbid obese subjects, we calculated new cut-offs of the most common steatosis indexes and found that a score based on insulin resistance (1/OGIS) and abdominal obesity (VAI) could represent a way to identify morbid obese subjects at risk of NASH.

Background Meningococcal meningitis (MM) is known to be responsible of high cost for the Public Health Administration. Aim of the work is to calculate the costs for the hospitalization of pediatric patients affected by MM. Methods We calculate the costs for the hospitalization of pediatric patients affected by MM in the acute phase (HAP) over a nine year period. We performed a MEDLINE search to verify the cost of MM HAP reported in other studies. Results At Bambino Gesù Children Hospital, the median cost of HAP was of 12,604 euro (range from 9203 to 35,050 euro). Comparing our data with the previous studies, we find out similar results of approximately 16,750 euro (range 12,000–20,000 euro). Discussion Despite the relative rarety of the disease, MM is associated to direct high cost of HAP. Conclusions Hospital costs are an important end-point in health economic evaluation of the disease and may be useful to policy makers and health economists to understand the potential benefit of improving meningococcal vaccination programmes.

BACKGROUND The aim of the study was to assess the prognostic significance of nephron-sparing surgery (NSS) without tumor size limits as a risk factor for relapse in children with unilateral Wilms Tumor (WT). METHODS A 28-y retrospective single-center review was performed. Prognostic relevance of age, gender, stage, histology, nephrectomy (N), and NSS was analyzed. RESULTS Sixty-nine cases (42 females and 27 males) with WT, off-therapy from 21 to 325 mo after chemotherapy mainly based on the International Society of Pediatric Oncology trials, were treated at our institution. Five cases were excluded (three children with synchronous bilateral WT and two adults with unilateral WT). Of 64 children with unilateral WT, 51 underwent N and 13 NSS without tumor size limits. Indeed, two-thirds of children who underwent NSS presented with a tumor diameter >4 cm. Overall, nine patients (14%) had a relapse (male-to-female ratio = 1:8). Initial surgery was N in eight cases and NSS in another one. Relapse rates in N and NSS groups were 15.7% and 7.7% (P = nonsignificant), respectively; the relapse rates in N and NSS groups were 8.6% and 7.7% (P = nonsignificant) for stages I-II unilateral WT cohort, respectively. On univariate analysis, factors correlated with probability of relapse were unfavorable histology (P

Little data is available on long-term renal impairment in survivors from childhood sarcoma. We investigated the prevalence of renal impairment and hypertension after very long-term follow-up in survivors who reached adulthood after treatment for childhood sarcoma.A cross-sectional single center study was performed. Outcomes included estimating glomerular filtration rate (eGFR), albuminuria, glycosuria, serum phosphate and magnesium, tubular reabsorption phosphate (TRP), chronic kidney disease (CKD) according to the "Kidney Disease: Improving Global Outcomes" (KDIGO) guidelines and blood pressure (BP).Out of 87 5-year sarcoma survivors, 30 adults (10F/20M, median age at diagnosis 9 years, median age at investigation 26 years, median follow-up 16 years, mean 19 years) were identified. Renal impairment was detected in four cases (13.3%); three of these fulfilled the criteria for CKD. Among the adult survivors, a subgroup of 15 cases (50%) had received ifosfamide without confounding factors such as a diagnosis of genito-urinary rhabdomyosarcoma or administration of other potentially nephrotoxic chemotherapy (platinum-based drugs or methotrexate); no renal dysfunction was detected in this subgroup. In the whole cohort of sarcoma survivors, hypertension was diagnosed in four cases (13.3%); BP was significantly correlated with body mass index [p .014].In our series of adult survivors treated for a diagnosis of sarcoma in their childhood, the prevalence of CKD was 10%. We found survivors treated with ifosfamide as the only nephrotoxic agent did not present glomerular or tubular toxicity at long term follow-up, but further studies including a larger number of cases are required to confirm it.

Background and Aims Very little information is available on whether docosahexaenoic acid (DHA) supplementation has a beneficial effect on liver fat and cardiovascular disease (CVD) risk factors in children with nonalcoholic fatty liver disease (NAFLD). In a double-blind, placebo-controlled randomized trial we investigated whether 6-month treatment with DHA improves hepatic fat and other fat depots, and their associated CVD risk factors in children with biopsy-proven NAFLD. Methods and Results Of 58 randomized children, 51 (25 DHA, 26 placebo) completed the study. The main outcome was the change in hepatic fat fraction as estimated by magnetic resonance imaging. Secondary outcomes were changes in visceral adipose tissue (VAT), epicardial adipose tissue (EAT), and left ventricular (LV) function, as well as alanine aminotransferase (ALT), triglycerides, body mass index-standard deviation score (BMI-SDS), and insulin sensitivity. At 6 months, the liver fat was reduced by 53.4% (95% CI, 33.4–73.4) in the DHA group, as compared with 22.6% (6.2–39.0) in the placebo group ( P = 0.040 for the comparison between the two groups). Likewise, in the DHA group VAT and EAT were reduced by 7.8% (0–18.3) and 14.2% (0–28.2%), as compared with 2.2% (0–8.1) and 1.7% (0–6.8%) in the placebo group, respectively ( P = 0.01 for both comparisons). There were no significant between-group changes for LV function as well as BMI-SDS and ALT, while fasting insulin and triglycerides significantly decreased in the DHA-treated children ( P = 0.028 and P = 0.041, respectively). Conclusions DHA supplementation decreases liver and visceral fat, and ameliorates metabolic abnormalities in children with NAFLD.

Nonalcoholic fatty liver disease (NAFLD), historically considered as the hepatic component of the metabolic syndrome, is a spectrum of fat-associated liver conditions in the absence of secondary causes that may progress to nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. Disease progression is closely associated with body weight or fatness, dyslipidemia, insulin resistance, oxidative stress, and inflammation. Recently, there has been a significant scientific interest into the relationship between vitamin D status and NAFLD. Because oxidative stress and inflammation might act as the common pathogenic mechanisms of NAFLD and vitamin D deficiency, and as both diseases are associated with insulin resistance, type 2 diabetes and cardiovascular disease, several studies have investigated the association between vitamin D deficiency and NAFLD/NASH, but with conflicting findings. Therefore, we sought to critically review the current evidence on the association between vitamin D deficiency and NAFLD/NASH, and to analyze and discuss some key variables that may interfere with this evaluation, such as host-, environment-, and heritability-related factors regulating vitamin D synthesis and metabolism; definitions of deficient or optimal vitamin D status with respect to skeletal and nonskeletal outcomes including NAFLD/NASH; methods of measuring 25(OH)D; and methods of diagnosing NAFLD as well as quantifying adiposity, e.g. the cardinal link between vitamin D deficiency and NAFLD.

Background and aims: The triglyceride (TG)/high-density lipoprotein-cholesterol (HDL-C) ratio has been reported as a useful marker of atherogenic lipid abnormalities, insulin resistance, and cardiovascular disease. We evaluated in a large sample of children and adolescents the association of TG/HDL-C ratio with early signs of morphological vascular changes and cardiometabolic risk factors including nonalcoholic fatty liver disease (NAFLD). Methods and results: The study population, including 548 children (aged 6e16 years), of whom 157 were normal-weight, 118 overweight, and 273 obese, had anthropometric, laboratory, liver and carotid ultrasonography (carotid artery intima-media thickness-cIMT) data collected. Subjects were stratified into tertiles of TG/HDL-C. There was a progressive increase in body mass index (BMI), BMI-SD score (SDS), waist circumference, blood pressure (BP), liver enzymes, glucose, insulin, homeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein (hsCRP), and cIMT values across TG/HDL-C tertiles. The odds ratios for central obesity, insulin resistance, high hsCRP, NAFLD, metabolic syndrome, and elevated cIMT increased significantly with the increasing tertile of TG/HDL-C ratio, after adjustment for age, gender, pubertal status, and BMI-SDS. In a stepwise multivariate logistic regression analysis, increased cIMT was associated with high TG/HDL-C ratio [OR, 1.81 (95% CI, 1.08e3.04); P < 0.05], elevated BP [5.13 (95% CI, 1.03e15.08); P < 0.05], insulin resistance [2.16 (95% CI, 1.30e3.39); P < 0.01], and NAFLD [2.70 (95% CI, 1.62e4.56); P < 0.01]. Conclusion: TG/HDL-C ratio may help identify children and adolescents at high risk for structural vascular changes and metabolic derangement.

Summary. Objectives: Our study was aimed to evaluate the efficacy of 7% hypertonic saline and 0.1%hyaluronicacid (7% HS‐HA)given by inhalation, in infantshospitalized for mild-to-moderate bronchiolitis. Methods: In a double-blind controlled study, 39 infants (23 boys)

Allergies are multifactorial diseases the onset of which depends also on genetic and environmental factors in early life. Thus, environmental factors can affect the immune response and modify lung development, thereby leading to asthma. The role of the factors used to date to predict asthma development is modest, and clinical criteria should always be considered in association with familiarity for atopy. The aim of this study is to evaluate the risk of asthma in a population with positive Skin Prick Test (SPT) (which is a reliable marker of atopy) to food allergens, regardless of clinical manifestations in the early years of life. The cohort of children enrolled in our study who had a positive SPT to food in the first three years of life had a prevalence of asthma after 7–14 years, double that of the general pediatric population. This prevalence increased significantly in patients with SPT positivity for food and inhalant allergens. We identified a correlation between the sensitization profile in children under the age of 36 months and the development of asthma during a period of 7–14 years. This study confirms that early sensitization is an important risk factor for the development of asthma, particularly in association with sensitization to inhalants, and that the persistence of food sensitization in school-age children and adolescents is associated to more severe asthma.

The genetic diversity of the host is believed to be the key of the diversity in the clinical presentation of bronchiolitis. The aim of this study was to determine whether the known rs12979860 and rs8099917 single nucleotide polymorphisms (SNPs) in interleukin (IL)28B region, influence clinical features and natural history of bronchiolitis. Both SNPs showed no significant association with the risk of hospitalization for respiratory syncytial virus (RSV), viral load, disease severity, and other clinical features of patients. Interestingly infants carrying IL28B rs12979860 TT genotype had lower age at hospital admission than that of infants carrying CC/CT genotypes. Overall our results indicate that both IL28B SNPs had no impact on the clinical course of bronchiolitis with the only exception of the IL28B rs12979860 SNP which increased the risk of hospitalization for bronchiolitis at early age.

Aim: To determine the incidence and predisposing factors for severe bronchiolitis in previously healthy term infants 0.8 mg/dL) and pulmonary consolidation on chest X-ray were more common among infants with severe disease. Severity was independently associated with younger age on admission

Educational self-management programs for children with asthma have now become a routine feature in the management of the disease, as international guidelines underline. We designed this trial to find out whether Aironet, an educational program developed for children with asthma, influenced asthma severity and improved parents' knowledge of the disease. In a multicenter, prospective, randomized controlled trial we enrolled 123 children, 72 boys, mean age 8.78 yr (+/-2.33 s.d.), with intermittent or mild persistent asthma. Participants were randomly assigned to an education group, who received Aironet at baseline and 2 months later (60 children), or to a control group who did not (63 children). Follow-up lasted 12 months and included out-patient clinic visits and spirometry at 2, 4 and 12 months. At baseline and at 12 months follow-up, parents were questioned about their knowledge of asthma, and their children's asthmatic attacks, use of systemic corticosteroids, family physician or hospital emergency room visits, hospitalizations and asthma-related school absences. Questionnaire replies at 12-month follow-up reported significantly fewer asthma attacks in patients who received the program than in those who did not (1.65 +/- 1.21 vs. 2.34 +/- 1.73; p < 0.05). For the subgroup of children who had > or =3 asthma attacks at baseline, parents' knowledge improved significantly more in the educational group than in the control group. The out-patient educational program Aironet reduces the number of asthma attacks in children with intermittent or mild persistent asthma and improves knowledge of the disease.

The prevalence of venous thrombosis (VT) in children with solid tumor and the role of different risk factors are not defined yet.A cross-sectional observational study was conducted to evaluate the prevalence of both symptomatic and asymptomatic catheter-associated thrombosis events in children affected with different solid tumors.Patients with a solid tumor, admitted as day-care, were consecutively enrolled over a period of 10 months. All of them had a central venous line. Physical examination, D-dimer serum tests, and eco-color-Doppler ultrasonography were performed once at any time before catheter removal.Forty-two patients (14 females and 28 males)-mean age 115 months-were evaluated. Five of the 42 patients (12%) had VT. In 4 of these, VT was catheter-related: 3 asymptomatic and 1 symptomatic. In the last patient, VT was clinically symptomatic and not catheter related. Patients with longer duration of catheter insertion presented with a higher rate of VT (P=0.05). Moreover, patients affected with neuroblastoma showed a higher rate of VT than the others with different solid tumors (P0.05).VT was visualized by echo-color-Doppler ultrasonography in 12% of the patients; it was asymptomatic in 7%. In our small series, VT was related to neuroblastoma disease and a longer duration of catheter insertion. Prospective and multicentric studies are required to select risk factors for VT in children with solid tumors.

Aim: The study evaluates a breastfeeding promotion program in an Italian neonatal intensive care unit (NICU) over a period of time. Methods: Clinical data of the newborns admitted in the NICU of the Bambino Gesu' Children's Hospital in Rome in 2002 were gathered (78; program implemented) and were compared to similar data collected in 1998 (76; prior to the program) and in 2000 (50; program activated). Breastfeeding management during hospitalization and infant feeding after discharge were examined through maternal interviews. Results: The general features of the newborns and their parents were comparable. In 2002, the rate of exclusively breastfeeding (at breast and/or expressed mother's milk) the first day at home was 51.2% and 64% in 2000 versus 21.2% in 1998 (p < 0.001). In the subset of newborns

To perform a systematic review assessing accuracy and completeness of diagnostic studies of procalcitonin (PCT) for early-onset neonatal sepsis (EONS) using the Standards for Reporting of Diagnostic Accuracy (STARD) initiative. EONS, diagnosed during the first 3 days of life, remains a common and serious problem. Increased PCT is a potentially useful diagnostic marker of EONS, but reports in the literature are contradictory. There are several possible explanations for the divergent results including the quality of studies reporting the clinical usefulness of PCT in ruling in or ruling out EONS. We systematically reviewed PubMed, Scopus, and the Cochrane Library databases up to October 1, 2014. Studies were eligible for inclusion in our review if they provided measures of PCT accuracy for diagnosing EONS. A data extraction form based on the STARD checklist and adapted for neonates with EONS was used to appraise the quality of the reporting of included studies. We found 18 articles (1998–2014) fulfilling our eligibility criteria which were included in the final analysis. Overall, the results of our analysis showed that the quality of studies reporting diagnostic accuracy of PCT for EONS was suboptimal leaving ample room for improvement. Information on key elements of design, analysis, and interpretation of test accuracy were frequently missing. Authors should be aware of the STARD criteria before starting a study in this field. We welcome stricter adherence to this guideline. Well-reported studies with appropriate designs will provide more reliable information to guide decisions on the use and interpretations of PCT test results in the management of neonates with EONS.

BACKGROUND: The aim was to investigate the role of physical and radiological findings before bronchoscopy in the diagnosis of foreign body aspiration (FBA). METHODS: We retrospectively reviewed the clinical records for 82 patients (mean age 26.4 +/- 21.4 months, range 9 months to 13.5 years; 49 males) with a history suggestive of foreign body aspiration. RESULTS: The presence of a foreign body in the airways was confirmed in 70 children (85.4%) (mean age 25 +/- 14.1 months, 45 boys). Of the 70 children, 63 patients (90%) were under 3 years of age, with a peak incidence during the second year. Of the 70 foreign bodies retrieved, 46 (60%) were vegetable and 35 (76%) of these were nuts. In 42% of the patients the foreign body was located in the right bronchial tree. The most frequent physical findings observed in our patients were persistent cough (75%), localized decreased breath sound (62.8%) and localized wheezing (30%). The clinical triad (concomitant cough, localized wheezing and decreased breath sound) was present in 11 patients (15.7%). All clinical findings had a high positive predictive value with poor sensitivity. In 11 patients (20%) chest X-rays were normal. Five foreign bodies (9.1%) were radiopaque. The most frequent radiological findings observed were localized air trapping (43.6%), followed by atelectasis (40%). The diagnostic sensitivity was 80% and the specificity 33% for the presence of a single positive radiological finding. CONCLUSIONS: Our study confirmed that clinical symptoms and radiological findings before bronchoscopy have a low diagnostic value in children with a history of FBA. Language: en

We tested the hypothesis that the use of a pacifier may affect the ability of some term infants to maintain effective oral breathing during prolonged nasal occlusion. Three nasal occlusion tests without a pacifier and 3 with a pacifier were alternately carried out in 20 healthy term infants (age 2–5 days). Once the infant commenced oral breathing, nasal occlusion was continued for up to 90 sec (prolonged nasal occlusion), provided the infant did not start crying and that arterial oxygen saturation (SaO2) did not drop to ≤ 80%. The response to nasal occlusion was considered maladaptive if oral breathing was accomplished with signs of upper airway obstruction. After nasal occlusion, the infants succeeded in starting oral breathing in all instances after a delay which was strongly correlated to the drop in SaO2 (P

Hemoptysis is a common complication in patients with cystic fibrosis (CF). Current approaches to patients with hemoptysis include conservative medical therapy, bronchial artery embolization (BAE), and surgery. We investigated the effectiveness of early BAE on the outcome in patients with minor bleeding.We reviewed the clinical records from the Cystic Fibrosis Service for eight consecutive patients treated with medical therapy who had undergone early BAE and eight matched patients treated with conservative medical therapy alone.We assessed the mean number of bleeding episodes, pulmonary exacerbations, lung function (FEV(1)), Shwachman score, and Nottingham Health Profile (NHP) scores, the year before BAE and for the 3 ensuing years.During a 3-year follow-up, patients who underwent embolization had significantly fewer bleeding episodes (p0.001) and pulmonary exacerbations (p0.006). Lung function declined significantly in both groups (p0.001). The modified Shwachman score declined significantly during the follow-up only in patients who did not undergo embolization (p0.001). Patients treated by early embolization had significantly better NHP scores, indicating a better quality of life (p0.05). None of the patients who underwent BAE had adverse reactions.Early BAE in patients with CF who have nonmassive hemoptysis is an effective, safe therapeutic approach offering better long-term control of recurrent bleeding and quality of life than medical therapy alone.

In the last 20 years, nonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide, primarily as a result of the epidemic of obesity. NAFLD is strongly associated with insulin resistance, glucose intolerance, and dyslipidemia and is currently regarded as the liver manifestation of the metabolic syndrome, a highly atherogenic condition even at a very early age. Patients with NAFLD including pediatric subjects have a higher prevalence of subclinical atherosclerosis, as shown by impaired flow-mediated vasodilation, increased carotid artery intima-media thickness, and arterial stiffness, which are independent of obesity and other established risk factors. More recent work has identified NAFLD as a risk factor not only for premature coronary heart disease and cardiovascular events, but also for early subclinical abnormalities in myocardial structure and function. Thus, we conducted a systematic review and meta-analysis to test the hypothesis that NAFLD is associated with evidence of subclinical cardiac structural and functional abnormalities.

Human herpes viruses (HHVs) have been frequently detected in the gastrointestinal (GI) tract and may contribute to the development of gastric cancer. In the present study, the detection rate and viral load of Epstein Barr virus (EBV), HHV-6 and Cytomegalovirus (CMV) were assessed in the GI tract of human immunodeficiency virus (HIV) positive patients and of uninfected patients. The analysis revealed a significantly higher detection rate of EBV and HHV-6 in HIV-infected individuals than in uninfected subjects (88.5 vs 63 %; p = 0.03). Moreover, EBV DNA load was significantly higher in the stomach of HIV patients than in controls. These data suggest that the HIV infection status may increase the persistence of these viruses in the GI compartment. Intriguingly, CMV DNA was undetectable in all biopsy specimens analyzed.

AIM: To investigate the potential association of circulating zonulin with the stage of liver disease in obese children with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD). METHODS: A case-control study was performed. Cases were 40 obese children with NAFLD. The diagnosis of NAFLD was based on magnetic resonance imaging (MRI) with high hepatic fat fraction (HFF ≥ 5%), and confirmed by liver biopsy with ≥ 5% of hepatocytes containing macrovesicular fat. Controls were selected from obese children with normal levels of aminotransferases, and without MRI evidence of fatty liver as well as of other causes of chronic liver diseases. Controls were matched (1-to 1) with the cases on age, gender, pubertal stage and as closely as possible on body mass index- standard deviation score. All participants underwent clinical examination, laboratory tests including zonulin, inflammatory and metabolic parameters, and MRI for measurement of HFF and visceral adipose tissue. RESULTS: Zonulin values were significantly greater in obese subjects with NAFLD than in those without NAFLD [median (interquartile range), 4.23 (3.18-5.89) vs 3.31 (2.05-4.63), P < 0.01]. In patients with NAFLD, zonulin concentrations increased significantly with the severity of steatosis and the Spearman’s coefficient revealed a positive correlation between zonulin values and steatosis (r = 0.372, P < 0.05); however, we did not find a significant correlation between zonulin and lobular inflammation (P = 0.23), ballooning (P = 0.10), fibrosis score (P = 0.18), or presence of nonalcoholic steatohepatitis (P = 0.17). Within the entire study population, zonulin levels were positively associated with gamma-glutamyl transferase, 2-h insulin, HFF, and negatively associated with whole-body insulin sensitivity index (WBISI), after adjustment for age, gender and pubertal status. When the associations were restricted to the group of NAFLD patients, 2-h insulin, hepatic fat, and WBISI retained statistical significance. CONCLUSION: Circulating zonulin is increased in children and adolescents with NAFLD and correlates with the severity of steatosis.

The combination of a proton pump inhibitor and two antibiotics (clarithromycin plus amoxicillin or metronidazole) has been the recommended first-line therapy since the first guidelines for Helicobacter pylori (H.pylori ) infection in children were published. In recent years, the success of eradication therapies has declined, in part due to the development of H. pylori resistant strains. Alternative anti-H. pylori treatments are currently becoming more popular than the traditional eradication methods. Components that may be used either as a monotherapy or, in combination with anti-microbials, resulting in a more effective anti-H. pylori therapy have been investigated in depth by several researchers. One of the potential therapies is probiotic cultures; promising results have been observed in initial studies with numerous probiotic strains. Nevertheless, many questions remain unanswered. In this article, we comprehensively review the possible mechanisms of action of probiotics on H. pylori infection, and present the results of published studies using probiotics as possible agents to control H. pylori infection in children. The effect of the addition of probiotics to the standard H. pylori eradication therapy for the prevention of antibiotic associated side-effects is also discussed.

With the aim of determining normal reference values for our sleep laboratory and evaluating the reliability of automated analysis for scoring polysomnographic studies in children, we recorded polysomnograms in 16 healthy boarding-school children. Sleep recordings were obtained with a computer system (Medilog SAC, Oxford Instruments). Polysomnographic variables were monitored continuously on a 16-channel recorder equipped with a video. Data were acquired on optical disk for computer-assisted data interpretation. Sleep stages and respiratory events were also scored visually by operator. Comparison with visual scores showed that the computer system significantly overscored wakefulness (W) (p

Aim Links between respiratory syncytial virus bronchiolitis and asthma are well known, but few studies have dealt with wheezing following bronchiolitis induced by other viruses. We assessed the risk factors for recurrent wheezing in infants hospitalised for acute viral bronchiolitis. Methods We followed 313 infants for three years after they were hospitalised for bronchiolitis, caused by 14 different viruses, to identify risk factors for recurrent wheezing. Parents provided feedback on wheezing episodes during telephone interviews 12 (n = 266), 24 (n = 242) and 36 (n = 230) months after hospitalisation. Results The frequency of wheezing episodes diminished during the follow-up period: 137 children (51.7%) at 12 months, 117 (48.3%) at 24 months and 93 (40.4%) at 36 months. The risk of wheeze after three years was OR = 7.2 (95% CI 3.9–13.3) if they had episodes of wheezing during the first year after bronchiolitis, 16.8 (8.7–32.7) if they had episodes of wheezing during the second year and 55.0 (22.7–133.2) if they wheezed during both years. Blood eosinophils >400 cells/μL (OR 7.7; CI 1.4–41.8) and rhinovirus infections (3.1; 1.0–9.4) were the major risk factors for recurrent wheezing. Conclusion Recurrent wheezing 36 months after infant bronchiolitis was associated with rhinoviruses and blood eosinophilia.

Background Preliminary results suggest that pertussis infection might be considered in infants during a seasonal respiratory syncytial virus (RSV) outbreak. Methods In order to analyze clinical features and laboratory findings in infants with pertussis hospitalized for acute respiratory symptoms during a seasonal RSV outbreak, we conducted a retrospective single-center study on 19 infants with pertussis (6 boys; median age 72 days) and 19 matched controls (RSV-bronchiolitis), hospitalized from October 2008 to April 2010. B. pertussis and RSV were detected from nasopharyngeal washes with Real Time-PCR. Results Infants with pertussis were less often breastfeed than infants with RSV bronchiolitis (63.2% vs 89.5%; p B. pertussis than in controls with bronchiolitis (23886 ± 16945 vs 10725 ± 4126 cells/mm3, p 3, p B. pertussis isolates for ptxA1, ptxP3, and prn2 genes showed the presence of gene variants. Conclusions When infants are hospitalized for acute respiratory symptoms, physicians should suspect a pertussis infection, seek for specific clinical symptoms, investigate lymphocyte and eosinophil counts and thus diagnose infection early enough to allow treatment.

Objectives. Associations between thyroid function and nonalcoholic fatty liver disease (NAFLD) are unknown in childhood. Thus, the aim of the present study was to investigate in 402 consecutive overweight/obese children the association between thyroid function tests and hepatic steatosis as well as metabolic variables.Methods. Hepatic steatosis was diagnosed by ultrasound after exclusion of infectious and metabolic disorders. Fasting serum samples were taken for determination of thyroid function (TSH, FT4, and FT3), along with alanine aminotransferase (ALT), lipid profile, glucose, insulin, and insulin resistance (IR).Results. Eighty-eight children (21.9%) had TSH above the normal range (>4.0 mIU/L). FT3 and FT4 were within the reference intervals in all subjects. Elevated TSH was associated with increased odds of having hepatic steatosis (OR 2.10 (95% CI, 1.22–3.60)), hepatic steatosis with elevated ALT (2.42 (95% CI, 1.29–4.51)), hypertriglyceridemia, elevated total cholesterol, and IR as well as metabolic syndrome (considered as a single clinical entity), after adjustment for age, gender, pubertal status, and body mass index-SD score (or waist circumference).Conclusions. In overweight/obese children, elevated TSH concentration is a significant predictor of hepatic steatosis and lipid and glucose dysmetabolism, independently of the degree of total and visceral obesity.

Several studies suggest that a substantial number of patients with normal serum alanine aminotransferase (ALT) levels, defined by current thresholds, have ongoing hepatic necro-inflammation and fibrosis, and are at risk of liver disease progression. A major problem lies in the definition of normality. The current upper limit of normal (ULN) for ALT was established in the 1980s when reference populations were likely to include many persons with hepatitis C virus infection and nonalcoholic fatty liver disease. Because ALT may be influenced, not only by liver disease, but also by other medical conditions, changing lifestyle factors and demographic determinants, the current ALT ULN threshold has recently been challenged. This review not only highlights current evidence on why and how ALT ULN should be redefined, but also discusses the current concerns about updating the ULN threshold for ALT.

We have previously demonstrated the association between bronchiolitis from Rhinovirus (RV) and recurrent wheezing after one yr of follow-up (Eur Respir J 2010; 36 (54) P2707). Our objective was to identify wheezing recurrence and related risk factors in infants with bronchiolitis from Respiratory Syncytial Virus (RSV), RV, Bocavirus (hBoV), Influenza A and B, Parainfluenza 1-3, Metapneumovirus, Adenovirus and Coronavirus detected from nasal washes with RT-PCR. 208 infants (mean age ± SD 2.4±2.1, range 0.07-11 months, 89 males) hospitalized with bronchiolitis were evaluated for recurrent wheezing (RW) during 3 yrs of follow-up. Demographic and clinical data were obtained from parents with a structured questionnaire and patient9s medical files. Of they 208 infants, 152 (73%) answered to the phone call. 104 viruses were identified from 92 infants: RSV in 68 (73.9%), RV in 15 (16.3%), hBoV in 17 (18.5%), RSV+hBoV in 10 (10.9%), other viruses in 4 (4.34%). 34.9% of the infants with bronchiolitis had RW at the 3rd yr of follow-up. The related risk factors for RW were blood eosinophils counts > 400 cells/mm 3 (OR 9.26; CI 95% 1.09,79.0), breast feeding more than 2 months (OR 2.43; CI 1.20,4.89) and bronchiolitis from RV (OR 3.17; CI 1.03,9.79). At the 3rd yr of follow-up, 66.7% of the infants with bronchiolitis from RV have RW comparing to 57.1% of the infants with bronchiolitis from hBoV, 39.7% of the infants with bronchiolitis from RSV, 30% of the infants with bronchiolitis from RSV+hBoV and 25% of the infants with bronchiolitis from other viruses. In conclusion infants with RW at the 3rd yr of follow-up after acute bronchiolitis seem to be those with atopic predisposition and a specific viral infection.

Ventilator-induced lung injury (VILI) contributes to mortality in ARDS. Particularly preinjured lungs are susceptible to VILI despite protective ventilation. We previously observed protection against VILI by Adrenomedullin (AM). Here we analyzed impact VILI on lung injury, pulmonary and systemic inflammation, bacterial burden and end-organ injury in established pneumonia. Further AM therapy was investigated. 24h after infection with S. pneumoniae mice were subjected to MV (12ml/kg, 6h) and AM treatment. Lung permeability, oxygenation, lung mechanics, lung and plasma cytokines and leukocytes, bacterial burden in lung, blood spleen, ALT, AST, creatinine and urine output were assessed. Expression of AM and its receptor complex (CRLR; RAMP1-3) were studied In pneumonia MV aggravated lung injury indicated by increased pulmonary permeability, oxygenation failure and worsening of lung mechanics. MV dramatically increased lung and blood cytokine levels in pneumonia, while lung leukocyte counts in pneumonia were not affected by MV. In pneumonia MV induced leukocytopenia and liver injury. Lung and blood bacterial burden was not affected by MV. MV and pneumonia increased lung AM expression. RAMP1-3 were upregulated in pneumonia but MV reduced its expression. AM protected against MV induced pulmonary hyperpermeability and deterioration of lung mechanics in pneumonia. AM did not alter inflammation but protected against VILI induced liver injury in pneumonia. MV aggravated lung injury and induced liver injury in pneumonia. MV may pave the way for progression of pneumonia towards sepsis. AM may be a promising adjuvant therapy to limit VILI in pneumonia induced ALI and may protect against end organ damage.

The association between bronchiolitis and recurrent wheezing remains controversial. In this prospective study, we assessed risk factors for recurrent wheezing during a 12-month follow-up in 313 infants aged

The relationship between viral load, disease severity and antiviral immune activation in infants suffering from respiratory syncytial virus (RSV)-associated bronchiolitis has not been well identified. The main objective of this study was to determine the existence of a correlation between RSV load and disease severity and also between different clinical markers and mRNA levels of the interferon stimulated gene (ISG)56 in infants hospitalized for bronchiolitis. We also evaluated whether viral load tended to be persistent over the course of the RSV infection. The levels of RSV-RNA were quantified in nasopharyngeal washings, collected from 132 infants infected with RSV as a single (90.15%) or as a dual infection with other respiratory viruses (9.85%). Results indicated that viral load was positively related to the clinical severity of bronchiolitis, the length of hospital stay, the levels of glycemia and the relative gene expression of ISG56, whereas an inverse correlation was observed with the levels of hemoglobin. We also found that the RSV load significantly decreased between the first and second nasopharingeal washings sample in most subjects. These results suggest that infants with high RSV load on hospital admission are more likely to have both more severe bronchiolitis and a higher airway activation of antiviral immune response.

ObjectivesEvidence of the association between vitamin D and cardiovascular risk factors in the young is limited. We therefore assessed the relationships between circulating 25-hydroxyvitamin D3(25(OH)D3) and metabolic syndrome (MetS), its components, and early atherosclerotic changes in 452 (304 overweight/obese and 148 healthy, normal weight) Caucasian children.MethodsWe determined serum 25(OH)D3concentrations in relation to MetS, its components (central obesity, hypertension, low high-density lipoprotein (HDL)-cholesterol, hypertriglyceridemia, glucose impairment, and/or insulin resistance (IR)), and impairment of flow-mediated vasodilatation (FMD) and increased carotid intima–media thickness (cIMT) – two markers of subclinical atherosclerosis.ResultsHigher 25(OH)D3was significantly associated with a reduced presence of MetS. Obesity, central obesity, hypertension, hypertriglyceridemia, low HDL-cholesterol, IR, and MetS were all associated with increased odds of having low 25(OH)D3levels, after adjustment for age, sex, and Tanner stage. After additional adjustment for SDS-body mass index, elevated blood pressure (BP) and MetS remained significantly associated with low vitamin D status. The adjusted odds ratio (95% confidence interval) for those in the lowest (27 ng/ml) of 25(OH)D3for hypertension was 1.72 (1.02–2.92), and for MetS, it was 2.30 (1.20–4.40). A similar pattern of association between 25(OH)D3, high BP, and MetS was observed when models were adjusted for waist circumference. No correlation was found between 25(OH)D3concentrations and either FMD or cIMT.ConclusionsLow 25(OH)D3levels in Caucasian children are inversely related to total adiposity, MetS, and hypertension.

Background There is still no study evaluating the influence of gestational age (GA) per se on C reactive protein (CRP) and procalcitonin (PCT) reference intervals. We therefore investigated how length of gestation, age (hours), and prenatal and perinatal variables might influence the levels of CRP and PCT. We also determined 95% age-specific reference intervals for CRP and PCT in healthy preterm and term babies during the early neonatal period. Methods One blood sample (one observation per neonate) was taken for CRP and PCT from each newborn between birth and the first 4 (for term), or 5 days (for preterm newborns) of life by using a high-sensitive CRP and PCT assays. Results Independently of gender and sampling time, GA had a significantly positive effect on CRP, and a significantly negative effect on PCT. Compared with healthy term babies, healthy preterm babies had a lower and shorter CRP response, and, conversely, an earlier, higher, and longer PCT response. CRP reference intervals were affected by a number of pro-inflammatory risk factors. Conclusions Age- and GA-specific reference ranges for both CRP and PCT should be taken into account to optimize their use in the diagnosis of early-onset neonatal sepsis.