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• ETI is safe in most liver transplanted patients with CF. • Close monitoring of liver function and tacrolimus level is warranted. • An improvement in lung function after ETI is found also in liver transplanted patients. Cystic Fibrosis (CF) liver disease progresses to liver failure requiring transplantation in about 3 % of patients, 0.7 % of CF patients are post liver transplant. The prognosis of CF has improved with the introduction of elexacaftor/tezacaftor/ivacaftor (ETI). Due to the paucity of data and concerns regarding interactions with immunosuppressive drug regimens, there is no general consensus on use of ETI post liver transplantation. The aim of this review is to report the safety and efficacy of ETI in CF patients who underwent liver transplantation. A systematic review was conducted through MEDLINE/Pubmed and EMBASE databases. English-written articles reporting clinical data on liver transplanted CF patients treated with ETI were included. Article quality was evaluated using the Critical Appraisal Checklist for Case Reports. Twenty cases were retrieved from 6 reports. Temporary discontinuation and/or dose reduction due to elevated transaminases was required in 5 cases. ETI restarted on a reduced dose was tolerated in 3 out of 5 patients, 1 patient tolerated full dose. Tacrolimus dose change was required in 14 cases, in 1 case ETI was discontinued due to tacrolimus toxicity. Improvement in percentage predicted FEV1 was noted in 15/19 patients (median +17 %, range 8 %–38 %). In the majority of liver transplanted patients ETI is well tolerated, although adverse events and liver function abnormalities may occur. Close monitoring of liver function and tacrolimus level is warranted. Significant improvement in lung function after ETI initiation is confirmed, highlighting the importance of accessing this medication for this group of patients. [ABSTRACT FROM AUTHOR]

Background and Aims: We evaluated the effectiveness and safety of pan‐genotypic regimens, glecaprevir/pibrentasvir (GLE/PIB), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/daclatasvir (SOF/DCV) and other direct‐acting antivirals (DAA) regimens for the treatment of hepatitis C virus (HCV)‐infected adolescents (12–18 years), older children (6–11 years), and young children (3–5 years). The purpose of this systematic review and meta‐analysis was to inform the World Health Organization (WHO) guidelines. Methods: We included clinical trials and observational studies published up to August 11, 2021, that evaluated DAA regimens in HCV‐infected adolescents, older children, and young children. We searched MEDLINE, EMBASE, and CENTRAL databases and key conference abstracts. Sustained virological response 12 weeks after the end of treatment (SVR12), adverse events (AEs), and treatment discontinuation were the outcomes evaluated. Risk of bias was assessed using a modified version of the ROBINS‐I tool. Data were pooled using random‐effects models, and certainty of the evidence was assessed using the GRADE approach. Results: A total of 49 studies including 1882 adolescents, 436 older children, and 166 young children were considered. The SVR12 was 100% (95% Confidence Interval: 96–100), 96% (90–100), and 96% (83–100) for GLE/PIB in adolescents, older, and young children, respectively; 95% (90–99), 93% (86–98), and 83% (70–93), for SOF/VEL, respectively; and 100% (97–100) and 100% (94–100) for SOF/DCV in adolescent and older children, respectively. There was a clear trend towards a higher rate of any reported AE from adolescents (50%), older children (53%), to young children (72%). Serious AEs and treatment discontinuations were uncommon in adolescents and older children (<1%) but slightly higher in young children (3%). Conclusions: All three pan‐genotypic DAA regimens were highly effective and well‐tolerated and are now recommended by the WHO for use in adults, adolescents, and children down to 3 years, which will simplify procurement and supply chain management. The evidence was based largely on single‐arm non‐randomized controlled studies. Moreover, there were also missing data regarding key variables such as route of HCV acquisition, presence or absence of cirrhosis, or HIV co‐infection that precluded evaluation of the impact of these factors on outcomes. PROSPERO Record: CRD42020146752. [ABSTRACT FROM AUTHOR]

Summary: Background: The effect of direct‐acting anti‐virals (DAAs) in children and adolescents with chronic hepatitis C virus (HCV) infection is difficult to determine, since few, aged between 3 and 18 years, have been enrolled in clinical trials, and some data come from observational studies. Aim: To summarise the evidence on efficacy and safety of DAAs in children and adolescents with chronic HCV infection. Methods: We performed a systematic review and meta‐analysis of prospective studies on the efficacy and safety of DAAs in subjects <18 years of age. We considered the sustained virological response at post‐treatment week 12 as efficacy outcome and adverse events as safety outcome. We considered intervention effect for each study arm by calculating the proportion of sustained virologic response at post‐treatment week 12 in subjects receiving all doses of treatment and proportion of adverse events in subjects receiving at least one dose of treatment. Pooled proportions were calculated using the Freeman‐Tukey double arcsine transformation. Random effects model was used for all analyses. Results: Among 39 included studies (1796 subjects), the pooled proportion among those receiving all doses of treatment and reaching sustained virologic response at post‐treatment week 12 was 100% (95% confidence interval: 100‐100). Considering subjects receiving at least one dose of treatment, lowest estimates were reported among children with cirrhosis (83%). Headache and fatigue were the most common adverse events. Serious adverse events were uncommon. Conclusions: Children and adolescents with chronic HCV infection can be safely treated with DAAs with similar efficacy as reported in adults. [ABSTRACT FROM AUTHOR]

Hepatitis C is a global public health threat. The introduction of direct-acting antivirals (DAAs) brings the prospect of curing the 71 million people living with the disease, dramatically changing the landscape of hepatitis C. The World Health Organization developed a roadmap for the elimination and cure of hepatitis C by 2030 with a clear goal with measurable targets. However, there is a lack of a well-defined strategy to tackle the hepatitis C virus (HCV) problem in children and adolescents vis-à-vis the adult population. Hepatitis C in children and adolescents can be addressed as part of a national policy for elimination in the whole population, namely macroelimination, or could be fragmented into a microelimination approach targeting the high-risk population groups. Children born to HCV-infected mothers, adolescents who are injecting drugs, migrants, and those suffering from inherited blood diseases are important target populations. After the U.S. Food and Drug Administration approval for the use of DAAs in children aged 3 years and above, evidence from clinical trials and real-world experience was accumulated using brand and generic medicines, with sustained virological response rates exceeding 95%. The evidence created should guide policies on the management of hepatitis C in children and adolescents. There are many challenges in managing HCV in this left-behind marginalized population. The lack of awareness and epidemiological data, consent age, prohibitive prices of medicines, and absence of policies on access to diagnostics, treatment, and linkage to care are among the many barriers to service delivery that should be addressed to achieve the elimination goal by 2030. [ABSTRACT FROM AUTHOR]

The burden of paediatric Hepatitis C virus (HCV) infection across Europe is unknown, as are current policies regarding monitoring and treatment. This collaborative study aimed to collect aggregate data to characterise the population of ≤18‐year‐olds with HCV infection in specialist follow up in a 12‐month period (2016) across the PENTAHep European consortium, and investigate current policies around monitoring and treatment. A cross‐sectional, web‐based survey was distributed in April 2017 to 50 paediatricians in 19 European countries, covering patients' profile, and monitoring and treatment practices. Responses were received from 38/50 clinicians collectively caring for 663 children with chronic HCV infection of whom three‐quarters were aged ≥6 years and 90% vertically infected. HCV genotype 1 was the most common (n 380; 57.3%), followed by genotype 3, 4 and 2. Seventeen children (3%) with chronic HCV infection were diagnosed with cirrhosis, and six were reported to have received liver transplantation for HCV‐related liver disease. The majority (n 425; 64.1%) of the European children with HCV infection remained treatment‐naive in 2016. Age affected clinicians' attitudes towards treatment; 94% reported being willing to use direct‐acting antivirals, if available, in adolescents (aged ≥11 years), 78% in children aged 6‐10 and 42% in those 3‐5 years of age (Pearson correlation coefficient −0.98; P 0.0001). This survey provides the largest characterisation of the population of children in clinical follow‐up for chronic HCV infection in Europe, alongside important contextual information on their management and treatment. Discussion is needed around strategies and criteria for use of direct‐acting antivirals in these children. [ABSTRACT FROM AUTHOR]

See Article on Page 319 [ABSTRACT FROM AUTHOR]

A retrospective multicentre study conducted in Italy analyzed hospitalization trends for bronchiolitis in infants between October 2019 and March 2023. The study found that bronchiolitis cases, particularly those caused by the respiratory syncytial virus (RSV), experienced a significant reduction during the 2020-2021 winter due to preventive measures implemented during the COVID-19 pandemic. However, subsequent winters saw a notable and sustained increase in bronchiolitis hospitalizations, with the 2022-2023 winter period experiencing a 47% higher rate compared to the pre-pandemic winter of 2019-2020. The changing seasonality of bronchiolitis, including altered patterns of RSV circulation, poses challenges for disease control strategies and immunoprophylaxis measures. Further research is needed to monitor the epidemiology of bronchiolitis and inform public health interventions. [Extracted from the article]

LINKED CONTENT: This article is linked to Indolfi et al and Garrido & Macedo papers. To view these articles, visit https://doi.org/10.1111/apt.16037 and https://doi.org/10.1111/apt.16546 [ABSTRACT FROM AUTHOR]

Neonatal haemochromatosis is a rare alloimmune gestational disease with a high mortality. The hallmark of neonatal haemochromatosis is severe neonatal liver failure associated with extrahepatic siderosis. Thus far, no pituitary dysfunction has been reported to result from the tissue damage associated with extrahepatic siderosis. The present report describes a neonate with neonatal haemochromatosis and secondary hypothyroidism associated with pituitary iron deposition. Both the conditions were successfully treated by ABO-incompatible liver transplantation. Pituitary gland dysfunction is another possible extrahepatic manifestation of neonatal haemochromatosis, and it is reversible after liver transplantation. [ABSTRACT FROM AUTHOR]

Erythema nodosum (EN), although relatively uncommon in the pediatric population, is the most frequent type of panniculitis in children. The present study aimed to report all the cases of children admitted to our tertiary pediatric hospital with the diagnosis of EN to evaluate the epidemiology, clinical manifestations, etiology, treatment, and the course of this disease in the pediatric age. This observational study retrospectively considered all children evaluated to the emergency room (ER) of Meyer Children's University Hospital, Florence, Italy, discharged with a diagnosis of EN over a 12-year period (from January 2009 to December 2021). Clinical and laboratory data were recorded using a standardized report form. Sixty-eight patients with EN were included. The etiologic diagnosis of EN was made in 38 children (55.9%): 29 (42.6%) had infection-related EN (in particular EBV and β-hemolytic streptococcus), 6 (8.8%) had Crohn's disease, 1 celiac disease, 1 Sjogren syndrome, and 1 Hodgkin lymphoma. In 30 patients (45%), no definitive diagnosis was reached, and they were defined as having idiopathic EN. Most of the laboratory tests were nonspecific. No statistical differences were found in the demographic and clinical data, and the main diagnostic laboratory parameters between patients with idiopathic EN versus those with secondary EN. Conclusion: Since EN can be isolated or the first manifestation of heterogeneous underlying pathologies, some of which can be severe and life-threatening, it is important to recognize it and carry out all the necessary etiological diagnostic investigations to understand its etiology and start the specific treatment. What is Known: • Erythema nodosum (EN) is the most frequent type of panniculitis in children. • It has been associated with a wide spectrum of disorders, such as different types of infection, malignancies, chronic inflammations, and drugs. What is New: • No statistical differences can be found in clinical features as well as laboratory data, between patients with idiopathic EN versus those with secondary EN. • A broad spectrum of investigations and a proper follow-up should be taken into account in order to prevent a delayed or missed secondary EN diagnosis. [ABSTRACT FROM AUTHOR]

Highlights: [•] Streptococcus pneumoniae is present in the nasopharyngeal swab of the majority of children 0–5 years. [•] Streptococcus pneumoniae is present in the nasopharyngeal swab of children vaccinated with 7-valent pneumococcal conjugate vaccine. [•] within the short term (1 year) from vaccination, the carriage of the 7 vaccine serotypes of Streptococcus pneumoniae decreases and increases in the following years. [Copyright &y& Elsevier]

The rs12979860 single nucleotide polymorphism located on chromosome 19q13.13 near the interferon L3 gene (formerly and commonly known as interleukin 28B gene) has been associated in adults with both spontaneous and treatment induced clearance of hepatitis C virus. Although the exact mechanism of these associations remains unclear, it suggests that variation in genes involved in the immune response against the virus favours viral clearance. Limited and preliminary data are available on this issue in children. The aim of the present study was to evaluate, in a representative cohort of children with perinatal infection, the potential association between rs12979860 single nucleotide polymorphism and the outcome of hepatitis C virus infection. Alleles and genotypes frequencies were evaluated in 30 children who spontaneously cleared the virus and in 147 children with persistent infection and were compared with a population sample of ethnically matched controls with unknown hepatitis C status obtained using the 1000 Genomes Project data. The C allele and the C/C genotype showed greater frequencies in the clearance group (76.7% and 56.7%, respectively) when compared with both children with viral persistence (C allele 56.5%, p = 0.004; C/C genotype 32.7%, p = 0.02) and with the ethnically matched individuals (C allele 59.7%, p = 0.02; C/C genotype 34.7%, p = 0.03). Children with the C/C genotype were 2 times more likely to clear hepatitis C virus relative to children with the C/T and T/T genotypes combined (odds ratio: 2.7; 90% confidence intervals: 1.3–5.8). The present study provides the evidence that the rs12979860 single nucleotide polymorphism influences the natural history of hepatitis C virus in children. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection has been associated with autoimmunity and extrahepatic manifestations in adults. Few data are available on these topics in children. Nonorgan specific auto-antibodies development is part of the natural course of chronic hepatitis C in children. Smooth muscle autoantibody is the most common autoantibody found, while liver-kidney microsomal type-1 antibody positivity is the most peculiar autoimmune feature of children with HCV infection. The clinical significance of non-organ specific autoantibodies in the course of paediatric chronic hepatitis C is still debated. Autoantibody positivity can be considered neutral for most patients, while it can be associated with negative connotations for others, especially those positive for liver-kidney microsomal type-1 autoantibody. Subclinical hypothyroidism but not autoimmune thyroiditis has been demonstrated in HCV infection in children, while only few cases of HCV-associated membranoproliferative glomerulonephritis have been described. Single reports are available in the literature reporting the anecdotal association between chronic hepatitis C and other extrahepatic manifestations such as myopathy and opsoclonus-myoclonus syndrome. Despite the low incidence of extrahepatic manifestations of chronic hepatitis C in children, overall, available data suggest a careful monitoring. [ABSTRACT FROM AUTHOR]

Indolfi G, Heaton N, Smith M, Mieli-Vergani G, Zuckerman M. Effect of early EBV and/or CMV viremia on graft function and acute cellular rejection in pediatric liver transplantation. Clin Transplant 2012: 26: E55-E61. © 2011 John Wiley & Sons A/S. Abstract: Background: The clinical impact of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections in the early post-transplantation period are poorly documented. We investigated the prevalence and timing of EBV and CMV infections during the first 21 d post-transplantation in relation to graft function and acute cellular rejection in a large cohort of pediatric liver transplantation recipients. Patients and methods: Clinical, biochemical, virological, and histopathological data of 62 consecutive children who received a liver transplant were reviewed retrospectively. Results: Seventeen patients (27%) developed EBV and 11 (18%) CMV viremia (mean interval from surgery: 7.6 d, SD 3.6 and 8.7 d, SD 6.4, respectively). EBV and CMV viremia were more common as a consequence of reactivation than of primary infection. EBV viremic recipients had more often abnormal bilirubin levels [p = 0.01; OR 5.8: 95% CI 1.3-25.5]. Acute rejection was diagnosed in 20 recipients (32.3%). No correlation was found between rejection and EBV and CMV serology before transplantation and viremia after transplantation (mean interval between the diagnosis of rejection and the detection of EBV DNA and CMV DNA: one d, SD 4.4 and five d, SD 9.2, respectively). Conclusion: EBV and CMV viremia occur at a very early-stage post-transplantation and do not appear to affect the short-term outcome of the transplant. [ABSTRACT FROM AUTHOR]

The aims of this study were to identify demographic, clinical and laboratory characteristics associated with reactive thrombocytosis useful for clinical management and to evaluate potential complications of this condition in a cohort of children selected for they young age as at high risk of reactive thrombocytosis. Retrospective analysis of medical records of 239 children among 902 aged 1-24 months, hospitalized during a 12-month period, and discharged with a diagnosis of infectious disease was performed. One hundred and nineteen children out of 239 (49.8%) presented thrombocytosis (>500 platelets × 109/L; normal range 150-499 × 109/L), 81/119 (68%) on admission. The incidences of thrombocytosis or extreme thrombocytosis (>1,000 × 109/L) were 13.2% (119/902) and 0.8% (7/902). Thrombocytotic children had higher counts of white blood cells and had been treated more frequently with steroids (36/82, 43.9% vs. 5/53, 9.4%; p = 5 × 10-5; relative risk 7.51, 95% confidence intervals 2.71-20.82). No significant difference was found in relation to sex, age, fever, C reactive protein level, diagnoses and antibiotic therapy. Two out of 239 (0.8%) enrolled children, both thrombocytotic and with other acquired risk factors, developed thrombosis. In conclusion, reactive thrombocytosis in children aged 1 up to 24 months is frequent and unrelated to markers of disease activity or degree of inflammation. [ABSTRACT FROM AUTHOR]

Objective The reported data on thyroid function and anti-thyroid autoantibodies in adults with untreated hepatitis C virus (HCV) infection are controversial. Data are scarce for HCV-infected children, and only in those treated with interferon-α (IFN-α). We investigated thyroid function and anti-thyroid autoantibodies in a cohort of untreated children with vertically acquired, chronic, HCV infection. Design and patients FT4 and TSH serum levels (measured by immunometric assays) and anti-thyroglobulin (TgA) and anti-thyroperoxidase (TPOA) antibodies (evaluated by fluorescence enzymatic immunoassays) were studied in 36 consecutive HCV-infected children and 150 age- and sex-matched controls. The prevalence of thyroid involvement was also related to family history of autoimmune disease, distribution of HCV genotypes, and duration and activity of HCV infection. Results Four out of 36 (11·1%) HCV-infected children and 4/150 controls (2·7%) showed subclinical hypothyroidism [ P = 0·04; relative risk (RR) 4·56, 95% confidence interval (CI) 1·08–19·21]. None of these had anti-thyroid autoantibodies. Two out of 36 (5·6%) HCV-infected children and 1/150 (0·7%) controls had increased TgA values with normal levels of TSH ( P > 0·05). Subclinical hypothyroidism and anti-thyroid autoantibodies were not related to family history of autoimmune disease, duration of infection, HCV viral load, liver function or different HCV genotype distribution, but seemed to be related to the presence of active HCV infection. Conclusions Our data suggest a role for HCV infection in the development of nonautoimmune thyroid disease in untreated HCV-infected children, confirming previous studies in adults. Clinicians should be aware of thyroid dysfunction even in untreated children. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Erythema nodosum in children: a cohort study from a tertiary pediatric hospital in Italy" published in the European Journal of Pediatrics. The correction addresses an error in the affiliations of the authors. The correct affiliations are provided in the correction notice. The original article has been corrected. The publisher, Springer Nature, remains neutral regarding jurisdictional claims and institutional affiliations. The authors of the article are Sarah Abu-Rumeileh, Federica Barbati, Giuseppe Indolfi, and Sandra Trapani. [Extracted from the article]

Background: Respiratory Syncytial Virus (RSV) infection mainly affects newborns, infants and young children aged < 2 years. Since an RSV vaccine is in the European Medicines Agency's waitlist validation, nowadays the prevention only includes passive immunization with monoclonal antibodies (mAb). In the present study we aimed at investigating Italian paediatricians' knowledge, attitudes and behaviours towards RSV and its prevention. Methods: From February to May 2023, an anonymous online questionnaire, with answers based on the Likert scale, was administered to a sample of Italian paediatricians' members of the Italian Society of Paediatrics. Descriptive and inferential statistical analyses were performed using STATA 17. Results: The paediatricians who answered the questionnaire were 507, mostly women (70.6%), aged 30–45 (33.1%), employed in hospitals in 66.6% of cases. The 10.8% of respondents reported that RSV is transmitted only among children younger than 2 years of age and 80.33% of participants that school-age children are not at risk of developing severe forms of RSV disease. The 25% of participants thought that active immunization is currently available to prevent RSV infection and 35.7% that does not exist passive immunization to prevent RSV for infants and newborns aged < 2 years. The 97.5% of physicians managed bronchiolitis cases and 65.6% of participants did not prescribe the administration of mAb. Higher age, seniority and RSV knowledge score were found to be associated with having a higher mAb knowledge score (p < 0.001) and having a higher RSV knowledge was associated with a higher mAb knowledge score (p < 0.001). The logistic regression model found that the odds of a positive attitude towards mAB knowledge score increased by over 3 times (OR 3.23, 95% CI [1.41, 7.40], p = 0.006) for being female and the odds of a positive attitude towards mAB knowledge score increased by almost 10 times (OR 9.73, 95% CI [3.06, 30.89], p < 0.001) for a one-unit increase in RSV knowledge score. Conclusions: Paediatricians' limited knowledge or awareness could represent a barrier to the implementation of preventive strategies against RSV infection. Strategies to improve paediatricians' education on RSV prevention are, therefore, crucial. [ABSTRACT FROM AUTHOR]

Paediatric Menetrier disease (PMD) is a protein-losing gastropathy, presenting with generalized oedema and abdominal symptoms. PMD commonly has an acute course and may be associated with Cytomegalovirus (CMV) infection. The aim of this retrospective study is to assess the epidemiological and clinical data, diagnostic procedures, treatment and outcome of CMV-associated PMD. The medical charts of the patients with PMD and CMV infection diagnosed at our hospital have been reviewed. Then, a systematic literature's review of all the cases of PMD and a selection of those associated with CMV infection have been performed. Three previously healthy boys were admitted for vomiting and oedema. Endoscopy showed hypertrophic gastric folds and CMV infection was diagnosed. Albumin was administered in all cases, with clinical resolution within few weeks. In literature, PMD has been described in 150 children and the association between CMV and PMD was found in 89 cases. Clinical and laboratory data, radiological and histological exams, therapy and outcome were reviewed.Conclusions: Basing on the present experience and on the current knowledge, PMD has a benign course without long-term sequelae. Although PMD is rare in children, we recommend paediatricians to consider CMV-related PMD when facing children with vomiting and diffuse oedema. What is Known: • Paediatricians should consider Menetrier disease (MD) when facing oedematous child complaining of abdominal symptoms with hypoalbuminemia, without proteinuria and liver dysfunction. • Typical ultrasound features (hypertrophic gastric folds) suggest such condition which requires endoscopy and biopsy for definitive diagnosis. What is New: • A familial susceptibility to CMV gastric infection has been recently suggested; thus when suspecting MD, the family history of gastric diseases should be investigated. • Menetrier disease has been found associated with other unusual conditions either benign (such as gastric bezoar) or malign as neoplasms (acute lymphatic leukaemia and adenocarcinoma) even in children. [ABSTRACT FROM AUTHOR]

Background & Aims: The aim of this study was to assess the effect of treatment with sofosbuvir/velpatasvir (SOF/VEL) on the health‐related quality of life (HRQL) of children with chronic hepatitis C. Methods: In the non‐commercial, non‐randomized, open‐label PANDAA‐PED study, 50 children aged 6–18 years with chronic hepatitis C were treated with a fixed dose of SOF/VEL. All patients achieved sustained virologic response 12 weeks after the end of treatment (SVR12). Evaluation of HRQL was performed twice: at baseline (before the treatment) and during the SVR12 analysis using the KIDSCREEN‐27 questionnaires, which included 5 dimensions of HRQL, for child self‐reporting and parent proxy reporting. The normal range for the population was set to T values of 50 ± 10 points. Child–parent agreement was analysed using the intra‐class correlation coefficient (ICC) and Bland–Altman test. Results: Mean T values were within the normal range for all dimensions, both before and after treatment. There was a significant improvement in physical well‐being based on the children's self‐assessment (from 48.53 to 51.21, p =.03). In addition, a trend towards better scores in the 'social support & peers' part of the parent proxy evaluation (from 45.98 to 48.66, p =.06) was noticed. After the treatment, the proportion of children self‐assessing their physical well‐being as below normal significantly decreased from 17% to 5% (p =.007). HRQL scores were not associated with patients' sex, but in most cases, younger age correlated with better HRQL. Evaluation of the ICC for child self‐reports versus parent proxy reports revealed poor to moderate agreement for most single measures. Bland–Altman analysis showed that in all dimensions, both before and after treatment, the limits of agreement (LoAs) exceeded ±5 points (half of the SD and considered a maximum allowed difference). Conclusions: A significant proportion of children with chronic hepatitis C have decreased HRQL in all dimensions, but effective treatment with SOF/VEL leads to an improvement in some areas of well‐being. As the effect of HCV on HRQL is more pronounced in older patients, treatment of younger children should be indicated to prevent them from experiencing decreased HRQL due to ongoing HCV infection in the future. [ABSTRACT FROM AUTHOR]

This study aims to investigate the sensitivity of microscopy, culture and polymerase chain reaction on three gastric aspirates (GAs) in the microbiological confirmation of active pulmonary tuberculosis (TB) and to identify possible changes in sensitivity derived from the collection of a different number of aspirates. Children with clinical and radiological diagnoses of active pulmonary TB who underwent three GAs between March 2007 and June 2019 were retrospectively evaluated. Clinical, radiological, and microbiological data were collected. The sensitivity of microbiological tests on GAs was calculated. Moreover, differences in sensitivity according to age and radiological pattern were investigated. Overall, 156 children with active pulmonary TB were enrolled with a median age of 51.5 (IQR: 25.2–113.2) months. Microbiological investigations on the first GA showed a sensitivity of 34% (95%CI 26.7, 42), the cumulative sensitivity of first and second GAs was 40.4% (95%CI 32.7, 48.5) and of the three GAs was 47.4% (95%CI 39.8, 55.2). The collection of three GAs leads to an overall increase in sensitivity of the first GA by 13.4% (95%CI 2.8, 24.1%; p=0.014). Moreover, the increase in sensitivity was significantly higher in children ≤ 4 years of age and in those with uncomplicated TB (p=0.008). Conclusions: Performing a higher number of GAs increases the sensitivity of microbiological confirmation of active pulmonary TB, particularly in children ≤ 4 years and with an uncomplicated radiological pattern. What is known: • The diagnosis of paediatric tuberculosis is a challenge for paediatricians • Despite their low sensitivity gastric aspirates represent the standard sample for microbiological confirmation of active pulmonary tuberculosis in children • Most international guidelines recommend performing three sequential gastric aspirates on three consecutive days What is new: • A significant increase in global sensitivity by 13.4% was found by the collection of three gastric aspirates compared to the first one • Performing a higher number of gastric aspirates increases the sensitivity of microbiological confirmation, particularly in children ≤ 4 years and with an uncomplicated radiological pattern [ABSTRACT FROM AUTHOR]

A case study of a eight years month-old boy is presented with a history of chronic hepatitis C, and whose aminotransferases increased and plasma viral load rebounded. Topics discussed include presence of anti- hepatitis C virus (HCV), HCV latency in the liver, and plan of treating pegylated interferon and ribavirin.

Background: Mutations in lysyl-tRNA synthetase (KARS1), an enzyme that charges tRNA with the amino acid lysine in both the cytoplasm and mitochondria, have been associated thus far with autosomal recessive Charcot–Marie–Tooth type CMTRIB, hearing loss type DFNB89, and mitochondrial encephalohepatopathy (MEH) featuring neurodevelopmental disorders with microcephaly, white matter changes, and cardiac and hepatic failure in less than 30 patients. Case presentation: We report the clinical, biochemical and molecular findings of a 14-month-old girl with severe MEH compatible clinical features, profound sensorineural hearing loss, leopard spot retinopathy, pancytopenia, and advanced liver disease with portal hypertension leading to death at the age of 30 months. Conclusions: Whole exome sequencing identified two rare variants in KARS1 gene. Our report expands the allelic and clinical features of tRNA synthase disorders. Moreover, with our report we confirm the usefulness of WES as first tier diagnostic method in infants with complex multisystem phenotypes. [ABSTRACT FROM AUTHOR]

Aim: The aim of this narrative review was to provide a comprehensive summary of the characteristics of gastrointestinal (GI) involvement in the most common paediatric primary vasculitides.Methods: We used PubMed to primarily identify papers, reviews, case series and editorials published in English from 2000 until 31 January 2020. Based on this, we report the prevalence, clinical manifestations, diagnostic approaches and management of GI involvement in each vasculitis.Results: Vasculitides are inflammatory blood vessel diseases, and the majority can affect the GI system with vascular, GI tract or solid organ involvement. GI involvement can sometimes complicate and delay the correct diagnosis. Clinical findings are usually nonspecific symptoms, such as fever, abdominal pain, nausea, vomiting and diarrhoea. Bleeding should alert paediatricians to the possibility of severe complicated vasculitis. Diagnosis relies mostly on imaging. If it goes unrecognised, GI involvement in paediatric vasculitis is a serious cause of morbidity and even mortality, related to bowel ischaemia and perforation. Treatment of GI symptoms depends on the type of vasculitis and usually involves high-dose steroids and immunosuppressants.Conclusion: GI manifestations in the most common paediatric primary vasculitides were usually nonspecific, diagnosis mostly relied on imaging, and treatment usually involved high-dose corticosteroids and immunosuppressants. [ABSTRACT FROM AUTHOR]

Background and Aims: The aim of this non‐commercial, open‐label, real‐life, non‐randomized clinical trial was to analyse the efficacy and safety of a pangenotypic regimen sofosbuvir/velpatasvir (SOF/VEL) in patients aged 6–18 years with chronic hepatitis C virus (HCV) infection. Methods: Fifty patients qualified for the 12‐week treatment were divided into two weight groups: 15 children weighting between 17 and <30 kg received a fixed dose of 200/50 mg of SOF/VEL (tablet) once daily, and 35 patients weighting ≥30 kg were treated with 400/100 mg SOF/VEL. The primary endpoint of the study was efficacy defined as sustained viral response (undetectable HCV RNA using an real‐time polymerase chain reaction method) at 12 weeks posttreatment (SVR12). Results: Median age of the participants was 10 (IQR 8–12) years, 47 were infected vertically, and 3 patients were previously ineffectively treated with pegylated interferon and ribavirin. Thirty‐seven participants were infected with HCV genotype 1, 10 with HCV genotype 3 and the remaining 3 with genotype 4. There was no case of cirrhosis. SVR12 was 100%. Thirty‐three reported adverse events (AEs) were considered related to the administration of SOF/VEL, all of them were mild or moderate. Children presenting with AEs were older compared to these without AEs: 12 (9.5–13) versus 9 (IQR 8–11) years (p = 0.008). Conclusions: Results of the PANDAA‐PED study indicated a 100% effectiveness of a 12‐week therapy with SOF/VEL in children aged 6–18 years with chronic HCV infection and its good safety profile, in particular in younger patients. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 3-year-old girl with bleeding and diagnosed with lupus anticoagulant-hypoprothrombinemia syndrome (LAHS) and coeliac disease (CD). Physical examination was normal which showed only diffuse multiple subcutaneous haematomas. The article discusses LAHS characterized by the presence of low prothrombin activity (PA). Clinicians should keep in mind that LA is associated with bleeding and the possibility of association between CD and LA which is rare in children.

A letter to the editor is presented commenting on the etiology of immune (idiopathic) thrombocytopenic purpura (ITP) and portal vein thrombosis in children.

In children, clinical recognition of stroke and determination of its exact etiology are extremely difficult. The authors described a case of cryptogenic stroke in a 14-year-old-boy with asymptomatic atrial septal defect and hypercoagulable state. Paradoxical embolism was hypothesized as the responsible etiopathological mechanism. It is crucial to increase clinician awareness of stroke in children. [ABSTRACT FROM AUTHOR]

Present two cases of full-term neonates with normal fetal monitoring were transferred to a neonatal intensive care unit because of a diagnosis of sudden acute perinatal asphyxia. Details of the medical examinations of two male infants; The signs of intoxication from local anesthetic; Findings of a high plasma concentration of mepivacaine in one and lidocaine and prilocaine in the other; Discussion of local anesthetic and pain relief for mothers during delivery; Reasons for the misdiagnosis.

The Coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C) have been variably associated with thromboembolic events (TEs) in children. The aim of our study was to assess the prevalence of TEs in children hospitalized during a five-year period in a tertiary pediatric hospital, particularly in patients with COVID-19 and MIS-C. Overall, 38 patients were discharged with the diagnosis of TE: 20 in the pre-pandemic and 18 in the pandemic period. The prevalence of TEs was the same (0.08%) in the pre-pandemic and pandemic periods. The occurrence of TEs was higher in patients with COVID-19 or MIS-C (6/517, 1.16%) when compared to children without these conditions in the pandemic and in the pre-pandemic periods. The prevalence of TEs in children with MIS-C was significantly higher than the prevalence in patients with COVID-19. Five out of six of the patients with COVID-19 or MIS-C developing a TE had at least one predisposing factor to thrombosis. In conclusion, our study shows an increased prevalence of TEs in children hospitalized with COVID-19 or MIS-C, if compared to children without COVID-19 or MIS-C in the pandemic period and in the pre-pandemic period. The prevalence of TEs was significantly higher in patients with MIS-C. [ABSTRACT FROM AUTHOR]

Background Current guidelines recommend that infants born to women with hepatitis C virus (HCV) viremia be screened for HCV antibody at age 18 months and, if positive, referred for RNA testing at 3 years to confirm chronic infection. This policy is based, in part, on analyses that suggest that 25%–40% of vertically acquired HCV infections clear spontaneously within 4–5 years. Methods Data on 179 infants with HCV RNA and/or anti-HCV evidence of vertically acquired infection in 3 prospective European cohorts were investigated. Ages at clearance of infection were estimated taking account of interval censoring and delayed entry. We also investigated clearance in initially HCV RNA–negative infants in whom RNA was not detectable until after 6 weeks. Results Clearance rates were initially high then declined slowly. Apparently, many infections clear before they can be confirmed. An estimated 65.9% (95% credible interval [CrI], 50.1–81.6) of confirmed infections cleared by 5 years, at a median 12.4 (CrI, 7.1–18.9) months. If treatment were to begin at age 6 months, 18 months, or 3 years, at least 59.0% (CrI, 42.0–76.9), 39.7% (CrI, 17.9–65.9), and 20.9% (CrI, 4.6–44.8) of those treated would clear without treatment. In 7 (6.6%) confirmed infections, RNA was not detectable until after 6 weeks and not until after 6 months in 2 (1.9%). However, all such cases subsequently cleared. Conclusions Most confirmed infection cleared by age 3 years. Treatment before age 3, if it was available, would avoid loss to follow-up but would result in substantial overtreatment. [ABSTRACT FROM AUTHOR]

Background It is widely accepted that the risk of hepatitis C virus (HCV) vertical transmission (VT) is 5%–6% in monoinfected women, and that 25%–40% of HCV infection clears spontaneously within 5 years. However, there is no consensus on how VT rates should be estimated, and there is a lack of information on VT rates "net" of clearance. Methods We reanalyzed data on 1749 children in 3 prospective cohorts to obtain coherent estimates of overall VT rate and VT rates net of clearance at different ages. Clearance rates were used to impute the proportion of uninfected children who had been infected and then cleared before testing negative. The proportion of transmission early in utero, late in utero, and at delivery was estimated from data on the proportion of HCV RNA positive within 3 days of birth, and differences between elective cesarean and nonelective cesarean deliveries. Results Overall VT rates were 7.2% (95% credible interval [CrI], 5.6%–8.9%) in mothers who were human immunodeficiency virus (HIV) negative and 12.1% (95% CrI, 8.6%–16.8%) in HIV-coinfected women. The corresponding rates net of clearance at 5 years were 2.4% (95% CrI, 1.1%–4.1%), and 4.1% (95% CrI, 1.7%–7.3%). We estimated that 24.8% (95% CrI, 12.1%–40.8%) of infections occur early in utero, 66.0% (95% CrI, 42.5%–83.3%) later in utero, and 9.3% (95% CrI, 0.5%–30.6%) during delivery. Conclusions Overall VT rates are about 24% higher than previously assumed, but the risk of infection persisting beyond age 5 years is about 38% lower. The results can inform design of trials of interventions to prevent or treat pediatric HCV infection, and strategies to manage children exposed in utero. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Spontaneous Clearance of Hepatitis C Virus in Vertically Infected Children. Any Clue for Treatment?."

The article provides information on the skin disease called podoconiosis. The disease is the result of progressive obliterating endolymphangitism, induced by the absorption of ultrafine silica particles through the skin of the feet, especially when a person is exposed to red clay soil. The early signs of the said disease are recurrent episodes of burning and edema of one foot. It is noted in the article that established lymphedema can progress to severe elephantiasis.

Bartonella henselae is an unusual and rarely suspected osteomyelitis etiologic agent. We present a case of low back‐pain in a 10‐year‐old female which lead to a challenging diagnostic work‐up due to subtle imaging findings. The diagnosis was Bartonella henselae vertebral osteomyelitis mimicking bone tumor. Bartonella infection should be included in the differential diagnosis of pediatric back pain associated with fever, especially if there is a history of exposure to cats. MRI is the most sensitive radiographic technique to define bone lesions, but in case of non‐specific findings, the biopsy of the lesion is mandatory. [ABSTRACT FROM AUTHOR]

Background: Cerebrotendinous xanthomatosis (CTX) is a disorder of bile acid (BA) metabolism due to biallelic mutations in CYP27A1. The deposition of cholesterol and cholestanol in multiple tissues results, manifesting as neurologic disease in adults or older children. Neonatal cholestasis (NC) as a presentation of CTX is rare; it may self‐resolve or persist, evolving to require liver transplantation (LT). Methods: We present in the context of similar reports an instance of CTX manifest as NC and requiring LT. Results: A girl aged 4mo was evaluated for NC with normal serum gamma‐glutamyl transpeptidase activity. An extensive diagnostic work‐up, including liver biopsy, identified no etiology. Rapid progression to end‐stage liver disease required LT aged 5mo. The explanted liver showed hepatocyte loss and micronodular cirrhosis. Bile salt export pump (BSEP), encoded by ABCB11, was not demonstrable immunohistochemically. Both severe ABCB11 disease and NR1H4 disease—NR1H4 encodes farsenoid‐X receptor, necessary for ABCB11 transcription—were considered. However, selected liver disorder panel sequencing and mass‐spectrometry urinary BA profiling identified CTX, with homozygosity for the predictedly pathogenic CYP27A1 variant c.646G > C p.(Ala216Pro). Variation in other genes associated with intrahepatic cholestasis was not detected. Immunohistochemical study of the liver‐biopsy specimen found marked deficiency of CYP27A1 expression; BSEP expression was unremarkable. Aged 2y, the girl is free from neurologic disease. Conclusions: Bile acid synthesis disorders should be routinely included in the NC/"neonatal hepatitis" work‐up. The mutually supportive triple approach of BA profiling, immunohistochemical study, and genetic analysis may optimally address diagnosis in CTX, a treatable disease with widely varying presentation. [ABSTRACT FROM AUTHOR]

The aim of our study was to better define the clinical pattern of diencephalic syndrome, a rare but potentially lethal cause of failure to thrive in infancy. Poor weight gain or weight loss, the characteristic presenting feature, often firstly attributed to gastrointestinal or endocrinological or genetic diseases, is secondary to a malfunctioning hypothalamus, caused by a diencephalic tumor. Due to its unexpected clinical onset, diagnostic delay and misdiagnosis are common. We described a case series of 3 children with diencephalic syndrome admitted at our Hospital, over a 5-year period. Furthermore, a narrative review on all pediatric cases published in the last seventy years was performed. Clinical pattern, timing to diagnosis, neuroimaging, management, and outcome were analyzed. Our three cases are singularly described in all clinical and diagnostic findings. Overall, 100 children were selected; all these cases as well as our children presented with failure to thrive: 96% had body mass index or weight-length/height ratio lower than 5th percentile. Vomiting and hyperactivity are reported in 35 and 26% of cases, respectively. The neurological features, mainly nystagmus reported in 43%, may occur late in the disease course. In conclusion, the diagnostic delay is the hallmark of diencephalic syndrome, confirming the lack of knowledge by clinicians. The poor weight gain/loss despite adequate length growth and food intake, especially in children with hyperactivity and good psychomotor development, should alert pediatricians towards this condition, before neurological signs/symptoms occurrence. [ABSTRACT FROM AUTHOR]

Introduction and objectives: Immunoglobulin A vasculitis (IgAV), the most common childhood vasculitis, is associated with gastrointestinal (GI) involvement in 50–75% of cases. The aim of this study was to describe the characteristics of GI involvement in a cohort of hospitalized children with IgAV. Methods: We retrospectively evaluated patients hospitalized for IgAV at Meyer Children's University Hospital, from January 2010 to December 2020. The children's families were interviewed by phone and asked about disease relapses. Results: In the study period, 118 children had GI involvement, corresponding to 75% of children hospitalized for IgAV. Their median age was 7 years (interquartile range 6–9). The most frequent GI manifestations were abdominal pain (96%), bleeding (71%, mostly occult), vomiting (58%), and diarrhea (17%). GI complications, observed in 18%, were intussusception (14%), appendicitis (3%), gallbladder hydrops (2%), and ileal perforation (1%). Abdomen ultrasound, performed in all cases, was abnormal in 68%. Abdomen X-ray, performed in 19 patients, showed pathologic findings in 84% of them. Selected children with severe manifestations also underwent abdomen computed tomography (2/118; 2%) and GI endoscopy (5/118; 4%). Steroids were used in 80 (67.8%) cases. The use of second- and third-line therapies was necessary in three cases. Relapses, investigated in 80 cases (68%), occurred in 21% of them. Key Points • The present retrospective study describes a cohort of 118 patients hospitalized for gastrointestinal (GI) involvement in immunoglobulin A vasculitis (IgAV) at a tertiary care children's hospital from January 2010 to December 2020. • The most frequent GI manifestations were abdominal pain (96%), vomiting (58%), and diarrhea (17%). GI bleeding was reported in 71% of children, and it was occult in most cases. • GI complications, occurring in 18% of cases, were intussusception (14%), appendicitis (3%), gallbladder hydrops (2%), and ileal perforation (1%). • Steroid treatment has been successfully used in severe GI manifestations; however, our data do not support its association with low relapse risk. Conclusions: The present study describes a large pediatric cohort of GI involvement in IgAV. Steroid treatment should be used when GI manifestations are severe. The association of steroid use with relapse risk is not currently established. [ABSTRACT FROM AUTHOR]

Purpose: Biallelic pathogenic NBAS variants manifest as a multisystem disorder with heterogeneous clinical phenotypes such as recurrent acute liver failure, growth retardation, and susceptibility to infections. This study explores how NBAS-associated disease affects cells of the innate and adaptive immune system. Methods: Clinical and laboratory parameters were combined with functional multi-parametric immunophenotyping methods in fifteen NBAS-deficient patients to discover possible alterations in their immune system. Results: Our study revealed reduced absolute numbers of mature CD56dim natural killer (NK) cells. Notably, the residual NK cell population in NBAS-deficient patients exerted a lower potential for activation and degranulation in response to K562 target cells, suggesting an NK cell–intrinsic role for NBAS in the release of cytotoxic granules. NBAS-deficient NK cell activation and degranulation was normalized upon pre-activation by IL-2 in vitro, suggesting that functional impairment was reversible. In addition, we observed a reduced number of naïve B cells in the peripheral blood associated with hypogammaglobulinemia. Conclusion: In summary, we demonstrate that pathogenic biallelic variants in NBAS are associated with dysfunctional NK cells as well as impaired adaptive humoral immunity. [ABSTRACT FROM AUTHOR]

Background: Pneumococcal serotyping is usually performed by Quellung reaction, considered the gold standard test. However the method cannot be used on culture-negative samples. Molecular methods can be a useful alternative. The aim of the study was to evaluate the use of Multiplex-sequential-PCR (MS-PCR) or Realtime-PCR on blood samples for diagnosis and serotyping of invasive pneumococcal disease (IPD) in a pediatric clinical setting. Methodology/Principal Findings: Sensitivity and specificity of MS-PCR and Realtime-PCR have been evaluated both on 46 well characterized pneumococcal isolates and on 67 clinical samples from children with culture-negative IPD. No difference in sensitivity and specificity between MS-PCR and Realtime PCR was found when the methods were used on isolates: both methods could type 100% isolates and the results were always consistent with culture-based methods. On the contrary, when used on clinical samples 43/67 (64.2%) were typeable by MS-PCR and 61/67 (91.0%) by Realtime-PCR (p = 0.0004,K Cohen 0.3, McNemar's P<0.001). Non-typeability by MS-PCR was associated in 18/20 cases (90.0%) with low bacterial load. The difference between the two methods was present both when they were used on normally sterile fluids (respectively 31/33 (93.9%) typeable samples for Realtime-PCR and 24/33 (72.7%) for MS-PCR, p = 0.047, 95%CL 0.03-0.98; K Cohen 0.3; McNemar's p = 0.0016) and when they were used on nasopharyngeal swabs (respectively 30/34 (88.2%) typeable samples for Realtime-PCR and 19/34 (55.9%) for MS-PCR, p = 0.007, 95%CL 0.04-0.66); the presence of multiple pneumococcal serotypes in nasopharyngeal swabs was found more frequently by Realtime PCR (19/30; 63.3%) than by Multiplex-sequential PCR (3/19; 15.8%; p = 0.003;95%CL 1.87-39.97). Conclusions/Significance: In conclusion, both MS-PCR and Realtime PCR can be used for pneumococcal serotyping of most serotypes/serogroups directly on clinical samples from culture-negative patients but Realtime-PCR appears more sensitive. [ABSTRACT FROM AUTHOR]

The sample collection procedure for SARS-CoV-2 has a strong impact on diagnostic capability, contact tracing approach, ultimately affecting the infection containment performance. This study demonstrates that self-collected nasal-swab has shown to be a valid and well tolerated procedure to SARS-CoV-2 surveillance in a healthcare system. More significantly, no performance adequacy difference was detected in self-administered swabs between healthcare worker (HCW) and non-HCW which allows to speculate that this procedure could be successfully extended to the entire population for mass screening. [ABSTRACT FROM AUTHOR]

The aims of this prospective study were as follows: (1) to describe the natural history of chronic hepatitis B virus (HBV) infection in a large cohort of untreated children followed at a single centre and (2) to evaluate whether or not the new European Association for the Study of Liver (EASL) classification for the phases of HBV infection in adults can be used for children. All children who presented at the Liver Unit of our hospital from 1 January 1987 to 31 December 2019 and were diagnosed with chronic HBV infection were enrolled. The final sample consisted of 152 children. The median duration of the follow‐up was 83 months (range 7‐232). At baseline, 125 patients (82.2%) were HBeAg positive (85.3% abnormal alanine aminotransferase (ALT) levels), and 24 (15.8%) were HBeAg‐negative (93.3% abnormal ALT). At the end of the observation period, 62 of the HBeAg‐positive patients (40.7%) achieved HBeAg seroconversion (median age 9.45 years, range 0.8‐19) and 2 (1.4%) achieved HBsAg seroconversion. Elevated ALT serum levels at baseline (P =.011), lower baseline HBV DNA levels (P <.001) and Asian ethnicity (P =.0001) were identified as predisposing factors towards HBeAg seroconversion. EASL criteria could not be applied to 43.3% and 43.5% of the children at baseline and at end of observation, respectively, that were grouped into an undetermined phenotype category. According to the results of the present study, the new EASL guidelines for adults with HBV infection cannot be applied in a satisfactory manner in children. [ABSTRACT FROM AUTHOR]

We describe a case of bilateral parenchymal consolidation with sudden respiratory distress in a preterm baby as a complication of peripherally inserted central catheter (PICC) dislocation. The X-rays showed bilateral pulmonary consolidation with the catheter tip initially located in the right, and later in the left pulmonary artery. The catheter was withdrawn. As soon as the catheter was repositioned all clinical signs and symptoms disappeared. Neonatologists should consider the possibility of dramatic respiratory distress deriving from PICC dislocation. Careful tip catheter placement and conscientious monitoring may reduce morbidity. [ABSTRACT FROM AUTHOR]

Salpingitis is an acute inflammation of the fallopian tubes and is extremely uncommon in patients who are sexually inactive or premenarchal. We describe a 15-year-old sexually inactive patient with recurrent bilateral salpingitis. After the second episode, she underwent an exploratory laparoscopy and was diagnosed with chronic appendicitis. Appendicular involvement should be kept in mind in recurrent salpingitis episodes, especially if previous imaging studies do not show signs of appendicitis. Imaging studies should be repeated in experienced centers in case of recurrent episodes. Laparoscopy is the gold standard for the diagnosis of salpingitis and can confirm appendicular or other abdominal involvement. Early diagnosis can help to prevent recurrent episodes of salpingitis and thus reduce the risk of sequelae. [ABSTRACT FROM AUTHOR]

Summary: Russia has one of the highest prevalences of paediatric chronic hepatitis C infection (CHC). Our aim was to provide a detailed characterization of children and adolescents with CHC including treatment outcomes. Thus, an observational study of children with CHC aged <18 years was conducted in three hepatology centres from November 2014 to May 2017. Of 301 children (52% male), 196 (65%) acquired HCV vertically, 70 (23%) had a history of blood transfusion or invasive procedures, 1 injecting drug use and 34 (11%) had no known risk factors. Median age at HCV diagnosis was 3.1 [interquartile range, IQR 1.1, 8.2] and 10.8 [7.4, 14.7] at last follow‐up. The most common genotype was 1b (51%), followed by 3 (37%). Over a quarter of patients (84, 28%) had raised liver transaminases. Of 92 with liver biopsy, 38 (41%) had bridging fibrosis (median age 10.4 [7.1, 14.1]). Of 223 evaluated by transient elastography, 67 (30%) had liver stiffness ≥5.0 kPa. For each year, increase in age mean stiffness increased by 0.09 kPa (95% CI 0.05, 0.13, P < 0.001). There was significant correlation between liver stiffness and biopsy results (Tau‐b = 0.29, P = 0.042). Of 205 treated with IFN‐based regimens, 100 (49%) had SVR24. Most children (191, 93%) experienced adverse reactions, leading to treatment discontinuation in 6 (3%). In conclusion, a third of children acquired HCV via nonvertical routes and a substantial proportion of those with liver biopsy had advanced liver disease. Only half of children achieved SVR24 with IFN‐based regimens highlighting the need for more effective and better‐tolerated treatments with direct‐acting antivirals. Further studies are warranted in Russia on causes and prevention of nonvertical transmission of HCV in children. [ABSTRACT FROM AUTHOR]

• Serotypes 1, 3, 19A and 7F were the most common types in pediatric PPE in the pre-PCV13 era. • Serotypes 1 and 3 decreased by 91.8% and 31.5%, respectively, while serotypes 7F and 19A disappeared in vaccinated children. • The impact of PCV13 might be underestimated due to the improvement of surveillance and diagnostic methods. • A significant shift to non-PCV13 serotypes was not found in PPE during the 12-year follow-up. • Realtime PCR is significantly more sensitive than culture in the diagnosis of PPE. Etiology and serotyping of parapneumonic effusion (PPE) and the impact of vaccination was evaluated over a 12-year period, before and after the PCV13 introduction (2011) for Italian children From 0 to 16 years of age. Five hundred and two children were evaluated; 226 blood and 356 pleural fluid samples were obtained and tested using Realtime-PCR and culture. In the pre-PCV13 era S. pneumoniae was the most frequent pathogen identified (64/90; 71.1%) with a large predominance of serotypes 1 (42.4%), 3 (23.7%), 7F (5.1%) and 19A (11.9%). The impact of vaccination, calculated on children 0–8 years of age, demonstrated a significant reduction of PPE: with an incidence rate of 2.82 (95%CL 2.32–3.41) in the pre-PCV13 era and an age-standardized rate (ASR) of 0.66 (95% CL 0.37–1.99) in the post-PCV13 era, p < 0.0001. No increase in non-PCV13 serotypes was recorded. S. pneumoniae remained the most frequent pathogen identified in the post-PCV13 era in unvaccinated children with an unchanged serotype distribution: respectively 26/66 (39.4%), 25/66 (37.9%), 5/66 (7.6%), and 4/66 (6.1%) for 1, 3, 7F and 19A. On the other hand 7F and 19A disappeared in vaccinated children and serotype 1 and 3 decreased by 91.8% and 31.5%, respectively. Realtime PCR was significantly more sensitive than culture both in pleural fluid (79.7% vs 12.5%) and in blood (17.8% vs 7.4%). In conclusion, our findings indicate that routine immunization with PCV13 has significantly reduced the burden of childhood PPE in vaccinated children, without increasing PPE due to other bacteria and without serotype shift. Moreover, the impact of PCV13 may be underestimated due to the increase in pneumococcal surveillance in Italy. Data has also shown that Real-time PCR is an essential tool to better define the etiology of PPE and to monitor vaccination plans. Longer studies will be necessary to evaluate the role of herd protection in PPE prevention. [ABSTRACT FROM AUTHOR]