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Objective: Vitamin D deficiency is a common public health issue worldwide. The purpose of this study was to investigate the vitamin D status and its potential determinants in children residing in Sardinia (40°N), Italy. Methods: Children were enrolled over a 12-month period. Serum 25(OH)D was measured by an immunochemiluminescence assay. A questionnaire was used to gather information on other variables, including passive smoke exposure. Results: A total of 182 children (males: 51.7%; median age: 9 years) were included. Mean±standard deviation serum 25(OH)D was 25.2±8.3 ng/mL for the whole group. The majority (n=123, 67.6%) had vitamin D sufficient values >20 ng/mL, while 32.4% (n=59) had vitamin D insufficient/deficient values (≤20 ng/mL). Among the variables investigated, passive smoke exposure was significantly associated with insufficient 25(OH)D levels (p<0.0001). Conclusion: Our results confirm that hypovitaminosis D is common in Italian children. Furthermore, passive smoke exposure was identified as a significant risk factor for hypovitaminosis D. [ABSTRACT FROM AUTHOR]

This article discusses the emerging pattern of gastrointestinal (GI) toxicity associated with the use of deferasirox film-coated tablets (DFX FCT) in adult patients with transfusion-dependent β-thalassemia (TDT). The study reviews eight case reports and presents four new cases of adult patients with TDT who experienced GI toxicity while receiving DFX FCT treatment. The symptoms included diarrhea, abdominal pain, and fever, and in some cases, the toxicity was initially misdiagnosed as unrelated to the treatment. Discontinuation of DFX FCT resulted in the resolution of symptoms. The article emphasizes the need for further research to understand the mechanisms underlying DFX-related GI toxicity and to establish a common approach for prevention, early recognition, and management of adverse events in patients undergoing chronic DFX treatment. [Extracted from the article]

Luspatercept is a recently approved drug for treating anemia in individuals with transfusion-dependent beta-thalassemia. However, it is contraindicated for pregnant and lactating women due to observed teratogenic effects in animal studies. Two cases are presented in the article where women became pregnant while undergoing luspatercept therapy. In both cases, the pregnancies resulted in healthy newborns, but the article emphasizes the importance of effective contraception during treatment and the need for factual information and counseling in the event of pregnancy. The article also mentions the potential risks associated with luspatercept and the consideration of termination if concerns about teratogenic effects arise. [Extracted from the article]

The aim of this study is the evaluation of the safety and the efficacy of long-term combination therapy deferasirox plus desferrioxamine and deferasirox plus deferiprone in a large group of transfusion-dependent thalassemia patients with high values of serum ferritin and/or magnetic resonance, indicative of severe liver and cardiac iron accumulation. Sixteen adults with transfusion-dependent thalassemia were treated simultaneously with deferasirox plus desferrioxamine, while another 42 patients (seven children) were treated with deferasirox plus deferiprone. The hepatic and cardiac iron overload was assessed prior to treatment and then annually with magnetic resonance imaging, and the serum ferritin was measured monthly. Adverse events were checked at each transfusion visit. The safety of both the combinations was consistent with established monotherapies. Both treatments were able to decrease the serum ferritin and liver iron concentration over time, depending on the level of compliance with therapy. Cardiac iron measured as R2* did not significantly change in patients treated with deferasirox plus desferrioxamine. Most patients with MRI indicative of myocardial siderosis at the beginning of treatment reached normal values of cardiac iron at the last determination if treated with deferasirox plus desferrioxamine. The greatest limitation of these therapies was low patient adherence to the two drugs, which is not surprising considering that the need for an intensive chelation is generally linked to previous issues of compliance. [ABSTRACT FROM AUTHOR]

Infant botulism (IB) is defined as a potentially life-threatening neuroparalytic disorder affecting children younger than 12 months. It is caused by ingestion of food or dust contaminated by Clostridium botulinum spores, which germinate in the infant's large bowel and produce botulinum neurotoxin. Although the real impact of IB is likely underestimated worldwide, the USA has the highest number of cases. The limited reporting of IB in many countries is probably due to diagnostic difficulties and nonspecific presentation. The onset is usually heralded by constipation, followed by bulbar palsy, and then by a descending bilateral symmetric paralysis; ultimately, palsy can involve respiratory and diaphragmatic muscles, leading to respiratory failure. The treatment is based on supportive care and specific therapy with Human Botulism Immune Globulin Intravenous (BIG-IV), and should be started as early as possible. The search for new human-like antibody preparations that are both highly effective and well tolerated has led to the creation of a mixture of oligoclonal antibodies that are highly protective and can be produced in large quantities without the use of animals. Ongoing research for future treatment of IB involves the search for new molecular targets to produce a new generation of laboratory-produced antitoxins, and the development of new vaccines with safety and efficacy profiles that can be scaled up for clinical use. This narrative literature review aims to provide a readable synthesis of the best current literature on microbiological, epidemiological and clinical features of IB, and a practical guide for its treatment. [ABSTRACT FROM AUTHOR]

Ceftriaxone is an antibiotic agent frequently used in paediatric hospital practice for the treatment of severe bacterial infections. The use of this agent can result in cholelithiasis and/or biliary sludge, more commonly in children than in adults. This systematic review was aimed at analysing available literature concerning ceftriaxone‐associated biliary pseudolithiasis in paediatric patients, with a special emphasis on the clinical aspects. A literature analysis was performed using Medline and Embase electronic databases (articles published in English up to December 2019), with the search terms and combinations as follows:'ceftriaxone', 'cholelithiasis', 'biliary sludge' 'gallstones' 'neonates' 'children' 'clinical aspects' 'management'. Several case reports, case series and prospective/retrospective studies have documented a relationship between ceftriaxone treatment and biliary pseudolithiasis in the paediatric population, even though literature data regarding neonates and infants are scarce. Ceftriaxone‐associated biliary pseudolithiasis is dose‐dependent and usually asymptomatic but, sometimes, it may present with abdominal pain, nausea and emesis. Abdominal ultrasonography should be performed when this complication is suspected. Generally, ceftriaxone‐associated cholelithiasis resolves over a variable period of time (days to months) after cessation of therapy. Therefore, a conservative approach to this condition is advocated, but a prolonged follow‐up may be necessary. A personalized assessment of factors predisposing to ceftriaxone‐associated biliary pseudolithiasis before prescribing the drug can allow to minimize the risk of developing it, with significant advantages in terms of human and economic costs. [ABSTRACT FROM AUTHOR]

A point mutation (P56S) in the gene-encoding vesicle-associated membrane-protein-associated protein B (VAPB) leads to an autosomal-dominant form of amyotrophic lateral sclerosis (ALS), classified as ALS-8. The mutant VAPB is characterized by ER-associated aggregates that lead to a complete reorganization of ER structures. Growing evidences suggest VAPB involvement in ALS pathomechanisms. In fact, numerous studies demonstrated VAPB alteration also in sporadic ALS (sALS) and showed the presence of its aggregates when others ALS-related gene are mutant. Recently, the identification of new biomarkers in peripheral blood mononuclear cells (PBMCs) has been proposed as a good noninvasive option for studying ALS. Here, we evaluated VAPB as a possible ALS pathologic marker analyzing PBMCs of sALS patients. Immunofluorescence analysis (IFA) showed a peculiar pattern of VAPB aggregates in sALS, not evident in healthy control (HC) subjects and in Parkinson’s disease (PD) PBMCs. This specific pattern led us to suppose that VAPB could be misfolded in sALS. The data indirectly confirmed by flow cytometry assay (FCA) showed a reduction of VAPB fluorescent signals in sALS. However, our observations were not associated with the presence of a genetic mutation or altered gene expression of VAPB. Our study brings further evidences of the VAPB role in ALS as a diagnostic biomarker. [ABSTRACT FROM AUTHOR]

Hypovitaminosis D in childhood is a re-emerging public health problem in developed countries. New life style habits, current “epidemics” of obesity in children and adolescents worldwide, and other preventable risk factors may play a role in favoring the occurrence of vitamin D deficiency. In addition to skeletal consequences, hypovitaminosis D has been found to be involved in the development of serious health extra-skeletal problems in childhood, including atopy and autoimmunity. The increasing concerns about the global health impact of vitamin D deficiency make further research necessary to fill the gaps of knowledge in this field, and particularly to establish universally accepted “normal” serum 25(OH)D levels in the pediatric population, and to improve strategies for the screening, prevention and treatment of hypovitaminosis D. This review discusses the key points of hypovitaminosis D in childhood in the light of new knowledge, and highlights the limitations of current strategies to control this condition. [ABSTRACT FROM AUTHOR]

Recent studies have shown that infants with intrauterine growth restriction (IUGR) undergo catch-up growth during infancy. The aim of our study was to evaluate the postnatal growth in a cohort of IUGR infants born in a tertiary-level Obstetric University Hospital of Northern Sardinia. An observational retrospective study was conducted on 12 IUGR (group A) and 12 control infants (group B) by measuring the anthropometric parameters of weight (W), length (L) and head circumference (HC) from birth to the 3rd postnatal year. At birth, significant differences were found between group A and group B with regard to all the auxological parameters (W, mean 1846.6 versus 3170.8 g, p < 0.0001; HC, 30.1 versus 34.4 cm, p < 0.0001; L, mean 43.4 versus 49.4 cm, p < 0.0001). During the 1st year, 8 of 12 (70%) IUGR infants exhibited a significant catch-up growth in the 3 anthropometric parameters and a regular growth until the 3rd year of follow-up. The majority but not all infants born with IUGR in our series showed significant postnatal catch-up growth essentially during the first 12 months of life. An improved knowledge of the causes of IUGR will help to develop measures for its prevention and individualized treatment. [ABSTRACT FROM AUTHOR]

Biliary atresia (BA) is the most common cause of neonatal cholestasis and the most common indication for liver transplantation in children. The availability of a vaccine against the rotavirus could verify whether its use could alter the rotavirus infection rate and BA prevalence. However, Das et al showed that rotavirus antigenemia was more common in non-breastfed children with severe rotavirus linked diarrhoea and it correlated with stool rotavirus load and disease severity.[7] Mode of delivery I , i another potential but uncertain rotavirus issue B , b [[8]] has not been reported in depth. [Extracted from the article]

Chronic hepatitis B (CHB) in children shows a variety of clinical presentations, which influence its natural course and treatment options. This report provides an overview of the ongoing strategies in pediatric CHB management. Interferon-α represents the first choice of treatment in children showing HBV replication and hepatic inflammation (immune active CHB), while the recommendation is to monitor inactive/immune-tolerant children (normal transaminases and low/absent viral replication). When circumstances preclude the use of Interferon-α and in cases of compensated/decompensated cirrhosis, entecavir for children above 2 years of age or tenofovir for children above 12 years of age are the nucleos(t)ide analogues recommended by the most recent guidelines. [ABSTRACT FROM AUTHOR]

Biliary atresia (BA) is an infantile inflammatory cholangiopathy of unknown etiology although epidemiologic studies and animal models utilizing rotavirus (RV) have suggested a role for viral infection. Proinflammatory and profibrotic cytokines have been detected in infants with BA. The purpose of our study was to investigate the susceptibility of human cholangiocytes (H69 cells) to infection with RRV and to determine if this infection resulted in cytokine secretion. Infection of H69 cells by RRV was noncytolytic and resulted in a time-dependent increase in the release of both infectious virions and cytokines IL-6 and IL-8 into the supernate. The greatest difference in cytokine supernatant levels between infected and mock-infected cells was noted at 24 hours postinfection (h p.i.) for IL-8, 556 ± 111 versus 77 ± 68 pg/mL (p<0.0001), and at 48 h p.i. for IL-6, 459 ± 64 versus 67 ± 2 pg/mL (p<0.0001). Production of both cytokines following RRV infection was significantly reduced by pretreating the H69 cells with inhibitors of mitogen-activated protein kinase (MAPK). Conclusion. RRV can infect human cholangiocytes resulting in the production of proinflammatory and profibrotic cytokines via the MAPK pathway. RRV-infected H69 cells could be a useful model system for investigating the viral hypothesis of BA. [ABSTRACT FROM AUTHOR]

Family-related factors may affect serum vitamin D levels Vitamin D deficiency in childhood is a re-emerging public health problem. Regardless of BMI, siblings exhibited a significantly high concordance for serum vitamin D levels (rho = 0.94, I P i < .0001), suggesting that the vitamin D status of close family members was a predictor of vitamin D status in children. [Extracted from the article]

Background: The HLA DRB1 *08 allele associated with primary biliary cholangitis (PBC) among Caucasians is of low frequency in the Sardinian population., Objective: The aim of our study was to type a cohort of PBC patients from the island of Sardinia for HLA class II antigens., Methods: Twenty Sardinian patients affected by PBC, 14 with autoimmune hepatitis (AIH) and 89 healthy controls (HCs) were typed for HLA class II alleles by dot-blot analysis., Results: The PBC-associated HLA DRB1 *08 allele was detected in none of the studied individuals. The DRB1 *0301- DQB1 *0201 was the prevalent HLA haplotype, detected in 19 (47.5%) out of 40 PBC haplotypes (OR = 3.0; 95% CI 1.5-6.2) and in 11 (39.3%) out of 28 AIH haplotypes (OR = 2.2; 95% CI 0.94-5.0), but in only 41 (23%) out of 178 HC haplotypes. Moreover, PBC patients showed an increased frequency of homozygosity for the DQB1 *0201 allele (35% compared with 6.7% of the HCs; OR = 7.5; 95% CI 2.2-25.7). The frequency of the DRB1*11 allele in the PBC group was about half of that seen in the Sardinian HCs (7.5% vs 15.7%) ( p  = ns)., Conclusions: Our study confirmed the low frequency of the HLA DRB1 *08 allele among Sardinians, either in the general population or PBC patients. The high prevalence of the HLA DRB1 *0301- DQB1 *0201 haplotype is a distinctive genetic feature of PBC among Sardinians. Our study strengthens the hypothesis that still unknown genetic, epigenetic, and environmental factors must be involved in the pathogenesis of different HLA-associated liver diseases, and it represents a pathfinder that warrants exploration in a future extensive study.

Background and Objectives: Migration flux is an increasing phenomenon in Italy, and it raises several public health issues and concerns in pediatric infectious diseases. This study investigated the clinical characteristics and outcomes of a pediatric population at high-risk for tuberculosis (TB) and the potential role of immigration as a risk factor., Design: We performed an observational retrospective study of children referred to the only Pediatric Infectious Diseases Unit for Northern Sardinia over a 6-year-period (2009-2014). Main variables assessed included TB skin test (TST), confirmed by quantiFERON Gold in Tube test, thorax X-ray (TX), microbiological culture, direct microscopy for acid-fast bacilli and molecular assays., Results: Of the 246 children (mean age = 5.8 ± 3.9 years) identified, 222 (90.2%) were native to Sardinia and 24 (9.8%) were immigrants. The majority of children (n=205; 83%) were TB-exposed but not infected based on a negative TST and TX. Among the TST positive group (n= 39; 16%), 19 (49%) had latent TB (TX negative), while 20 (51%) had active TB (TX positive). The percent of TST positive children was significantly higher in the immigrant than the native group (42.5% versus 14%, p<0.001). Clinical presentations included pulmonary involvement with hilar lymphadenopathy (72%), pleurisy (13,5%), lateral-cervical lymphadenopathy (9%), pneumonia with calcifications (4.5%) and disseminated TB (4.5%). One child had multidrug-resistant tuberculosis., Conclusions: Pediatric TB represents a relevant and potentially worsening public health problem in Northern Sardinia. A strict surveillance system and appropriate treatment can prevent the most severe forms and reduce TB transmission., Competing Interests: Competing interests: The authors have declared that no competing interests exist.

Non-alcoholic fatty liver disease (NAFLD) in children is becoming a major health concern. A "multiple-hit" pathogenetic model has been suggested to explain the progressive liver damage that occurs among children with NAFLD. In addition to the accumulation of fat in the liver, insulin resistance (IR) and oxidative stress due to genetic/epigenetic background, unfavorable lifestyles, gut microbiota and gut-liver axis dysfunction, and perturbations of trace element homeostasis have been shown to be critical for disease progression and the development of more severe inflammatory and fibrotic stages [non-alcoholic steatohepatitis (NASH)]. Simple clinical and laboratory parameters, such as age, history, anthropometrical data (BMI and waist circumference percentiles), blood pressure, surrogate clinical markers of IR (acanthosis nigricans), abdominal ultrasounds, and serum transaminases, lipids and glucose/insulin profiles, allow a clinician to identify children with obesity and obesity-related conditions, including NAFLD and cardiovascular and metabolic risks. A liver biopsy (the "imperfect" gold standard) is required for a definitive NAFLD/NASH diagnosis, particularly to exclude other treatable conditions or when advanced liver disease is expected on clinical and laboratory grounds and preferably prior to any controlled trial of pharmacological/surgical treatments. However, a biopsy clearly cannot represent a screening procedure. Advancements in diagnostic serum and imaging tools, especially for the non-invasive differentiation between NAFLD and NASH, have shown promising results, e.g., magnetic resonance elastography. Weight loss and physical activity should be the first option of intervention. Effective pharmacological treatments are still under development; however, drugs targeting IR, oxidative stress, proinflammatory pathways, dyslipidemia, gut microbiota and gut liver axis dysfunction are an option for patients who are unable to comply with the recommended lifestyle changes. When morbid obesity prevails, bariatric surgery should be considered., Competing Interests: Conflict-of-interest statement: The authors declare there are no conflicts of interest in the content of this review.

After completing this article, readers should be able to: 1. Describe the procedure and interpretation of the laboratory evaluation of hepatitis. 2. Recognize the signs and symptoms of acute and chronic hepatitis.3. Describe the immediate and long-term complications of hepatitis. 4. List the multiple causes of hepatitis in an older child.