Syphilitic hepatitis in infants, the forgotten disease that hepatologists have to brush up on: from a case series to a revision of literature.

Clinical manifestations of congenital syphilis (CS) include liver disease with/without impaired liver function, identified as syphilitic hepatitis. Hepatic involvement may be dramatic; therefore, early diagnosis is crucial to provide treatment and prevent fatal outcomes. A new resurgence of CS cases has been described in recent years worldwide. We reported our experience with a case series of infants hospitalized for liver disease with a final diagnosis of CS, highlighting the wide spectrum of liver involvement, the rapid progression in cases with late diagnosis, and the pitfalls of the management of this forgotten but reemerging disease. A retrospective analysis of CS patients with hepatic presentation in the period 2008-2023 was conducted. We collected five cases (three female) with a median age of 13.8 days (range 1-84 days). In three cases, mothers were not screened for syphilis during pregnancy, and in two cases, they were seronegative in the first trimester screening. None practiced specific therapy during pregnancy. Hepatic involvement was characterized by hepatosplenomegaly, in four cases associated with cholestatic jaundice and in three cases with liver failure. Rapid plasma reagin (RPR) and Treponema pallidum hemagglutination assay (TPHA) were positive in all cases in mothers and infants. CS presented with multiorgan involvement and was fatal in one case.Conclusions: It is important to consider CS in infants with cholestasis and acute liver failure, but also in sick infants with isolated hepatomegaly. Early recognition of infants with CS is critical to identify missed cases during pregnancy and to start early treatment.

Laryngeal Mask for Minimally-Invasive Surfactant Administration: A Narrative Review.

The cornerstone of treatment for respiratory distress syndrome in preterm infants is surfactant administration, traditionally performed through an invasive procedure involving tracheal intubation and mechanical ventilation. Consequently, there has been a growing interest in exploring less invasive methods of surfactant delivery to mitigate the associated risks. Currently, several techniques are under evaluation, including intratracheal instillation using a thin catheter, aerosolized or nebulized administration, and guided administration by supraglottic airway devices. One such method is surfactant administration through laryngeal or supraglottic airway, which involves placing a laryngeal mask without the need for laryngoscopy and administering surfactant through the device. The simplicity of laryngeal mask insertion could potentially streamline the surfactant delivery process, eliminating the necessity for advanced skills. This narrative review aimed to assess the current evidence in the literature regarding the benefits and risks associated with surfactant administration through a laryngeal supraglottic airway.

Association of Very Rare NOTCH2 Variants with Clinical Features of Alagille Syndrome.

BACKGROUND: Alagille syndrome (ALGS) is a rare autosomal dominant genetic disease caused by pathogenic variants in two genes: Jagged Canonical Notch Ligand 1 (JAG1) and Notch Receptor 2 (NOTCH2). It is characterized by phenotypic variability and incomplete penetrance with multiorgan clinical signs. METHODS: Using Next Generation Sequencing (NGS), we analyzed a panel of liver-disease-related genes in a population of 230 patients with cholestasis and hepatopathies. For the rare variants, bioinformatics predictions and pathogenicity classification were performed. RESULTS: We identified eleven rare NOTCH2 variants in 10 patients, two variants being present in the same patient. Ten variants had never been described before in the literature. It was possible to classify only two null variants as pathogenic, whereas the most of variants were missense (8 out of 11) and were classified as uncertain significance variants (USVs). Among patients with ALGS suspicion, two carried null variants, two carried variants predicted to be pathogenic by bioinformatics, one carried a synonymous variant and variants in glycosylation-related genes, and two carried variants predicted as benign in the PEST domain. CONCLUSIONS: Our results increased the knowledge about NOTCH2 variants and the related phenotype, allowing us to improve the genetic diagnosis of ALGS.

Perceptions and Expectations of Youth Regarding the Respect for Their Rights in the Hospital.

Information obtained from children themselves regarding the characteristics of the ideal hospital that ensure well-being during a hospital stay is scarce. Here, we report the opinions, perceptions, and expectations of 700 children and adolescents about their experiences, assessed through a mixed-method research approach with age-appropriate questionnaires, three open-ended questions, and an analysis of optional pictorial and textual narratives. Most children indicated that, while they acknowledged the expertise of hospital staff, they also noted several shortcomings, e.g., insufficiently understandable medical information as well as emotional and cognitive support. The continuity of schooling and the right to suffer as little as possible were also critical issues. Adolescents valued in particular the quality of care and services provided, the hospital's adherence to equality and non-discrimination rights, and protection systems but negatively perceived several aspects related to play and participation. Significant differences in the co-occurrences of the most frequently used text terms with the keywords "hospital" and "child/adolescent" between age groups highlight variations in the way patients perceive and articulate their experiences within the hospital setting depending on the cognitive processes linked to age. In drawings, prevailing attention was placed on the physical context of the hospital room, with figures expressing mostly negative emotions. Specifically, in this regard, the main emotion in children was sadness, and, in adolescents, it was fear. Overall, these insights are pivotal in the context of our research objectives as they shed light on the nuanced preferences, needs, and perspectives of children and adolescents during their hospital stays. Recognizing the identified shortcomings, we propose recommendations emphasizing the improvement of medical communication clarity, enhancement of emotional and cognitive support, and the improvement of programs to avoid instructional gaps during hospital stays. Addressing these specific needs is critical for a more comprehensive approach to pediatric healthcare provision.

Celiac Disease on the Bed-Side: Embedding Case Finding and Screening in Hospitalized Children.

BACKGROUND: Strategies for diagnosing celiac disease (CD) include case-finding and population-screening programs. Case finding consists of testing individuals at increased risk for the disease due to symptoms or associated conditions. Screening programs are widespread campaigns, which definitely perform better in terms of unveiling CD diagnoses but nowadays are still debatable. The global prevalence of CD is around 1% but it almost doubles when considering screening programs among school children. Within this framework, we aimed to estimate the prevalence of CD among hospitalized children in the Pediatric Department of a Southern Italy University Hospital in the period from January 2018 through December 2021. In addition, we attempted to explore, at the time of diagnosis, the prevalence of leading clinical alerts due to malabsorption/malnutrition such as anemia or failure to thrive or due to systemic inflammation/immune dysfunction as hypertransaminasemia and thyroid dysfunction. METHODS: Data records of pediatric patients admitted as inpatients and tested by anti-transglutaminase IgA antibodies (TGA-IgA) were retrospectively analyzed. CD was diagnosed according to either 2012 or 2020 ESPGHAN guidelines, depending on the year of diagnosis. CD autoimmunity (CDA) was a wider group defined within our protocol if patients had elevated TGA-IgA on at least one occasion, regardless of anti-endomysial antibodies (EMA-IgA) and without biopsy confirmation. RESULTS: During the observation period, 3608 pediatric patients were admitted and 1320 were screened for CD (median age 5 years, IQR 2-9 years; CD test rate: 36.6% out of all admissions). The available prevalence of newly diagnosed CD was 1.59% (21 patients diagnosed) and the available prevalence of CDA was 3.86% (51 subjects). Among CD patients, underweight/malnourished children accounted for 28.6% (6 out of 21). CONCLUSIONS: The estimated prevalence of CD diagnoses within our setting was comparable to the most recent population-screening programs. The estimated prevalence of CDA was even higher. A hospital-admission CD testing during routine blood draws might be a non-invasive, cost-effective and valuable approach to reduce discrepancy of prevalence between case-finding and population-screening programs.

Pediatric Acute Liver Failure.

Pediatric acute liver failure (PALF) has recently become a subject of great interest when multiple clusters of non-A to non-E severe acute hepatitis in otherwise healthy young children with a median age of 2 years were reported around the world [...].

Thrombotic Features as the Primary Cause of SARS-CoV-2 Related Acute Abdomen in Children.

OBJECTIVES: We performed a retrospective case control study to evaluate the histological characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive pediatric patients undergoing laparoscopic exploration for acute abdomen symptoms. To our knowledge this is the first study that analyzes histopathological characteristics of abdominal tissues in SARS-CoV-2 children. STUDY DESIGN: We enrolled 8 multisystem inflammatory syndrome in children (MIS-C) patients and 4 SARS-CoV-2 positive patients who underwent intestinal resection versus 36 control appendectomies from 2 pediatric tertiary referral centers between March 2020 and July 2021. Surgical resection samples were evaluated on several histological sections focusing on general inflammatory pattern and degree of inflammation. Peculiar histological features (endotheliitis and vascular thrombosis) were semi-quantitatively scored respectively in capillary, veins, and arteries. RESULTS: All SARS-CoV-2 related surgical samples showed thrombotic patterns. Those patterns were significantly less frequent in SARS-CoV-2 negative appendectomies ( P = 0.004). The semi-quantitative score of thrombosis was significantly higher ( P = 0.002) in patients with SARS-CoV-2 related procedures. CONCLUSIONS: Our results showed that SARS-CoV-2 can cause thrombotic damage in abdominal tissues both in the acute phase of the infection (SARS-CoV-2 related appendectomies) and secondary to cytokine storm (MIS-C).

Pregnancy and Metabolic-Associated Fatty Liver Disease.

Metabolic-associated fatty liver disease (MAFLD), the term proposed to substitute nonalcoholic fatty liver disease, comprises not only liver features but also potentially associated metabolic dysfunctions. Since experimental studies in mice and retrospective clinical studies in humans investigated the association between nonalcoholic fatty liver disease during pregnancy and the adverse clinical outcomes in mothers and offspring, it is plausible that MAFLD may cause similar or worse effects on mother and the offspring. Only a few studies have investigated the possible association of maternal MAFLD with more severe pregnancy-related complications. This article provides an overview of the evidence for this dangerous liaison.

Treatment with an ileal bile acid transporter inhibitor in patients with TJP2 deficiency.

There are no published data on the use of odevixibat, a selective ileal bile acid transporter (IBAT) inhibitor, in children with tight junction protein 2 (TJP2) deficiency (also named as PFIC-4). We describe a case series of five children treated with odevixibat. After treatment, serum bile acids (sBA) decreased compared to baseline [mean value: 244 (±125), vs 38 (±34) µmol/L; p = 0.007]; reduction in sBA was >70% from baseline (or <70 µmol/L) in all. Improvements in pruritus were reported in all patients. The drug was well tolerated. IBAT inhibitors should be considered a valuable treatment option in patients with TJP2 deficiency.

Vitamin D Levels in the Pre- and Post-COVID-19 Pandemic Periods and Related Confinement at Pediatric Age.

Coronavirus disease 2019 (COVID-19) restrictions have been correlated with vitamin D deficiency in children, but some uncertainties remain. We retrospectively studied vitamin 25-(OH) D blood levels in 2182 Italian children/adolescents hospitalized for various chronic diseases in the year before (n = 1052) and after (n = 1130) the nationwide lockdown. The type of underlying disease, gender, and mean age (91 ± 55 and 91 ± 61 months, respectively) of patients included in the two periods were comparable. Although mean levels were the same (p = 0.24), deficiency status affected a significantly higher number of subjects during the lockdown period than in the pre-COVID period (p = 0.03), particularly in summer (p = 0.02), and there was also a smoothing of seasonal variations in vitamin D levels. Particularly at risk were males (OR = 1.22; p = 0.03), the 1-5 year age group (OR = 1.57; p < 0.01) and the 6-12 year age group (OR = 1.30; p = 0.04). Infants appeared not to be affected (p = 1.00). In the post-COVID period, the risk of vitamin D deficiency was unchanged in disease-specific groups. However, the proportion of deficiency or severe deficiency differed significantly in the subgroup with endocrinopathy (higher; Chi-square p = 0.04), and with respiratory problems and obesity (lower; Chi-square p = 0.01 and p < 0.01, respectively). Conflicting/opposite literature results advocate for further studies to clearly indicate the need for supplementation during possible future periods of confinement.

Multiple Sclerosis-Related Dietary and Nutritional Issues: An Updated Scoping Review with a Focus on Pediatrics.

PURPOSE: Lifestyle/dietetic habits play an important role in the development and progression of multiple sclerosis (MS) disease. Here, we examine the basic pathomechanisms underlying intestinal and brain barrier modifications in MS and consider diets and dietary supplementations proposed over time to complement pharmacological therapies for improving disease outcome both in adults and in children. METHODS: Scoping literature search about evidence-based findings in MS-related gut-brain axis (GBA) pathophysiology and nutritional issues at all ages. FINDINGS: Data show that (1) no universal best diet exists, (2) healthy/balanced diets are, however, necessary to safeguard the adequate intake of all essential nutrients, (3) diets with high intakes of fruits, vegetables, whole grains, and lean proteins that limit processed foods, sugar, and saturated fat appear beneficial for their antioxidant and anti-inflammatory properties and their ability to shape a gut microbiota that respects the gut and brain barriers, (4) obesity may trigger MS onset and/or its less favorable course, especially in pediatric-onset MS. Vitamin D and polyunsaturated fatty acids are the most studied supplements for reducing MS-associated inflammation. CONCLUSIONS: Pending results from other and/or newer approaches targeting the GBA (e.g., pre- and probiotics, engineered probiotics, fecal-microbiota transplantation), accurate counseling in choosing adequate diet and maintaining physical activity remains recommended for MS prevention and management both in adults and children.

Case Report: Add-on treatment with odevixibat in a new subtype of progressive familial intrahepatic cholestasis broadens the therapeutic horizon of genetic cholestasis.

Odevixibat, an ileal bile acid transporter (IBAT) inhibitor, is effective for the treatment of pruritus in children diagnosed with progressive familial intrahepatic cholestasis (PFIC) type 1 and 2. There are no studies showing the efficacy of Odevixibat in children with different subtypes of PFIC. We describe the case of a 6-year-old girl with chronic cholestatic jaundice. In the last 12 months laboratory data showed high serum levels of bilirubin (total bilirubin x 2.5 ULN; direct bilirubin x 1.7 ULN) and bile acids (sBA x 70 ULN), elevated transaminases (x 3-4 ULN), and preserved synthetic liver function. Genetic testing showed homozygous mutation in ZFYVE19 gene, which is not included among the classic causative genes of PFIC and determined a new non-syndromic phenotype recently classified as PFIC9 (OMIM # 619849). Due to the persistent intensity of itching [score of 5 (very severe) at the Caregiver Global Impression of Severity (CaGIS)] and sleep disturbances not responsive to rifampicin and ursodeoxycholic acid (UDCA), Odevixibat treatment was started. After treatment with odevixibat we observed: (i) reduction in sBA from 458 to 71 µmol/L (absolute change from baseline: -387 µmol/L), (ii) reduction in CaGIS from 5 to 1, and (iii) resolution of sleep disturbances. The BMI z-score progressively increased from -0.98 to +0.56 after 3 months of treatment. No adverse drug events were recorded. Treatment with IBAT inhibitor was effective and safe in our patient suggesting that Odevixibat may be potentially considered for the treatment of cholestatic pruritus also in children with rare subtypes of PFIC. Further studies on a larger scale could lead to the increasing of patients eligible for this treatment.