Longitudinal evaluation of liver stiffness in three pediatric patients with veno-occlusive disease.

Liver stiffness measurement by transient elastography is a non-invasive ultrasound-based technique used mainly for the evaluation of liver fibrosis in patients with chronic liver diseases. Some authors have suggested that it could be useful in the assessment of hepatic complications during hematopoietic stem cell transplant (HSCT), especially veno-occlusive disease (VOD) or sinusoidal obstructive syndrome (SOS). Here, we present the evaluation of liver stiffness in three patients who developed severe hepatic VOD/SOS after HSCT. Liver stiffness measurement values were normal before transplant and afterward until the diagnosis of VOD/SOS when a dramatic increase was observed. After the VOD/SOS specific treatment, the values of stiffness showed a similar pattern of progressive reduction in all the three patients, with normalization after two weeks. In this report, we discuss the role of LSM in the management of patients after the diagnosis of VOD/SOS.

Biomarkers for Serious Bacterial Infections in Febrile Children.

Febrile infections in children are a common cause of presentation to the emergency department (ED). While viral infections are usually self-limiting, sometimes bacterial illnesses may lead to sepsis and severe complications. Inflammatory biomarkers such as C reactive protein (CRP) and procalcitonin are usually the first blood exams performed in the ED to differentiate bacterial and viral infections; nowadays, a better understanding of immunochemical pathways has led to the discovery of new and more specific biomarkers that could play a role in the emergency setting. The aim of this narrative review is to provide the most recent evidence on biomarkers and predictor models, combining them for serious bacterial infection (SBI) diagnosis in febrile children. Literature analysis shows that inflammatory response is a complex mechanism in which many biochemical and immunological factors contribute to the host response in SBI. CRP and procalcitonin still represent the most used biomarkers in the pediatric ED for the diagnosis of SBI. Their sensibility and sensitivity increase when combined, and for this reason, it is reasonable to take them both into consideration in the evaluation of febrile children. The potential of machine learning tools, which represent a real novelty in medical practice, in conjunction with routine clinical and biological information, may improve the accuracy of diagnosis and target therapeutic options in SBI. However, studies on this matter are not yet validated in younger populations, making their relevance in pediatric precision medicine still uncertain. More data from further research are needed to improve clinical practice and decision making using these new technologies.

Pediatric Gaucher Disease Presenting with Massive Splenomegaly and Hepatic Gaucheroma.

Gaucher Disease (GD) is a condition resulting from an autosomal recessive inheritance pattern, characterized by a deficiency of the lysosomal enzyme beta-glucocerebrosidase. This leads to the accumulation of glucocerebroside and other glycolipids in multiple tissues, causing damage to various organ systems. The diagnosis of GD can be challenging due to its heterogeneity, non-specific symptoms, and variability across different geographic regions and age groups. Although GD is suspected based on symptoms or signs, the diagnosis is confirmed through the measurement of deficient b-glucocerebrosidase activity and the identification of biallelic pathogenic variants in the GBA gene. Intravenous enzyme replacement therapy (ERT) is recommended for GD patients. In this paper, we report a case of a 2-year and 8-month-old girl with massive splenomegaly and radiological finding of hepatic gaucheroma, in whom a genetic study showed homozygous mutation on the GBA gene at c.1448T>C (p.Leu483Pro) and certified the diagnosis of GD. This patient represents the youngest child reported to have gaucheroma and also the first one presenting with gaucheroma at the diagnosis and not during the follow up, highlighting that GD should be routinely included in the differential diagnosis of children presenting with splenomegaly and hepatomegaly, taking into account that the early start of ERT can change the natural history of the disease-preventing serious complications.

Treatment options for children with multi-drug resistant tuberculosis.

INTRODUCTION: According to the latest report from the World Health Organization (WHO), approximately 10.0 million people fell ill with tuberculosis (TB) in 2020, 12% of which were children aged under 15 years. There is very few experience on treatment of multi-drug resistant (MDR)-TB in pediatrics. AREAS COVERED: The aim of this review is to analyze and summarize therapeutic options available for children experiencing MDR-TB. We also focused on management of MDR-TB prophylaxis. EXPERT OPINION: The therapeutic management of children with MDR-TB or MDR-TB contacts is complicated by a lack of knowledge, and the fact that many potentially useful drugs are not registered for pediatric use and there are no formulations suitable for children in the first years of life. Furthermore, most of the available drugs are burdened by major adverse events that need to be taken into account, particularly in the case of prolonged therapy. A close follow-up with a standardized timeline and a comprehensive assessment of clinical, laboratory, microbiologic and radiologic data is extremely important in these patients. Due to the complexity of their management, pediatric patients with confirmed or suspected MDR-TB should always be referred to a specialized center.

Novel Insights into Fungal Infections Prophylaxis and Treatment in Pediatric Patients with Cancer.

Invasive fungal diseases (IFDs) are a relevant cause of morbidity and mortality in children with cancer. Their correct prevention and management impact patients' outcomes. The aim of this review is to highlight the rationale and novel insights into antifungal prophylaxis and treatment in pediatric patients with oncological and hematological diseases. The literature analysis showed that IFDs represent a minority of cases in comparison to bacterial and viral infections, but their impact might be far more serious, especially when prolonged antifungal therapy or invasive surgical treatments are required to eradicate colonization. A personalized approach is recommended since pediatric patients with cancer often present with different complications and require tailored therapy. Moreover, while the Aspergillus infection rate does not seem to increase, in the near future, new therapeutic recommendations should be required in light of new epidemiological data on Candidemia due to resistant species. Finally, further studies on CAR-T treatment and other immunotherapies are needed in patients with unique needs and the risk of complications. Definitive guidelines on IFD treatment considering the evolving epidemiology of antifungal resistance, new therapeutic approaches in pediatric cancer, novel antifungal drugs and the importance of an appropriate antifungal stewardship are urgently needed.

Antimicrobial Prophylaxis and Modifications of the Gut Microbiota in Children with Cancer.

In children with cancer, chemotherapy can produce cytotoxic effects, resulting in immunosuppression and an augmented risk of febrile neutropenia and bloodstream infections. This has led to widespread use of antibiotic prophylaxis which, combined with intensive chemotherapy treatment, could have a long-term effect on the gastrointestinal microbiome. In this review, we aimed to analyze the current literature about the widespread use of antibiotic prophylaxis in children experiencing infectious complications induced by chemotherapy and its effects on the gut microbiome. Our review of the literature shows that antimicrobial prophylaxis in children with cancer is still a trending topic and, at the moment, there are not enough data to define universal guidelines. Children with cancer experience long and painful medical treatments and side effects, which are associated with great economic and social burdens, important psychological consequences, and dysbiosis induced by antibiotics and also by chemotherapy. Considering the importance of a healthy gut microbiota, studies are needed to understand the impact of dysbiosis in response to therapy in these children and to define how to modulate the microbiome to favor a positive therapeutic outcome.

Insights into the role of intestinal microbiota in hematopoietic stem-cell transplantation.

The gut microbiota (GM) is able to modulate the human immune system. The development of novel investigation methods has provided better characterization of the GM, increasing our knowledge of the role of GM in the context of hematopoietic stem-cell transplantation (HSCT). In particular, the GM influences the development of the major complications seen after HSCT, having an impact on overall survival. In fact, this evidence highlights the possible therapeutic implications of modulation of the GM during HSCT. Insights into the complex mechanisms and functions of the GM are essential for the rational design of these therapeutics. To date, preemptive and curative approaches have been tested. The current state of understanding of the impact of the GM on HSCT, and therapies targeting the GM balance is reviewed herein.