A novel, dominant disease mechanism of distal renal tubular acidosis with specific variants in ATP6V1B1.

Background And Hypothesis: ATP6V1B1 encodes a subunit of the vacuolar H+-ATPase and pathogenic variants are associated with autosomal recessive distal renal tubular acidosis (dRTA) with deafness. Heterozygous variants predicted to affect a specific amino acid, Arg394, have been recurrently reported in dRTA but their significance has been unclear. We hypothesised that these variants are associated with a dominant disease mechanism.

IL-17 family members exert an autocrine pro-inflammatory loop in CF respiratory epithelial cells ex vivo.

Background: Lungs of people with Cystic Fibrosis (pwCF) are characterized by chronic inflammation and infection with P. aeruginosa. High levels of IL-17 A and F have been observed in sputum of pwCF and the interleukin-17(IL-17) family (A-to-F) has been suggested to play a key role in CF pulmonary disease.

Exploring auxiliary liver transplantation in the era of transplant oncology - A proposal for a new liver splitting program (ALERT-50).

Total hepatectomy and liver transplantation has emerged as a game-changing strategy in the treatment of several liver-confined primary or metastatic tumors, opening the new era of transplant oncology. However, the expansion of indications is going to worsen the chronic scarcity of organs, and new strategies are needed to enlarge the donor pool. A possible source of organs could be developing split liver transplantation (SLT) programs.

Endoscopic retrograde cholangiopancreatography in children with pediatric congenital biliary dilatation associated with pancreatobiliary maljunction: experience from a tertiary center.

Background: Congenital biliary dilatation (CBD) is a congenital malformation of the main biliary tract usually associated with the pancreatobiliary maljunction (PBM), determining stone formation, cholangitis, pancreatitis, and cholangiocarcinoma. The role of endoscopic retrograde cholangiopancreatography (ERCP) in treatment and diagnosis has not been established yet. Therefore, the aim of our study is to define the actual role of ERCP in children with CBD.

Impact of Platelet Transfusion at Different Doses in Oncohematology Pediatric Inpatients and Outpatients: A Retrospective Study.

Background: Platelet (PLT) transfusion is an essential strategy to prevent bleeding in children with thrombocytopenia associated to cancer treatment. However, data on optimal pediatric dosing and transfusion thresholds are limited.

Methods: This retrospective study analyzed data from 607 pediatric patients with hematologic malignancies, nonmalignant disorders, and solid tumors who developed hypoproliferative thrombocytopenia during therapy.

A new epidemic wave of Bordetella pertussis in paediatric population: impact and role of co-infections in pertussis disease.

Background: In recent months, Bordetella pertussis has reappeared after maintaining a low rate for many years. Although pertussis is usually characterized by a favorable course, several factors can contribute to the severity of the disease, such as mixed respiratory infections. In this study, we evaluate B.

Intensified Induction Therapy for Newly Diagnosed, Localized Skeletal Ewing Sarcoma (ISG/AIEOP EW-1): A Randomized, Open-Label, Phase 3, Non-Inferiority Trial.

Background: Several studies have shown that the intensity of treatment in Ewing sarcoma has an impact on outcome. The present trial tested the non-inferiority of intensive, shorter, induction chemotherapy (25 weeks total treatment time) compared to the standard treatment (37 weeks) in non-metastatic Ewing sarcoma (ES) at onset.

Procedure: This national, multicenter, parallel, randomized, controlled, open-label, non-inferiority, phase III trial was conducted in 14 specialized hospitals in Italy.

Proposed resources required for a comprehensive program for CCT CHD imaging.

Background: Cardiac Computed Tomography (CCT) is increasingly used for evaluation of congenital heart disease (CHD) in patients of all ages. Pediatric and adult congenital heart disease (ACHD) surgical programs require high quality CCT imaging as part of the multimodality imaging support expected of comprehensive care centers. Despite these expectations, there are no benchmarks or defined programmatic elements specific to the performance of CCT in patients with CHD.

Genomic reanalysis of a pan-European rare-disease resource yields new diagnoses.

Genetic diagnosis of rare diseases requires accurate identification and interpretation of genomic variants. Clinical and molecular scientists from 37 expert centers across Europe created the Solve-Rare Diseases Consortium (Solve-RD) resource, encompassing clinical, pedigree and genomic rare-disease data (94.5% exomes, 5.

In vitro ILC differentiation from human HSCs.

The Innate Lymphoid Cells (ILCs) are a family of innate immune cells composed by the Natural Killer (NK) cells and the helper ILCs (hILCs) (ILC1, ILC2, ILC3), both developing from a common ILC precursor (ILCP) derived from hematopoietic stem cells (HSCs). A correct ILC reconstitution is crucial, particularly in patients receiving HSC transplantation (HSCT), the only therapeutic option for many adult and pediatric high-risk hematological malignancies. Indeed, mainly thanks to their cytotoxic activity, NK cells have a strong Graft-versus-Leukemia (GvL) effect.

Modified lung ultrasound score for improved monitoring of pARDS on ECMO, a case report.

Background: Lung ultrasound scoring is a validated tool for assessing lung pathology. However, existing scoring systems typically overlook the size of consolidations, limiting their accuracy in certain clinical scenarios.

Case Presentation: We describe the first application of adding the maximum consolidation depth in centimeters (cm) to the conventional score.

Donor-derived GD2-specific CAR T cells in relapsed or refractory neuroblastoma.

Allogeneic chimeric antigen receptor (CAR) T cells targeting disialoganglioside-GD2 (ALLO_GD2-CART01) could be a therapeutic option for patients with relapsed or refractory, high-risk neuroblastoma (r/r HR-NB) whose tumors did not respond to autologous GD2-CART01 or who have profound lymphopenia. We present a case series of five children with HR-NB refractory to more than three different lines of therapy who received ALLO_GD2-CART01 in a hospital exemption setting. Four of them had previously received allogeneic hematopoietic stem cell transplantation.

Biomarkers in Ataxia-Telangiectasia: a Systematic Review.

Ataxia-Telangiectasia (A-T) is a very rare multisystem disease of DNA repair, associated with progressive disabling neurological symptoms, respiratory failure, immunodeficiency and cancer predisposition, leading to premature death. There are no curative treatments available for A-T but clinical trials have begun. A major limiting factor in effectively evaluating therapies for A-T is the lack of suitable outcome measures and biomarkers.

Ocrelizumab dose selection for treatment of pediatric relapsing-remitting multiple sclerosis: results of the OPERETTA I study.

Background: The presented study identified the appropriate ocrelizumab dosing regimen for patients with pediatric-onset multiple sclerosis (POMS).

Methods: Patients with POMS aged 10-17 years were enrolled into cohort 1 (body weight [BW] < 40 kg, ocrelizumab 300 mg) and cohort 2 (BW ≥ 40 kg, ocrelizumab 600 mg) during a 24-week dose-exploration period (DEP), followed by an optional ocrelizumab (given every 24 weeks) extension period.

Primary Endpoints: pharmacokinetics, pharmacodynamics (CD19 B-cell count); secondary endpoint: safety; exploratory endpoints: MRI activity, protocol-defined relapses, Expanded Disability Status Scale (EDSS) score change.

Cenobamate as add-on treatment for SCN8A developmental and epileptic encephalopathy.

Objectives: Developmental and epileptic encephalopathies (DEEs) caused by pathogenic variants in SCN8A are associated with difficult-to-treat and early-onset seizures, developmental delay/intellectual disability, impaired quality of life, and increased risk of early mortality. High doses of sodium channel blockers are typically used to treat SCN8A-DEE caused by gain-of-function (GoF) variants. However, seizures are often drug resistant, and only a few patients achieve seizure freedom.

Laparoscopic varicocelectomy: Does intraoperative lymphography with vital dye influence the outcome?

Introduction: Vital dyes lymphography during laparoscopic varicocelectomy (LV) has been suggested to allow for lymphatic mapping thereby allowing for lymphatic sparing (LS) and subsequent reduction of hydrocele formation. Intratesticular injection of the dye seems to achieve the best lymphatic visualization, however, the potential toxicity of some agents, is a cause of concern for the risk of testicular pathological changes. We report our experience with LV, to test the hypothesis that Intraoperative lymphography with methylene blue (BL), is safe and reduces the rate of post-operative hydrocelectomy.

Predictive factors of health related quality of life in children and adolescents with celiac disease: An Italian multicenter study on behalf of the SIGENP.

Background: In pediatric patients, celiac disease (CD) may influence the health-related quality of life (HRQoL).

Aims: The study aimed to assess HRQoL and further characterise the clinical factors associated with reduced HRQoL, in a large multicenter pediatric cohort with CD.

Methods: The disease-specific questionnaire CD Dutch Questionnaire (CDDUX) and the generic questionnaire Paediatric Quality of Life Inventory (PedsQL) were used to assess the HRQoL.

Predisposing Potential Risk Factors for Severe Anorexia Nervosa in Adolescents.

Background: Anorexia nervosa is a serious eating disorder that mainly affects children and adolescents. Most patients present with extreme body dissatisfaction and an obsessive focus on body weight and food. Anorexia nervosa is a complex and multifactorial condition characterised by biological, psychological, and social factors.

Dent disease: Clinical Practice Recommendations.

Dent disease is a rare X-linked tubulopathy that is characterized by low-molecular-weight (LMW) proteinuria associated with hypercalciuria, which may lead to nephrolithiasis, nephrocalcinosis, and kidney failure between the 3rd and the 5th decades of life in 30-80% of affected males. The disease is most often associated with various manifestations of proximal tubular dysfunction. Affected individuals may present nephrotic range proteinuria which may be misinterpreted and cause diagnostic delay.

Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.

Status of Sepsis Care in European Hospitals: Results from an International Cross-Sectional Survey.

Rationale: Early detection, standardized therapy, adequate infrastructure and strategies for quality improvement should constitute essential components of every hospital's sepsis plan.

Objectives: To investigate the extent to which recommendations from the sepsis guidelines are implemented and the availability of infrastructure for the care of patients with sepsis in acute hospitals.

Methods: A multidisciplinary cross-sectional questionnaire was used to investigate sepsis care in hospitals.

Open-label evaluation of oral trehalose in patients with neuronal ceroid lipofuscinoses.

The neuronal ceroid lipofuscinoses (NCLs) are incurable pediatric neurodegenerative diseases characterized by accumulation of lysosomal material and dysregulation of autophagy. Given the promising results of treatment with trehalose, an autophagy inducer, in cell and animal models of NCL, we conducted an open-label, non-placebo-controlled, non-randomized 12-month prospective study in NCL patients receiving oral trehalose (4 g/day). All were treated with a commercially available formulation for 6 months, followed by a 6-month washout.

Extended clinical phenotypes and treatment modalities in 32 JAGN1-deficient patients. A multicenter study by EBMT IEWP.

JAGN1 (Jagunal-homolog1) is a ER-resident transmembrane protein which is part of the early secretory pathway and granulocyte colony-stimulating factor receptor mediated signaling. Autosomal recessively inherited variants in the JAGN1 gene lead to congenital neutropenia, early-onset bacterial infections, aphthosis and skin abscesses due to aberrant differentiation and maturation of neutrophils. In addition, bone metabolism disorders and a syndromic phenotype, including facial features, short stature and neurodevelopmental delay, have been reported in affected patients.

Safety of Nirmatrelvir-Ritonavir Administration in Children With Immunodeficiency and/or Comorbidities With SARS-CoV-2 Infection: A Retrospective Clinical Report.

Introduction: Despite the generally mild course of COVID-19 in children, immunocompromised patients may experience complications or severe infection. This study reports the clinical outcomes of pediatric patients treated with nirmatrelvir and ritonavir (N/R) for SARS-CoV-2 infection.

Methods: We retrospectively reported the data of children with any immunodeficiency with COVID-19 who received N/R treatment between March 2022 and June 2023 at the Bambino Gesù Children's Hospital.