Bambino Gesù Children's Hospital

Core myopathies are congenital diseases with clinical, pathological and genetic heterogeneity. Main histological features are fiber "cores" showing a focally reduced oxidative enzyme activity. Dusty Core Disease (DuCD) differs from Central Core Myopathy for the presence of irregular areas, without clear borders and round/ovoidal shape, and myofibrillar disorganization characterized by reddish purple granular material depositions. This disorder is defined clinically by severe phenotypes with early onset of disease and molecularly by low level of RyR1 in muscle. Until now DuCD was associated only to biallelic recessive RYR1 mutations. We analyzed the clinical aspects, pathological features and mutational spectrum of four DuCD patients, belonging to our cohort of Congenital Myopathy probands. Molecular analysis detected 5 different RYR1 pathogenic variants, two of them so far unreported. Patients presented a heterogeneous phenotype ranging from severe recessive infantile forms to moderate dominant adult-onset presentations. Histological, immunological and ultrastructural techniques were employed to validate these dominant cases, which expand our knowledge on the inheritance of this subgroup of diseases.

Electronic portfolios (e-portfolios) are increasingly used in healthcare professional education (HPE) to support learning, reflection and professional development. Despite their broad adoption, there is limited synthesis on how e-portfolios are structurally designed and pedagogically implemented across healthcare programmes and on the implications for clinical teachers. A narrative review was conducted following the Scale for the Assessment of Narrative Review Articles (SANRA). Literature search was conducted in PubMed, Web of Science, Scopus and CINAHL between January and February 2025. Twelve studies published between 2012 and 2024 were included. Data were analysed to explore e-portfolio structures, educational uses and reported effects on reflection and learning. E-portfolios were implemented in various educational and clinical settings, showing considerable variation in platform design, structural components and curricular integration. Common features included reflective writing, documentation of clinical experiences, feedback mechanisms and assessment rubrics. Studies reported that e-portfolios integrated into structured pedagogical frameworks and supported by training and mentoring promote reflective practice, student engagement and professional identity development. Conversely, inconsistent implementation, technological barriers or checklist-oriented designs were associated with superficial engagement and limited educational value. The educational value of e-portfolios in HPE lies less in the technology itself and more in how these tools are pedagogically designed, supported and contextualised within clinical education. For clinical educators, attention to flexibility, relevance to practice and ongoing guidance may be key to promoting meaningful reflection rather than procedural completion. Further research is needed to identify best practices and improve adaptability in different healthcare education contexts.

Innate immune cells respond rapidly to environmental cues through signal-regulated transcription factors (SRTFs) that sense changes in the tissue microenvironment. Signal transducer and activator of transcription (STAT) proteins are critical regulators of cytokine signaling and determine polarized immune responses. Herein, we reveal that activated type 2 innate lymphocytes (ILC2s) express STAT4, a SRTF canonically linked to type 1 immunity. STAT4 expression is induced in ILC2s upon activation by the alarmin IL-25 and linked with accumulation of lung inflammatory ILC2s (iILC2s). Despite elevated STAT4 expression, iILC2s do not acquire type 1 features, such as interferon (IFN)-γ production or T-bet expression and do not respond to IL-12 stimulation. Instead, STAT4 is activated by type I IFNs and supports the maintenance of the iILC2 pool. Transcriptomic analysis of Stat4-deficient ILC2s reveals enhanced type I IFN signaling and impaired proliferation, suggesting that STAT4 functions to antagonize IFN-driven suppression. Our data uncover a novel regulatory axis in which IL-25-induced STAT4 expression equips ILC2s to modulate interferon responses and to prevent aberrant autocrine function of type I IFNs, thus sustaining inflammatory effector populations during immune activation. These findings broaden the understanding of ILC2 activation and suggest new avenues for modulating innate lymphocytes in inflammatory diseases.

BackgroundA spectrum of adverse events overlapping with Post-acute Sequelae of SARS-CoV-2 infection (PASC) occurs in some patients following SARS-CoV-2 vaccination including small fiber neuropathy (SFN) and cognitive symptoms.AimsAccruing information regarding disease course and immune response imbalances in these patients.MethodsWe studied 71 previously healthy patients with neurological symptoms following SARS-CoV-vaccination. All had negative neurological workup for central/peripheral involvement (MR, EMG/EN). Cutaneous biopsy (21pts.) and peripheral blood sampling (20pts) were performed for anti-idiotype Ab analysis (ACE-2,NRP-1) (ELISA, IF) and for Flowcytometric analysis.ResultsParesthesia, cognitive impairment and autonomic symptoms agreed with SFN international definition. Comparative differences included abrupt onset, presence of simultaneous diverse paresthesia across multiple body regions frequently affecting the facial and cervical regions (44%) and the trunk (26%), associated to dysautonomia. Median time from vaccination to symptom manifestation was 3 days (mean ± SD: 8.76 ± 17.4 days). Symptom severity was still high (5.9 ± 1.9 mean+SD) at the time of evaluation and sampling, (382 ± 133 days from onset. Reduced small fiber density was observed in 19/21 biopsies. Anti-ACE-2 antibodies in 9/71pts. (12%) and 4/19 (21%) vaccinated HD sera and NRP-1 reactivity in 14/71 (20%) patient and 1/19 (5%) HD sera were not significantly increased. Peripheral NKG2D+CD8+ and NKG2D+DNAM-1+CD4+ T-cells were increased. Circulating inflammatory CD34+ cells were increased and generated in vitro a prevalence of NKG2D+DNAM-1+ T-cells.ConclusionPASC-vac SFN is associated with persistent immune imbalances common to other immune-mediated diseases. Additional effort to identify immune mechanisms unleashing PASC-vac SFN will contribute to modulate future early interventions for these patients and refine vaccine design.

Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by bone fragility and severe spinal deformities, with scoliosis affecting up to 80% of patients and often progressing despite bracing. Surgical management is challenging due to poor bone quality and high complication risk. Advances in pedicle screw-based constructs and multimodal strategies, including traction and bisphosphonates, have improved outcomes and enabled the successful correction of deformities. This review analyzes radiographic and surgical results of modern posterior spinal fusion (PSF) in OI-associated spinal deformity. A systematic search of PubMed, Scopus, Embase, Cochrane Library, and Google Scholar (inception to May 2025) was performed using search terms such as "osteogenesis imperfecta", "brittle bone disease", "posterior spinal fusion", "spinal arthrodesis", "scoliosis" and "spinal deformity". Extracted data covered demographics, OI type, traction techniques, instrumentation, radiographic and surgical outcomes, complications, and patient-reported outcome measures (PROMs). The risk of bias was assessed using the MINORS tool, and reporting followed PRISMA guidelines. The initial search identified 264 articles, of which 8 met the inclusion criteria, including 149 patients with OI (mean age 15.5years). All studies were retrospective case series (level IV evidence). Cement augmentation was used in 31.5% of cases and apical osteotomies in 37.5%. Preoperative main curves ranged from 75.5° to 96°, with a mean correction rate of 49.5% after PSF. Both coronal and sagittal radiographic parameters improved postoperatively. The mean operative time was 410.6minutes, blood loss averaged 1,375mL, and hospital stay was 7.9days. The overall complication rate was 27.5%, with 10.7% requiring unplanned reoperation. Modern pedicle screw-based constructs appear to provide more consistent radiographic correction in OI-associated scoliosis compared to earlier in situ fusion techniques. Although these procedures still entail significant blood loss and long operative times, their complication rates remain acceptable given patient complexity. Future multicenter high-quality studies should focus on optimizing implant density, screw augmentation, rod material, osteotomies, and integrating navigation and new biomaterials to standardize treatment strategies.

Leukemia is the most common childhood cancer, accounting for one-third of malignancies in this age group. Testicular infiltration in pediatric leukemia patients represents a manifestation of leukemic dissemination beyond the bone marrow and can occur at diagnosis or be a sign of relapse. Testicular infiltration may occur particularly in specific leukemia subtypes, such as acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) and is an important prognostic factor, as it may indicate an increased risk of leukemia relapse. Therefore, rigorous follow-up is essential to detect testicular infiltration early and initiate appropriate treatment. This study aims to evaluate cases of leukemia with testicular infiltration in two pediatric oncology referral centers in two different countries. We conducted a retrospective study of patients presenting with secondary testicular infiltration due to leukemia over a 14-year period (January 2010 to December 2023). During the study period, we identified 24 patients who developed testicular infiltration secondary to leukemia. All cases of testicular infiltration were diagnosed at the time of disease relapse. Fourteen patients presented with isolated testicular relapse, while the remaining patients had additional relapse sites in combination with testicular recurrence: bone marrow (10 cases) and central nervous system (2 cases). The mean age at diagnosis was 7.91 years. The average leukocyte count at diagnosis was 56 211/mm3, with only five patients presenting with leukocyte counts above 100 000/mm3. Four children (16.6%) were diagnosed with T-cell ALL, 20 (83.4%) with B-cell ALL. Fifteen patients (62.5%) underwent hematopoietic stem cell transplantation, including two haploidentical transplants. Twelve patients (50%) died-three due to disease progression and one from disseminated fusariosis. Data regarding the cause of death were unavailable for the remaining patients. The average follow-up duration was 5.87 years, with an event-free survival of 2.085 years. Although rare, testicular infiltration in leukemia patients is a clinically significant phenomenon that may affect both prognosis and quality of life. Early diagnosis and appropriate treatment of the underlying leukemia are crucial to improve outcomes. Monitoring of testicular function and fertility-related concerns must also be addressed comprehensively in patient management. Future studies with larger cohorts and standardized management protocols are essential to establish clear guidelines for the diagnosis, treatment, and follow-up of patients with testicular relapse secondary to ALL. Given the low number of cases and the diversity of local resources worldwide (especially regarding radiotherapy and endocrine follow up), the best approach for each patient should be determined in multidisciplinary team discussions.