Background: Neurofibromatosis type 1 (NF1) is a rare multisystem disorder characterized by variable expressivity and increased tumor risk. Café-au-lait macules (CALMs) are a hallmark of the disease, often representing one of the earliest clinical manifestations and allowing a clinical NF1 diagnosis if six or more are present. In this study, we aimed to investigate the prognostic value of CALMs at birth in NF1 patients. Methods: We conducted a retrospective study in patients aged ≥ 4 years presenting with CALMs at our Institution between 2020 and 2021, with a minimum follow-up of four years. We retrospectively collected data on CALMs at birth and other clinical manifestations associated with NF1. Results: Among 208 patients evaluated, including 147 with a confirmed diagnosis of NF1, 110 did not show CALMs at birth, and 98 had at least one. The absence of CALMs at birth did not correlate with a lower likelihood of NF1. In contrast, the CALM number at birth directly correlated with the likelihood of NF1, up to 95% in patients with ≥5 macules. Additionally, a higher number of CALMs correlated with a greater prevalence of plexiform neurofibromas (p < 0.001). Conclusions: Our findings suggest that a higher number of CALMs may indicate a more severe form of NF1, with an increased risk of plexiform neurofibromas. These results emphasize the importance of a comprehensive evaluation of patients with CALMs, especially in case of multiple lesions, aiming at implementing early NF1 diagnosis, follow-up strategies, and overall patient management.

Background: Celiac disease (CD) is an immune-mediated, gluten-induced enteropathy with intestinal and extraintestinal manifestations. Chronic urticaria (CU) is a heterogeneous inflammatory skin disorder often considered idiopathic, but emerging evidence suggests possible autoimmune causes. Methods: We describe a pediatric case in which CU and angioedema were the sole clinical expressions of CD. We also conducted a scoping review of the literature to assess the prevalence of CD in CU patients and the therapeutic impact of a gluten-free diet (GFD). Results: The child’s CU resolved rapidly after initiating a GFD, with complete remission and normalization of anti-tissue transglutaminase at follow-up. Literature review shows that CD is significantly more common in CU patients than in the general population, and several case reports document remission of CU after GFD. However, leading guidelines for CD and CU do not currently recommend mutual screening, and pathophysiological mechanisms linking the two conditions remain incompletely understood. Conclusions: Chronic urticaria may be the sole clinical manifestation of CD. Screening for CD in patients with CU may be considered, particularly in those with autoimmune features or disease refractory to standard treatment. Initiating a GFD can lead to rapid symptom remission, reduce dependence on conventional therapies and improve quality of life.

Background: Empirical antibacterial therapy for febrile neutropenia requires adaptation to local epidemiology, a process that is often complex, time-consuming, and prone to human error. This study aims to address this challenge by developing a practical, data-driven tool to efficiently evaluate and adapt treatment protocols. Methods: We developed a novel, open-source computational script in Python (version 3.10), aided by large language models for code revision, to analyze antibiotic susceptibility data. The script was validated using a retrospective dataset of 237 Gram-negative bloodstream infections (BSIs) from 2015 to 2024 in cancer or hematopoietic stem cell transplant recipients at a tertiary care pediatric hospital in Italy. The script calculates efficacy metrics for both single agents and two-drug combinations. Results: Among the Gram-negative BSI strains analyzed, meropenem monotherapy demonstrated the highest efficacy (median 95.4%). In contrast, piperacillin/tazobactam and cefepime showed lower efficacy (80.3% and 81.8%, respectively). On the contrary, combination therapy, particularly with amikacin, significantly increased the efficacy of beta-lactams, elevating their effectiveness to a level comparable to meropenem. Conclusions: The developed script is a valuable tool for antimicrobial stewardship programs, offering a rapid and accessible method to validate international guidelines against local epidemiological data. While meropenem shows high efficacy, its broad use should be limited to prevent resistance. The combination of piperacillin–tazobactam and amikacin is identified as a robust and effective empirical treatment choice.

Background: The clinical presentation of ornithine transcarbamylase deficiency (OTCD) ranges from neonatal-onset hyperammonemia to milder, delayed symptoms, including impaired psychomotor development. Methods: We present the case of a male newborn from a dichorionic diamniotic twin pregnancy with no family history of metabolic disorders who developed desaturation, cyanosis and hypertonia in the early postnatal period, and was found to have severe hyperammonemia. Brain MRI revealed abnormalities in the white matter and basal ganglia, while elevated plasma glutamine and urine orotic acid confirmed the OTCD diagnosis. Due to the acute metabolic failure, continuous kidney replacement therapy was initiated to support metabolic clearance, alongside high-rate glucose, nitrogen scavengers, and urea cycle substrates. Despite intensive treatment the patient’s metabolic status continued to deteriorate, and he died a few days later. Results: Genetic testing by Sanger sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) identified a novel, hemizygous 9,896-bp genomic deletion involving exon 3 of the OTC gene, which was inherited from the mother and was absent in the unaffected twin. This finding, confirmed by long-PCR to identify the deletion breakpoints, is likely to result in complete enzyme deficiency. Conclusions: This case demonstrates the significant phenotypic variability of OTCD, which is largely influenced by the underlying genetic variant. We also conducted a literature review on the genotype-phenotype correlation of this rare disease to further highlight the importance of genetic testing and counseling for patient and carrier management and reproductive planning.