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Activating BRAF or NRAS mutations have been found in 80% of human sporadic melanomas, but only one of these genetic alterations could be detected in each tumour. This suggests that BRAF and NRAS ‘double mutants’ may not provide advantage for tumour growth, or may even be selected against during tumorigenesis. However, by applying mutant-allele-specific-amplification-PCR method to short-term melanoma lines, one out of 14 tumours was found to harbour both BRAFV600E and the activating NRASQ61R mutations. On the other hand, analysis of 21 melanoma clones isolated by growth in soft agar from this tumour indicated that 16/21 clones harboured a BRAFV600E, but were wild-type for NRAS, whereas the remaining had the opposite genotype (NRASQ61R/wild-type BRAF). When compared to BRAFV600E clones, NRASQ61R clones displayed reduced growth in soft agar, but higher proliferative ability in vitro in liquid medium and even in vivo after grafting into SCID/SCID mice. These data suggest that NRAS and BRAF activating mutations can coexist in the same melanoma, but are mutually exclusive at the single-cell level. Moreover, the presence of NRASQ61R or BRAFV600E is associated with distinct in vitro and in vivo growth properties of neoplastic cells.Oncogene (2006) 25, 3357–3364. doi:10.1038/sj.onc.1209379; published online 6 February 2006 [ABSTRACT FROM AUTHOR]

This retrospective, study compared the efficacy and safety of Ibuprofen-Lysinate (Arfen, intramuscular formulation, Group I, n=156) used during 2000-2005 and Sodium-ibuprofen (Pedea, intravenous solution, Group II, n=60) used during 2006-2008, for the prophylaxis of Patent Ductus Arteriosus in inborn neonates with gestational age ≤28 weeks. Ductus closure rate after prophylaxis was significantly higher (73.1% vs 50%; P=0.002) and surgical ligation significantly lower (8.2% vs 23.3%; P=0.005) in Group I. A smaller number of neonates of Group I vs Group II showed oliguria and hemorrhagic disease. [ABSTRACT FROM AUTHOR]

Objective: Obstetric complications may be an important factor in the development of schizophrenia. The aim of this study is to evaluate the role of these complications in the development of schizophrenia in adult life, with particular attention to the potential role of birth weight. Method: We carried out a case-control study, comprising schizophrenics and patients with diseases of the schizophrenia spectrum as cases, and their healthy male brothers as controls. Obstetric complications were assessed using the 'Midwife Protocol' of Parnas et al. Results: The main result was that birth weight may be a risk factor for schizophrenia, as indicated by odds ratio analysis. The confidence intervals are very wide and, without compromising the clinical significance of the results, they give a limited indication of the real entity of the risk. Conclusions: The results contribute to understanding of the role played by a single complications. [ABSTRACT FROM AUTHOR]

Subcutaneous fat necrosis (SCFN) in newborns is an uncommon and self-limiting non-infectious panniculitis. It can occur in the first weeks of life in full-term newborns with hypoxic-ischemic encephalopathy who underwent therapeutic hypothermia. Hypercalcemia may develop and has been implicated as the cause of several complications as nephrocalcinosis. Hypercalcemia has been previously reported to appear only after resolution of skin lesions. Herein, we report how hypercalcemia can be evident already at diagnosis of subcutaneous fat necrosis after therapeutic hypothermia and can be associated with an early onset developing nephrocalcinosis. We compare two cases of these uncommon findings and review the recent literature., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2025 De Rose, Maddaloni, Salvatori, Campi, Gatto, Martini, Savarese, Bersani, Ubertini, Serrao, Costa, Braguglia, Gallini, Vento and Dotta.)

Background: Anakinra is an interleukin-1 receptor antagonist (IL-1Ra). Since IL-1 has been shown to play a key role in the etiology of different autoinflammatory diseases, blocking its pathway has become an important therapeutic target, even in neonates., Aims: We aimed to report our experience in using anakinra to treat specific neonatal inflammatory conditions., Methods: We described the clinical management with anakinra of five cases of neonates or infants up to 3 months of age admitted to the neonatal intensive care unit (NICU) of Bambino Gesù Children's Hospital IRCCS in Rome (Italy) from 2020 onwards. Medical history and clinical data concerning NICU hospitalization were collected from the electronic medical records. Furthermore, we performed a literature review of off-label anakinra in the first 3 months of life, up to 5 April 2024. We excluded from this review cases of cryopyrin-associated periodic syndrome, deficiency of the interleukin-1 receptor antagonist, and mevalonate kinase deficiency, for which anakinra is a known treatment., Results: We reported three off-label cardiorespiratory reasons to use IL-1Ra from our series: (i) chronic lung disease with pulmonary hypertension, (ii) interstitial lung disease with pulmonary hypertension to facilitate the weaning from respiratory support, and (iii) post-surgical polyserositis if effusions accumulate despite drainage. In all our patients, the drug was administered at a dosage of 10 mg/kg/day. The route of administration was chosen based on the patient's clinical characteristics, with the subcutaneous and intravenous routes being comparable in efficacy. The duration of therapy was modulated based on the patient's clinical response, with a minimum duration of 4 months. A total of 308 retrieved articles were screened, and then full texts of records deemed eligible for inclusion were assessed. Based on the literature search and our five cases, a total of 17 infants were treated with anakinra outside its approved indications. The major off-label use was for hemophagocytic lymphohistiocytosis/macrophage activation syndrome, followed by multisystem inflammatory syndrome in children and Kawasaki disease, as in two of our cases., Conclusions: According to the results of our case series and review of the literature, the off-label use of anakinra in neonates with inflammatory conditions refractory to first-line therapy could be considered. Prospective, multicenter research is necessary to determine whether anakinra is a safe treatment option for these infants to prevent early inflammatory illnesses and in which situations it could enhance clinical results., Competing Interests: Declarations. Funding: This work was supported by the Italian Ministry of Health with the Current Research funds. Conflict of interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Ethics approval: This study reported only a retrospective analysis of data available through the institutional database. Personal data were restricted to essential information and were treated in order to guarantee the respect of the privacy of the involved patient, as specifically stated by Italian Law D. Lgs n.196 of 2003 about personal data protection. Therefore, the study did not require preliminary evaluation by the local ethical committee. The Scientific Director of “Bambino Gesù” Children’s Hospital IRCCS approved the publication of this manuscript (request Ronci Sara-RAP-2024-0004, date of approval: 09/07/2024). Consent to participate: All parents signed a written informed consent form before their children were subjected to intensive care, with the possibility of data relating to hospitalization being obtained anonymously and reproduced. Consent for publication: All parents signed a written informed consent form before their children were subjected to intensive care, with the possibility of data relating to hospitalization being obtained anonymously and reproduced. Availability of data and materials (data transparency): Not applicable. Code availability (software application or custom code): Not applicable. Author contributions: All authors were involved in writing the manuscript: DUDR designed the study, acquired and analyzed data from literature and patients’ data, and drafted the initial manuscript; FC designed the study, acquired and analyzed data from literature and patients’ data; CM, SR, SC, IS, IB, MPR and CA collected patients’ data and revised the manuscript; IC, PM, FDB, and AI critically reviewed the manuscript for important intellectual content; AD supervised the study and critically reviewed the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work. All authors contributed to the article and approved the submitted version., (© 2025. The Author(s).)