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Introduction: Artificial Intelligences (AIs) are changing the way information is accessed and consumed globally. This study aims to evaluate the information quality provided by AIs ChatGPT4 and Claude2 concerning reconstructive surgery for head and neck cancer., Methods: Thirty questions on reconstructive surgery for head and neck cancer were directed to both AIs and 16 head and neck surgeons assessed the responses using the QAMAI questionnaire. A 5-point Likert scale was used to assess accuracy, clarity, relevance, completeness, sources, and usefulness. Questions were categorised into those suitable for patients (group 1) and those for surgeons (group 2). AI responses were compared using t-Student and McNemar tests. Surgeon score agreement was measured with intraclass correlation coefficient, and readability was assessed with Flesch-Kincaid Grade Level (FKGL)., Results: ChatGPT4 and Claude2 had similar overall mean scores of accuracy, clarity, relevance, completeness and usefulness, while Claude2 outperformed ChatGPT4 in sources (110.0 vs. 92.1, p < 0.001). Considering the group 2, Claude2 showed significantly lower accuracy and completeness scores compared to ChatGPT4 (p = 0.003 and p = 0.002, respectively). Regarding readability, ChatGPT4 presented lower complexity than Claude2 (FKGL mean score 4.57 vs. 6.05, p < 0.001) requiring an easy-fairly easy English in 93% of cases., Conclusion: Our findings indicate that neither chatbot exhibits a decisive superiority in all aspects. Nonetheless, ChatGPT4 demonstrates greater accuracy and comprehensiveness for specific types of questions and the simpler language used may aid patient inquiries. However, many evaluators disagree with chatbot information, highlighting that AI systems cannot serve as a substitute for advice from medical professionals., (© 2024 The Author(s). Clinical Otolaryngology published by John Wiley & Sons Ltd.)

Objective: The present study challenges the appropriateness of considering invasion of the palatoglossus muscle (PGM) as a criterion for staging oropharyngeal squamous cell carcinoma (OPSCC) as T4., Study Design: Retrospective observational study., Setting: Tertiary University Hospital., Methods: This retrospective study included nonmetastatic OPSCC patients treated with curative intent at the University of Trieste, Italy from 2015 to 2021. Patients were categorized into 4 groups: (1) tumors classified as T1-T2 by both International Cancer Control (UICC) and American Joint Committee on Cancer (AJCC)-TNM; (2) T1-T2 tumors upgraded to T4 solely by UICC due to oropharyngeal PGM infiltration; (3) T1-T2 tumors upgraded to T4 by both UICC and AJCC due to oral PGM infiltration; (4) tumors classified as T3-T4 by both UICC and AJCC. Kaplan-Meier analysis estimated overall survival (OS) and disease-free survival (DFS). Multivariable Cox models, adjusted for clinical factors, assessed the impact of palatoglossus invasion on outcomes over 5 years., Results: A total of 121 consecutive patients with primary OPSCC were included (median [interquartile range] age 65 years [58-74]; 63% male). While patients with upgraded T4 category due to infiltration of the oral portion of the PGM exhibited a prognosis superimposable on that of other patients with advanced stage disease, those with upgraded T4 category due to infiltration of the oropharyngeal portion of the PGM displayed OS and DFS comparable to T1-T2 patients., Conclusion: Our findings highlight that invasion of the oropharyngeal portion of the PGM may not be a suitable criterion for staging OPSCC as T4. Further research involving larger and independent patient cohorts is strongly encouraged to corroborate these observations., (© 2024 The Author(s). Otolaryngology–Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Purpose: Omnitrope ® (a somatropin biosimilar), used to treat growth disturbances, is considered to have a good safety profile in children. Here, we present the analysis of final data of the Italian cohort of the PAtients TReated with Omnitrope ® (PATRO) Children study., Methods: This multicenter, open-label, longitudinal, post-marketing surveillance study enrolled eligible children during 2010-2018. The primary objective was to assess the long-term safety of Omnitrope ® by recording all adverse events (AEs), serious AEs, and adverse drug reactions (ADRs). A secondary objective was to evaluate the long-term effectiveness of Omnitrope ® using height measurements., Results: A total of 375 patients were included in the Italian cohort of the PATRO Children study. After a mean ± standard deviation (SD) follow-up duration of 40.9 ± 24.6 months, 607 AEs were reported in 58.4% of patients, mostly of mild (52.5%) or moderate (15.7%) severity. The most common AEs were headache (11.7%), elevated insulin-like growth factor (IGF)-1 (4.8%), abdominal pain (4.3%), and pyrexia (3.7%). Sixty-seven ADRs occurred in 52 patients (13.9%); the most common ADRs were elevated IGF-1 (3.5%) and insulin resistance (2.9%). Mean ± SD height standard deviation scores in treatment-naïve patients increased from -2.5 ± 0.7 at baseline (n = 318) to -1.3 ± 0.7 at 5 years (n = 56) and to -0.8 ± 0.7 at 7.5 years (n = 13)., Conclusions: This final analysis extends the interim analysis findings from the PATRO Children study and confirms the long-term safety and effectiveness of Omnitrope ® in Italian pediatric patients with growth disturbances., Competing Interests: Compliance with ethical standards. Conflict of interest: Lorenzo Iughetti has received fees for participation on advisory boards from Sandoz. Franco Antoniazzi has received research funding from Merck Serono and Sandoz, and fees for participation on advisory boards from BioMarin. Tommaso Aversa has consulted for Pfizer and Sandoz. Luca Persani has received fees for participation on advisory boards from Sandoz. Gabriella Pozzobon has received consulting fees and for participation on advisory boards from Sandoz, Merck Serono and Novo Nordisk. Emiliano Zecchi, Paolo Fedeli and Markus Zabransky are part of Sandoz Company Organization. Claudia Giavoli, Simonetta Bellone, Laura Guazzarotti, Maria Elisabeth Street, Emanuele Miraglia del Giudice, Stefano Stagi, Gianluca Tornese, Chiara Mameli, Laura Lucaccioni, Letizia Ragusa, Clara Zecchino, and Stefano Zucchini have no relevant financial or non-financial interests to disclose. Ethics approval: The study was reviewed and approved by each study site’s Independent Ethics Committee/Institutional Review Board. Research involving human participants: All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committees, with the 1964 Helsinki Declaration and its later amendments, and with the ethical principles outlined in the Oviedo Human Rights Convention. Consent to participate: All patients (or their parents/legal guardians) provided written informed consent before study inclusion., (© 2024. The Author(s).)

Objective: Structural epilepsies can manifest months or years after the occurrence of an initial epileptogenic insult, making them amenable for secondary prevention. However, development of preventive treatments has been challenged by a lack of biomarkers for identifying the subset of individuals with the highest risk of epilepsy after the epileptogenic insult., Methods: Four different rat models of epileptogenesis were investigated to identify differentially expressed circulating microRNA (miRNA) and isomiR profiles as biomarkers for epileptogenesis. Plasma samples were collected on day 2 and day 9 during the latency period from animals that did or did not develop epilepsy during long-term video-electroencephalographic monitoring. miRNAs and isomiRs were identified and measured in an unsupervised manner, using a genome-wide small RNA sequencing platform. Receiver operating characteristic analysis was performed to determine the performance of putative biomarkers., Results: Two days after an epileptogenic insult, alterations in the levels of several plasma miRNAs and isomiRs predicted epileptogenesis in a model-specific manner. One miRNA, miR-3085, showed good sensitivity (but low specificity) as a prognostic biomarker for epileptogenesis in all four models (area under the curve = .729, sensitivity = 83%, specificity = 64%, p < .05)., Significance: Identified plasma miRNAs and isomiRs are mostly etiology-specific rather than common prognostic biomarkers of epileptogenesis. These data imply that in preclinical and clinical studies, it may be necessary to identify specific biomarkers for different epilepsy etiologies. Importantly, circulating miRNAs like miR-3085 with high negative predictive value for epileptogenesis in different etiologies could be useful candidates for initial screening purposes of epileptogenesis risk., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Purpose: This retrospective cohort study aims to evaluate the clinical, oncological, and functional outcomes of transoral non-robotic surgery for oropharyngeal squamous cell carcinoma (OPSCC)., Materials and Methods: Data from 131 patients with surgically treated OPSCC (2010-2022) were analyzed. Patients who underwent exclusively transoral surgery were included in the study. The surgeries were performed under microscopic or endoscopic guidance and either a CO 2 laser or an ultrasound/radiofrequency scalpel was used as a cutting instrument, depending on the characteristics and location of the tumor. Functional outcomes were assessed in terms of length of hospital stay, tracheostomy rate, duration of feeding tube dependency and complications. Survival outcomes were assessed in terms of overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS)., Results: Of 74 included patients, transoral surgery demonstrated safety with no major complications. Tracheotomy was performed in 51.4 % of cases, and was maintained for a median of 10 days. Complete swallowing recovery was restored in 97.3 % of cases, after a median of 5 days. The median length of hospital stay was 12 days. At 5 years, OS was 68.2 %, PFS was 58.2 % and DSS was 83.6 %., Conclusion: The study confirms the safety and efficacy of a transoral approach for OPSCC. Having the capability to utilize and access a variety of tools provides the opportunity to tailor the technique to the individual patient and specific circumstances., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Gene therapy is emerging as an alternative option for individuals with drug-resistant focal epilepsy. Here, we explore the potential of a novel gene therapy based on Neuropeptide Y (NPY), a well-known endogenous anticonvulsant. We develop a lentiviral vector co-expressing NPY with its inhibitory receptor Y2 in which, for the first time, both transgenes are placed under the control of the minimal CamKIIa(0.4) promoter, biasing expression toward excitatory neurons and allowing autoregulation of neuronal excitability by Y2 receptor-mediated inhibition. Vector-induced NPY and Y2 expression and safety are first assessed in cultures of hippocampal neurons. In vivo experiments demonstrate efficient and nearly selective overexpression of both genes in granule cell mossy fiber terminals following vector administration in the dentate gyrus. Telemetry video-EEG monitoring reveals a reduction in the frequency and duration of seizures in the synapsin triple KO model. This study shows that targeting a small subset of neurons (hippocampal granule cells) with a combined overexpression of NPY and Y2 receptor is sufficient to reduce the occurrence of spontaneous seizures., (© 2024. The Author(s).)

Aim: To analyze the prevalence of anxiety and depression in a large cohort of adults with autoimmune diabetes, identifying sex-driven associated factors., Materials and Methods: In this cross-sectional study, we enrolled 553 consecutive adults with Type 1 diabetes mellitus or latent autoimmune diabetes in adults who came to the Division of Endocrinology of the S.Orsola-Malpighi Polyclinic, Bologna (Italy), to receive their second dose of SARS-CoV-2 vaccine. We administered the questionnaires: Hospital Anxiety and Depression Scale, Diabetes Distress Scale, Diabetes-related Quality of Life, Diabetes Treatment Satisfaction Questionnaire. We collected clinical and biochemical data and 14 days glucose metrics in patients with sensor use > 70% in a time span of ± 4 months from the questionnaires' administration. We excluded 119 patients from our analyses with missing data (final cohort n = 434: 79% of those enrolled)., Results: Anxiety and depression prevalence was respectively 30.4% and 10.8%. According to the multivariate analysis, higher diabete-related emotional burden, lower treatment satisfaction, but not physician-related distress, were risk factors for anxiety and depression; female sex was associated with anxiety (OR 0.51, 95% 0.31-0.81; p = 0.005); in women, depression was associated with increasing age (males vs. females OR 0.96 per 1 year increase, 95% CI 0.92-1.00; p = 0.036), whilst in men with HbA1c (OR 1.08 per 1 mmol/mol increase, 95% CI 1.03-1.13; p = 0.002)., Conclusion: Nearly 1/3 of patients with autoimmune diabetes suffers from anxiety and 1/10 from depression. These conditions are associated with independent modifiable and non-modifiable characteristics. For depression, these characteristics differ between males and females., (© 2024. The Author(s).)

Context: In the last decade the Sanger method of DNA sequencing has been replaced by next-generation sequencing (NGS). NGS is valuable in conditions characterized by high genetic heterogeneity such as neonatal diabetes mellitus (NDM)., Objective: To compare results of genetic analysis of patients with NDM and congenital severe insulin resistance (c.SIR) identified in Italy in 2003-2012 (Sanger) vs 2013-2022 (NGS)., Methods: We reviewed clinical and genetic records of 104 cases with diabetes onset before 6 months of age (NDM + c.SIR) of the Italian dataset., Results: Fifty-five patients (50 NDM + 5 c.SIR) were identified during 2003-2012 and 49 (46 NDM + 3 c.SIR) in 2013-2022. Twenty-year incidence was 1:103 340 (NDM) and 1:1 240 082 (c.SIR) live births. Frequent NDM/c.SIR genetic defects (KCNJ11, INS, ABCC8, 6q24, INSR) were detected in 41 and 34 probands during 2003-2012 and 2013-2022, respectively. We identified a pathogenic variant in rare genes in a single proband (GATA4) (1/42 or 2.4%) during 2003-2012 and in 8 infants (RFX6, PDX1, GATA6, HNF1B, FOXP3, IL2RA, LRBA, BSCL2) during 2013-2022 (8/42 or 19%, P = .034 vs 2003-2012). Notably, among rare genes 5 were recessive. Swift and accurate genetic diagnosis led to appropriate treatment: patients with autoimmune NDM (FOXP3, IL2RA, LRBA) were subjected to bone marrow transplant; patients with pancreas agenesis/hypoplasia (RFX6, PDX1) were supplemented with pancreatic enzymes, and the individual with lipodystrophy caused by BSCL2 was started on metreleptin., Conclusion: NGS substantially improved diagnosis and precision therapy of monogenic forms of neonatal diabetes and c.SIR in Italy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

There has been continuous progress in diabetes management over the last few decades, not least due to the widespread dissemination of continuous glucose monitoring (CGM) and automated insulin delivery systems. These technological advances have radically changed the daily lives of people living with diabetes, improving the quality of life of both children and their families. Despite this, hypoglycemia remains the primary side-effect of insulin therapy. Based on a systematic review of the available scientific evidence, this paper aims to provide evidence-based recommendations for recognizing, risk stratifying, treating, and managing patients with hypoglycemia. The objective of these recommendations is to unify the behavior of pediatric diabetologists with respect to the timely recognition and prevention of hypoglycemic episodes and the correct treatment of hypoglycemia, especially in patients using CGM or advanced hybrid closed-loop systems. All authors have long experience in the specialty and are members of the Italian Society of Pediatric Endocrinology and Diabetology. The goal of treating hypoglycemia is to raise blood glucose above 70 mg/dL (3.9 mmol/L) and to prevent further decreases. Oral glucose at a dose of 0.3 g/kg (0.1 g/kg for children using "smart pumps" or hybrid closed loop systems in automated mode) is the preferred treatment for the conscious individual with blood glucose <70 mg/dL (3.9 mmol/L), although any form of carbohydrate (e.g., sucrose, which consists of glucose and fructose, or honey, sugary soft drinks, or fruit juice) containing glucose may be used. Using automatic insulin delivery systems, the oral glucose dose can be decreased to 0.1 g/kg. Practical flow charts are included to aid clinical decision-making. Although representing the official position of the Italian Society of Pediatric Endocrinology and Diabetology (ISPED), these guidelines are applicable to the global audience and are especially pertinent in the era of CGM and other advanced technologies., 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., (Copyright © 2024 Zucchini, Tumini, Scaramuzza, Bonfanti, Delvecchio, Franceschi, Iafusco, Lenzi, Mozzillo, Passanisi, Piona, Rabbone, Rapini, Rigamonti, Ripoli, Salzano, Savastio, Schiaffini, Zanfardino, Cherubini and Diabetes Study Group of the Italian Society for Pediatric Endocrinology and Diabetes.)

Aims: While continuous glucose monitoring (CGM) and associated technologies have positive effects on metabolic control in young people with type 1 diabetes (T1D), less is known about their impact on quality of life (QoL). Here, we quantified CGM satisfaction and QoL in young people with T1D and their parents/caregivers to establish (i) the relationship between QoL and CGM satisfaction and (ii) the impact of the treatment regimen on QoL., Methods: This was a cross-sectional study of children and adolescents with T1D on different treatment regimens (multiple daily injections, sensor-augmented pumps and automated insulin delivery). QoL was assessed with the KINDL instrument, and CGM satisfaction with the CGM-SAT questionnaire was evaluated in both youths with T1D and their parents., Results: Two hundred and ten consecutively enrolled youths with T1D completed the KINDL and CGM-SAT questionnaires. The mean total KINDL score was greater than neutral in both subjects with T1D (3.99 ± 0.47) and parents (4.06 ± 0.40), and lower overall CGM-SAT scores (i.e., higher satisfaction) were significantly associated with higher QoL in all six KINDL subscales (p < 0.05). There were no differences in KINDL scores according to delivery technology or when participants were grouped according to optimal and sub-optimal glucose control., Conclusions: Higher satisfaction with recent CGMs was associated with better QoL in all dimensions. QoL was independent of both the insulin delivery technology and glycaemic control. CGM must be further disseminated. Attention on perceived satisfaction with CGM should be incorporated with the clinical practice to improve the well-being of children and adolescents with T1D and their families., (© 2024 Diabetes UK.)

Objective: To investigate glucose metrics and identify potential predictors of the achievement of glycemic outcomes in children and adolescents during their first 12 months of MiniMed 780G use., Research Design and Methods: This multicenter, longitudinal, real-world study recruited 368 children and adolescents with type 1 diabetes (T1D) starting SmartGuard technology between June 2020 and June 2022. Ambulatory glucose profile data were collected during a 15-day run-in period (baseline), 2 weeks after automatic mode activation, and every 3 months. The influence of covariates on glycemic outcomes after 1 year of MiniMed 780G use was assessed., Results: After 15 days of automatic mode use, all glucose metrics improved compared with baseline (P < 0.001), except for time below range (P = 0.113) and coefficient of variation (P = 0.330). After 1 year, time in range (TIR) remained significantly higher than at baseline (75.3% vs. 62.8%, P < 0.001). The mean glycated hemoglobin (HbA1c) over the study duration was lower than the previous year (6.9 ± 0.6% vs. 7.4 ± 0.9%, P < 0.001). Time spent in tight range (70-140 mg/dL) was 51.1%, and the glycemia risk index was 27.6. Higher TIR levels were associated with a reduced number of automatic correction boluses (P < 0.001), fewer SmartGuard exits (P = 0.021), and longer time in automatic mode (P = 0.030). Individuals with baseline HbA1c >8% showed more relevant improvement in TIR levels (from 54.3% to 72.3%)., Conclusions: Our study highlights the sustained effectiveness of MiniMed 780G among youth with T1D. Findings suggest that even children and adolescents with low therapeutic engagement may benefit from SmartGuard technology., (© 2024 by the American Diabetes Association.)

Neuroinflammation is associated with several neurological disorders including temporal lobe epilepsy. Seizures themselves can induce neuroinflammation. In an in vivo model of epilepsy, the supplementation of brain-derived neurotropic factor (BDNF) and fibroblast growth factor-2 (FGF-2) using a Herpes-based vector reduced epileptogenesis-associated neuroinflammation. The aim of this study was to test whether the attenuation of the neuroinflammation obtained in vivo with BDNF and FGF-2 was direct or secondary to other effects, for example, the reduction in the severity and frequency of spontaneous recurrent seizures. An in vitro model of neuroinflammation induced by lipopolysaccharide (LPS, 100 ng/mL) in a mouse primary mixed glial culture was used. The releases of cytokines and NO were analyzed via ELISA and Griess assay, respectively. The effects of LPS and neurotrophic factors on cell viability were determined by performing an MTT assay. BDNF and FGF-2 were tested alone and co-administered. LPS induced a significant increase in pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and NO. BDNF, FGF-2, and their co-administration did not counteract these LPS effects. Our study suggests that the anti-inflammatory effect of BDNF and FGF-2 in vivo in the epilepsy model was indirect and likely due to a reduction in seizure frequency and severity.

Glycemic abnormalities are a frequent finding in pediatric oncological patients, both during treatment and after its discontinuation. Moreover, impaired glucose tolerance (IGT), impaired fasting glycemia (IFG) and diabetes mellitus (DM) are not rarely diagnosed in non-oncological hematological diseases. To explore the current pediatric Italian approach to the diagnosis and the management of the glycemic alterations in this clinical setting and, thus, to identify and enforce current clinical needs, we submitted an online 23-items survey to all the Italian Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) centers, and surveys were descriptively analyzed. Thirty-nine AIEOP centers were involved in the study. In 2021, among 75278 children and adolescents affected by an oncological or a hematological disease, 1.2 and 0.65% developed DM, while IGT or IFG were widespread in 2.3 and 2.8%, respectively. The main causes of DM were the use of corticosteroids in patients with cancer and the iron overload in patients with thalassemia. Venous fasting plasma glycemia was the most used tool to detect glycemic abnormalities. The performance of oral glucose tolerance test (OGTT) was extremely limited, except when IFG occurred. Despite the diagnosis of DM, ∼45% of patients with cancer and 30% of patients with one hematological disease did not receive an appropriate treatment. In the other cases, insulin was the drug of first choice. Emerging technologies for diabetes care (glucose sensors and insulin pumps) are not largely used yet. The results of our study support the standardization of the care of the glycemic abnormalities during or after onco-hematologic diseases in the pediatric age. Despite the scarce data in pediatric literature, proper guidelines are needed.

In recent years, many pre-clinical studies have tested gene therapy approaches as possible treatments for epilepsy, following the idea that they may provide an alternative to conventional pharmacological and surgical options. Multiple gene therapy approaches have been developed, including those based on anti-sense oligonucleotides, RNA interference, and viral vectors. In this opinion article, we focus on translational issues related to viral vector-mediated gene therapy for epilepsy. Research has advanced dramatically in addressing issues like viral vector optimization, target identification, strategies of gene expression, editing or regulation, and safety. Some of these pre-clinically validated potential gene therapies are now being tested in clinical trials, in patients with genetic or focal forms of drug-resistant epilepsy. Here, we discuss the ongoing translational research and the advancements that are needed and expected in the near future. We then describe the clinical trials in the pipeline and the further challenges that will need to be addressed at the clinical and economic levels. Our optimistic view is that all these issues and challenges can be overcome, and that gene therapy approaches for epilepsy will soon become a clinical reality., (© 2023. The Author(s).)

Introduction: No studies have reported data on 3-year prevalence and recovery rates of self-reported COVID-19-related olfactory and gustatory dysfunction. The aim of the present study was to estimate the 3-year prevalence and recovery rate of self-reported COVID-19-related chemosensory dysfunction in a cohort of patients with antecedent mild COVID-19., Methods: This is a prospective observational study, measuring the prevalence of altered sense of smell or taste at follow-up and their variation from baseline, on adult patients consecutively assessed at Treviso and Trieste University Hospitals, who tested positive for SARS-CoV-2 RNA by polymerase chain reaction during March 2020., Results: Overall, out of 403 respondents, 267 patients (66.3%) reported an altered sense of smell or taste (SNOT-22 > 0) at baseline, while 56 (13.9%), 29 (7.2%), and 21 (5.2%) reported such alterations at 6-24 months, 2 years, and 3 years, respectively. Among the 267 patients with COVID-19-associated smell or taste dysfunction at baseline, 246 (92.1%) reported complete resolution at 3 years. Of the patients who still experienced smell or taste dysfunction 2 years after COVID-19, 27.6% and 37.9% recovered completely and partially, respectively, at the 3-year follow-up., Conclusion: Among subjects with antecedent mildly symptomatic SARS-CoV-2 infection, the 3-year prevalence and recovery rate of COVID-19-related alteration in sense of smell or taste was 5% and 92%, respectively. In approximately two-thirds of patients experiencing chemosensory dysfunction still 2 years after COVID-19, it is still possible to observe a delayed complete or partial recovery after a period of 3 years, while the remaining one-third of individuals continues to have unchanged persistent chemosensory alteration., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Neuroinflammation represents a dynamic process of defense and protection against the harmful action of infectious agents or other detrimental stimuli in the central nervous system (CNS). However, the uncontrolled regulation of this physiological process is strongly associated with serious dysfunctional neuronal issues linked to the progression of CNS disorders. Moreover, it has been widely demonstrated that neuroinflammation is linked to epilepsy, one of the most prevalent and serious brain disorders worldwide. Indeed, NLRP3, one of the most well-studied inflammasomes, is involved in the generation of epileptic seizures, events that characterize this pathological condition. In this context, several pieces of evidence have shown that the NLRP3 inflammasome plays a central role in the pathophysiology of mesial temporal lobe epilepsy (mTLE). Based on an extensive review of the literature on the role of NLRP3-dependent inflammation in epilepsy, in this review we discuss our current understanding of the connection between NLRP3 inflammasome activation and progressive neurodegeneration in epilepsy. The goal of the review is to cover as many of the various known epilepsy models as possible, providing a broad overview of the current literature. Lastly, we also propose some of the present therapeutic strategies targeting NLRP3, aiming to provide potential insights for future studies.

Aims: Continuous glucose monitoring (CGM) can improve glucometrics in children with type 1 diabetes (T1D), and its efficacy is positively related to glucose sensor use for at least 60% of the time. We therefore investigated the relationship between CGM satisfaction as assessed by a robust questionnaire and glucose control in pediatric T1D patients., Methods: This was a cross-sectional study of children and adolescents with T1D using CGM. The CGM Satisfaction (CGM-SAT) questionnaire was administered to patients and demographic, clinical, and glucometrics data were recorded., Results: Two hundred and ten consecutively enrolled patients attending 14 Italian pediatric diabetes clinics completed the CGM-SAT questionnaire. CGM-SAT scores were not associated with age, gender, annual HbA1c, % of time with an active sensor, time above range (TAR), time below range (TBR), and coefficient of variation (CV). However, CGM satisfaction was positively correlated with time in range (TIR, p < 0.05) and negatively correlated with glycemia risk index (GRI, p < 0.05)., Conclusions: CGM seems to have a positive effect on glucose control in patients with T1D. CGM satisfaction is therefore an important patient-reported outcome to assess and it is associated with increased TIR and reduced GRI., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Because the composition of body fluids reflects many physiological and pathological dynamics, biological liquid samples are commonly obtained in many experimental contexts to measure molecules of interest, such as hormones, growth factors, proteins, or small non-coding RNAs. A specific example is the sampling of biological liquids in the research of biomarkers for epilepsy. In these studies, it is desirable to compare the levels of molecules in cerebrospinal fluid (CSF) and in plasma, by withdrawing CSF and plasma in parallel and considering the time distance of the sampling from and to seizures. The combined CSF and plasma sampling, coupled with video-EEG monitoring in epileptic animals, is a promising approach for the validation of putative diagnostic and prognostic biomarkers. Here, a procedure of combined CSF withdrawal from cisterna magna and blood sampling from the lateral tail vein in epileptic rats that are continuously video-EEG monitored is described. This procedure offers significant advantages over other commonly used techniques. It permits rapid sampling with minimal pain or invasiveness, and reduced time of anesthesia. Additionally, it can be used to obtain CSF and plasma samples in both tethered and telemetry EEG recorded rats, and it may be used repeatedly across multiple days of experiment. By minimizing the stress due to sampling by shortening isoflurane anesthesia, measures are expected to reflect more accurately the true levels of investigated molecules in biofluids. Depending on the availability of an appropriate analytical assay, this technique may be used to measure the levels of multiple, different molecules while performing EEG recording at the same time.

Glycemia risk index (GRI) is a novel composite metric for the evaluation of the safety of glycemic management and control. The aim of this study was to evaluate GRI and its correlations with continuous glucose monitoring (CGM) metrics by analyzing real-life CGM data in 1067 children/adolescents with type 1 diabetes (T1D) using four different treatment strategies (intermittently scanned CGM [isCGM]-multiple daily injections [MDIs]; real-time CGM-MDIs; rtCGM-insulin pump; hybrid closed-loop [HCL] therapy). GRI was positively correlated with high blood glucose index, low blood glucose index, mean glycemia, its standard deviation, coefficient of variation, and HbA1c. The four treatment strategy groups showed significantly different GRI with the lowest value in the HCL group (30.8) and the highest in the isCGM-MDIs group (68.4). These findings support the use of GRI for the assessment of the glycemic risk and the safety of specific treatment in pediatric subjects with T1D.

Aims: Patient-reported outcomes (PROs) are increasingly important for assessing patient satisfaction with diabetes technologies. PROs must be assessed with validated questionnaires in clinical practice and research studies. Our aim was to translate and validate the Italian version of the continuous glucose monitoring (CGM) Satisfaction (CGM-SAT) scale questionnaire., Methods: Questionnaire validation followed MAPI Research Trust guidelines and included forward translation, reconciliation, backward translation, and cognitive debriefing., Results: The final version of the questionnaire was administered to 210 patients with type 1 diabetes (T1D) and 232 parents. The completion rate was excellent, with almost 100% of items answered. The overall Cronbach's coefficient was 0.71 and 0.85 for young people (patients) and parents indicating moderate and good internal consistency, respectively. Parent-young people agreement was 0.404 (95% confidence interval: 0.391-0.417), indicating moderate agreement between the two assessments. Factor analysis identified that factors assessing the "benefits" and "hassles" of CGM accounted for 33.9% and 12.9% of score variance in young people and 29.6% and 19.8% in parents, respectively., Discussion: We present the successful Italian translation and validation of the CGM-SAT scale questionnaire, which will be useful for assessing satisfaction with Italian T1D patients using CGM systems., (© 2023. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Aim: To analyze sleep quality and its relationships with clinical and biochemical features in a large cohort of adults with autoimmune diabetes., Methods: We administered to 553 patients with autoimmune diabetes the questionnaires: Pittsburgh Sleep Quality Index (PSQI), diabetes distress scale, diabetes-related quality of life and diabetes treatment satisfaction questionnaire. We excluded patients with missing HbA1c ± 4 months from PSQI administration or incorrect PSQI compilation (n = 110)., Results: Altered sleep quality was recorded in 142/443 subjects (32%), insufficient total sleep time in 177/443 (40%). The altered sleep quality group had higher HbA1c (median 56 mmol/mol [interquartile range-IQR 49-62] vs 59 [IQR 52-68]; P < 0.001), higher average HbA1c in the previous 36 months (59 mmol/mol [IQR 54-68] vs 56 [IQR 51-62]; P < 0.001), and more individuals with HbA1c > 53 mmol/mol (74.6% vs 62.8%; P = 0.014). Diabetes duration (P = 0.63), type of insulin delivery (P = 0.48) and glucose monitoring (P = 0.35) were uninfluential. Patients with altered sleep quality showed higher prevalence of autoimmune (42 vs 28%; P = 0.005) and mental diseases (12 vs 4%; P = 0.002); there were greater emotional distress, and lower quality of life and treatment satisfaction (P < 0.001 for all), irrespective of sex. Men with altered sleep quality had higher HbA1c and prevalence of autoimmune diseases. Women showed greater prevalence of psychiatric disorders. Average HbA1c of the previous 36 months, autoimmune or psychiatric disorders were independent predictive factors for altered sleep quality., Conclusion: One-third of the patients with autoimmune diabetes showed altered sleep quality, which associates with worse glycemic control, and autoimmune and mental disorders, with sex-specific differences., (© 2023. The Author(s).)

The coronavirus disease 2019 (COVID-19) pandemic has heavily affected health worldwide, with the various forms of diabetes in children experiencing changes at various levels, including epidemiology, diabetic ketoacidosis rates and medical care. Type 1 diabetes showed an apparent increase in incidence, possibly owing to a direct damage of the virus to the β-cell. Diabetic ketoacidosis also increased in association with the general fear of referring patients to the hospital. Most children with diabetes (both type 1 and type 2) did not show a worsening in metabolic control during the first lockdown, possibly owing to a more controlled diet by their parents. Glucose sensor and hybrid closed loop pump technology proved to be effective in all patients with type 1 diabetes during the pandemic, especially because the downloading of data allowed for the practice of tele-medicine. Telemedicine has in fact grown around the world and National Health Systems have started to consider it as a routine activity in clinical practice. The present review encompasses all the aspects related to the effects of the pandemic on the different forms of diabetes in children., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Temporal lobe epilepsy often manifests months or even years after an initial epileptogenic insult (e.g., stroke, trauma, status epilepticus) and, therefore, may be preventable. However, no such preventive treatment is currently available. Aim of this study was to test an antioxidant agent, 7,8-dihydroxyflavone (7,8-DHF), that is well tolerated and effective in preclinical models of many neurological disorders, as an anti-epileptogenic drug. However, 7,8-DHF also acts as a TrkB receptor agonist and, based on the literature, this effect may imply an anti- or a pro-epileptogenic effect. We found that low- (5 mg/kg), but not high-dose 7,8-DHF (10 mg/kg) can exert strong anti-epileptogenic effects in the lithium-pilocarpine model (i.e., highly significant reduction in the frequency of spontaneous seizures and in the time to first seizure after status epilepticus). The mechanism of these different dose-related effects remains to be elucidated. Nonetheless, considering its excellent safety profile and antioxidant properties, as well as its putative effects on TrkB receptors, 7,8-DHF represents an interesting template for the development of effective and well-tolerated anti-epileptogenic drugs., (© 2022. The Author(s).)

Background: Classic criteria for a maturity-onset diabetes of the young (MODY) diagnosis are often unable to identify all subjects, and traditional Sanger sequencing, using a candidate gene approach, leads to a high prevalence of missed genetic diagnosis, classified as MODY-X. Next generation sequencing (NGS) panels provide a highly sensitive method even for rare forms., Methods: We investigated 28 pediatric subjects suspected for MODY-X, utilizing a 15-gene NGS panel for monogenic diabetes (MD)., Results: NGS detected variants of uncertain significance (VUS), likely pathogenic or pathogenic for rarer subtypes of MODY, in six patients. We found variants in the wolframin gene ( WFS1 ), traditionally not considered in MD genetic screening panels, in three patients; KCNJ11 gene mutation, typically responsible for neonatal diabetes and rarely causing isolated diabetes in adolescents; INS gene mutation; a variant in the HNF1B gene in a young male with diabetes on sulfonylurea treatment., Conclusion: In our cohort, the availability of an NGS panel for MD was determined for the correct identification of MD subtypes in six patients with MODY-X. Our study underlines how a precise diagnosis utilizing NGS may have an impact on the management of different forms of MODY and, thus, lead to a tailored treatment and enable genetic counselling of other family members.

[This corrects the article .]., (Copyright © 2022 Cherubini, Marino, Scaramuzza, Tiberi, Bobbio, Delvecchio, Piccinno, Ortolani, Innaurato, Felappi, Gallo, Ripoli, Ricciardi, Pascarella, Stamati, Citriniti, Arnaldi, Monti, Graziani, De Berardinis, Giannini, Chiarelli, Zampolli, De Marco, Bracciolini, Grosso, De Donno, Piccini, Toni, Coccioli, Cardinale, Bassi, Minuto, D’Annunzio, Maffeis, Marigliano, Zanfardino, Iafusco, Rollato, Piscopo, Curto, Lombardo, Bombaci, Sordelli, Mameli, Macedoni, Rigamonti, Bonfanti, Frontino, Predieri, Bruzzi, Mozzillo, Rosanio, Franzese, Piredda, Cardella, Iovane, Calcaterra, Berioli, Lasagni, Pampanini, Patera, Schiaffini, Rutigliano, Meloni, De Sanctis, Tinti, Trada, Guerraggio, Franceschi, Cauvin, Tornese, Franco, Musolino, Maltoni, Talarico, Iannilli, Lenzi, Matteoli, Pozzi, Moretti, Zucchini, Rabbone and Gesuita.)

Background: Growth hormone deficiency (GHD) is the first and most common endocrine complication in pediatric brain tumor survivors (BTS). GHD can occur due to the presence of the tumor itself, surgery, or cranial radiotherapy (CRT)., Aims: This study aimed to evaluate management and adherence to current guidelines of the Italian centers engaged in the diagnosis and follow-up of GHD patients with BTS., Methods: A multidisciplinary scientific board of pediatric endocrinologists, oncologists and radiologists with neuroimaging expertise discussed and reviewed the main issues relating to the management of GHD in pediatric BTS and developed a survey. The survey included questions relating to organizational aspects, risk factors, diagnosis, definition of stable disease, and treatment. The online survey was sent to an expanded panel of specialists dedicated to the care of pediatric BTS, distributed among the three specialty areas and throughout the country (23 Italian cities and 37 Centers)., Results: The online questionnaire was completed by 86.5% (32 out of 37) of the Centers involved. Most had experience in treating these patients, reporting that they follow more than 50 BTS patients per year. Responses were analyzed descriptively and aggregated by physician specialty. Overall, the results of the survey showed some important controversies in real life adherence to the current guidelines, with discrepancies between endocrinologists and oncologists in the definition of risk factors, diagnostic work-up, decision-making processes and safety. Furthermore, there was no agreement on the neuroimaging definition of stable oncological disease and how to manage growth hormone therapy in patients with residual tumor and GHD., Conclusions: The results of the first Italian national survey on the management of GHD in BTS highlighted the difference in management on some important issues. The time to start and stop rhGH treatment represent areas of major uncertainty. The definition of stable disease remains critical and represents a gap in knowledge that must be addressed within the international guidelines in order to increase height and to improve metabolic and quality of life outcomes in cancer survivors with GHD., 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., (Copyright © 2022 Di Iorgi, Morana, Cappa, D’Incerti, Garrè, Grossi, Iughetti, Matarazzo, Parpagnoli, Pozzobon, Salerno, Sardi, Wasniewska, Zucchini, Rossi and Maghnie.)

Aim/hypothesis: To compare the frequency of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes in Italy during the COVID-19 pandemic in 2020 with the frequency of DKA during 2017-2019., Methods: Forty-seven pediatric diabetes centers caring for >90% of young people with diabetes in Italy recruited 4,237 newly diagnosed children with type 1 diabetes between 2017 and 2020 in a longitudinal study. Four subperiods in 2020 were defined based on government-imposed containment measures for COVID-19, and the frequencies of DKA and severe DKA compared with the same periods in 2017-2019., Results: Overall, the frequency of DKA increased from 35.7% (95%CI, 33.5-36.9) in 2017-2019 to 39.6% (95%CI, 36.7-42.4) in 2020 (p=0.008), while the frequency of severe DKA increased from 10.4% in 2017-2019 (95%CI, 9.4-11.5) to 14.2% in 2020 (95%CI, 12.3-16.4, p<0.001). DKA and severe DKA increased during the early pandemic period by 10.4% (p=0.004) and 8% (p=0.002), respectively, and the increase continued throughout 2020. Immigrant background increased and high household income decreased the probability of presenting with DKA (OR: 1.55; 95%CI, 1.24-1.94; p<0.001 and OR: 0.60; 95 CI, 0.41-0.88; p=0.010, respectively)., Conclusions/interpretation: There was an increase in the frequency of DKA and severe DKA in children newly diagnosed with type 1 diabetes during the COVID-19 pandemic in 2020, with no apparent association with the severity of COVID-19 infection severity or containment measures. There has been a silent outbreak of DKA in children during the pandemic, and preventive action is required to prevent this phenomenon in the event of further generalized lockdowns or future outbreaks., Competing Interests: No author reported any conflict of interest as regards this study. The following conflicts of interest pointed out are referred to a period from January 2020 to the submission of this manuscript. VCh’s institution has received research grants from AstraZeneca, Novonordisk, Eli Lilly, Movi, Dompè, and Menarini, and VCh received honoraria from Eli Lilly, Tandem, and Insulet for participating on speakers’ bureaus and scientific advisory boards. CR, DT, IRa, BPr, BPi, SZ, ST, and AR has received support Eli Lilly. In addition, SZ’s institution has received support from Pfeizer, ST, BPi, and DT have received support from Abbott and Theras. MM and AR have received support from Menarini. BPr and PB received honoraria for participating on speakers’ bureaus and scientific advisory boards for Sandoz. Lastly, RS has received research grants by Sanofi and received honoraria for participating on speakers’ bureaus and scientific advisory boards for Movi. The remaining 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., (Copyright © 2022 Cherubini, Marino, Scaramuzza, Tiberi, Bobbio, Delvecchio, Piccinno, Ortolani, Innaurato, Felappi, Gallo, Ripoli, Ricciardi, Pascarella, Stamati, Citriniti, Arnaldi, Monti, Graziani, De Berardinis, Giannini, Chiarelli, Zampolli, De Marco, Bracciolini, Grosso, De Donno, Piccini, Toni, Coccioli, Cardinale, Bassi, Minuto, D’Annunzio, Maffeis, Marigliano, Zanfardino, Iafusco, Rollato, Piscopo, Curto, Lombardo, Bombaci, Sordelli, Mameli, Macedoni, Rigamonti, Bonfanti, Frontino, Predieri, Bruzzi, Mozzillo, Rosanio, Franzese, Piredda, Cardella, Iovane, Calcaterra, Berioli, Lasagni, Pampanini, Patera, Schiaffini, Rutigliano, Meloni, De Sanctis, Tinti, Trada, Guerraggio, Franceschi, Cauvin, Tornese, Franco, Musolino, Maltoni, Talarico, Iannilli, Lenzi, Matteoli, Pozzi, Moretti, Zucchini, Rabbone and Gesuita.)