Approaching hemophagocytic lymphohistiocytosis

Hemophagocytic Lymphohistiocytosis (HLH) is a rare clinical condition characterized by sustained but ineffective immune system activation, leading to severe and systemic hyperinflammation. It may occur as a genetic or sporadic condition, often triggered by an infection. The multifaceted pathogenesis results in a wide range of non-specific signs and symptoms, hampering early recognition. Despite a great improvement in terms of survival in the last decades, a considerable proportion of patients with HLH still die from progressive disease. Thus, prompt diagnosis and treatment are crucial for survival. Faced with the complexity and the heterogeneity of syndrome, expert consultation is recommended to correctly interpret clinical, functional and genetic findings and address therapeutic decisions. Cytofluorimetric and genetic analysis should be performed in reference laboratories. Genetic analysis is mandatory to confirm familial hemophagocytic lymphohistiocytosis (FHL) and Next Generation Sequencing is increasingly adopted to extend the spectrum of genetic predisposition to HLH, though its results should be critically discussed with specialists. In this review, we critically revise the reported laboratory tools for the diagnosis of HLH, in order to outline a comprehensive and widely available workup that allows to reduce the time between the clinical suspicion of HLH and its final diagnosis

The Clinical Impact of Methotrexate-Induced Stroke-Like Neurotoxicity in Paediatric Departments: An Italian Multi-Centre Case-Series

IntroductionStroke-like syndrome (SLS) is a rare subacute neurological complication of intrathecal or high-dose (>= 500 mg) Methotrexate (MTX) administration. Its clinical features, evoking acute cerebral ischaemia with fluctuating course symptoms and a possible spontaneous resolution, have elicited interest among the scientific community. However, many issues are still open on the underlying pathogenesis, clinical, and therapeutic management and long-term outcome. Materials and MethodsWe retrospectively analyzed clinical, radiological and laboratory records of all patients diagnosed with SLS between 2011 and 2021 at 4 National referral centers for Pediatric Onco-Hematology. Patients with a latency period that was longer than 3 weeks between the last MTX administration of MTX and SLS onset were excluded from the analysis, as were those with unclear etiologies. We assessed symptom severity using a dedicated arbitrary scoring system. Eleven patients were included in the study. ResultsThe underlying disease was acute lymphoblastic leukemia type B in 10/11 patients, while fibroblastic osteosarcoma was present in a single subject. The median age at diagnosis was 11 years (range 4-34), and 64% of the patients were women. Symptoms occurred after a mean of 9.45 days (+/- 0.75) since the last MTX administration and lasted between 1 and 96 h. Clinical features included hemiplegia and/or cranial nerves palsy, paraesthesia, movement or speech disorders, and seizure. All patients underwent neuroimaging studies (CT and/or MRI) and EEG. The scoring system revealed an average of 4.9 points (+/- 2.3), with a median of 5 points (maximum 20 points). We detected a linear correlation between the severity of the disease and age in male patients. ConclusionsSLS is a rare, well-characterized complication of MTX administration. Despite the small sample, we have been able to confirm some of the previous findings in literature. We also identified a linear correlation between age and severity of the disease, which could improve the future clinical management

The Clinical Impact of Methotrexate-Induced Stroke-Like Neurotoxicity in Paediatric Departments: An Italian Multi-Centre Case-Series

Introduction: Stroke-like syndrome (SLS) is a rare subacute neurological complication of intrathecal or high-dose (≥500 mg) Methotrexate (MTX) administration. Its clinical features, evoking acute cerebral ischaemia with fluctuating course symptoms and a possible spontaneous resolution, have elicited interest among the scientific community. However, many issues are still open on the underlying pathogenesis, clinical, and therapeutic management and long-term outcome. Materials and Methods: We retrospectively analyzed clinical, radiological and laboratory records of all patients diagnosed with SLS between 2011 and 2021 at 4 National referral centers for Pediatric Onco-Hematology. Patients with a latency period that was longer than 3 weeks between the last MTX administration of MTX and SLS onset were excluded from the analysis, as were those with unclear etiologies. We assessed symptom severity using a dedicated arbitrary scoring system. Eleven patients were included in the study. Results: The underlying disease was acute lymphoblastic leukemia type B in 10/11 patients, while fibroblastic osteosarcoma was present in a single subject. The median age at diagnosis was 11 years (range 4–34), and 64% of the patients were women. Symptoms occurred after a mean of 9.45 days (± 0.75) since the last MTX administration and lasted between 1 and 96 h. Clinical features included hemiplegia and/or cranial nerves palsy, paraesthesia, movement or speech disorders, and seizure. All patients underwent neuroimaging studies (CT and/or MRI) and EEG. The scoring system revealed an average of 4.9 points (± 2.3), with a median of 5 points (maximum 20 points). We detected a linear correlation between the severity of the disease and age in male patients. Conclusions: SLS is a rare, well-characterized complication of MTX administration. Despite the small sample, we have been able to confirm some of the previous findings in literature. We also identified a linear correlation between age and severity of the disease, which could improve the future clinical management

Special Issue (1972) - Apparati realizzati per la generazione di segnali di tempo e frequenze campioni della stazione ricevente I.R.O.E.

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La comunicazione consapevole sui social media come strumento per combattere i casi di odio, razzismo, disinformazione e fake news"

La comunicazione costituisce la dimensione primaria della vita. Le forme di comunicazione, negli anni, hanno subito forti cambiamenti come conseguenza delle innovazioni tecnologiche legate alla comunicazione, con ricadute sia positive che negative. Negli anni siamo passati da una comunicazione di tipo gerarchico-patriarcale prima alla comunicazione di massa, poi alle recenti forme di comunicazione tramite web. Per gestire questi cambiamenti, servono nuovi modelli comunicativi, nuovi schemi e nuove strategie. E’emersa la necessità di combattere le nuove forme di disinformazione, e i casi di odio e razzismo sempre più diffusi nel web attraverso un comunicazione consapevole.. L’uso dei social media e della rete sono un fenomeno in forte aumento. Nel 2021, la popolazione mondiale passa in media più di 6 ore al giorno nel web. Una realtà che coinvolge sia i nativi digitali, sia, pur in forma minore, anche i cosiddetti immigrati digitali. Quello che accade nella rete e nella vita reale tende sempre più a sovrapporsi e viviamo nuove esperienze definite interrealtà e post-verità. L’infodemia, il tasso di analfabetismo funzionale e i bias cognitivi fanno sì che le nuove generazioni siano facili prede di fake news, cyber bullismo e altri fenomeni emergenti (grooming, sexiting, etc.). La pandemia ha ulteriormente acuito queste problematiche, costringendo molti giovani ad avere contatti con i compagni solo attraverso uno schermo. Anche la Commissione Europea si è interessata a questi fenomeni, promuovendo una istruzione adeguata per gli adolescenti. All’intero di questo obiettivo nasce il progetto “FAKE combattiamo attraverso la consapevolezza, la conoscenza e l'educazione”, che sarà presentato nell’ultimo capitolo

Long term follow-up of neurodegenerative Langerhans cell histiocytosis: report on 63 patients from the Italian registry

Neurodegenerative involvement in Langerhans cell histiocytosis (ND-LCH) is a rare but potentially devastating complication that can progress to disabling neurological manifestations. Despite advances in scientific research, there are still many open questions. Effective therapy is lacking: various treatments have been proposed achieving best results when initiated early. However, a standardized diagnostic approach to early identify patients in need of treatment is still a matter of debate. Lastly, only small cohorts of patients with short follow-up are reported so far, hampering knowledge about its natural history. Therefore, the aim of this study is to describe the long term follow-up of ND-LCH through the analysis of a large cohort of patients enrolled in the Italian LCH registry. In addition, we sought to identify predictors of ND-LCH progression to overt clinical manifestations. Out of the 637 patients enrolled in the Italian LCH Registry, 63 were referred for ND-LCH (10%) from 8 italian centres. Male to female ratio was 1.6. Median age at LCH diagnosis was 22 months. ND-LCH developed at a median of 59 months, with a delay of 2.9 years from the LCH diagnosis. Out of the 63 patients, 43 (68%) had multisystem disease, 13/43 with risk organ involvement. Diabetes insipidus and/or craniofacial bone lesions were reported in 51/63 (81%) patients; the remaining 12 patients were BRAF V600E mutated in 11/11 cases tested. Overall, 60% (38/63) patients were completely asymptomatic, 24% (15/63) had mild clinical manifestations including abnormal neurological examination and/or evoked potentials but without overt clinical picture, 16% (10/63) developed overt symptoms. The patients were followed-up for a median of 8.5 years (1– 22.5 years) from ND-LCH diagnosis with a multidisciplinary protocol including: brain MRI, evoked potential and neurological examination. Brain MRI worsened in 13/63 (21%) patients over a median of 1.5 years (1-12 years). Clinical ND-LCH developed after a median time of 2.5 years (range, 0-8 years) from ND-LCH diagnosis. Thirty of the 63 patients (17 pauci-symptomatic, 11 symptomatic, 2 asymptomatic but with severe alterations on brain MRI) received high dose immunoglobulin (n=24), chemotherapy (n=3), mitogen-activated protein kinase inhibitors alone (n=2) or combined with immunoglobulin (n=1). Overall, 17/30 patients (57%) were stable or improved, the others worsened and started second line therapy. The remaining 33 patients (27 asymptomatic, 3 mild and 3 overt clinical symptoms) were not treated and remained stable in 94% of cases (31/33). At univariable analysis, the risk of overt clinical symptoms increased with reactivations (OR 6.40, 95%CI 1.31-31.16, p=0.018), severe brain MRI alteration (grading 3-4) at ND-LCH diagnosis (OR 10.40, 95%CI 2.94-36.81, p<0.001) and MRI worsening during follow-up (OR 10.25, 95%CI 2.58-40.79, p=0.001). The predictive value of reactivation and MRI worsening were confirmed at multivariable analysis. In conclusion, patients with ND-LCH accounts for the 10% of the Italian cohort and were follow-up for a median time of 8.5y, that is the longest follow-up reported so far. Patients presenting with mild radiological lesions (grading 1-2) at ND-LCH onset and the absence of clinical and neurophysiological alterations remained almost stable during follow-up; conversely, history of LCH reactivation and the presence of severe radiological alterations (grading 3-4) or worsening on brain MRI predisposed to the onset of neurological overt clinical symptoms. These results may lay the basis for patient selection for treatment and different monitoring strategies

L'animazione socio-culturale finalizzata alla promozione della cultura di Pace, un'esperienza pilota a Livorno.

Inizialmente descriverò chi è l’animatore e che funzione svolge. Verrà definita l’animazione socio-culturale secondo E.Limbos, la formazione degli animatori e le caratteristiche che deve avere un percorso di animazione. Mi soffermerò sulla stimolazione di gruppi di giovani, sulle tecniche che possono essere attuate e sul tipo di comunicazione che caratterizza l’opera di questa figura educativa. Nella seconda parte verrà trattato il tema dell’educazione alla Pace, gli obbiettivi e i temi che ne fanno parte. Sottolineerò gli aspetti metodologici che accomunano l’animazione socio-culturale e l’educazione alla pace in quanto gli strumenti di animazione che vengono usati da quest’ultima sono pratiche di animazione socio-culturale che tratta argomenti riguardanti la cultura di Pace. Nella terza parte esporrò la mia esperienza di tirocinio, il percorso formativo che ho seguito nell’ambito dell’animazione, l’argomento degli incontri di animazione con i ragazzi delle scuole medie superiori, cioè lo sviluppo sostenibile, gli strumenti di animazione usati dall’equips del tirocinio e i risultati della nostra azione