1,720,982 research outputs found
DIAGNOSTIC APPROACH TO MONOGENIC INFLAMMATORY BOWEL DISEASE WITH NEXT-GENERATION SEQUENCING TECHNOLOGIES.
Full text linkBackground & aims: Up to 15% inflammatory bowel diseases (IBD) rising before the age of 6 years, defined as Very-Early-Onset IBD (VEO-IBD), may have a monogenic disease. More rarely monogenic defects are found in later onset IBD. Monogenic IBD are associated with high morbidity and mortality and timely genetic diagnosis is essential for adequate treatment. Due to the wide phenotypic and genetic heterogeneity of these conditions, it is often difficult to reach a genetic diagnosis and the best diagnostic approach is still debated. Next generation sequencing (NGS) techniques have been proposed as a screening tool especially in patients with poorly defined phenotypes. In a cohort study that included patients with VEO-IBD and Early-onset IBD with severe/atypical phenotypes (EO-IBD s/a) we aimed to: describe the genetic diagnoses and their therapeutic implications, define the clinical characteristics associated with monogenicity, suggest a diagnostic approach to monogenic IBD. Methods: Clinical information of patients with VEO-IBD and EO-IBD s/a referred to 3 Italian Centers for a genetic work-up over 10 years (2008-2017) were collected. From 2015 newly diagnosed patients and patients without a previous genetic diagnosis were screened using NGS, except patients with disease specific features in whom candidate gene analysis was chosen. Results: 93 patients were collected and 14 (15%) reached a genetic diagnosis. Selective sequencing was performed in 47 patients (50%), NGS in 84 patients (90%). Causative defects were revealed by NGS in 5 patients (NOD2, TTC37, DKC1, XIAP, FERMT3) and candidate sequencing in 8 patients (2WAS, CYBA, CYBB, FOXP3, 2CD40L, XIAP). In 8 of 9 patients diagnosed with candidate sequencing, the analysis was guided by the presence of disease specific features. One patient, with unspecific presentation, underwent sequential sequencing of multiple genes over 15 months before reaching the diagnosis (XIAP). NGS identified a new NOD2 mutation previously missed with single gene approach. One patient with WAS, in whom Sanger sequencing had not revealed mutations, was diagnosed externally through WGS which revealed a large genomic inversion. Genetic diagnosis impacted patient management in 10 patients (71%): 6 underwent bone marrow transplant (2XIAP, 2WAS, 2CD40L, FOXP3), 1 gene therapy, 2 anti-infective prophylaxis and 1 introduced danazole (DKC1). Patients with monogenic IBD more frequently had a history of infections (71%vs30%; p<.001), thrombocytopenia (21% vs 3%; p.003), hemophagocytosis (21% vs 3%; p.02), and disease onset ≤ 1 month of life (36% vs 1%; p<.001) when compared to the non-monogenic group. Conclusion: We suggest using NGS in all patients presenting with non-specific clinical profiles and selective gene sequencing when clinical characteristics suggestive of specific monogenic conditions are present
L'epistassi nel bambino
No full textEpistaxis is very common in children and usually originates from small anastomotic vessels in the anterior septum as a consequence of local trauma. In most cases bleeding is self-limiting and can be easily managed with direct compression of the nasal ala. Recurrent episodes of epistaxis might be difficult to manage definitively and often raise concern about possible bleeding disorders. The paper discusses the initial assessment and management of epistaxis in children, including when to suspect a systemic cause and when to refer to the ear, nose and throat specialist
Trisomia e torcicollo
No full textUp to 15% of children with Down syndrome have atlanto-axial instability (AAI) due to constitutional ligament hyperlaxity. Symptomatic disease occurs in 3% of patients: most frequently neurological symptoms of spinal cord compression slowly progress over time but complications from vertebral dislocation can manifest with sudden painful torticollis. While asymptomatic cases require no intervention, symptomatic cases are at risk for irreversible neurological damage and require prompt recognition and surgical stabilization of cervical spine. The paper describes the case of a 10-year-old girl with Down syndrome and AAI who presented with painful torticollis caused by rotatory dislocation of C1-C2. Torticollis was initially misdiagnosed as myogenic. Vertebral dislocation was recognized one month after the onset of symptoms and appropriately managed with surgical stabilization of cervical spine
What Are the Targets of Inflammatory Bowel Disease Management
No full textWith recent evidence suggesting that keeping the inflammatory process under tight control prevents long-term disability, the aim of treatments in inflammatory bowel disease (IBD) has shifted from symptom control toward the resolution of bowel inflammation. Mucosal healing is currently recognized as the principal treatment target to be used in a "treat to target" paradigm, whereas histologic healing and normalization of biomarkers are being evaluated as potential future targets. Although symptom relief is no longer a sufficient target, patient experience with the disease is of unquestionable importance and should be assessed in the form of patient-reported outcomes, to be used as a co-primary target with an objective measure of disease activity. IBD in is a heterogeneous disease; thus besides defining common treatment targets, every effort should be made to deliver a personalized treatment plan based on the risk factors for disease progression and individual drug metabolism to improve treatment success
Cosa deve sapere il pediatra della linfoistiocitosi emofagocitica attraverso i casi degli specializzandi
No full textHemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening syndrome caused by severe hypercytokinemia due to a highly stimulated but ineffective immune response. HLH is not a disease by its own but is rather a common final consequence of an inherited or acquired inability of the immune system to cope with a trigger, which in most cases is an infection. HLH in autoinflammatory and autoimmune conditions is usually termed macrophage activation syndrome (MAS) and can be as severe as other forms of HLH. In absence of treatment HLH has a high mortality rate due to the overwhelming immune activation, and early recognition with prompt immunosuppressive treatment may be life saving. The paper presents four cases of HLH/MAS: each one has a different underlying cause and shows a possible presenting picture of the disease, helping paediatrician to recognize it
Pediatria dal vivo. Trucchi del mestiere, diagnosi a colpo d'occhio, gli errori più comuni
No full textLa buona professione ha le sue basi nella conoscenza della materia e nell’impegno (e nella fatica) di tenerla aggiornata. Ma, nella pratica quotidiana, molto contano anche altri tesori, accumulati, giorno dopo giorno, attraverso il continuo embricarsi del sapere con l’esperienza personale. È questa personalissima, individuale, ricchezza che costituisce in concreto la nostra identità professionale. E che ci aiuta a utilizzare il sapere stesso nel modo più efficace (trucchi del mestiere), a svolgere la professione in maniera pronta (colpo d’occhio) e ancor più a farlo con sicurezza: sapendo evitare (o riducendo al massimo del possibile) gli errori che più comunemente vengono commessi. Questo testo si propone di condividere un po’ dell’esperienza macinata dagli autori, tradotta in messaggi e promemoria pratici, direttamente fruibili. Può essere letto a piccole dosi, un trucco o una diagnosi a colpo d’occhio o un errore alla volta. E forse conviene farlo proprio così. Ogni argomento è presentato, già dal titolo, quasi come uno slogan. Ma viene anche approfondito con la discussione di un caso reale o qualche nota ed esperienza della letteratura. Conciso e completo nello stesso tempo
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