1,721,013 research outputs found
Neurological paraneoplastic syndromes: An update
Purpose of reviewTo describe recent advances in the diagnosis and treatment of paraneoplastic neurological syndromes (PNS).Recent findingsPNS are rare complications of cancer caused by an immune cross-reaction between antigens expressed by tumor cells and neurons. The target of the immune attack can be an intracellular antigen or a cell-surface antigen. Although both types of autoimmunity are 'paraneoplastic', as indirectly triggered by the presence of a tumor, they profoundly differ in terms of clinical profile, pathogenesis and outcome. PNS associated with antibodies to intracellular antigens (icPNS) are characterized by relentless progression and poor response to treatment, because of rapid and permanent neuronal loss. PNS associated with antibodies to cell-surface antigens (csPNS) generally show favorable response to immune therapy and good functional outcome, as they result from reversible neuronal dysfunction.SummaryThe spectrum of paraneoplastic autoimmunity has dramatically expanded following the discovery of cell-surface antibodies. Novel antibodies are incessantly discovered, some of which have a solid association with cancer. As csPNS usually respond to immune therapy, the optimization of current treatment strategies should have high priority to improve therapeutic results and prevent relapses
Trattamento delle pseudoartrosi diafisarie di avambraccio mediante placca semitubulare e innesto osseo autoplastico
Neurological complications of chimeric antigen receptor T cells and immune-checkpoint inhibitors: ongoing challenges in daily practice
PURPOSE OF REVIEW: The aim of this review is to summarize the most recent advances in the management of neurological toxicities associated with immune-checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR)-T cells. RECENT FINDINGS: The advent of cancer immunotherapies has dramatically improved the prognosis of several refractory and advanced neoplasms. Owing to their mechanism of action, cancer immunotherapies have been associated with a variety of immune-related adverse events (irAE). Neurological irAE are uncommon compared with other irAE, but they are associated with significant morbidity and mortality. Despite the efforts to draft common protocols and guidelines, the management of neurological irAE remains challenging. Our ability to predict the development of neurotoxicity is still limited, hampering to elaborate prevention strategies. Treatment heavily relies on the administration of high-dose corticosteroids that, however, have the potential to impair oncological efficacy. The experimentation of novel strategies to avoid resorting to corticosteroids is hindered by the lack of an adequate understanding of the pathogenetic mechanisms driving the development of irAE. SUMMARY: In this review, we will discuss the most recent advances on the diagnosis and management of neurological irAE associated with ICIs and CAR-T cells, focusing on the issues that remain most challenging in clinical practice
Current therapeutic approaches to diffuse grade II and III gliomas
The 2016 WHO classification of Tumors of the Central Nervous System brought major conceptual and practical changes in the classification of diffuse gliomas, by combining molecular features and histology into ‘integrated’ diagnoses. In diffuse gliomas, molecular profiling has thus become essential for nosological purposes, as well as to plan adequate treatment strategies and identify patients susceptible of target therapy. WHO grade II (low grade) and grade III (anaplastic) diffuse gliomas form a heterogeneous group of neoplasms, also known as ‘lower-grade gliomas’, characterized by a wide range of malignant potential. Molecular profile accounts for this biological diversity, and provides an accurate prognostic stratification of tumors in this group. Treatment strategies in lower-grade gliomas are ultimately based on molecular profile and WHO grade, as well as on patient characteristics such as age and Karnofsky performance status. The purpose of this review is to summarize recent advances in the classification of grade II and III gliomas, synthesize current treatment schemes according to molecular profile and describe ongoing research and future perspectives for the use of target therapies
Gut microbiome alterations in anti-NMDA receptor encephalitis: caveats for result interpretation
Diagnosis and therapy of acute disseminated encephalomyelitis and its variants
Acute disseminated encephalomyelitis (ADEM) is traditionally regarded as a monophasic demyelinating disorder of the central nervous system occurring in children after infection or vaccination. ADEM in children has a polysymptomatic presentation that includes encephalopathy, fever and meningeal signs. In adults, encephalopathy is less frequent and the clinical presentation is usually dominated by long tract involvement. Despite the initial clinical severity, the functional outcome is favorable in most cases. ADEM is a subgroup within the broader spectrum of postinfectious neurological syndromes (PINSs), which includes variants characterized by additional peripheral nervous system involvement, and variants characterized by a relapsing or chronic progressive course. The literature on the matter is scarce, mostly consisting of retrospective studies. The aims of this paper are to review the clinical and paraclinical profile of ADEM and its variants, to identify potential predictors of outcome, to summarize current treatment strategies and to outline research perspectives
The clinical use of IDH1 and IDH2 mutations in gliomas
Introduction: Mutations in the genes isocitrate dehydrogenase (IDH) 1 and 2 have been reported in a limited number of tumors. In gliomas, IDH mutations are primarily detected in WHO grade II–III tumors and represent a major biomarker with diagnostic, prognostic, and predictive implications. The recent development of IDH inhibitors and vaccines suggests that the IDH mutation is also an appealing target for therapy. Areas covered: This review focuses on the role of IDH mutations in diffuse gliomas. Besides discussing their role in gliomagenesis, we will emphasize the role of IDH mutations in clinical practice as a diagnostic, prognostic and predictive biomarker, and as a potential therapeutic target. Noninvasive detection of the IDH mutation by means of liquid biopsy and MR spectroscopy will also be discussed. Expert commentary: While IDH mutation is a consolidated diagnostic and prognostic biomarker in clinical practice, its role in oncogenesis is far from being elucidated, and there are several pending issues. The routine use of noninvasive techniques for detection and monitoring of the IDH status remains challenging. Although the IDH mutation is a very early alteration in gliomagenesis, it may then be omitted during tumor progression. This observation has important implications when designing targeted clinical trials
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