Eculizumab is a monoclonal antibody blocking the terminal complement protein C5. As demonstrated in the phase III randomized, placebo-controlled, REGAIN clinical trial, eculizumab is efficacious in ...acetylcholine receptor antibody (AChR-Ab)-positive refractory generalized myasthenia gravis (gMG) (Myasthenia Gravis Foundation of America—MGFA class II–IV). It has not been studied in severe myasthenic exacerbation or myasthenic crisis (MGFA V). A 73-year-old man diagnosed with myasthenia gravis AChR-Ab positivity came to our observation for symptoms of bulbar and ocular weakness and unresponsiveness or intolerability to conventional immunosuppressive therapies (prednisone and azathioprine). Due to the recurrent clinical worsening with intubation over a short-term period, the patient was treated with eculizumab. After 15 days of eculizumab treatment, we observed a significant recovery of clinical condition. We discharged the patient to an outpatient regimen, where he is continuing with maintenance doses of eculizumab and slowly tapering steroid intake. The use of eculizumab in myasthenic crises is still anecdotal. Our case aims to provide eculizumab benefit for refractory severe gMG in a practical, real-world setting beyond the criteria of the REGAIN study. Further studies are needed to evaluate the efficacy and safety of eculizumab in myasthenic crises.
The analysis of how the European Union (EU) affects domestic political competition and political parties has mainly been centred on elections, whereas studies on parliaments have focused more on ...institutional adaptation. However, parliaments also provide forums for debating alternative domestic and EU policies. This study examines how Europe is used in parliamentary competition in Italy and Spain by analysing party discourses in investiture and budget debates. Covering two decades (1986-2006), the study investigates whether or not the EU has gained importance over time in the way parties use European policies, the evolution of party positions towards the EU and, more generally, the consequences of integration for party policies and discourse.
Amongst the chief targets of immune-checkpoint inhibitors (ICIs), namely the Programmed cell death protein 1 (PD-1)/PD-Ligands (Ls) axis, most research has focused on PD-L1, while to date PD-L2 is ...still under-investigated. However, emerging data support PD-L2 relevant expression in malignancies of the head and neck area, mostly in head and neck squamous cell carcinoma (HNSCC) and salivary gland cancers (SGCs). In this context, ICIs have achieved highly heterogeneous outcomes, emphasizing an urgent need for the identification of predictive biomarkers. With the present review, we aimed at describing PD-L2 biological significance by focusing on its tissue expression, its binding to PD-1 and RGMb receptors, and its impact on physiological and anti-cancer immune response. Specifically, we reported PD-L2 expression rates and significant clinical correlates among different head and neck cancer histotypes. Finally, we described the biology of soluble PD-L2 form and its potential application as a prognostic and/or predictive circulating biomarker.
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•Immune-checkpoint inhibitors achieved variable results in head and neck malignancies.•Except for PD-L1 in HNSCC, few validated predictive markers are available.•Research concerning PD-1/PDLs axis has neglected PD-L2.•Head and neck cancer expresses PD-L2, correlating with clinical/prognostic outcomes.•Soluble PD-L2 is a promising, minimally invasive liquid biopsy biomarker.
Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is an entity with peculiar clinical and molecular characteristics, which mainly arises from the reticulated ...epithelium lining the crypts of the palatine tonsils and the base of the tongue. The only head and neck site with a definite etiological association between persistent high-risk (HR) HPV infection and development of SCC is the oropharynx. HPV-positive malignancies represent 5-20% of all HNSCCs and 40-90% of those arising from the oropharynx, with widely variable rates depending on the geographic area, population, relative prevalence of environment-related SCC and detection assay. HPV-16 is by far the most common HR HPV genotype detected in oropharyngeal SCC (OPSCC), and the only definitely carcinogenic genotype for the head and neck region. Patients with HPV-induced OPSCC are more likely to be middle-aged white men, non-smokers, non-drinkers or mild to moderate drinkers, with higher socioeconomic status and better performance status than subjects with HPV-unrelated SCC. HPV-induced HNSCCs are often described as non-keratinizing, poorly differentiated or basaloid carcinomas, and are diagnosed in earlier T-category with a trend for a more advanced N-category, with cystic degeneration, than the HPV-unrelated carcinomas. HPV positivity is associated with better response to treatment and modality-independent survival benefit. Treatment selection in HPV-related oropharyngeal carcinoma is becoming a critical issue, and although there is no evidence from randomized, controlled trials to support a treatment de-escalation in HPV-positive SCC, some investigators argue that intensive combined modality strategies may represent an overtreatment.
Este artículo es la transcripción de la Lectio Magistralis que pronunció el profesor Oreste Massari con motivo de su jubilación como profesor de universidad y que se celebró el 31 de octubre de 2017 ...en Roma. A lo largo de su vida intelectual y académica ha analizado en profundidad la evolución de los partidos y el sistema de partidos italiano así como la experiencia de los partidos británicos, especialmente el partido laborista, el modelo Westminster y consideraciones generales sobre el liderazgo político, los modelos de partido y la relación de los partidos con la democracia. Su trayectoria intelectual nos muestra cómo ha cambiado el sistema político italiano en los últimos 40 años así como la evolución y el desarrollo conceptual del análisis de los partidos y sistemas de partidos en general, el desarrollo de la ciencia política italiana y europea y, finalmente, los retos a los que se enfrentan los partidos y la democracia en los próximos años.
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