Advanced-Metastatic Non-Small-Cell Lung Cancer EGFR-mutated in Italy: patient management costs and potential productivity losses:

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are established therapies for previously untreated advanced/metastatic non-small cell lung cancer (NSCLC) EGFR-mutated patients. Osimertinib, a third-generation TKI, has recently received the same first-line indication. This study aims at investigating management costs and potential productivity losses in Italy in this patient setting, given all the available therapeutic options. Two analyses were performed. The first evaluates first-line yearly management costs and potential productivity losses per patient, for each first-line treatment. The second, performed nationally and regionally, models all lines of treatments and costs over a five-year period, through different market-share scenarios – considering osimertinib adoption as new therapy in 60% of patients as the most probable one – and line-switch/mortality probabilities. Using this model, patients' total months of treatment and development/progression of brain metastases were also analyzed. The first analysis shows that first-line management costs and potential productivity losses are minimized by osimertinib (first-line yearly expenditure of €25.942, 8%-12% less than TKIs). The second analysis, based on a five-year horizon and on all therapy lines, shows that total management costs and potential productivity losses decrease by increasing the adoption of osimertinib as a first-line therapy (€7.4m cumulative lower cost with osimertinib at 60% compared to 0%). Considering the average month of therapy, where results are not affected by the length of the therapy, with osimertinib at 60% on naïve patients, monthly management costs and productivity losses are 10% lower than in the non-osimertinib scenario. In advanced, metastatic EGFR-mutated NSCLC, the use of osimertinib as the first-line treatment could reduce patient management costs and potential productivity losses

Disability weights for castration-resistant prostate cancer : an empirical investigation

Introduction: Health state valuation and diagnostic-therapeutic pathways at the junction between nonmetastatic and metastatic castration-resistant prostate cancer (CRPC) are not well documented. We aimed at: (i) estimating the disability weights (DWs) for health states across a continuum of disease from asymptomatic non-metastatic (nmCRPC) to symptomatic metastatic state (mCRPC); (ii) mapping the diagnostic-therapeutic pathway of nmCRPC in Italy. Methods: Structured qualitative interviews were performed with clinical experts to gather information on nmCRPC clinical pathway. An online survey was administered to clinical experts to estimate DWs for four CRPC health states defined from interviews and literature review (i.e., nmCRPC, asymptomatic mCRPC, symptomatic mCRPC, mCRPC in progression during or after chemotherapy). Clinicians' preferences for health states were elicited using the Person-Trade-Off (PTO) and Visual Analogue Scale (VAS) methods. DWs associated with each health state, from 0 (best imaginable health state) and 1 (worst imaginable health state), were estimated. Results: We found that the management of nmCRPC is heterogeneous across Italian regions and hospitals, especially with respect to diagnostic imaging techniques. DWs for PTO ranged from 0.415 (95% confidence interval [CI] 0.208-0.623) in nmCRPC to 0.740 (95% CI 0.560-0.920) in mCRPC, in progression during or after chemotherapy. DWs for VAS ranged between 0.246 (95% CI 0.131-0.361) in nmCRPC to 0.689 (95% CI 0.583-0.795) in mCRPC, in progression during or after chemotherapy.Conclusions: Estimated DWs suggest that delaying transition to a metastatic state might ease the disease burden at both patient and societal levels

Disease Reactivation after Fingolimod Discontinuation in Pregnant Multiple Sclerosis Patients

Recent studies estimated an incidence of 4-25% of disease rebound after withdrawal of fingolimod (FTY) for any reason, but specific data on disease reactivation after FTY withdrawal due to pregnancy are limited. The aim of the study was to evaluate the frequency and predictors of disease reactivation in patients who stopped FTY for pregnancy. A multicentre retrospective cohort study was conducted in four Italian MS centres in 2013-2019. Both planned and unplanned pregnancies were included. The annualized relapse rate (ARR) was calculated before FTY treatment, during FTY treatment, during pregnancy and during the year after delivery. In total, 27 patients (mean age 29 years) were included. The ARR 1 year before FTY treatment was 1.3. Patients were exposed to FTY for a median of 2.9 years. The ARR was 0.04 during the last year before conception (p < 0.001 compared with the ARR before FTY treatment). Eleven patients became pregnant after a mean of 88 days following FTY discontinuation, whereas 16 patients stopped FTY after pregnancy confirmation. Relapses were observed in 22% of patients during pregnancy and in 44% in the postpartum period. ARR increased both during pregnancy (0.49; p = 0.027) and in the first year after delivery (0.67; p < 0.001) compared to the last year before pregnancy. Compared with radiological assessment before pregnancy, more patients showed new or enlarging T2 lesions (63% vs 30%; p = 0.02) and gadolinium-enhancing lesions (44% vs 0; p = 0.0001) on brain Magnetic Resonance Imaging. Relapses during pregnancy were the only significant predictor for postpartum relapses (OR 1.9, 95% CI 1.11-3.1). One case of spontaneous abortion and no cases of abnormal foetal development were observed. Despite adequate and prolonged control of disease activity, women who discontinue FTY because of pregnancy are at risk for disease reactivation. In patients who relapsed during pregnancy, the initiation of high-efficacy disease modifying drugs (DMDs) soon after delivery is advisable to prevent postpartum relapses

An atypical case of acute disseminated encephalomyelitis associated with cytomegalovirus infection

We present the case of a young man admitted to our hospital for persistent headache associated with fever, retrorbitary pain and vomiting, who rapidly developed encephalopathy with drowsiness, paraplegia, hypoesthesia with a D6 sensory level and urinary retention. Brain and spinal cord MRI revealed findings compatible with acute disseminated encephalomyelitis (ADEM) and microbiological tests documented a cytomegalovirus (CMV) infection. CMV infection is extraordinarily associated with ADEM, but must be included in microbiological tests, because early diagnosis and treatment ameliorate the neurological outcome

Transient hair loss during treatment with dimethyl-fumarate for multiple sclerosis

Introduction Dimethyl-fumarate is a recently approved drug for relapsing-remitting Multiple Sclerosis in Italy. Clinical case A 55-year-old woman started therapy with dimethyl-fumarate on June 2014; it was well-tolerated aside from moderate flushing. Starting September 2014 she noticed a progressive hair loss, that neither the dermatological examination nor clinical and medical history nor blood investigations could explain. The hair loss slowed down after two months and was followed by a hair growth back. Discussion Transient hair loss is not a reported side effect of dimethyl-fumarate therapy but by excluding any known cause we attributed it to the beginning of the new therapy

L’epistolario di Anton Francesco Gori: saggi critici, antologia delle lettere e indice dei mittenti

Il volume raccoglie alcuni saggi dedicati alla figura di Anton Francesco Gori, insostituibile punto di riferimento degli studi antiquari toscani della prima metà del Settecento e stimolo cogente della nascente disciplina dell’etruscheria. Il Gori non fu soltanto come lo definì il Muratori "un solipso dell’erudizione", ma il perno organizzativo della cultura fiorentina come delle principali iniziative bibliografiche e pubblicistiche del tempo. Oltre alle numerose opere pubblicate e conosciute rimane da indagare l’ingente corrispondenza del Gori comprendente le sue carte manoscritte e l’immensa mole di lettere a lui inviate, raccolte nell’Epistolario conservato alla Biblioteca Marucelliana di Firenze oggetto di un "Progetto strategico" dell’Università degli Studi di Firenze finalizzato alla catalogazione, studio, informatizzazione e immissione in rete. Il volume si colloca nell’ambito del progetto e comprende alcuni saggi dedicati alla collezione del Gori come alle figure di alcuni dei suoi importanti corrispondenti, una succinta, ma significativa antologia delle lettere, prova della varietà e della eterogeneità degli argomenti trattati e infine un indice completo dell’Epistolario per mittent

Magnetic resonance imaging pattern recognition in sporadic Inclusion-Body Myositis

In sporadic inclusion body myositis (IBM), additional tools are needed to confirm the diagnosis, particularly in clinically atypical or pathologically unproven patients. The aims of this study were to refine the pattern of muscle MRI in IBM and to assess its accuracy in differentiating IBM frorm other myopathies that overlap with it clinically or pathologically

Sativex\uae effects on promoter methylation and on CNR1/CNR2 expression in peripheral blood mononuclear cells of progressive multiple sclerosis patients

Multiple sclerosis (MS) is a chronic demyelinating central nervous system (CNS) disease that involve oligodendrocyte loss and failure to remyelinate damaged brain areas causing a progressive neurological disability. Studies in MS mouse model suggest that cannabinoids ameliorate symptoms as spasticity, tremor and pain reducing inflammation via cannabinoid-mediated system. The aim of our study is to investigate the changes in cannabinoid type 1 (CNR1) and 2 (CNR2) receptors mRNA expression levels and promoter methylation in peripheral blood mononuclear cells (PBMCs) of MS secondary progressive (MSS-SP) patients treated with Sativex\uc2\uae. Our cohort included MSS-SP patients, that at the time of Sativex\uc2\uae treatment, are treated (n\uc2\ua0=\uc2\ua07), not treated (n\uc2\ua0=\uc2\ua011) or that had terminated interferon-\uce\ub2-1b (IFN-\uce\ub2-1b) therapy (n\uc2\ua0=\uc2\ua012). By Methylation Sensitive High Resolution Melting (MS-HRM), we characterized the methylation profile of CNR1 and CNR2 promoter region, while the relative mRNA transcript levels of these two genes were evaluated in the same samples by Quantitative Real-Time PCR (qRT-PCR) analysis. We did not find different pattern of cytosine-phosphate-guanine (CpG) methylation in the CNR1/CNR2 promoter region of all MSS-SP patients treated with Sativex\uc2\uae. In addition, CNR1 and CNR2 expression did not significantly differ in MSS-SP patients not treated with IFN-\uce\ub2-1b vs. them that have suspended, while in MSS-SP patients treated with IFN-\uce\ub2-1b during Sativex\uc2\uae therapy we found a specific decrease of the CNR2 expression levels. These results suggest that the different expression of cannabinoid receptors by Sativex\uc2\uae treatment in leukocytes might be regulated through a molecular mechanism that involve interferon modulation

Expression Profile of Long Non-Coding RNAs in Serum of Patients with Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic progressive inflammatory disease of the central nervous system (CNS) that leads to severe neurological disability. There is an interest in potential biomarkers that could provide information predicting disease activity and progression. Long non-coding RNAs (lncRNAs) have been reported to be involved in the pathogenesis of various human disorders, such as oncologic, cardiovascular, and neurodegenerative diseases. No studies have so far explored a potential link between lncRNAs and MS pathology. We screened 84 lncRNAs, involved in autoimmunity and human inflammatory response, in the serum of relapsing-remitting MS (RR-MS) patients (n = 12), age-matched controls (n = 12), and in patients with idiopathic inflammatory myopathy (IIM) (n = 12). We used the following criteria for lncRNAs analysis: fold change >2 and p < 0.05. According to these criteria, by real-time PCR, we identified three lncRNAs up-regulated in RR-MS patients respectively to controls: nuclear paraspeckle assembly transcript 1 (NEAT1), taurine up-regulated 1 (TUG1), and 7SK small nuclear (RN7SK RNA). Literature data showed that NEAT1, TUG1, and RN7SK RNA play an important role in neurodegenerative processes. Our results indicate that these lncRNAs may be involved in MS pathogenesis. Additional experimental data are needed to clarify the molecular mechanisms through which lncRNAs up-regulation may have a role in MS

Idiopathic inflammatory myopathies evaluated by near infrared spectroscopy

Introduction: We evaluated whether near infrared spectroscopy (NIRS) can determine the metabolic patterns of dermatomyositis (DM), polymyositis (PM), and inclusion body myositis (IBM). Methods: We enrolled 10 consecutive patients affected by DM, 11 by PM, 9 by IBM, and 3 groups of healthy controls. We measured changes in oxygenated and deoxygenated hemoglobin/myoglobin in the extensor digitorum communis during venous and arterial occlusion testing (VOT) and post-occlusion hyperemia. Results: DM showed lower oxygen consumption (P=0.04) during VOT and reduced oxygen supply after VOT (P=0.04) versus controls. IBM showed higher oxygen consumption (P=0.04) during VOT and higher oxygen supply after VOT (P=0.03) than controls. DM showed reduced oxidative metabolism compared with IBM (P=0.001) and impaired ability to supply oxygen compared with PM (P= 0.03) and IBM (P= 0.001). Discussion: NIRS differentiates samples of DM and IBM patients from controls, but it cannot distinguish PM patients from a sample of healthy subjects. © 2014 Wiley Periodicals, Inc