Rituximab suppresses disease activity after natalizumab withdrawal: an exploratory study

Background Natalizumab is highly effective in reducing multiple sclerosis disease activity; however it carries a risk of progressive multifocal leukoencephalopathy, that represents the main reason of drug discontinuation. After natalizumab withdrawal, reactivation of disease is soon observed and, until now, it is not known which treatment strategy should be followed after natalizumab discontinuation. Aim of this study is to evaluate rituximab efficacy in controlling disease activity after natalizumab withdrawal

Successful pregnancy and disease outcomes in a NMOSD patient treated with tocilizumab

Abstract Background Neuromyelitis Optica Spectrum Disorder (NMOSD) is an autoimmune relapsing disease involving the central nervous system with predominant inflammatory attack of optic nerves, spinal cord and area postrema, often leading to severe disability. Women with NMOSD typically experience adverse pregnancy outcomes and high relapse rates during pregnancy and the postpartum period. Case report Herein we present a case of pregnancy in a young NMOSD woman treated with tocilizumab. The course of her pregnancy was clinically unremarkable and treatment whit Tocilizumab was well tolerated. Conclusions This case raises the possibility that the modulation of immune system by inhibitors of the IL-6 pathway could a promising therapeutic option for pregnancy in NMOSD patient

Effects of PPARγ agonists on the expression of leptin and vascular endothelial growth factor in breast cancer cells.

The obesity hormone leptin has been implicated in breast cancer development. Breast cancer cells express the leptin receptor and are able to synthesize leptin in response to obesity-related stimuli. Furthermore, leptin is a positive regulator of vascular endothelial growth factor (VEGF) and high levels of both proteins are associated with worse prognosis in breast cancer patients. Peroxisome proliferator-activated receptor (PPAR) ligands are therapeutic agents used in patient with Type 2 diabetes and obesity which have recently been studied for their potential anti-tumor effect. Here, we studied if these compounds, ciglitazone and GW1929, can affect the expression of leptin and VEGF in breast cancer cells. In MDA-MB-231 and MCF-7 breast cancer cells, treatment with submolar concentrations of ciglitazone and GW1929 elevated the expression of leptin and VEGF mRNA and protein, and increased cell viability and migration. These effects coincided with increased recruitment of PPAR to the proximal leptin promoter and decreased association of a transcriptional factor Sp1 with this DNA region

RELAZIONE TRA HANDGRIP E FAMILIARITÀ AL DIABETE DI TIPO 2: UNO STUDIO PILOTA/ RELATIONSHIP BETWEEN TYPE 2 DIABETES AND HANDGRIP: RESULTS OF A PILOT STUDY

Obiettivo: È stata analizzata la possibile relazione, su un campione della popolazione siciliana, tra il grado di familiarità al diabete di tipo 2, i parametri antropometrici ed alcuni test di forza specifica. Materiali e metodi: In modalità random sono stati selezionati 88 uomini e 27 donne, distinti in FH- (assenza di familiarità per il diabete di tipo 2), FH+ (con un componente in linea indiretta con la malattia) ed FH++ (con un genitore affetto dalla malattia). Sono stati rilevati i parametri antropometrici, i parametri cardiovascolari ed è stato rilevato l’handgrip ad entrambe le mani. Le differenze tra i gruppi sono state analizzate con il test ANOVA ed attraverso correlazioni parametriche abbiamo verificato eventuali associazioni (Pearson). Risultati: È emerso che uomini e donne FH++ tendono ad avere un significativo incremento dell’indice di massa corporea (p<0,05) associato ad un incremento statisticamente significativo dei valori basali di pressione arteriosa diastolica (p<0,05). Non sono emerse differenze statisticamente significative tra i gruppi (FH- vs FH+ vs FH++) relativamente ai valori di handgrip espressi dalla mano destra e sinistra, in valore assoluto e relativo. Dallo studio delle correlazioni emerge una importante influenza del peso corporeo sul rendimento dei soggetti al test dell’handgrip (>.40). Conclusioni: La familiarità diretta al diabete di tipo 2 si correla con degli incrementi statisticamente significativi del peso corporeo e dei valori pressori cardiovascolari, indicando che questa popolazione risulta essere maggiormente a rischio per l’evoluzione della stessa malattia. Progetti di prevenzione sono auspicabili in tal senso. L’handgrip risulta essere fortemente correlato ai parametri antropometrici, pertanto indirettamente anche con la familiarità alla malattia. Un’estensione dello studio è auspicabile, al fine di poter meglio comprendere i fenomeni.Objectives: the purpose of this study was to analyze the relationship between family history to type 2 diabetes, anthropometrics characteristics and some fitness tests. Materials and methods: we randomly selected 88 men and 27 women, distinguishing on FH- (absence of family history to type 2 diabetes), on FH+ (with a familiar component with disease) and FH++ (with parent affected to diabetes). We recorded anthropometric parameters, basal blood pressure values and handgrip of both hands. The differences between the groups were analyzed with ANOVA test and Pearson’s correlation. Results: participants FH++ of both sexes showed a statistically significant increase of body mass index (p<0,05) and a significant increase of basal diastolic blood pressure (p<0,05). No family history-related differences were found on handgrip results in absolute and relative values, but the lower numbers of subgroups might have affected the statistical analysis. Correlation analysis showed that parameters like body weight, body mass index and body surface area are able to influence the handgrip test of both hands. Conclusion: family history to type 2 diabetes is strongly related to body weight and basal blood pressure values, confirming that FH++ participants have a major risk to develop disease compared to FH- participants. Handgrip test is strongly related to anthropometric parameters. The sample size represents the major limit of the study. More data are needed to confirm the association between variables

Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (&lt;1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score &gt; 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p &lt; 0.001), RR = 2.19 for ICU admission (p &lt; 0.001), and RR = 2.43 for death (p &lt; 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR&nbsp;=&nbsp;2.05, 95%CI&nbsp;=&nbsp;1.39–3.02, p&nbsp;&lt;&nbsp;0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR&nbsp;=&nbsp;0.42, 95%CI&nbsp;=&nbsp;0.18–0.99, p&nbsp;=&nbsp;0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon