Integrated Antitumor Activities of Cellular Immunotherapy with CIK Lymphocytes and Interferons against KIT/PDGFRA Wild Type GIST

: Gastrointestinal stromal tumors (GISTs) are rare, mesenchymal tumors of the gastrointestinal tract, characterized by either KIT or PDGFRA mutation in about 85% of cases. KIT/PDGFRA wild type gastrointestinal stromal tumors (wtGIST) account for the remaining 15% of GIST and represent an unmet medical need: their prevalence and potential medical vulnerabilities are not completely defined, and effective therapeutic strategies are still lacking. In this study we set a patient-derived preclinical model of wtGIST to investigate their phenotypic features, along with their susceptibility to cellular immunotherapy with cytokine-induced killer lymphocytes (CIK) and interferons (IFN). We generated 11 wtGIST primary cell lines (wtGISTc). The main CIK ligands (MIC A/B; ULBPs), along with PD-L1/2, were expressed by wtGISTc and the expression of HLA-I molecules was preserved. Patient-derived CIK were capable of intense killing in vitro against wtGISTc resistant to both imatinib and sunitinib. We found that CIK produce a high level of granzyme B, IFNα and IFNγ. CIK-conditioned supernatant was responsible for part of the observed tumoricidal effect, along with positive bystander modulatory activities enhancing the expression of PD-L1/2 and HLA-I molecules. IFNα, but not In, had direct antitumor effects on 50% (4/8) of TKI-resistant wtGISTc, positively correlated with the tumor expression of IFN receptors. wtGIST cells that survived IFNα were still sensitive to CIK immunotherapy. Our data support the exploration of CIK immunotherapy in clinical studies for TKI-resistant wtGIST, proposing reevaluation for IFNα within this challenging setting

A real opportunity to modify cardiovascular risk through primary care and prevention: A pilot study

Cardiovascular diseases (CVDs) represent a major threat to health and primary prevention outstands as the most effective instrument to face this issue, addressing multiple risk factors at a time and influencing behavioral patterns. Community nurses have been involved in many interdisciplinary prevention activities, resulting in effective control of CV risk factors. We conducted a pilot study aiming at describing the impact on the CV risk profile of an 18-month interdisciplinary intervention on lifestyle habits. From September 2018 to May 2020, four general practitioners (GPs) working in the Roman neighborhood of Torresina recruited patients having a cardiovascular risk score (CRS) equal to or higher than 3% and lower than 20%; those patients were included in a nutritional, physical, and psychological counseling program. Assessments of patients' health status were led at baseline, 6, 12, and 18 months by a nutritionist, a physiotherapist, a psychologist, their GPs, and a community nurse. The CRS was estimated at every examination, based on the Italian Progetto Cuore algorithm. A total of 76 patients were included (mean age of 54.6 years; 33 men and 43 women). Mean CRS showed a significant reduction between baseline and 12 months (from 4.9 to 3.8); both total cholesterol and systolic blood pressure (SBP) significantly decreased at 6 months of follow-up (respectively, from 211.1 to 192 and from 133.1 to 123.1). Nonetheless, the reduction was later maintained only for SBP. However, during the last 6 months of the intervention, the COVID-19 pandemic broke out, thus, it is not possible to know how much the results achieved at 18 months were influenced by the restrictive measures introduced by the Italian government. When stratifying according to the presence of hypertension/diabetes and physical activity, no differences in the CRS could be highlighted between the two groups. Our pilot study proved that an interdisciplinary counseling intervention program can improve CV risk profile and could be further spread to people that, according to their CRS, would benefit more from changes in lifestyles

Clinical patterns of hepatocellular carcinoma in nonalcoholic fatty liver disease: A multicenter prospective study

107noNonalcoholic fatty liver disease (NAFLD) represents the hepatic manifestation of metabolic syndrome and may evolve into hepatocellular carcinoma (HCC). Only scanty clinical information is available on HCC in NAFLD. The aim of this multicenter observational prospective study was to assess the clinical features of patients with NAFLD-related HCC (NAFLD-HCC) and to compare them to those of hepatitis C virus (HCV)-related HCC. A total of 756 patients with either NAFLD (145) or HCV-related chronic liver disease (611) were enrolled in secondary care Italian centers. Survival was modeled according to clinical parameters, lead-time bias, and propensity analysis. Compared to HCV, HCC in NAFLD patients had a larger volume, showed more often an infiltrative pattern, and was detected outside specific surveillance. Cirrhosis was present in only about 50% of NAFLD-HCC patients, in contrast to the near totality of HCV-HCC. Regardless of tumor stage, survival was significantly shorter (P = 0.017) in patients with NAFLD-HCC, 25.5 months (95% confidence interval 21.9-29.1), than in those with HCV-HCC, 33.7 months (95% confidence interval 31.9-35.4). To eliminate possible confounders, a propensity score analysis was performed, which showed no more significant difference between the two groups. Additionally, analysis of patients within Milan criteria submitted to curative treatments did not show any difference in survival between NAFLD-HCC and HCV-HCC (respectively, 38.6 versus 41.0 months, P = nonsignificant) Conclusions: NAFLD-HCC is more often detected at a later tumor stage and could arise also in the absence of cirrhosis, but after patient matching, it has a similar survival rate compared to HCV infection; a future challenge will be to identify patients with NAFLD who require more stringent surveillance in order to offer the most timely and effective treatment. (Hepatology 2016;63:827-838)openopenPiscaglia F.; Svegliati-Baroni G.; Barchetti A.; Pecorelli A.; Marinelli S.; Tiribelli C.; Bellentani S.; Bernardi M.; Biselli M.; Caraceni P.; Domenicali M.; Garuti F.; Gramenzi A.; Lenzi B.; Magalotti D.; Cescon M.; Ravaioli M.; Del Poggio P.; Olmi S.; Rapaccini G.L.; Balsamo C.; Di Nolfo M.A.; Vavassori E.; Alberti A.; Benvegnau L.; Gatta A.; Giacomin A.; Vanin V.; Pozzan C.; Maddalo G.; Giampalma E.; Cappelli A.; Golfieri R.; Mosconi C.; Renzulli M.; Roselli P.; Dell'isola S.; Ialungo A.M.; Risso D.; Marenco S.; Sammito G.; Bruzzone L.; Bosco G.; Grieco A.; Pompili M.; Rinninella E.; Siciliano M.; Chiaramonte M.; Guarino M.; Camma C.; Maida M.; Costantino A.; Barcellona M.R.; Schiada L.; Gemini S.; Lanzi A.; Stefanini G.F.; Dall'aglio A.C.; Cappa F.M.; Suzzi A.; Mussetto A.; Treossi O.; Missale G.; Porro E.; Mismas V.; Vivaldi C.; Bolondi L.; Zoli M.; Granito A.; Malagotti D.; Tovoli F.; Trevisani F.; Venerandi L.; Brandi G.; Cucchetti A.; Bugianesi E.; Vanni E.; Mezzabotta L.; Cabibbo G.; Petta S.; Fracanzani A.; Fargion S.; Marra F.; Fani B.; Biasini E.; Sacco R.; Morisco F.; Caporaso N.; Colombo M.; D'ambrosio R.; Croce L.S.; Patti R.; Giannini E.G.; Loria P.; Lonardo A.; Baldelli E.; Miele L.; Farinati F.; Borzio M.; Dionigi E.; Soardo G.; Caturelli E.; Ciccarese F.; Virdone R.; Affronti A.; Foschi F.G.; Borzio F.Piscaglia, F.; Svegliati-Baroni, G.; Barchetti, A.; Pecorelli, A.; Marinelli, S.; Tiribelli, C.; Bellentani, S.; Bernardi, M.; Biselli, M.; Caraceni, P.; Domenicali, M.; Garuti, F.; Gramenzi, A.; Lenzi, B.; Magalotti, D.; Cescon, M.; Ravaioli, M.; Del Poggio, P.; Olmi, S.; Rapaccini, G. L.; Balsamo, C.; Di Nolfo, M. A.; Vavassori, E.; Alberti, A.; Benvegnau, L.; Gatta, A.; Giacomin, A.; Vanin, V.; Pozzan, C.; Maddalo, G.; Giampalma, E.; Cappelli, A.; Golfieri, R.; Mosconi, C.; Renzulli, M.; Roselli, P.; Dell'Isola, S.; Ialungo, A. M.; Risso, D.; Marenco, S.; Sammito, G.; Bruzzone, L.; Bosco, G.; Grieco, A.; Pompili, M.; Rinninella, E.; Siciliano, M.; Chiaramonte, M.; Guarino, M.; Camma, C.; Maida, M.; Costantino, A.; Barcellona, M. R.; Schiada, L.; Gemini, S.; Lanzi, A.; Stefanini, G. F.; Dall'Aglio, A. C.; Cappa, F. M.; Suzzi, A.; Mussetto, A.; Treossi, O.; Missale, G.; Porro, E.; Mismas, V.; Vivaldi, C.; Bolondi, L.; Zoli, M.; Granito, A.; Malagotti, D.; Tovoli, F.; Trevisani, F.; Venerandi, L.; Brandi, G.; Cucchetti, A.; Bugianesi, E.; Vanni, E.; Mezzabotta, L.; Cabibbo, G.; Petta, S.; Fracanzani, A.; Fargion, S.; Marra, F.; Fani, B.; Biasini, E.; Sacco, R.; Morisco, F.; Caporaso, N.; Colombo, M.; D'Ambrosio, R.; Croce, L. S.; Patti, R.; Giannini, E. G.; Loria, P.; Lonardo, A.; Baldelli, E.; Miele, L.; Farinati, F.; Borzio, M.; Dionigi, E.; Soardo, G.; Caturelli, E.; Ciccarese, F.; Virdone, R.; Affronti, A.; Foschi, F. G.; Borzio, F

[The new 15-valent pneumococcal conjugate vaccine for the prevention of S. pneumoniae infections in pediatric age: a Health Technology Assessment]

Questo capitolo sintetizza gli aspetti più rilevanti emersi dalla valutazione HTA del vaccino coniugato antipneumococcico 15-valente (PCV15) per la prevenzione delle infezioni da S. pneumoniae in età pediatrica

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 > 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 < 0.001), RR = 2.19 for ICU admission (p < 0.001), and RR = 2.43 for death (p < 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 = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 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

SISMIKO:emergency network deployment and data sharing for the 2016 central Italy seismic sequence

At 01:36 UTC (03:36 local time) on August 24th 2016, an earthquake Mw 6.0 struck an extensive sector of the central Apennines (coordinates: latitude 42.70° N, longitude 13.23° E, 8.0 km depth). The earthquake caused about 300 casualties and severe damage to the historical buildings and economic activity in an area located near the borders of the Umbria, Lazio, Abruzzo and Marche regions. The Istituto Nazionale di Geofisica e Vulcanologia (INGV) located in few minutes the hypocenter near Accumoli, a small town in the province of Rieti. In the hours after the quake, dozens of events were recorded by the National Seismic Network (Rete Sismica Nazionale, RSN) of the INGV, many of which had a ML > 3.0. The density and coverage of the RSN in the epicentral area meant the epicenter and magnitude of the main event and subsequent shocks that followed it in the early hours of the seismic sequence were well constrained. However, in order to better constrain the localizations of the aftershock hypocenters, especially the depths, a denser seismic monitoring network was needed. Just after the mainshock, SISMIKO, the coordinating body of the emergency seismic network at INGV, was activated in order to install a temporary seismic network integrated with the existing permanent network in the epicentral area. From August the 24th to the 30th, SISMIKO deployed eighteen seismic stations, generally six components (equipped with both velocimeter and accelerometer), with thirteen of the seismic station transmitting in real-time to the INGV seismic monitoring room in Rome. The design and geometry of the temporary network was decided in consolation with other groups who were deploying seismic stations in the region, namely EMERSITO (a group studying site-effects), and the emergency Italian strong motion network (RAN) managed by the National Civil Protection Department (DPC). Further 25 BB temporary seismic stations were deployed by colleagues of the British Geological Survey (BGS) and the School of Geosciences, University of Edinburgh in collaboration with INGV. All data acquired from SISMIKO stations, are quickly available at the European Integrated Data Archive (EIDA). The data acquired by the SISMIKO stations were included in the preliminary analysis that was performed by the Bollettino Sismico Italiano (BSI), the Centro Nazionale Terremoti (CNT) staff working in Ancona, and the INGV-MI, described below

Le attività del gruppo operativo INGV "SISMIKO" durante la sequenza sismica "Amatrice 2016",

SISMIKO è un gruppo operativo dell’Istituto Nazionale di Geofisica e Vulcanologia (INGV) che coordina tutte le Reti Sismiche Mobili INGVPublishedLecce3T. Sorgente sismica4T. Sismicità dell'Italia8T. Sismologia in tempo reale1SR TERREMOTI - Sorveglianza Sismica e Allerta Tsunami2SR TERREMOTI - Gestione delle emergenze sismiche e da maremoto3SR TERREMOTI - Attività dei Centr