Efficient Non-Viral Reprogramming of Myoblasts to Stemness with a Single Small Molecule to Generate Cardiac Progenitor Cells

The current protocols for generation of induced pluripotent stem (iPS) cells involve genome integrating viral vectors which may induce tumorgenesis. The aim of this study was to develop and optimize a non-viral method without genetic manipulation for reprogramming of skeletal myoblasts (SMs) using small molecules

Impact of immunochemotherapy with R-bendamustine or R-CHOP for treatment naïve advanced-stage follicular lymphoma: A subset analysis of the FOLL12 trial by Fondazione Italiana Linfomi

: We conducted a post hoc analysis of the FOLL12 trial to determine the impact of different initial immunochemotherapy (ICT) regimens on patient outcomes. Patients were selected from the FOLL12 trial, which included adults with stage II-IV follicular lymphoma (FL) grade 1-3a and high tumor burden. Patients were randomized 1:1 to receive either standard ICT followed by rituximab maintenance (RM) or the same ICT followed by a response-adapted approach. ICT consisted of rituximab-bendamustine (RB) or rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHOP), per physician's decision. A total of 786 patients were included in this analysis, 341 of whom received RB and 445 R-CHOP. RB was more frequently prescribed to older subjects, females, patients without bulky disease, and those with grade 1-2 FL. After a median of 56 months of follow-up, R-CHOP and RB had similar progression-free survival (PFS) (Hazard Ratio for RB 1.11, 95% CI 0.87-1.42, p = 0.392). Standard RM was associated with improved PFS compared to response-adapted management both after R-CHOP and RB. Grade 3-4 hematologic adverse events were more frequent with R-CHOP during induction treatment and more frequent with RB during RM. Grade 3-4 infections were more frequent with RB. RB was also associated with a higher incidence of transformed FL. R-CHOP and RB showed similar activity and efficacy, but with different safety profiles and long-term events, suggesting that the treating physician should carefully select the most appropriate chemotherapy regimen for each patient based on patient's individual characteristics, choices, and risk profile

Two novel missense mutations in EPOR gene causes erythrocytosis in two unrelated patients

Description of two novel EPOR mutations causing hyperactivity, increase proliferation, and differentation sustaining the erythrocytotic phenotype of the patient

Carta Geologica d'Italia alla scala 1:50.000 con note illustrative: Foglio 082 Asiago.

Il Foglio n. 082 ASIAGO della Carta Geologica d’Italia, alla scala 1:50.000, è stato realizzato nell’ambito del Progetto CARG (Legge 305/89), con una convenzione tra il Servizio Geologico Nazionale (ora APAT) e la Regione Veneto. La carta è stata realizzata dalla Regione Veneto e dal Dipartimento di Geologia, Paleontologia e Geofisica dell’Università degli Studi di Padova, con la collaborazione del personale delle citate strutture; per la Regione del Veneto (Segreteria all’Ambiente e Territorio, segretario regionale Roberto Casarin; Direzione Geologia e Attività Estrattive, dirigente regionale Andrea Costantini): F. Toffoletto responsabile del progetto, E. Schiavon direttore per la parte applicativa, coadiuvato da F. Mastellone; R. Campana responsabile dell’informatizzazione coadiuvato da V. Perna; per l’Università degli Studi di Padova: G. Barbieri coordinatore scientifico sostituito al suo pensionamento (1.10.2003) da P. Grandesso, già direttore di rilevamento. I rilievi geologici sono stati eseguiti da: G. Barbieri, R. Campana, M. Cucato, P. Gianolla, P. Grandesso, A. Guermani, B. Monopoli, G. Paiero, G. Roghi, A. Schiavo, G.L. Trombetta e D. Zampieri, con contributi di G. Dalla Valle, M. Franceschi, A. Gillarduzzi, M. Scarano, e M. Zannol. I sondaggi geognostici sono stati realizzati a cura del Servizio Forestale Regionale di Belluno (dirigente F. Cristofoletti coadiuvato da C. Gnech). Le Note Illustrative sono state curate da G. Barbieri e P. Grandesso, alla stesura delle quali hanno contribuito A. Zanferrari (basamento cristallino), V. De Zanche, P. Gianolla, G. Roghi (successioni permo-triassiche), M. Cucato (geologia del Quaternario), D. Zampieri (tettonica), W. Del Piero, P. Mietto, E. Schiavon (aspetti applicativi). 8 Il Foglio ricade quasi interamente nella Provincia di Vicenza e comprende territori dei Comuni di Arsiero, Asiago, Bassano del Grappa, Caltrano, Calvene, Campolongo sul Brenta, Cogollo del Cengio, Conco, Enego, Foza, Gallio, Lugo di Vicenza, Lusiana, Pedemonte, Roana, Rotzo, Tonezza del Cimone, Valdastico e Valstagna e parzialmente nella Provincia di Trento, nei Comuni di Borgo Valsugana, Grigno, Lavarone, Levico, Luserna. L’area studiata comprende in tutto o in parte le seguenti tavolette I.G.M., alla scala 1:25.000: “M. Verena”, “Rotzo”, “Arsiero”, “Conco”, “Caltrano”, “M. Lisser”, “Valstagna”, “Asiago”, “Cima Dodici”. Per i rilievi di campagna sono state utilizzate le sezioni della carta tecnica regionale, alla scala 1:10.000: “Cima Manderiolo”, “Cima Portule”, “Spitz Keserle”, “Passo della Forcellona”, “Cascina di Campovecchio”, “Monte Meatta”, “Monte Longara”, “Monte Tonderecar”, “Valdastico”, “Roana”, “Asiago”, “Valstagna”, “Arsiero”, “Cesuna”, “Monte Gusella” e “Conco”. I rilievi geologici sono stati eseguiti negli anni 2000-2003

Lenalidomide maintenance after autologous haematopoietic stem-cell transplantation in mantle cell lymphoma: results of a Fondazione Italiana Linfomi (FIL) multicentre, randomised, phase 3 trial

BACKGROUND: Fit patients with mantle cell lymphoma aged 18-65 years are usually given cytarabine and rituximab-based induction regimens followed by autologous haematopoetic stem-cell transplantation (HSCT). We investigated whether post-autologous HSCT maintenance with lenalidomide improves progression-free survival in this population.METHODS: This open-label, randomised, multicentre, phase 3 trial was done at 49 haematology and oncology units in Italy and Portugal. Eligible patients had Ann Arbor stage III or IV treatment-naive mantle cell lymphoma (or stage II plus bulky disease [ 655 cm] or B symptoms), and had evidence of cyclin D1 overexpression or the translocation t(11;14)(q13;q32). Patients were aged 18-59 years with Eastern Cooperative Oncology Group (ECOG) performance status 0-3, or aged 60-65 years with ECOG 0-2. After an optional prephase with vincristine and steroids (intravenous vincristine 1\ub74 mg/m2 on day 1, oral prednisone 100 mg [total dose] on days 1-5), patients were given three courses of R-CHOP (21-day cycle, intravenous rituximab 375 mg/m2 on day 1; intravenous doxorubicin 50 mg/m2, vincristine 1\ub74 mg/m2, and cyclophosphamide 750 mg/m2 on day 2; oral prednisone 100 mg/m2 on day 2-6). Patients then received one cycle of high-dose CTX (intravenous cyclophosphamide 4 g/m2 on day 1, intravenous rituximab 375 mg/m2 on day 4). After restaging, patients received two cycles of R-HD-cytarabine (high-dose intravenous cytarabine 2 g/m2 every 12 h on days 1-3, intravenous rituximab 375 mg/m2 on days 4 and 10). Patients with complete remission or partial remission proceeded to autologous HSCT and responding patients (complete remission or partial remission) with haematological recovery were randomly assigned (1:1) to receive 24 courses of oral lenalidomide maintenance (15 mg per day for patients with platelets >100\u2008*\u2008109 cells per L or 10 mg per day for platelets 60-100\u2008*\u2008109 cells per L, days 1-21 every 28 days) for 24 months, or observation. The primary endpoint was progression-free survival, measured in the randomised population. This study is registered with EudraCT (2009-012807-25) and ClinicalTrials.gov (NCT02354313).FINDINGS: Between May 4, 2010, and Aug 24, 2015, 303 patients were screened for inclusion and 300 patients were enrolled (median age 57 years, IQR 51-62; 235 [78%] male). 95 patients were excluded before randomisation, mostly due to disease progression, adverse events, and inadequate recovery. 104 patients were randomly assigned to the lenalidomide maintenance group and 101 patients to the observation group. 11 (11%) of 104 patients assigned to lenalidomide did not start treatment (3 withdrew, 6 adverse events or protocol breach, 2 lost to follow-up). At a median follow-up of 38 months after randomisation (IQR 24-50), 3-year progression-free survival was 80% (95% CI 70-87) in the lenalidomide group versus 64% (53-73) in the observation group (log-rank test p=0\ub7012; hazard ratio 0\ub751, 95% CI 0\ub730-0\ub787). 41 (39%) of 104 patients discontinued lenalidomide for reasons including death or progression. Treatment-related deaths were recorded in two (2%) of 93 patients in the lenalidomide group (1 pneumonia, 1 thrombotic thrombocytopenic purpura), and one (1%) of 101 in the observation group (pneumonia). 59 (63%) of 93 patients in the lenalidomide group had grade 3-4 haematological adverse events versus 12 (12%) of 101 patients in the observation group (p<0\ub70001). 29 (31%) of 93 patients in the lenalidomide group and eight (8%) of 101 patients in the observation group had grade 3-4 non-haematological adverse events (p<0\ub70001), of which infections were the most common.Serious adverse events were reported in 22 (24%) of 93 patients in the lenalidomide group and five (5%) of 101 patients in the observation group. Pneumonia and other infections were the most common serious adverse events.INTERPRETATION: Despite non-negligibile toxicity, lenalidomide after autologous HSCT improved progression-free survival in patients with mantle cell lymphoma, highlighting the role of maintenance in mantle cell lymphoma.FUNDING: Fondazione Italiana Linfomi and Celgene

Efficacy of a new nutraceutical formulation: L-tryptophan, probiotics, charcoal, chamomile, mint, and licorice (COLONIR®) in the improvement of gastrointestinal symptoms in subjects with irritable bowel syndrome

Background: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders. IBS is characterized by recurrent chronic abdominal pain and altered bowel habits in the absence of organic damage. Although there are reviews and guidelines for treating IBS, the complexity and diversity of IBS presentation make treatment difficult. Treatment of IBS focuses on relieving symptoms as mild signs and symptoms can often be controlled by managing stress and by making changes in diet and lifestyle. The use of nutraceutical compounds has been advocated as a possible alternative treatment in patients with IBS. COLONIR® (Omega Pharma Srl, Milan, Italy) may be an alternative or adjuvant treatment in patients with gastrointestinal symptoms. This study aimed to evaluate the effect of this new nutraceutical formulation in inducing symptoms remission and improve gastrointestinal habits. Methods: An initial cohort of 1004 consecutive patients referred to 25 different Units of Internal Medicine a/o Gastroenterology in Italy to perform colonoscopy for intestinal symptoms was asked to participate. Patients were treated for 2 months with three doses of nutraceuticals/day after meals namely COLONIR®. Patients were assessed at baseline and after 2 months to evaluate the frequency and severity of gastrointestinal symptoms in the past seven days with a questionnaire based on ROMA IV criteria. Results: After 2 months, 899 patients completed the follow-up. COLONIR® achieved a statistically significant reduction of severity of symptoms in the study population without any documented side effects. Conclusions: These promising results, here reported, need to be confirmed, valuating the efficacy of COLONIR® in relieving gastrointestinal symptoms in IBS patients in further studies

Ibrutinib improves survival compared with chemotherapy in mantle cell lymphoma with central nervous system relapse

Central nervous system (CNS) relapse of mantle cell lymphoma (MCL) is a rare phenomenon with dismal prognosis, where no standard therapy exists. Since the covalent Bruton tyrosine kinase (BTK) inhibitor ibrutinib is effective in relapsed/refractory MCL and penetrates the blood–brain barrier (BBB), on behalf of Fondazione Italiana Linfomi and European Mantle Cell Lymphoma Network we performed a multicenter retrospective international study to investigate the outcomes of patients treated with ibrutinib or chemoimmunotherapy. In this observational study, we recruited patients with MCL with CNS involvement at relapse who received CNS-directed therapy between 2000 and 2019. The primary objective was to compare the overall survival (OS) of patients treated with ibrutinib or BBB crossing chemotherapy. A propensity score based on a multivariable binary regression model was applied to balance treatment cohorts. Eighty-eight patients were included. The median age at study entry was 65 years (range, 39-87), 76% were males, and the median time from lymphoma diagnosis to CNS relapse was 16 months (range, 1-122). Patients were treated with ibrutinib (n = 29, ibrutinib cohort), BBB crossing chemotherapy (ie, high-dose methotrexate ± cytarabine; n = 29, BBB cohort), or miscellaneous treatments (n = 30, other therapy cohort). Both median OS (16.8 vs 4.4 months; P =.007) and median progression-free survival (PFS) (13.1 vs 3.0 months; P =.009) were superior in the ibrutinib cohort compared with the BBB cohort. Multivariable Cox regression model revealed that ibrutinib therapeutic choice was the strongest independent favorable predictive factor for both OS (hazard ratio [HR], 6.8; 95% confidence interval [CI], 2.2-21.3; P 24 months from first MCL diagnosis (HR for death, 2.4; 95% CI, 1.1-5.3; P =.026; HR for death or progression, 2.3; 95% CI, 1.1-4.6; P =.023). The addition of intrathecal (IT) chemotherapy to systemic CNS-directed therapy was not associated with superior OS (P =.502) as the morphological variant (classical vs others, P =.118). Ibrutinib was associated with superior survival compared with BBB-penetrating chemotherapy in patients with CNS relapse of MCL and should be considered as a therapeutic option