Long-term follow-up of Philadelphia chromosome-positive (Ph+) chronic myeloid leukaemia (CML) in children and adolescents managed at a single institution over a 20-year period

Chronic myeloid leukaemia (CML) is rare in childhood. In our Institution we managed 30 consecutive Ph+CML patients aged <18 years, according to our adults’ guidelines. Patients with HLA-identical related donor (RD) underwent stem cell transplant (SCT). Since 1989, patients without RD were systematically treated with -interferon (IFN) (median dosage: 6 MU/day). Of 18/19 evaluable patients, 17 (94.5%) achieved haematologic response (HR), 11/17 (65%) cytogenetic response (CyR), complete (CCyR) in 4 (23.5%). Three patients remain in CCyR, 2 achieved BCR-ABL transcript disappearance. Of 13 patients without CCyR, 5 underwent SCT, 4 switched to STI571, 4 progressed. All patients receiving STI571 in chronic phase (CP) obtained sustained CCyR and 3 a persistent molecular response. 8-year survival among IFN-treated patients, censored or not for subsequent therapies, is 62% and 63%. Overall, 13/30 patients underwent SCT: 5 HLA-identical-RD, 5 matched unrelated donor, 2 mismatched-RD, 1 unrelated mismatched umbilical cord blood. Eight allotransplanted patients (6/6 in 1st CP) are in cytogenetic and molecular remission with 8-year survival of 61% from SCT and 69% from diagnosis. In our 20-year experience, the use of IFN in children without matched RD led to prolonged cytogenetic and molecular responses and long-term survival, without impairing the outcome of subsequent SCT

Implant insertion torque value in immediate loading : a retrospective study

The aim of this study is to verify if the Insertion Torque Value (ITV) of 32 Ncm for immediate loading protocol (ILP), as indicated by literature, is still, with the advance in implant research, a real significant cut-off for long-term implant survival. In this retrospective study, data from 224 patients that during three years of clinical practice, were submitted to the insertion of 322 implants with immediate loading protocol, have been recorded, pooled and analyzed. Data were organized based on Insertion Torque Value (ITV): > 32 Ncm (CG) and 32 Ncm are still characterized by a lower crestal bone resorption, there are no statistically significant differences among the two groups for what concerning the failure rate during the 2 years of follow-up and OR. These results permit us to suppose that the cut-off of ITV >32 Ncm for immediate loading implants, could be reduced to inferior values. However further studies are necessary to indicate precise clinical guidelines

Private equity and venture capital in Italy

This paper examines private equity and venture capital in Italy. The first part looks at the main features of the Italian market and its recent evolution; the second part considers the results of a survey of firms and intermediaries designed to gather information regarding contract features and the characteristics of investee firms and investing intermediaries. Finally, the paper discusses the main obstacles to the development of the sector using information from the survey of intermediaries.private equity, venture capital

Standardization of body composition status in patients with advanced urothelial tumors: the role of a CT-based aI-powered software for the assessment of sarcopenia and patient outcome correlation

Background: Sarcopenia is a well know prognostic factor in oncology, influencing patients' quality of life and survival. We aimed to investigate the role of sarcopenia, assessed by a Computed Tomography (CT)-based artificial intelligence (AI)-powered-software, as a predictor of objective clinical benefit in advanced urothelial tumors and its correlations with oncological outcomes. Methods: We retrospectively searched patients with advanced urothelial tumors, treated with systemic platinum-based chemotherapy and an available total body CT, performed before and after therapy. An AI-powered software was applied to CT to obtain the Skeletal Muscle Index (SMI-L3), derived from the area of the psoas, long spine, and abdominal muscles, at the level of L3 on CT axial images. Logistic and Cox-regression modeling was implemented to explore the association of sarcopenic status and anthropometric features to the clinical benefit rate and survival endpoints. Results: 97 patients were included, 66 with bladder cancer and 31 with upper-tract urothelial carcinoma. Clinical benefit outcomes showed a linear positive association with all the observed body composition variables variations. The chances of not experiencing disease progression were positively associated with ∆_SMI-L3, ∆_psoas, and ∆_long spine muscle when they ranged from ~10-20% up to ~45-55%. Greater survival chances were matched by patients achieving a wider ∆_SMI-L3, ∆_abdominal and ∆_long spine muscle. Conclusions: A CT-based AI-powered software body composition and sarcopenia analysis provide prognostic assessments for objective clinical benefits and oncological outcomes

The clinical efficacy of nitrofurantoin for treating uncomplicated urinary tract infection in adults: a systematic review of randomized control trials

OBJECTIVE: To provide an updated systematic review of randomized control trials (RCTs) to investigate the clinical and microbiological efficacy of nitrofurantoin compared to other antibiotics or placebo for treatment of uncomplicated urinary tract infections (uUTI). A secondary aim is to assess whether nitrofurantoin use is associated with increased side effects compared to other treatment regimens.SUMMARY: The review was performed according to PRISMA guidelines. We searched 4 databases for articles published from database inception to May 6, 2020: (1) PubMed electronic database of the National Library of Medicine, (2) Web of Science, (3) Embase, and (4) Cochrane Library. Nine RCTs were selected for the review. RCTs were a mixture of double-blind, single-blind, and open-label trials. The most common comparators were trimethoprim-sulfamethoxazole and fosfomycin tromethamine. Overall study quality was poor with a high risk of bias. The clinical cure rates in nitrofurantoin ranged from 51 to 94% depending on the length of follow-up, and bacteriological cure rates ranged from 61 to 92%. Overall the evidence suggests that nitrofurantoin is at least comparable with other uUTI treatments in terms of efficacy. Patients taking nitrofurantoin reported fewer side effects than other drugs and the most commonly reported were gastrointestinal and central nervous system symptoms. Key Messages: Evidence on the clinical and bacteriological efficacy of nitrofurantoin is sparse, with a lack of new data, and hampered by high risk of bias. Although no firm conclusions can be made on the current base of evidence, the studies generally suggest that nitrofurantoin is at least comparable to other common uUTI treatments in terms of clinical and bacteriological cure. More robust research with well-designed double-blinded RCTs is needed

Strong Double Higgs Production at the LHC

The hierarchy problem and the electroweak data, together, provide a plausible motivation for considering a light Higgs emerging as a pseudo-Goldstone boson from a strongly-coupled sector. In that scenario, the rates for Higgs production and decay differ significantly from those in the Standard Model. However, one genuine strong coupling signature is the growth with energy of the scattering amplitudes among the Goldstone bosons, the longitudinally polarized vector bosons as well as the Higgs boson itself. The rate for double Higgs production in vector boson fusion is thus enhanced with respect to its negligible rate in the SM. We study that reaction in pp collisions, where the production of two Higgs bosons at high pT is associated with the emission of two forward jets. We concentrate on the decay mode hh -> WW^(*)WW^(*) and study the semi-leptonic decay chains of the W's with 2, 3 or 4 leptons in the final states. While the 3 lepton final states are the most relevant and can lead to a 3 sigma signal significance with 300 fb^{-1} collected at a 14 TeV LHC, the two same-sign lepton final states provide complementary information. We also comment on the prospects for improving the detectability of double Higgs production at the foreseen LHC energy and luminosity upgrades.Comment: 54 pages, 26 figures. v2: typos corrected, a few comments and one table added. Version published in JHE

A Clinical Prognostic Model Based on Machine Learning from the Fondazione Italiana Linfomi (FIL) MCL0208 Phase III Trial

BACKGROUND Multicenter clinical trials are producing growing amounts of clinical data. Machine Learning (ML) might facilitate the discovery of novel tools for prognostication and disease-stratification. Taking advantage of a systematic collection of multiple variables, we developed a model derived from data collected on 300 patients with mantle cell lymphoma (MCL) from the Fondazione Italiana Linfomi-MCL0208 phase III trial (NCT02354313). METHODS We developed a score with a clustering algorithm applied to clinical variables. The candidate score was correlated to overall survival (OS) and validated in two independent data series from the European MCL Network (NCT00209222, NCT00209209); Results: Three groups of patients were significantly discriminated: Low, Intermediate (Int), and High risk (High). Seven discriminants were identified by a feature reduction approach: albumin, Ki-67, lactate dehydrogenase, lymphocytes, platelets, bone marrow infiltration, and B-symptoms. Accordingly, patients in the Int and High groups had shorter OS rates than those in the Low and Int groups, respectively (Int→Low, HR: 3.1, 95% CI: 1.0-9.6; High→Int, HR: 2.3, 95% CI: 1.5-4.7). Based on the 7 markers, we defined the engineered MCL international prognostic index (eMIPI), which was validated and confirmed in two independent cohorts; Conclusions: We developed and validated a ML-based prognostic model for MCL. Even when currently limited to baseline predictors, our approach has high scalability potential

A Clinical Prognostic Model Based on Machine Learning from the Fondazione Italiana Linfomi (FIL) MCL0208 Phase III Trial

SIMPLE SUMMARY: The interest in using Machine-Learning (ML) techniques in clinical research is growing. We applied ML to build up a novel prognostic model from patients affected with Mantle Cell Lymphoma (MCL) enrolled in a phase III open-labeled, randomized clinical trial from the Fondazione Italiana Linfomi (FIL)—MCL0208. This is the first application of ML in a prospective clinical trial on MCL lymphoma. We applied a novel ML pipeline to a large cohort of patients for which several clinical variables have been collected at baseline, and assessed their prognostic value based on overall survival. We validated it on two independent data series provided by European MCL Network. Due to its flexibility, we believe that ML would be of tremendous help in the development of a novel MCL prognostic score aimed at re-defining risk stratification. ABSTRACT: Background: Multicenter clinical trials are producing growing amounts of clinical data. Machine Learning (ML) might facilitate the discovery of novel tools for prognostication and disease-stratification. Taking advantage of a systematic collection of multiple variables, we developed a model derived from data collected on 300 patients with mantle cell lymphoma (MCL) from the Fondazione Italiana Linfomi-MCL0208 phase III trial (NCT02354313). Methods: We developed a score with a clustering algorithm applied to clinical variables. The candidate score was correlated to overall survival (OS) and validated in two independent data series from the European MCL Network (NCT00209222, NCT00209209); Results: Three groups of patients were significantly discriminated: Low, Intermediate (Int), and High risk (High). Seven discriminants were identified by a feature reduction approach: albumin, Ki-67, lactate dehydrogenase, lymphocytes, platelets, bone marrow infiltration, and B-symptoms. Accordingly, patients in the Int and High groups had shorter OS rates than those in the Low and Int groups, respectively (Int→Low, HR: 3.1, 95% CI: 1.0–9.6; High→Int, HR: 2.3, 95% CI: 1.5–4.7). Based on the 7 markers, we defined the engineered MCL international prognostic index (eMIPI), which was validated and confirmed in two independent cohorts; Conclusions: We developed and validated a ML-based prognostic model for MCL. Even when currently limited to baseline predictors, our approach has high scalability potential

Combined Large Cell Neuroendocrine Carcinomas of the Lung: Integrative Molecular Analysis Identifies Subtypes with Potential Therapeutic Implications

Combined large cell neuroendocrine carcinoma (CoLCNEC) is given by the association of LCNEC with adeno or squamous or any non-neuroendocrine carcinoma. Molecular bases of CoLCNEC pathogenesis are scant and no standardized therapies are defined