Plasma miRNA-based signatures in CRC screening programs

Colorectal cancer (CRC) screening programs help diagnose cancer precursors and early cancers and help reduce CRC mortality. However, currently recommended tests, the fecal immunochemical test (FIT) and colonoscopy, have low uptake. There is therefore a pressing need for screening strategies that are minimally invasive and consequently more acceptable to patients, most likely blood based, to increase early CRC identification. MicroRNAs (miRNAs) released from cancer cells are detectable in plasma in a remarkably stable form, making them ideal cancer biomarkers. Using plasma samples from FIT-positive (FIT+) subjects in an Italian CRC screening program, we aimed to identify plasma circulating miRNAs that detect early CRC. miRNAs were initially investigated by quantitative real-time PCR in plasma from 60 FIT+ subjects undergoing colonoscopy at Fondazione IRCCS Istituto Nazionale dei Tumori, then tested on an internal validation cohort (IVC, 201 cases) and finally in a large multicenter prospective series (external validation cohort [EVC], 1121 cases). For each endoscopic lesion (low-grade adenoma [LgA], high-grade adenoma [HgA], cancer lesion [CL]), specific signatures were identified in the IVC and confirmed on the EVC. A two-miRNA-based signature for CL and six-miRNA signatures for LgA and HgA were selected. In a multivariate analysis including sex and age at blood collection, the areas under the receiver operating characteristic curve (95% confidence interval) of the signatures were 0.644 (0.607–0.682), 0.670 (0.626–0.714) and 0.682 (0.580–0.785) for LgA, HgA and CL, respectively. A miRNA-based test could be introduced into the FIT+ workflow of CRC screening programs so as to schedule colonoscopies only for subjects likely to benefit most.     

Results From a Large,Multicenter, Retrospective Analysis On Radium223 Use in Metastatic Castration-resistant Prostate Cancer (mCRPC) in the Triveneto Italian Region

Background

Radium 223 was introduced for metastatic castration-resistant prostate cancer based on the results of a randomized controlled trial showing risk reduction for death and skeletal events. Our aim was to evaluate the outcome of patients receiving radium 223 in a real-world setting.

The Italian multicenter experience with edaravone in amyotrophic lateral sclerosis

Journal of Neurology - The aim of the study is to analyze the ALS disease progression and respiratory function of Italian patients treated with edaravone (EVN), as well as the adherence to, and the...     

Nucleus–cytoplasm cross-talk in the aging brain

Aging is a primary risk factor for fatal neurodegenerative disorders, yet the mechanisms underlying physiological healthy aging and pathological aging, and how these mechanisms can divert one scenario to the other, are not completely understood. In recent years, reports indicate that alterations in nucleocytoplasmic transport may be a hallmark of both healthy and pathological aging. In this review, I summarize recent evidence supporting this information, specifically focusing on the association between the nucleocytoplasmic transport and aging of the brain, indicating both common and case-specific mechanisms and their interplay, and pointing out alterations of these mechanisms as regulatory “switches” for the fate of the aging brain. Importantly, some of these alterations are intervenable druggable targets, paving the way to a future pharmacotherapeutic intervention.     

Piezoelectric bone surgery for impacted lower third molar extraction compared with conventional rotary instruments: a systematic review,meta-analysis,and trial sequential analysis

The aim of this study was to evaluate whether piezoelectric bone surgery (PBS) for impacted lower third molar extraction reduces the surgical time and risk of intra- and postoperative complications in comparison with conventional rotary instruments. This meta-analysis followed the PRISMA guidelines and was registered in the PROSPERO database. The PubMed, Embase, Scopus, and OpenGrey databases were screened for articles published from January 1, 1990 to December 31, 2018. Selection criteria included randomized controlled trials (RCTs) comparing PBS with conventional rotary instruments for impacted lower third molar extraction and reporting any of the clinical outcomes (intra- and postoperative complications and duration of surgery) for both groups. A risk of bias assessment was performed using the Cochrane Collaboration tool. A meta-analysis was performed, and the power of the meta-analytic findings was assessed by trial sequential analysis (TSA). Strong evidence suggests that PBS prolongs the duration of surgery and low evidence suggests that PBS reduces postoperative morbidity (pain and trismus) in comparison with rotary instruments. Data were insufficient to determine whether PBS reduces neurological complications and postoperative swelling in comparison with burs.     

Enamel hypoplasia in coeliac children: a potential clinical marker of early diagnosis.

AIM: To assess at the scansion electron microscope (SEM) the structural aspects of enamel hypoplasia (EH) in coeliac disease (CD) with the aim to investigate our hypothesis of a possible significant difference between structural characteristics of EH in CD affected patients and EH of non-coeliac patients. If the presence of specific features of the EH associated with CD were demonstrated, these findings would represent for the dentist early non-invasive clinical markers of diagnosis of CD in case of suspected disease. METHODS: We analysed at SEM two samples of enamel fragments from hypoplasic teeth, both deciduous and permanent, harvested from 10 coeliac children (18 permanent teeth, 6 deciduous teeth; study group) and 10 non-coeliac children (16 permanent teeth, 4 deciduous teeth; control group) treated for dental caries, dental extractions for extensive caries lesions or deciduous teeth exfoliation. RESULTS: Significant structural differences were noted between EH of non-coeliac patients and same dental ? lesion in the group with CD. In the study group, EH defects were predominantly located on the central and lateral incisors, upper and lower, both deciduous and permanent, and on the first permanent molars, and were always simmetrical. EH of permanent teeth of CD affected patients was characterised by prisms more irregularly distributed with irregular margins and less interprismatic substance than observed in non-coeliac EH. The deciduous teeth of the study group showed shorter enamel prisms with a non-parallel direction up to convergence and less interprismatic substance than observed in the control group. CONCLUSION: This morphological analysis at SEM of the hypoplasic enamel defects of a group of coeliac children, the first published in literature, demonstrates that the EH of deciduous and permanent teeth in CD is highly hypomineralised with shorter prisms, more irregularly distributed and less interprismatic substance than observed in the non-coeliac EH. More data are needed to validate the significance OF our observations with the aim to assess if this simple, non-invasive microscopic analysis can be considered effective for the early identification of silent cases of CD that otherwise would not be diagnosed in the paediatric age.     

Liver Transplantations and Brain Dead Donors With Alcohol Abuse

Background and aim

Liver grafts from donors with chronic and active history of alcohol abuse are usually immediately ruled out for use in liver transplantation (LT). The aim of our study is to evaluate the use of those grafts.