The Gastropack Access System as a Model to Access Gastroenterology Services for Gastroscopy Appropriateness in Patients with Upper Gastrointestinal Symptoms: A Comparison with the Open Access System

Esophagogastroduodenoscopy (EGD) appropriateness in Open-Access System (OAS) is a relevant issue. The Gastropack Access System (GAS) is a new system to access gastroenterological services, based on the partnership between Gastroenterologists and GPs. This study aims to evaluate if GAS is superior to OAS in terms of EGDS appropriateness. Secondarily, we evaluated the diagnostic yield of EGDS according to ASGE guidelines. The GAS was developed in an area of Bologna where General Practitioners (GPs) could decide to directly prescribe EGDS through OAS or referring to GAS, where EGDS can be scheduled after contact between GPs and specialists sharing a patient’s clinical information. Between 2016 and 2019, 2179 cases (M:F = 861:1318, median age 61, IQR 47.72) were referred to GAS and 1467 patients (65%) had a prescription for EGDS; conversely, 874 EGDS were prescribed through OAS (M:F = 383:491; median age 58 yrs, IQR 45.68). Indication was appropriate in 92% in GAS (1312/1424) versus 71% in OAS (618/874), p < 0.001. The rate of clinically significant endoscopic findings (CSEF) was significantly higher in GAS (49% vs. 34.8%, p < 0.001). Adherence to ASGE guidelines was not related to CSEF; however, surveillance for pre-malignant conditions was independently related to CSEF. All neoplasm were observed in appropriate EGD. GAS is an innovative method showing extremely high rates of appropriateness. ASGE guidelines confirmed their validity for cancer detection, but their performance for the detection of other conditions needs to be refined

Neurofibromatosis 1 - mutant microglia exhibit sexually-dimorphic cyclic AMP-dependent purinergic defects

As critical regulators of brain homeostasis, microglia are influenced by numerous factors, including sex and genetic mutations. To study the impact of these factors on microglia biology, we employed genetically engineered mice that model Neurofibromatosis type 1 (NF1), a disorder characterized by clinically relevant sexually dimorphic differences. While microglia phagocytic activity was reduced in both male and female heterozygous Nf1 mutant (Nf1+/-) mice, purinergic control of phagocytosis was only affected in male Nf1+/- mice. ATP-induced P2Y-mediated membrane currents and P2RY12-dependent laser lesion-induced accumulation of microglial processes were also only impaired in male, but not female Nf1+/-, microglia. These defects resulted from Nf1+/- male-specific defects in cyclic AMP regulation, rather than from changes in purinergic receptor expression. Cyclic AMP elevation by phosphodiesterase blockade restored the male Nf1+/- microglia defects in P2Y-dependent membrane currents and process motility. Taken together, these data establish a sex-by-genotype interaction important to microglia function in the adult mouse brain

RNA delivery by extracellular vesicles in mammalian cells and its applications.

The term 'extracellular vesicles' refers to a heterogeneous population of vesicular bodies of cellular origin that derive either from the endosomal compartment (exosomes) or as a result of shedding from the plasma membrane (microvesicles, oncosomes and apoptotic bodies). Extracellular vesicles carry a variety of cargo, including RNAs, proteins, lipids and DNA, which can be taken up by other cells, both in the direct vicinity of the source cell and at distant sites in the body via biofluids, and elicit a variety of phenotypic responses. Owing to their unique biology and roles in cell-cell communication, extracellular vesicles have attracted strong interest, which is further enhanced by their potential clinical utility. Because extracellular vesicles derive their cargo from the contents of the cells that produce them, they are attractive sources of biomarkers for a variety of diseases. Furthermore, studies demonstrating phenotypic effects of specific extracellular vesicle-associated cargo on target cells have stoked interest in extracellular vesicles as therapeutic vehicles. There is particularly strong evidence that the RNA cargo of extracellular vesicles can alter recipient cell gene expression and function. During the past decade, extracellular vesicles and their RNA cargo have become better defined, but many aspects of extracellular vesicle biology remain to be elucidated. These include selective cargo loading resulting in substantial differences between the composition of extracellular vesicles and source cells; heterogeneity in extracellular vesicle size and composition; and undefined mechanisms for the uptake of extracellular vesicles into recipient cells and the fates of their cargo. Further progress in unravelling the basic mechanisms of extracellular vesicle biogenesis, transport, and cargo delivery and function is needed for successful clinical implementation. This Review focuses on the current state of knowledge pertaining to packaging, transport and function of RNAs in extracellular vesicles and outlines the progress made thus far towards their clinical applications

Liver transplantation and recurrence of Hepatitis C

Il capitolo tratta delle indicazioni al trapianto di fegato per epatite C e della recidiva della patologia dopo il trapianto stesso

A RETROSPECTIVE STUDY ON INTRAHEPATIC CHOLESTASIS OF PREGNANCY: MARKERS OF PREMATURE DELIVERY

Background: Intrahepatic Cholestasis of Pregnancy (ICP) carries with it a higher frequency of premature delivery (20 to 60%), a marker ofperinatal morbility/mortality. Therefore, it is important to identify markers of premature delivery. Aim: To retrospectively evaluate, in a large case study, the presence of markers predictive of premature delivery. Materials and Methods: Clinical records of all patients diagnosed with ICP in Policlinic S.Orsola-Malpighi (Bologna, Italy) from January 2001 until December 2007 have been collected. For all patients the following informations were available: subjective pruritus evaluation, standard biochemical parameters, serum bile acids (BA) determination, abdomen ultrasonography and APGAR index. From diagnosis until a week after delivery, biochemistry and fetal health have been controlled weekly. Student\u2019s t Test, Mann-Whitney, Pearson\u2019s correlation test and a stepwiselogistic regression analysis were performed as appropriate. Results: 169 clinical records have been gathered. Patients with premature delivery, compared to those who delivered closer to term, presented a significantly earlier appearance of pruritus (r = 0.4858) and higher levels of chenodeoxycholic acid (r = −0.2835). No significant differences were observed for APGAR index and rate of fetal complications according to treatment and time of delivery. Two fetal deaths occurred (fetal infection by Parvovirus B19 and haemolysis for ABO incompatibility) before week 34 with serum BA below 20 mM/l. According to the multivariate analysis, the only variable associated with preterm delivery is the early onset of cholestasis, that exposes to a risk twice than normal (OR = 2.044; 95% CI 1.40−2.98; p = 0.0002). Conclusions: The strongest predictor of premature delivery in our population is the time of onset of pruritus with an OR of 2.044