👤 Stefano Brunelli

Evaluate the association between functional recovery and a panel of specific neuronal biomarkers, in a cohort of stroke patients. Serum levels of neuronal specific enolase (NSE), neurofilament light chain (NfL), brain derived neurotrophic factor (BDNF), amyloid-β Linear regression was performed to predict changes in clinical scales during follow up, according to baseline biomarkers levels. NSE at T0 was a significant predictor of improvement in FAC and RMI, where the higher the NSE concentration, the smaller the improvement. Therefore, baseline NSE explained 39% of the variation in FAC and 31% in RMI over time. No significant differences were observed with respect to other scales or other biomarkers. This exploratory study suggested that serum NSE may be a predictor of functional mobility recovery in post-acute stroke patients and represents a useful tool for patients' stratification. Show less

The pancreatic microenvironment has a defensive role against cancer but it can acquire tumor-promoting properties triggered by multiple mechanisms including alterations in the equilibrium between proteases and their inhibitors. The identification of proteolytic events, targets and pathways would set the basis for the design of new therapeutic approaches. Here we demonstrate that spheroids isolated from human and murine healthy pancreas and co-transplanted orthotopically with pancreatic ductal adenocarcinoma (PDAC) in mouse pancreas inhibited tumor growth. The effect was mediated by trypsin-generated fibronectin (FN) fragments released by pancreatic spheroids. Tumor inhibition was observed also in a model of acute pancreatitis associated with trypsin activation. Mass spectrometry proteomic analysis of fragments and mAb against different FN epitopes identified the FN type III domain as responsible for the activity. By inhibiting integrin α5β1, FAK and FGFR1 signaling, the fragments induced tumor cell detachment and reduced cell proliferation. Consistent with the mutual relationship between the two pathways, FGF2 restored both FGFR1 and FAK signaling and promoted PDAC cell adhesion and proliferation. FAK and FGFR inhibitors additively inhibited PDAC growth in vitro and in orthotopic in vivo models. This study identifies a novel role for pancreatic trypsin and fibronectin cleavage as a mechanism of protection against cancer by the pancreatic microenvironment. The finding of a FAK-FGFR cross-talk in PDAC support the combination of FAK and FGFR inhibitors for PDAC treatment to emulate the protective effect of the normal pancreas against cancer. Show less

Acute hyperlipidaemic pancreatitis (HP) may develop in pregnancy in patients with genetic predisposition. There are no accepted guidelines for the management of this rare but life-threatening condition in pregnancy. Plasma exchange (PEX) was suggested as a suitable option to treat HP in pregnancy; however, further evidence from case reports/case series are needed. Three PEX procedures (2000 ml of plasma replaced with 5% albumin) were performed in one week in a pregnant patient at 25 weeks of gestational age with severe HP. Triglyceride related genes (LPL, APOA5, APOE, GPIHBP1, GPD1, LMF1, CREB3L3) were screened by DNA sequencing. Medline and Embase databases were searched electronically in January 2018 using different combinations of the relevant medical subject headings for "pancreatitis in pregnancy" and "therapeutic apheresis". Gene profiling assessed a combined heterozygous state for the variants pSer19Trp of the APOA5 gene and pCys130Arg of the APOE (allele E4) gene. PEX led to significant and progressive reduction of triglyceride plasma levels along with cholesterol and C-reactive protein. Meanwhile a fast improvement of pregnant clinical condition was observed. This allowed the delivery at term of a healthy newborn without gestational complications. An outcome hardly achievable in patients managed exclusively by a pharmacological approach. PEX led to a positive maternal outcome in absence of foetal and gestational complications in a case of severe HP in pregnancy. As clinical trials are lacking, case reports still represent the best way to reasonably implement clinical management of this rare but life-threatening disease. Show less