Catholic University of the Sacred Heart

About: Catholic University of the Sacred Heart is a education organization based out in Milan, Lombardia, Italy. It is known for research contribution in the topics: Population & Medicine. The organization has 13592 authors who have published 31048 publications receiving 853961 citations.

Prevalence of mutations in LEP, LEPR, and MC4R genes in individuals with severe obesity.

Abstract: Obesity is a major public health concern; despite evidence of high heritability, the genetic causes of obesity remain unclear. In this study, we assessed the presence of mutations in three genes involved in the hypothalamic leptin-melanocortin regulation pathway (leptin, LEP; leptin receptor, LEPR; and melanocortin-4 receptor, MC4R), which is important for energy homeostasis in the body, in a group of patients with severe obesity. For this study, we selected 77 patients who had undergone bariatric surgery and had a pre-operative body mass index (BMI) >35 kg/m2, early onset and a family history of being overweight. Candidate genes were screened by direct sequence analysis to search for rare genetic variations. The common LEP -2548 G/A polymorphism was also evaluated for its influence on the BMI (in obesity patients) and for obesity risk, using a case-control study involving 117 healthy individuals. Two different non-synonymous alterations in MC4R were found in two patients: the p.(Thr112Met), previously described in the literature as a probable gene involved in the obesity phenotype, and the novel p.(Tyr302Asp) variant, predicted to be pathogenic by in silico evaluations and family segregation studies. The LEP -2548 G/A polymorphism was not associated with the BMI or obesity risk. In conclusion, we have reported a novel mutation in MC4R in a family of Italian patients with severe obesity. Screening for MC4R could be important for directing the carriers of mutations towards therapy including partial agonists of the MC4R that could normalize their appetite and inhibit compulsive eating. Next-generation sequencing could be used to clarify the genetic basis of obesity in the future.

Philadelphia chromosome-negative classical myeloproliferative neoplasms: Revised management recommendations from European LeukemiaNet

Abstract: This document updates the recommendations on the management of Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-neg MPNs) published in 2011 by the European LeukemiaNet (ELN) consortium. Recommendations were produced by multiple-step formalized procedures of group discussion. A critical appraisal of evidence by using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology was performed in the areas where at least one randomized clinical trial was published. Seven randomized controlled trials provided the evidence base; earlier phase trials also informed recommendation development. Key differences from the 2011 diagnostic recommendations included: lower threshold values for hemoglobin and hematocrit and bone marrow examination for diagnosis of polycythemia vera (PV), according to the revised WHO criteria; the search for complementary clonal markers, such as ASXL1, EZH2, IDH1/IDH2, and SRSF2 for the diagnosis of myelofibrosis (MF) in patients who test negative for JAK2V617, CALR or MPL driver mutations. Regarding key differences of therapy recommendations, both recombinant interferon alpha and the JAK1/JAK2 inhibitor ruxolitinib are recommended as second-line therapies for PV patients who are intolerant or have inadequate response to hydroxyurea. Ruxolitinib is recommended as first-line approach for MF-associated splenomegaly in patients with intermediate-2 or high-risk disease; in case of intermediate-1 disease, ruxolitinib is recommended in highly symptomatic splenomegaly. Allogeneic stem cell transplantation is recommended for transplant-eligible MF patients with high or intermediate-2 risk score. Allogeneic stem cell transplantation is also recommended for transplant-eligible MF patients with intermediate-1 risk score who present with either refractory, transfusion-dependent anemia, blasts in peripheral blood > 2%, adverse cytogenetics, or high-risk mutations. In these situations, the transplant procedure should be performed in a controlled setting.

Papillary cannulation and sphincterotomy techniques at ERCP: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline

Abstract: This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It provides practical advice on how to achieve successful cannulation and sphincterotomy at minimum risk to the patient. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence. Main recommendations 1 ESGE suggests that difficult biliary cannulation is defined by the presence of one or more of the following: more than 5 contacts with the papilla whilst attempting to cannulate; more than 5 minutes spent attempting to cannulate following visualization of the papilla; more than one unintended pancreatic duct cannulation or opacification (low quality evidence, weak recommendation). 2 ESGE recommends the guidewire-assisted technique for primary biliary cannulation, since it reduces the risk of post-ERCP pancreatitis (moderate quality evidence, strong recommendation). 3 ESGE recommends using pancreatic guidewire (PGW)-assisted biliary cannulation in patients where biliary cannulation is difficult and repeated unintentional access to the main pancreatic duct occurs (moderate quality evidence, strong recommendation). ESGE recommends attempting prophylactic pancreatic stenting in all patients with PGW-assisted attempts at biliary cannulation (moderate quality evidence, strong recommendation). 4 ESGE recommends needle-knife fistulotomy as the preferred technique for precutting (moderate quality evidence, strong recommendation). ESGE suggests that precutting should be used only by endoscopists who achieve selective biliary cannulation in more than 80 % of cases using standard cannulation techniques (low quality evidence, weak recommendation). When access to the pancreatic duct is easy to obtain, ESGE suggests placement of a pancreatic stent prior to precutting (moderate quality evidence, weak recommendation). 5 ESGE recommends that in patients with a small papilla that is difficult to cannulate, transpancreatic biliary sphincterotomy should be considered if unintentional insertion of a guidewire into the pancreatic duct occurs (moderate quality evidence, strong recommendation). In patients who have had transpancreatic sphincterotomy, ESGE suggests prophylactic pancreatic stenting (moderate quality evidence, strong recommendation). 6 ESGE recommends that mixed current is used for sphincterotomy rather than pure cut current alone, as there is a decreased risk of mild bleeding with the former (moderate quality evidence, strong recommendation). 7 ESGE suggests endoscopic papillary balloon dilation (EPBD) as an alternative to endoscopic sphincterotomy (EST) for extracting CBD stones 8 ESGE does not recommend routine biliary sphincterotomy for patients undergoing pancreatic sphincterotomy, and suggests that it is reserved for patients in whom there is evidence of coexisting bile duct obstruction or biliary sphincter of Oddi dysfunction (moderate quality evidence, weak recommendation). 9 In patients with periampullary diverticulum (PAD) and difficult cannulation, ESGE suggests that pancreatic duct stent placement followed by precut sphincterotomy or needle-knife fistulotomy are suitable options to achieve cannulation (low quality evidence, weak recommendation). ESGE suggests that EST is safe in patients with PAD. In cases where EST is technically difficult to complete as a result of a PAD, large stone removal can be facilitated by a small EST combined with EPBD or use of EPBD alone (low quality evidence, weak recommendation). 10 For cannulation of the minor papilla, ESGE suggests using wire-guided cannulation, with or without contrast, and sphincterotomy with a pull-type sphincterotome or a needle-knife over a plastic stent (low quality evidence, weak recommendation). When cannulation of the minor papilla is difficult, ESGE suggests secretin injection, which can be preceded by methylene blue spray in the duodenum (low quality evidence, weak recommendation). 11 In patients with choledocholithiasis who are scheduled for elective cholecystectomy, ESGE suggests intraoperative ERCP with laparoendoscopic rendezvous (moderate quality evidence, weak recommendation). ESGE suggests that when biliary cannulation is unsuccessful with a standard retrograde approach, anterograde guidewire insertion either by a percutaneous or endoscopic ultrasound (EUS)-guided approach can be used to achieve biliary access (low quality evidence, weak recommendation). 12 ESGE suggests that in patients with Billroth II gastrectomy ERCP should be performed in referral centers, with the side-viewing endoscope as a first option; forward-viewing endoscopes are the second choice in cases of failure (low quality evidence, weak recommendation). A straight standard ERCP catheter or an inverted sphincterotome, with or without the guidewire, is recommended by ESGE for biliopancreatic cannulation in patients who have undergone Billroth II gastrectomy (low quality evidence, strong recommendation). Endoscopic papillary ballon dilation (EPBD) is suggested as an alternative to sphincterotomy for stone extraction in the setting of patients with Billroth II gastrectomy (low quality evidence, weak recommendation). In patients with complex post-surgical anatomy ESGE suggests referral to a center where device-assisted enteroscopy techniques are available (very low quality evidence, weak recommendation).