Biliary phosphatidylcholine and lysophosphatidylcholine profiles in sclerosing cholangitis

AIM:To analyze phospholipid profiles in intrahepatic bile from patients with primary sclerosing cholangitis(PSC)and secondary sclerosing cholangitis(SSC).METHODS:Intrahepatic bile specimens collected via endoscopic retrograde cholangiography from 41 patients were analyzed.Fourteen of these patients were diagnosed with PSC,10 with SSC,11 with choledocholithiasis or no identifiable biliary disease,and 6 with cholangiocellular carcinoma(CCC).Bile acid,cholesterol,protein,and bilirubin contents as well as pancreas lipase activity in bile were determined by biochemical methods.Phosphatidylcholine(PC)and lysophosphatidylcholine(LPC)species were quantified using nanoelectrospray ionization tandem mass spectrometry.RESULTS:Bile from all the examined patient groups showed a remarkably similar PC and LPC species composition,with only minor statistical differences.Total biliary PC concentrations were highest in controls(8030±1843 mol/L)and lowest in patients with CCC(1969±981 mol/L)(P=0.005,controls vs SSC and CCC,respectively,P<0.05).LPC contents in bile were overall low(4.2%±1.8%).Biliary LPC/PC ratios and ratios of biliary PC to bilirubin,PC to cholesterol,PC to protein,and PC to bile acids showed no intergroup differences.CONCLUSION:PC and LPC profiles being similar in patients with or without sclerosing cholangitis,these phospholipids are likely not of major pathogenetic importance in this disease group.

Ustekinumab: “Real-world” outcomes and potential predictors of nonresponse in treatment-refractory Crohn’s disease

BACKGROUND Ustekinumab was approved in Europe for the treatment of adults with moderate to severe Crohn's disease(CD)in 2016,and there is an urgent need for data on its everyday use.AIM To obtain data on the daily use of ustekinumab.METHODS This is a retrospective monocentric study.Patients with moderate to severe CD who began ustekinumab therapy at the inflammatory bowel diseases outpatient clinic of the Heidelberg University Hospital between December 2016 and March 2018 were selected based on electronic patient files.The primary study endpoint was combined steroid-free clinical remission or steroid-free clinical response at 24±6 wk of ustekinumab therapy.Secondary study endpoints were:achievement of mucosal healing,sonographic and magnetic resonance imaging response,biochemical response,the need for intestinal surgery within 24±6 wk after treatment initiation,the occurrence of adverse events,treatment discontinuation due to nonresponse or adverse events,improvement of extraintestinal manifestations,clinical response at 48±6 wk of therapy,and association of response with nucleotid oligodimerisation domain 2 mutations.RESULTS Fifty-seven patients with CD(5.3%anti-tumour necrosis factorαnaive,63.2%having undergone at least one intestinal surgery)were included in the study.Twenty patients(35.1%)achieved steroid-free clinical remission,6(10.5%)steroid-free clinical response and 31(54.4%)were non-responders.Treatment discontinuation due to adverse events occurred in two patients(3.5%).Male sex,the presence of extraintestinal manifestations and the use of steroids at baseline were predictors of nonresponse to ustekinumab therapy.CONCLUSION In a“real-world”treatment-refractory cohort of patients with CD,ustekinumab appeared efficacious and safe.