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Diagnostic delay in inflammatory bowel diseases in a German population

World Journal of Gastroenterology 2024年第29期30卷 3465-3478页

作者： Elisabeth Blüthner Annalena Dehe Carsten Büning Britta Siegmund Matthias Prager Jochen Maul Alexander Krannich Jan Preiß Bertram Wiedenmann Florian Rieder Raneem Khedraki Frank Tacke Andreas Sturm Anja Schirbel Department of Hepatology and Gastroenterology Campus Virchow-Klinikum and Campus CharitéMitteCharité-Universitätsmedizin BerlinBerlin 10117Germany Department of Gastroenterology Vivantes Klinikum im FriedrichshainBerlin 10249Germany Department of Internal Medicine Krankenhaus WaldfriedeBerlin 14163Germany Department of Gastroenterology Infectious Diseases and RheumatologyCharité-Universitätsmedizin BerlinBerlin 12203Germany Praxis für Gastroenterologie Berlin Zehlendorf Berlin 14195Germany Gastroenterologie am Bayrischen Platz Berlin 10825Germany Clinical Trial Office Charité-Universitätsmedizin BerlinBerlin 10117Germany Department of Gastroenterology Diabetology and HepatologyVivantes Klinikum NeuköllnBerlin 10117Germany Department of Gastroenterology Hepatology and NutritionDigestive Diseases and Surgery InstituteThe Cleveland Clinic FoundationClevelandOH 44195United States Department of Internal Medicine DRK Kliniken Berlin WestendBerlin 14050Germany Gastroenterologie im Havelland Straße der EinheitFalkensee 14612Germany

BACKGROUND Early diagnosis is key to prevent bowel damage in inflammatory bowel disease(IBD).Risk factor analyses linked with delayed diagnosis in European IBD patients are scarce and no data in German IBD patients *** To identify risk factors leading to prolonged diagnostic time in a German IBD *** Between 2012 and 2022,430 IBD patients from four Berlin hospitals were enrolled in a prospective study and asked to complete a 16-item questionnaire to determine features of the path leading to IBD *** diagnostic time was defined as the time from symptom onset to consulting a physician(patient waiting time)and from first consultation to IBD diagnosis(physician diagnostic time).Univariate and multivariate analyses were performed to identify risk factors for each time *** The total diagnostic time was significantly longer in Crohn’s disease(CD)compared to ulcerative colitis(UC)patients(12.0 vs 4.0 mo;P<0.001),mainly due to increased physician diagnostic time(5.5 vs 1.0 mo;P<0.001).In a multivariate analysis,the predominant symptoms diarrhea(P=0.012)and skin lesions(P=0.028)as well as performed gastroscopy(P=0.042)were associated with longer physician diagnostic time in CD *** UC,fever was correlated(P=0.020)with shorter physician diagnostic time,while fatigue(P=0.011)and positive family history(P=0.046)were correlated with longer physician diagnostic *** We demonstrated that CD patients compared to UC are at risk of long diagnostic *** efforts should focus on shortening the diagnostic delay for a better outcome in these patients.

关键词： Diagnostic time Diagnostic delay Crohn’s disease Ulcerative colitis Germany

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Bone-targeting engineered small extracellular vesicles carrying anti-miR-6359-CGGGAGC prevent valproic acid-induced bone loss

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Signal Transduction and Targeted Therapy 2024年第2期9卷 751-765页

作者： Xudong Xie Peng Cheng Liangcong Hu Wu Zhou Detai Zhang Samuel Knoedler Guodong Liu Yuan Xiong Hang Xue Yiqiang Hu Barbara Kern Doha Obed Adriana CPanayi Lang Chen Chenchen Yan Ze Lin Guandong Dai Bobin Mi Yingze Zhang Guohui Liu Department of Orthopedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration Wuhan 430022China Department of Clinical Laboratory Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022P.R.China Division of Plastic Surgery Brigham and Women’s HospitalHarvard Medical SchoolBostonMA 02152USA Department of Plastic Surgery and Hand Surgery Klinikum Rechts der IsarTechnical University of MunichMunichGermany Medical Center of Trauma and War Injuries Daping HospitalArmy Medical UniversityChonqing 400042China Department of Plastic Surgery Campus CharitéMitte|Campus Virchow-KlinikumCharité-Universitätsmedizin Berlincorporate member of Freie Universität BerlinHumboldt-Universität zu Berlin and Berlin Institute of HealthBerlinGermany Berlin Institute of Health Charité-Universitätsmedizin BerlinBerlinGermany Department of Plastic AestheticHand and Reconstructive SurgeryHannover Medical SchoolHannoverGermany Department of Hand Plastic and Reconstructive SurgeryMicrosurgeryBurn CenterBG Trauma Center LudwigshafenUniversity of HeidelbergLudwig-Guttmann-Strasse 1367071 Ludwigshafen/RhineGermany Pingshan District People’s Hospital of Shenzhen Pingshan General Hospital of Southern Medical UniversityShenzhenGuangdong 518118China Department of Orthopaedic Surgery The Third Hospital of Hebei Medical UniversityNO.139 Ziqiang RoadShijiazhuang 050051China

The clinical role and underlying mechanisms of valproic acid(VPA)on bone homeostasis remain ***,we confirmed that VPA treatment was associated with decreased bone mass and bone mineral density(BMD)in both patients and *** effect was attributed to VPA-induced elevation in osteoclast formation and *** RNA-sequencing,we observed a significant rise in precursor miR-6359 expression in VPA-treated osteoclast precursors in vitro,and further,a marked upregulation of mature miR-6359(miR-6359)in vivo was demonstrated using quantitative real-time PCR(qRT-PCR)and miR-6359 fluorescent in situ hybridization(miR-6359-FISH).Specifically,the miR-6359 was predominantly increased in osteoclast precursors and macrophages but not in neutrophils,T lymphocytes,monocytes and bone marrow-derived mesenchymal stem cells(BMSCs)following VPA stimulation,which influenced osteoclast differentiation and bone-resorptive ***,VPA-induced miR-6359 enrichment in osteoclast precursors enhanced reactive oxygen species(ROS)production by silencing the SIRT3 protein expression,followed by activation of the MAPK signaling pathway,which enhanced osteoclast formation and activity,thereby accelerating bone ***,there are no medications that can effectively treat VPA-induced bone ***,we constructed engineered small extracellular vesicles(E-sEVs)targeting osteoclast precursors in bone and naturally carrying anti-miR-6359 by introducing of EXOmotif(CGGGAGC)in the 3’-end of the anti-miR-6359 *** confirmed that the E-sEVs exhibited decent bone/osteoclast precursor targeting and exerted protective therapeutic effects on VPA-induced bone loss,but not on ovariectomy(OVX)and glucocorticoid-induced osteoporotic models,deepening our understanding of the underlying mechanism and treatment strategies for VPA-induced bone loss.

关键词： miR protective stimulation

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Editorial on“Short-and long-term outcomes after hemihepatectomy for perihilar cholangiocarcinoma:does left or right side matter?”

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Hepatobiliary Surgery and Nutrition 2022年第3期11卷 470-472页

作者： Christian Benzing Johann Pratschke Moritz Schmelzle Department of Surgery Campus Charité Mitte/Campus Virchow-KlinikumExperimental Surgery and Regenerative MedicineCharité-Universitätsmedizin BerlinBerlinGermany

Perihilar cholangiocarcinoma(PHC)is a malignant tumor known for its aggressive tumor biology(1).The only curative therapeutic approach is major hepatectomy with extrahepatic bile duct ***,these procedures are associated with a very high postoperative mortality of up to 20%(1,2).And even after successful surgical tumor resection,tumor recurrence occurs in the course of many patients resulting in low overall survival(OS)rates(3).

关键词： hepatectomy mortality tumor

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Mucosa-associated microbiota alterations in primary sclerosing cholangitis(PSC)before and after liver transplantation-who is calling the shots?

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Hepatobiliary Surgery and Nutrition 2023年第5期12卷 795-797页

作者： Münevver Demir Michael Sigal Department of Hepatology and Gastroenterology Campus Virchow-Klinikum and Campus CharitéMitteCharitéUniversitätsmedizin BerlinBerlinGermany Berlin Institute for Medical Systems Biology Max Delbrück Center for Molecular MedicineBerlinGermany

Primary sclerosing cholangitis(PSC)is an immune-related chronic cholangiopathy associated with high rates of progression to liver cirrhosis and the need for liver *** PSC is frequently associated with inflammatory bowel disease(IBD),several studies have investigated the role of the gut-liver axis in PSC and emerging evidence indicates that gut and bile microbiota are associated with the onset and progression of PSC[reviewed in(1)].

关键词： Primary sclerosing cholangitis(PSC) liver transplantation Klebsiella microbiota mucosal microbiota

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Somatic mutant clone screening: scan for novel NASH target genes in mouse liver

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Signal Transduction and Targeted Therapy 2023年第9期8卷 3902-3903页

作者： Tian Lan Adrien Guillot Frank Tacke Lab of Gastroenterology and Hepatology State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduChina Department of Gastroenterology West China HospitalSichuan UniversityChengduChina Department of Hepatology&Gastroenterology Charité-Universitätsmedizin BerlinCampus Virchow-Klinikum and Campus CharitéMitteBerlinGermany

In a landmark study recently published in Cell,Wang et *** a novel method of somatic adeno-associated virus(AAV)-transposon in vivo clonal screening(termed MOSAICS),which is capable to generate multiple mutant hepatocyte clones within the same tissue and thereby to scan for non-alcoholic steatohepatitis(NASH)target genes(Fig.1).1 Non-alcoholic fatty liver disease(NAFLD)is the most common liver disease affecting about 20–30%of the global population and associated with metabolic *** can progress to NASH,characterized by liver inflammation,steatosis and hepato-cyte ballooning,and NAFLD/NASH can lead to fibrosis,cirrhosis,and ultimately liver *** decades,researchers have been seeking to understand its pathogenesis and to discover ther-apeutic strategies to treat NAFLD/***,up to now,there is still no specific pharmacotherapy available.

关键词： balloon NAFLD inflammation

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Identification and treatment of biliary complications after liver transplantation:more relevant than ever

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Hepatobiliary Surgery and Nutrition 2022年第3期11卷 443-445页

作者： Simon Moosburner Johann Pratschke Nathanael Raschzok Department of Surgery Campus CharitéMitte/Campus Virchow-KlinikumExperimental SurgeryCharité-Universitätsmedizin BerlinFreie Universität BerlinHumboldt-Universität zu Berlin and Berlin Institute of HealthBerlinGermany BIH charitéClinician Scientist Program Berlin Institute of Health(BIH)BerlinGermany

Liver transplantation remains the treatment of choice for patients with end-stage liver *** the increasing demand for liver transplantation,the spectrum of potential grafts has been widened and includes now not only regular grafts from donation after brain death(DBD)but also organs from donation after cardiac death(DCD),split liver and living donor grafts,as well as so-called“marginal grafts”from donors with extended criteria such as significant steatosis hepatis or older age(1).These grafts are associated with higher rates of early allograft dysfunction and primary non-function-which stresses the healthcare system with increased length of hospital stay for patients and higher costs(2,3).Moreover,marginal grafts are at risk for biliary complications such as anastomotic and non-anastomotic strictures as well as biliary leakages,which is caused by more severe ischemia reperfusion injury and in consequence reduced micro perfusion of the biliary tract(4).

关键词： liver organs death treatment

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Tumor–stromal cross-talk modulating the therapeutic response in pancreatic cancer

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Hepatobiliary & Pancreatic Diseases International 2018年第5期17卷 461-472页

作者： Christopher C.M.Neumann Ellen von Horschelmann Anja Reutzel-Selke Elisabeth Seidel Igor Maximilian Sauer Johann Pratschke Marcus Bahra Rosa Bianca Schmuck Department of Surgery Campus Charité Mitte Campus Virchow-KlinikumExperimental SurgeryCharité-Universitatsmedizin BerlinBerlinGermany Berlin Institute of Health Department of SurgeryCampus CharitéMitte and Campus Virchow-KlinikumAugustenburger Platz 113353 BerlinGermany

Background: Pancreatic ductal adenocarcinoma(PDAC) is a highly malignant solid tumor with a dismal prognosis. The stroma component makes up to 90% of the tumor mass and is thought to be one of the main reasons for the tumor’s high chemoresistance. Cancer associated fibroblasts(CAFs) have previously been identified to be the key stromal players. This is the first time we provide detailed in vitro experiments investigating tumor–stromal interactions when exposed to three well-known chemotherapeutic agents. Methods: Monocultures, indirect and direct co-cultures of two PDAC cell lines(AsPC and Panc-1) and six primary patients derived CAFs were treated with gemcitabine, nab-paclitaxel and the γ-secretaseinhibitor(GSI) DAPT. The cell viability of each component was measured with XTT. Finally, IL-6 concentrations of the supernatants were analyzed. Results: On the contrary to PDAC cell lines, CAF monocultures hardly responded to any treatment which suggested that stroma(CAFs) itself is more resistant to standard chemo-treatments than the epithelial cancer cells. Moreover, only a weak chemotherapeutic response was observed in direct co-cultures of cancer cells with CAFs. A change in the morphology of direct co-cultures was accompanied with the chemoresistance. CAFs were observed to build cage-like structures around agglomerates of tumor cells. High levels of IL-6 were also associated with a reduced response to therapy. Indirect co-cultures make the tumor–stromal interaction more complex. Conclusions: CAFs are highly chemoresistant. Direct cell–cell contact and high levels of IL-6 correlate with a high chemoresistance.

关键词： Pancreatic cancer Tumor microenvironment Cancer associated fibroblasts Cancer–stroma co-culture Atroma targeted therapy

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Influence of skeletal muscle mass on graft regeneration after living-donor liver transplantation

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Hepatobiliary Surgery and Nutrition 2021年第4期10卷 564-566页

作者： Deniz Uluk Johann Pratschke Georg Lurje Department of Surgery Campus CharitéMitte|Campus Virchow-KlinikumCharité-Universitätsmedizin BerlinBerlinGermany

Body composition(BC)is defined as the relative proportion of fat,water,protein,and mineral components in the body and varies greatly among *** skeletal muscle depletion is frequently seen in severely ill patients,sarcopenia,defined as a pathological reduction of skeletal muscle mass(SMM)and strength,is one of the most significant features of the metabolic imbalance related to end stage liver disease(ESLD).

关键词： skeletal liver donor

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An inflammatory subtype of pancreatic ductal adenocarcinoma is associated with poor prognosis and increased perioperative mortality

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Journal of Pancreatology 2019年第3期2卷 107-112页

作者： Benzing Christian Klein Fritz Pelzer Uwe Sinn Marianne Pratschke Johann Bahra Marcus campus charité-mitte and campus Virchow Klinikum Charité-Universitätsmedizin BerlinBerlinGermany Department of Hematology Oncology and Tumor ImmunologyCharité-Universitätsmedizin BerlinBerlinGermany

Pancreatic ductal adenocarcinoma(PDAC)is a malignancy characterized by an aggressive tumor *** present analysis seeks to identify and analyze a cohort that meets criteria for"inflammatory"PDAC(IPDAC).All patients who underwent a curative resection for PDAC at our institution between 1989 and 2015 were included in the retrospective *** with histological proven adenocarcinoma and elevated C-reactive protein(CRP)(≥6 mg/L)serum concentrations,but no other suspicion of infection were *** provide a matched control group with normal CRP serum levels from the same patient ***-six(6.8%)of 532 patients meet our criteria for an IPDAC group ***-hospital(30 days)mortality was 13.9%in the IPDAC group vs 0%in the control group(P=.020).Median follow-up was 183.8 months(standard deviation[SD]=53.3,range 14.3-285.4).Median overall survival was 8.5 months(SD=16.8,range 0.3-89.6)in the IPDAC group and 24.8 months(SD=19.4,range 0.7-80.4)in the control group(P=.002).Patients indicating an IPDAC in our cohort had a significantly and clinical meaningful decreased overall survival and a higher perioperative morbidity and mortality.

关键词： Cholangitis CRP Inflammatory carcinoma PDAC

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Influence of the body mass index on postoperative outcome and long-term survival after pancreatic resections in patients with underlying malignancy

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Hepatobiliary Surgery and Nutrition 2019年第3期8卷 201-210页

作者： Philippa Seika Fritz Klein Uwe Pelzer Johann Pratschke Marcus Bahra Thomas Malinka Department of Surgery Charite Campus Mitte and Charite Campus Virchow KlinikumCharité-Universitatsmedizin BerlinBerlinGermany Department of Hematology/Oncology/Tumorimmunology Campus Virchow KlinikumCharité-Universitatsmedizin BerlinBerlinGermany

Background:While the long-term survival rate among patients with pancreatic and periampullary carcinomas remains low,it can be influenced by various *** purpose of this retrospective study was to investigate the effects of body mass index(BMI)on postoperative complications and patient survival after pancreatic resections for underlying malignancy over a 20-year observation ***:We analyzed 1,384 patients,918 patients with pancreatic ductal adenocarcinoma(PDAC)(66.3%),229 patients with distal cholangiocarcinoma(16.5%),206 ampullary carcinoma patients(14.8%),and 31 duodenal carcinoma patients(2.2%).Patients were classified into four groups(group 130.0)according to their BMI(kg/m2).We analyzed differences in postoperative complications,postoperative length of hospital stays,reoperations,postoperative mortality and survival rate among the ***:Within a mean observation period of 687.7[2–8,500]days,735(53.1%)patients *** were important differences in postoperative complications(group 1,16.2%;group 2,20.3%;group 3,27.2%,group 4,41.6%)with the type of postoperative complications also varying between the *** 1-,5-,10-and 15-year survival rates were 66.4%,25.5%,17.9%,and 12.1%,respectively,with survival rates varying amongst the four ***:Patients with a BMI between 18.5 and 30 show better postoperative outcomes,regarding complications,hospitalization duration,and reoperation rates than underweight or obese ***-term survival depends strongly on postoperative complications while patients with a higher BMI show better long-term survival rates.

关键词： Pancreatic resection body mass index(BMI) outcome long-term survival

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