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Retrospective study of the incidence, risk factors, treatment outcomes of bacterial infections at uncommon sites in cirrhotic patients

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World Journal of Hepatology 2024年第3期16卷 418-427页

作者： Sophie Schneitler Christina Schneider Markus Casper frank lammert Marcin Krawczyk Sören L Becker Matthias Christian Reichert Institute of Medical Microbiology and Hygiene Saarland UniversityHomburg 66421Germany Department of Medicine II Saarland University Medical CenterHomburg 66421Germany Health Sciences Hannover Medical SchoolHannover 30625Germany Laboratory of Metabolic Liver Diseases Department of GeneralTransplant and Liver SurgeryCentre for Preclinical ResearchMedical University of WarsawWarsaw 02-097Poland

BACKGROUND Bacterial infections(BI)negatively affect the natural course of *** most frequent BI are urinary tract infections(UTI),pneumonia,and spontaneousbacterial peritonitis(SBP).AIM To assess the relevance of bacterial infections beyond the commonly recognized types in patients with cirrhosis and to investigate their relationship with other clinical *** We retrospectively analyzed patients with cirrhosis and BI treated between 2015 and 2018 at our tertiary care *** were classified as typical and atypical,and clinical as well as laboratory parameters were compared between the two *** In a cohort of 488 patients with cirrhosis,we identified 225 typical BI(95 UTI,73 SBP,72 pulmonary infections)and 74 atypical BIs,predominantly cholangitis and soft tissue infections(21 each),followed by intra-abdominal BIs(n=9),cholecystitis(n=6),head/throat BIs(n=6),osteoarticular BIs(n=5),and endocarditis(n=3).We did not observe differences concerning age,sex,or etiology of cirrhosis in patients with typical vs atypical *** BIs were more common in patients with more advanced cirrhosis,as evidenced by Model of End Stage Liver Disease(15.1±7.4 vs 12.9±5.1;P=0.005)and Child-Pugh scores(8.6±2.5 vs 8.0±2;P=0.05).CONCLUSION Atypical BIs in cirrhosis patients exhibit a distinct spectrum and are associated with more advanced stages of the ***,the work-up of cirrhosis patients with suspected BI requires detailed work-up to elucidate whether typical BI can be identified.

关键词： Bacterial infection Empirical antibiotic therapy End-stage liver disease Escherichia coli Multi-resistant pathogens

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A common variant in the precursor miR-146a sequence does not predispose to cholangiocarcinoma in a large European cohort

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Hepatobiliary & Pancreatic Diseases International 2012年第4期11卷 412-417页

作者： Florentina Mihalache Aksana Hblinger Monica Acalovschi Tilman Sauerbruch frank lammert Vincent Zimmer Department of Medicine Ⅱ Saarland University Hospital66421 HomburgGermany Department of Medicine Ⅲ University Iuliu Hatieganu Department of Internal Medicine Ⅰ University Hospital Bonn

BACKGROUND:Micro-RNAs(miRNAs) are small,non-coding RNA species considered to fine-tune basic cellular functions by modulating target gene translation and/or mRNA stability.A common G/C polymorphism(rs2910164) in the precursor(pre-) miR-146a gene engaged in NF-κB signaling and apoptosis pathways has been reported to modulate the genetic risk of hepatocellular carcinoma by increased G-allelic production of mature *** investigated rs2910164 in a large Europeanbased cholangiocarcinoma(CCA) ***:We recruited 182 CCA patients and 350 controls in three academic medical *** for rs2910164 was performed by PCR-based assays with 5’-nuclease and fluorescence *** frequencies were tested for consistency with the Hardy-Weinberg equilibrium using an exact test;allelic and genotypic differences between the patients and controls were assessed by the Chi-square test and Armitage’s trend *** subgroup analyses included gender,tumor localization(extra-versus intrahepatic CCA) and early-onset ***:Genotype distributions were consistent with the Hardy-Weinberg *** significant differences in either allele or genotype distributions were detected between the CCA and control groups or the respective subgroups ***,there was a trend for a protective effect of the heterozygous single-nucleotide polymorphism state GC,as indicated by an underrepresentation in the CCA group in general(29% vs 35%;P=0.18) and,in particular,for extrahepatic tumor sites(26% vs 35%;OR=0.67;95% CI,0.43-1.02;P=0.065).CONCLUSIONS:Our data do not support a prominent contribution of the pre-miR-146a sequence variant in the genetic predisposition to ***,current studies functionally characterizing rs2910164 have proposed that distinct repertoires of target genes are addressed by genotype-specific mature miR146a *** the detected trend towards a potentially protective role of GC heterozygosity,a subtle modulation of g

关键词： miR-146a miR-SNP biliary tract cancer cholangiocarcinoma genetic risk

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Pancreatic cancer risk variant ABO rs505922 in patients with cholangiocarcinoma

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World Journal of Gastroenterology 2011年第41期17卷 4640-4642页

作者： Marcin Krawczyk Florentina Mihalache Aksana Hblinger Monica Acalovschi frank lammert Vincent Zimmer Department of Medicine Ⅱ Saarland University Medical Center Department of Medicine Ⅲ University Iuliu Hatieganu Department of Internal MedicineⅠ University Hospital Bonn

The aim of this study was to investigate an association between the development of cholangiocarcinoma(CCA)and the ABO variant rs505922(known to increase pan-creatic cancer risk)in a large cohort of European individuals with *** total,180 individuals with CCA and 350 CCA-free controls were *** ABO variant rs505922 was genotyped using a polymerase chain reaction-based *** between this single nucleotide polymorphism(SNP)and CCA was tested in contingency *** allele distributions nor association tests and regression analysis provided evidence for an increased risk of CCA among carriers of the ABO variant(all P > 0.05).Nevertheless,we documented a deviation from Hardy-Weinberg equilibrium in the entire CCA cohort(P = 0.028)and for patients with intrahe-patic(P = 0.037)but not extrahepatic tumor localization(P > 0.05).The association tests did not provide evidence for a prominent role of the investigated SNP in the genetic risk of ***,Hardy-Weinberg disequilibrium in the entire cohort and the intrahepatic CCA subgroup warrants future studies investigating a potential CCA risk modulation by individual blood groups.

关键词： ABO Biliary tract cancer Blood groups Genetic risk Single nucleoUde polymorphism

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Childhood obesity, cardiovascular and liver health: a growing epidemic with age

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World Journal of Pediatrics 2020年第5期16卷 438-445页

作者： Maria Felicia Faienza Mariangela Chiarito Emilio Molina-Molina Harshitha Shanmugam frank lammert Marcin Krawczyk Gabriele D'Amato Piero Portincasa Section of Pediatrics Department of Biomedical Sciences and Human OncologyUniversity of Bari"Aldo Moro"BariItaly Clinica Medica"A.Murri" Department of Biomedical Sciences and Human OncologyUniversity of Bari"Aldo Moro"BariItaly Department of MedicineⅡ Saarland University Medical CenterSaarland UniversityHomburgGermany Laboratory of Metabolic Liver Diseases Center for Preclinical ResearchDepartment of GeneralTransplant and Liver SurgeryMedical University of WarsawWarsawPoland Neonatal Intensive Care Unit Di Venere HospitalBariItaly

Background The frequency of childhood obesity has increased over the last 3 decades,and the trend constitutes a worrisome epidemic *** the raising obesity risk,key aspects to consider are accurate body mass index classification,as well as metabolic and cardiovascular,and hepatic *** sources The authors performed a systematic literature search in PubMed and EMBASE,using selected key words(obesity,childhood,cardiovascular,liver health).In particular,they focused their search on papers evaluating the impact of obesity on cardiovascular and liver *** We evaluated the current literature dealing with the impact of excessive body fat accumulation in childhood and across adulthood,as a predisposing factor to cardiovascular and hepatic *** also evaluated the impact of physical and dietary behaviors starting from childhood on cardio-metabolic *** The epidemic of obesity and obesity-related comorbidities worldwide raises concerns about the impact of early abnormalities during childhood and *** key abnormalities in this context include cardiovascular diseases,and non-alcoholic fatty liver *** metabolic screenings and associated comorbidities should start as early as possible in obese children and ***,improving dietary intake and increasing physical activity performance are to date the best therapeutic tools in children to weaken the onset of obesity,cardiovascular diseases,and diabetes risk during adulthood.

关键词： Cardiovascular Childhood Liver health Obesity

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Technological insights:combined impedance manometry for esophageal motility testing-current results and further implications

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World Journal of Gastroenterology 2006年第39期12卷 6266-6273页

作者： Huan Nam Nguyen Gerson Ricardo Souza Domingues frank lammert Department of Internal Medicine University of Technology RWTH-Aachen Germany Department of Internal Medicine Gama Filho Unisverity Rio de Janeiro Brazil Department of Internal Medicine University of Bonn Germany

This review focuses on current aspects of the novel technology of combined impedance manometry for esophageal motility testing. It presents methodological features, summarizes current results and discusses implications for further research. The combined technique assesses simultaneously bolus transport and associated peristalsis, thus allowing detailed analysis of the relationships between bolus transit and esophageal motility. Recent studies demonstrate that combined impedance manometry provides important additional information about esophageal motility as compared to conventional manometry: (1) monitoring of bolus transport patterns, (2) calculation of bolus transit parameters, (3) evaluation of bolus clearance, (4) monitoring of swallow associated events such as air movement and reflux, and (5) investigation of the relationships between bolus transit and LES relaxation. Studies with healthy subjects have identified several useful parameters for comprehensive assessment of eosphageal function. These parameters were found to be pathological in patients with classical achalasia, mild GERD, and ineffective esophageal motility. The technology of combined impedance manometry provides an important new tool for esophageal function testing, advancing both clinical and basic research. However, several important issues remain to be standardized to make the technique suitable for widely clinical use.

关键词： Combined impedance manometry Esophageal function testing Review

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Cholesterol crystal binding of biliary immunoglobulin A: visualization by fluorescence light microscopy

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World Journal of Gastroenterology 2001年第2期7卷 198-202页

作者： frank lammert Stefan Südfeld Norbert Busch Siegfried Matern Department of Medicine III University of Technology (RWTH) AachenGermany

AIM: To assess potential contributions of biliary IgA for crystal agglomeration into gallstones, we visualized cholesterol crystal binding of biliary IgA. METHODS: Crystal binding biliary proteins were extracted from human gallbladder bile using lectin affinity *** IgA was isolated from the bound protein fraction by immunoaffinity chromatography. Pure cholesterol monohydrate crystals were incubated with biliary IgA and fluoresceine isothiocyanate (FITC)conjugated anti IgA at 37 degree. Samples were examined under polarizing and fluorescence light microscopy with digital image processing. RESULTS: Binding of biliary IgA to cholesterol monohydrate crystals could be visualized with FITC conjugated anti IgA *** fluorescence occurred at crystal edges and dislocations. Controls without biliary IgA or with biliary IgG showed no significant fluorescence. CONCLUSION: Fluorescence light microscopy provided evidence for cholesterol crystal binding of biliary IgA. Cholesterol crystal binding proteins like IgA might be important mediators of crystal agglomeration and growth of cholesterol gallstones by modifying the evolving crystal structures in vivo.

关键词： Crystallization Bile Cholelithiasis Cholesterol Chromatography, Affinity Fluorescent Antibody Technique Humans Image Processing, Computer-Assisted Immunoglobulin A, Secretory Microscopy, Fluorescence Research Support, Non-U.S. Gov't

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Postprandial transduodenal bolus transport is regulated by complex peristaltic sequence

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World Journal of Gastroenterology 2006年第37期12卷 6008-6016页

作者： Huan Nam Nguyen Ron Winograd Gerson Ricardo Souza Domingues frank lammert Department of Medicine Ⅲ Division of Gastroenterology Aachen University (RWTH) Aachen Germany

AIM: To study the relationship between the patterns of postprandial peristalsis and transduodenal bolus transport in healthy subjects. METHODS: Synchronous recording of chyme transport and peristaltic activity was performed during the fasting state and after administration of a test meal using a special catheter device with cascade configuration of impedance electrodes and solid-state pressure transducers. The catheter was placed into the duodenum, where the f irst channel was located in the f irst part of the duodenum and the last channel at the duodenojejunal junction. After identif ication of previously def ined chyme transport patterns the associated peristaltic patterns were analyzed. RESULTS: The interdigestive phase 3 complex was reliably recorded with both techniques. Of 497 analyzed impedance bolus transport events, 110 (22%) were short-spanned propulsive, 307 (62%) long-spanned propulsive, 70 (14%) complex propulsive, and 10 (2%) retrograde transport. Short-spanned chyme transports were predominantly associated with stationary or propagated contractions propagated over short distance. Long-spanned and complex chyme transports were predominantly associated with propulsive peristaltic patterns, which were frequently complex and comprised multiple contractions. Propagated double wave contraction, propagated contraction with a clustered contraction, and propagated cluster of contractions have been identif ied to be an integralted part of a peristaltic sequence in human duodenum. CONCLUSION: Combined impedancometry and manometry improves the analysis of the peristaltic patterns that are associated with postprandial transduodenal chymetransport. Postprandial transduodenal bolus transport is regulated by propulsive peristaltic patterns, which are frequently complex but well organized. This f inding should be taken into consideration in the analysis of intestinal motility studies.

关键词： Transduodenal bolus transport Organization of duodenal peristalsis Combined impedance manometry

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Occult celiac disease prevents penetrance of hemochromatosis

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World Journal of Gastroenterology 2005年第21期11卷 3323-3326页

作者： Andreas Geier Carsten Gartung Igor Theurl Guenter Weiss frank lammert Christoph G.Dietrich Ralf Weiskirchen Heinz Zoller Benita Hermanns Siegfried Matern Department of Internal Medicine Ⅲ Aachen University (RWTH) AachenGermany Department of Internal Medicine University of Innsbruck InnsbruckAustria Department of Clinical Chemistry and Pathobiochemistry Aachen University(RWTH) AachenGermany Department of Pathology Aachen University (RWTH) AachenGermany Department of Internal Medicine Ⅲ Aachen University(RWTH) Aachen Germany

AIM:To report a patient with C282Y homozygocity,depleted body iron and intestinal atrophy caused by celiac disease (CD) who experienced resolution of the enteropathy with subsequent normalization of iron metabolism upon gluten free diet. METHODS:To obtain information on the tissue distribution and quantitative expression of proteins involved in duodenal iron trafficking,we determined the expression of divalent-metal transporter 1 (DMT1),ferroportin 1 (FP1) and transferrin receptor (TfR1) by means of immunohist-ochemistry and real-time PCR in duodenal biopsies of this patient. RESULTS:Whereas in hereditary hemochromatosis patients without CD, DMT1 expression was up-regulated leading to excessive uptake of iron, we identified a significant reduction in protein ana mRNA expression of DMT1 as a compensatory mechanism in this patient with HH and CD. CONCLUSION:Occult CD may compensate for increased DMT1 expression in a specific subset of individuals with homozygous C282Y mutations in the hemochromatosis (HFE) gene,thus contributing to the low penetrance of HH.

关键词： Hemochromatosis Celiac disease Divalentmetal transporter 1 Transferrin receptor Iron metabolism

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Innovative immunohistochemistry identifies MMP-9 expressing macrophages at the invasive front of murine HCC

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World Journal of Hepatology 2010年第5期2卷 175-179页

作者： Martin Roderfeld Timo Rath frank lammert Christian Dierkes Jürgen Graf Elke Roeb Justus-Liebig-University Giessen Department of Medicine ⅡGastroenterologyGiessen 35385Germany Department of Internal Medicine Ⅱ Saarland University HospitalSaarland University Justus-Liebig-University Giessen Department of Pathology Philipps-University Marburg Department of Anaesthesiology and Intensive Care35033 Marburg and Pas-senger Medical CareDeutsche Lufthansa AGFrankfurt 60546Germany

AIM:To investigate the proteolytic contribution of tumor-associated macrophages(TAM)in tumor invasion,we analyzed whether TAM at the invasive front of small HCC in Abcb4-/--mice show an enhanced expression of MMP-9. METHODS:Liver cryosections of the hepatocellular carcinoma(HCC)invasive front from 12 mo old Abcb4-/--mice were stained for collagen typeⅠand MMP-9 using Alexa488 and Alexa568 labeled secondary ***,the Alexa568 dye was bleached and the macrophage marker F4/80 was visualized using Alexa568 labeled secondary ***, photographs of the invasive tumor front were digitally overlaid and analyzed. RESULTS:After complete bleaching of the primary dye,specific fluorescence staining of a third antigen, here F4/80,was successfully performed on the same histological *** this method,we were able to identify conglomerates of matrix metalloproteinase (MMP-9)expressing macrophages within the tumor capsule of HCC. CONCLUSION:MMP-9 expressing macrophages are involved in matrix remodelling at the invasive tumor front of *** described staining protocol provides a simple yet powerful extension of conventional immuno-histochemistry,facilitating visualization of at least three different antigens plus nuclei in one single histological section.

关键词： Fluorescence staining Hepatocellular carcinoma Matrix metalloproteinase Tumor associated macrophages

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欧洲中央银行（ECB）

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城市环境设计 2020年第4期 162-173页

作者：沃尔夫·狄·普瑞克斯 Magdalena Baczkowska Markus Baumann Michael Beckert Johannes Behrens Hilde Benda Marcelo Bernardi Nico Boyer Jan Brosch Timo Carl Anna Rita Cedroni Jasmin Dieterle Sabrina Dlugosch Jan Ruben Fischer Brigitte Fuchs Sergio Gonzales Gesine G?rlich Martin Gruber Guthu Hallstein Sebastian Haffner Simone Hainz Sascha Hempel Rob Henderson Emanuele Iacono Martin Jelinek Rashmi Krishna Jois Ivana Jug frank Pascal Kaul Matt Kirkham Daniela Kr?hnert Bernward Krone Christian Labud Anke lammert Monika Lyzyczka Steven M Christian Maeder Dimitra Mamou Ariane Marx Christoph Maurer Matthias Niemeyer Martin Oberascher Ross Olson Renate Ott Gerhard Pfeiler Ellen Pietrzyk James Pike Robert Pippan Jakob Przybylo Anna Ptaszynska Stephanie Rathgeber Carmen Renz Salome Reves Donna Riedel Akvile Rimantaite Pete Rose Penelope Rüttimann Stefan Rutzinger Oliver Sachse Kristina Schinegger Benjamin Schmidt Marita Schnepper Thomas Siegl Ebru Simsek-Lenk Denise Sokolowski Augustin Solorzano Anja Sorger Andrea St?llenwerk Ernst Stockinger Crystal K.H Tang Jürgen Tiltmann Markus Tritthart Josef Tr?ster Günther Weber Andreas Weissenbach Clemens Werb Judith Werkh?user Markus Wings Eva Wolf Barbara Zeleny Thomas Zengger Zeyneb Badur Fabien Barthelemey Oliver Cassik Alejandro Corena Alexander Daxb?ck Mario Dign?ss Helmut Fr?tscher Annegret Haider Christian Halm Gregor Kassl Gernot K?fer Alexander Laber Anita Lischka Rangel Malinov Oliver Martinz Philipp Munz Barbara Roller Nicole Rumpler Wolfgang Ruthensteiner Stefan Salchinger Stefan Schadenb?ck Thomas Schwed Hannes Schwed Eckart Schwerdtfeger Sylvia Spernbauer Christoph Treberspurg Johannes Weigl Paul Raftery European Central Bank/RobertMetsch Markus Pillhofer

项目大事记/CHRONOLOGY竞赛/Competition:第一阶段/Phase 1:2003;第二阶段/Phase 2:2003-2004;修改阶段/Revision Phase:2004;优化阶段/Optimization Phase:2005规划设计起始时间/Start of Planning:2005前期工程/Preliminary Site Works:2008主体施工/Main Construction Works:2010竣工/Completion:2014项目参数/PROJECT DATA用地面积/Site Area:120 000m2建筑毛面积/Gross Floor Area:185 000m2

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