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| 1 | Molecular targets in the treatment of alcoholic hepatitis显示文摘Alcohol related costs to health and society are high. One of the most serious complications of alcohol misuse to the individual is the development of alcoholic hepatitis (AH), a clinical syndrome of jaundice and progressive inflammatory liver injury in patients with a history of recent heavy alcohol use. It has a poor outcome and few existing successful therapies. The use of glucocorticoids in patients with severe AH is still controversial and there remains a group of patients with glucocorticoid-resistant disease. However, as our understanding of the pathogenesis of the condition improves there are opportunities to develop new targeted therapies with specific actions to control liver inflammation without having a detrimental effect on the immune system as a whole. In this article we review the molecular mechanisms of AH concentrating on the activation of the innate and adaptive immune response. We consider existing treatments including glucocorticoids, anti-tumor necrosis factor therapy and pentoxifylline and their limitations. Using our knowledge of the disease pathogenesis we discuss possible novel therapeutic approaches. New targets include pro-inflammatory cytokines such as interleukin (IL)-17, chemokines and their receptors (for example IL-8, CXCL9 and CXCR3) and augmentation of anti-inflam- matory molecules such as IL-10 and IL-22. And there is also future potential to consider combination therapy to selectively modulate the immune response and gain control of disease. | Ashwin D Dhanda Richard WL Lee Peter L Collins C Anne McCune | 2012 | World Journal of Gastroenterology2012，18，39： | 9 |
| 2 | Randomized trial in malignant biliary obstruction:Plastic vs partially covered metal stents显示文摘AIM:To compare efficacy and complications of par-tially covered self-expandable metal stent(pcSEMS)to plastic stent(PS)in patients treated for malignant,infrahilar biliary obstruction.METHODS:Multicenter prospective randomized clinical trial with treatment allocation to a pcWallstent(SEMS)or a 10 French PS.Palliative patients aged≥18,for infrahilar malignant biliary obstruction and a Karnofsky performance scale index>60%from 6 participating North American university centers.Primary endpoint was time to stent failure,with secondary outcomes of death,adverse events,Karnofsky performance score and short-form-36 scale administered on a three-monthly basis for up to 2 years.Survival analyses were performed for stent failure and death,with Cox proportional hazards regression models to determine significant predictive characteristics.RESULTS:Eighty-five patients were accrued over 37mo,42 were randomized to the SEMS group and 83patients were available for analyses.Time to stent failure was 385.3±52.5 d in the SEMS and 153.3±19.8 d in the PS group,P=0.006.Time to death did not differ between groups(192.3±23.4 d for SEMS vs211.5±28.0 d for PS,P=0.70).The only significant predictor was treatment allocation,relating to the time to stent failure(P=0.01).Amongst other measured outcomes,only cholangitis differed,being more common in the PS group(4.9%vs 24.5%,P=0.029).The small number of patients in follow-up limits longitudinal assessments of performance and quality of life.From an initially planned 120 patients,only 85 patients were recruited.CONCLUSION:Partially covered SEMS result in a longer duration till stent failure without increased complication rates,yet without accompanying measurable benefits in survival,performance,or quality of life. | Peter L Moses Khalid M AlNaamani Alan N Barkun Stuart R Gordon Roger D Mitty M Stanley Branch Thomas E Kowalski Myriam Martel Viviane Adam | 2013 | World Journal of Gastroenterology2013，19，46： | 6 |
| 3 | Burden of Clostridium difficile infection between 2010 and 2013:Trends and outcomes from an academic center in Eastern Europe显示文摘AIM:To analyze the incidence and possible risk factors in hospitalized patients treated with Clostridium difficile infection(CDI).METHODS:A total of 11751 patients were admitted to our clinic between 1 January 2010 and 1 May2013.Two hundred and forty-seven inpatients were prospectively diagnosed with CDI.For the risk analysis a 1:3 matching was used.Data of 732 patients matched for age,sex,and inpatient care period and unit were compared to those of the CDI population.Inpatient records were collected from an electronic hospital database and comprehensively reviewed.RESULTS:Incidence of CDI was 21.0/1000 admissions(2.1%of all-cause hospitalizations and 4.45%of total inpatient days).The incidence of severe CDI was 12.6%(2.63/1000 of all-cause hospitalizations).Distribution of CDI cases was different according to the unit type,with highest incidence rates in hematology,gastroenterology and nephrology units(32.9,25 and24.6/1000 admissions,respectively) and lowest rates in 1.4%(33/2312) in endocrinology and general internal medicine(14.2 and 16.9/1000 admissions)units.Recurrence of CDI was 11.3%within 12 wk after discharge.Duration of hospital stay was longer in patients with CDI compared to controls(17.6 ± 10.8d vs 12.4 ± 7.71 d).CDI accounted for 6.3%of allinpatient deaths,and 30-d mortality rate was 21.9%(54/247 cases).Risk factors for CDI were antibiotic therapy[including third-generation cephalosporins or fluoroquinolones,odds ratio(OR) = 4.559;P < 0.001],use of proton pump inhibitors(OR = 2.082,P< 0.001),previous hospitaiization within 12 mo(OR = 3.167,P < 0.001),previous CDI(OR = 15.32;P < 0.001),while presence of diabetes mellitus was associated with a decreased risk for CDI(OR = 0.484;P< 0.001).Treatment of recurrent cases was significantly different from primary infections with more frequent use of vancomycin alone or in combination(P < 0.001),and antibiotic therapy duration was longer(P < 0.02).Severity,mortality and outcome of primary infections and relapsing cases did not significantly differ.CONCLUSION:CDI was accounted for significant burden with longer hospitaiization and adverse outcomes.Antibiotic,PPI therapy and previous hospitaiization or CDI were risk factors for CDI. | Zsuzsanna Kurti Barbara D Lovasz Michael D Mandel Zoltan Csima Petra A Golovics Bence D Csako Anna Mohas Lorant Gnczi Krisztina B Gecse Lajos S Kiss Miklos Szathmari Peter L Lakatos | 2015 | World Journal of Gastroenterology2015，21，21： | 6 |
| 4 | Is liver biopsy necessary in the management of alcoholic hepatitis?显示文摘Acute alcoholic hepatitis(AAH)is characterised by deep jaundice in patients with a history of heavy alcohol use,which can progress to liver failure.A clinical diagnosis of AAH can be challenging to make in patients without a clear alcohol history or in the presence of risk factors for other causes of acute liver failure.Other causes of acute on chronic liver failure such as sepsis or variceal haemorrhage should be considered.Liver biopsy remains the only reliable method to make an accurate diagnosis.However,there is controversy surrounding the use of liver biopsy in patients with AAH because of the risks of performing a percutaneous biopsy and limitations in access to transjugular biopsy.We review the existing literature and find there are few studies directly comparing clinical and histological diagnosis of AAH.In the small number of studies that have been conducted the correlation between a clinical and histological diagnosis of AAH is poor.Due to this lack of agreement together with difficulties in accessing transjugular liver biopsy outside tertiary referral centres and research institutions,we cannot advocate universal biopsy for AAH but there remains a definite role for liver biopsy where there is clinical diagnostic doubt or dual pathology.Italso adds value in a clinical trial context to ensure a homogeneous trial population and to further our understanding of the disease pathology.Further prospective studies are required to determine whether non-invasive markers can be used to accurately diagnose AAH. | Ashwin D Dhanda Peter L Collins C Anne McCune | 2013 | World Journal of Gastroenterology2013，19，44： | 4 |
| 5 | Axitinib plus gemcitabine versus placebo plus gemcitabine in patients with advanced pancreatic adenocarcinoma: a double-blind randomised phase 3 study显示文摘 | Hedy L Kindler Tatsuya Ioka Dirk J Richel Jaafar Bennouna Richard Létourneau Takuji Okusaka Akihiro Funakoshi Junji Furuse Young Suk Park Shinichi Ohkawa Gregory M Springett Harpreet S Wasan Peter C Trask Paul Bycott Alejandro D Ricart Sinil Kim Eric Van | 2011 | Lancet Oncology2011，，3： | 4 |
| 6 | Preoperative immunonutrition in patients undergoing liver resection:A prospective randomized trial显示文摘BACKGROUND Preoperative supplementation with immunonutrients, including arginine and n-3 fatty acids, has been shown in a number of systematic reviews to reduce infectious complications in patients who have undergone gastrointestinal surgery. Limited information, however, is available on the benefits of nutritional supplementation enriched with arginine and n-3 fatty acids in patients undergoing liver resection.AIM To evaluate the effects of preoperative nutritional supplementation enriched with arginine and n-3 fatty acids on inflammatory and immunologic markers and clinical outcome in patients undergoing liver resection.METHODS Thirty-four patients undergoing liver resection were randomized to either five days of preoperative Impact? [1020 kcal/d, immunonutrition(IMN) group], or standard care [no supplementation, standard care(STD) group]. Nutritional status was measured at study entry by subjective global assessment(SGA).Functional assessments(grip strength, fatigue and performance status) were carried out at study entry, on the day prior to surgery, and on postoperative day(POD) 7 and 30. Inflammatory and immune markers were measured at study entry, on the day prior to surgery, and POD 1, 3, 5, 7, 10 and 30. Postoperative complications were recorded prospectively until POD30.RESULTS A total of 32 patients(17 IMN and 15 STD) were analysed. All except four patients were SGA class A. The plasma ratio of(eicosapentaenoic acid plus docosahexaenoic acid) to arachidonic acid was higher in IMN patients on the day prior to surgery and POD 1, 3, 5 and 7(P < 0.05). Plasma interleukin(IL)-6 concentrations were elevated in the IMN group(P = 0.017 for POD7). No treatment effect was detected for functional measures, immune response(white cell count and total lymphocytes) or markers of inflammation(C-reactive protein,tumour necrosis factor-α, IL-8, IL-10). There were 10 patients with infectious complications in the IMN group and 4 in the STD group(P = 0.087). Median hospital stay was 9(range 4–49) d in the IMN group and 8(3-34) d in the STD group(P = 0.476).CONCLUSION In well-nourished patients undergoing elective liver resection, this study failed to show any benefit of preoperative immunonutrition. | Kylie Russell Han-Guang Zhang Lyn K GillANDers Adam SJR Bartlett Helena L Fisk Philip C Calder Peter J Swan Lindsay D Plank | 2019 | World Journal of Hepatology2019，11，3： | 3 |
| 7 | Inflammatory bowel disease course in Crohn's disease:Is the natural history changing?显示文摘Crohn’s disease(CD)is a multifactorial potentially debilitating disease.It has a variable disease course,but the majority of patients eventually develop penetrating or stricturing complications leading to repeated surgeries and disability.Studies on the natural history of CD provide invaluable data on its course and clinical predictors,and may help to identify patient subsets based on clinical phenotype.Most data are available from referral centers,however these outcomes may be different from those in population-based cohorts.New data suggest the possibility of a change in the natural history in Crohn’s disease,with an increasing percentage of patients diagnosed with inflammatory disease behavior.Hospitalization rates remain high,while surgery rates seem to have decreased in the last decade.In addition,mortality rates still exceed that of the general population.The impact of changes in treatment strategy,including increased,earlier use of immunosuppressives,biological therapy,and patient monitoring on the natural history of the disease are still conflictive.In this review article,the authors summarize the available evidence on the natural history,current trends,and predictive factors for evaluating the disease course of CD. | Petra A Golovics Michael D Mandel Barbara D Lovasz Peter L Lakatos | 2014 | World Journal of Gastroenterology2014，20，12： | 2 |
| 8 | DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice显示文摘 | Meira Lisiane B Bugni James M Green Stephanie L Lee Chung-Wei Pang Bo Borenshtein Diana Rickman Barry H Rogers Arlin B Moroski-Erkul Catherine A McFaline Jose L Schauer David B Dedon Peter C Fox James G Samson Leona D | 2008 | Journal of Clinical Investigation2008，，7： | 2 |
| 9 | Non-steroidal anti-inflammatory drugs and risk of neoplastic progression in Barrett’s oesophagus: a prospective study显示文摘 | Thomas L Vaughan Linda M Dong Patricia L Blount Kamran Ayub Robert D Odze Carissa A Sanchez Peter S Rabinovitch Brian J Reid | 2005 | Lancet Oncology2005，，12： | 2 |
| 10 | Pancreatic Enzyme Replacement Therapy in Patients With Exocrine Pancreatic Insufficiency Due to Chronic Pancreatitis: A 1-Year Disease Management Study on Symptom Control and Quality of Life显示文摘 | Jan G. D’Haese Güralp O. Ceyhan Ihsan Ekin Demir Peter Layer Waldemar Uhl Matthias L?hr Reinhard Rychlik Konstantinos Pirilis York Z?llner Birgit Gradl Douglas Foerster Julia M?bius Friederike Henniges Helmut Friess | 2014 | Pancreas2014，，： | 2 |
| 11 | Prevalence and predictors of hospitalization in Crohn's disease in a prospective population-based inception cohort from 2000-2012显示文摘AIM: To analyze the prevalence, length and predictors of hospitalization in the biological era in the populationbased inception cohort from Veszprem province.METHODS: Data of 331 incident Crohn's disease(CD) patients diagnosed between January 1, 2000 and December 31, 2010 were analyzed(median age at diagnosis: 28; IQR: 21-40 years). Both in- and outpatient records were collected and comprehensively reviewed.RESULTS: Probabilities of first CD-related hospitalization and re-hospitalization were 32.3%, 45.5%,53.7% and 13.6%, 23.9%, 29.8%, respectively after one, three and five years of follow-up in Kaplan-Meier analysis. First-year hospitalizations were related to diagnostic procedures(37%), surgery or disease activity(27% and 21%). Non-inflammatory disease behavior at diagnosis(HR = 1.32, P = 0.001) and perianal disease(HR = 1.47, P = 0.04) were associated with time to first CD-related hospitalization, while disease behavior change(HR = 2.38, P = 0.002) and need for steroids(HR = 3.14, P = 0.003) were associated with time to first re-hospitalization in multivariate analyses.Early CD-related hospitalization(within the year of diagnosis) was independently associated with need for immunosuppressives(OR = 2.08, P = 0.001) and need for surgeries(OR = 7.25, P < 0.001) during the disease course.CONCLUSION: Hospitalization and re-hospitalization rates are still high in this cohort, especially during the first-year after the diagnosis. Non-inflammatory disease behavior at diagnosis was identified as the pivotal predictive factor of both hospitalization and rehospitalization. | Petra A Golovics Laszlo Lakatos Michael D Mandel Barbara D Lovasz Zsuzsanna Vegh Zsuzsanna Kurti Istvan Szita Lajos S Kiss Tunde Pandur Peter L Lakatos | 2015 | World Journal of Gastroenterology2015，21，23： | 2 |
| 12 | Coal mine methane gas recovery by hydrate formation in a fixed bed of silica sand particles显示文摘 | Zhong D L Nagu D Peter E | 2013 | Energy Fuels2013，27，8： | 1 |
| 13 | Intra-organizational networking for innovation-based corporate entrepreneur- ship 显示文摘 | Kelley D Peters L O'Connor G C | 2009 | Journal of Business Venturing2009，24，3： | 1 |
| 14 | Protein kinase C in culture human placental trophoblasts: identification of isoforms and role in cAMP signaling显示文摘 | Peter L Andras D | 1996 | Biochem J1996，320，： | 1 |
| 15 | Using finite element methods to analyze ancient architecture: an example from the north american arctic 显示文摘 | Richard L Peter D | 2009 | Archaeol Sci2009，36，10： | 1 |
| 16 | Environ- mental Assessment in The Netherlands: Effectively Governing Environmental Protection? A Discourse A- nalysis 显示文摘 | HENS R FRANK VAN L PETER D | 2012 | Environmental Impact Assessment Re- view In Press Corrected Proof2012，20，： | 1 |
| 17 | Promising results with chemoradiafion in patients with sinonasal undifferentiated carcinoma显示文摘 | Rischin D Porceddu S Peters L | 2004 | Head Neck2004，26，5： | 1 |
| 18 | The contribution of Chinese exports to climate change显示文摘 | WEBER C L PETERS G P GUAN D | | 0，，09： | 1 |
| 19 | Clongying and nucleotide of Newcastle disease virus haemagglutinin-neuram inidase mRNA:identification of a putative sialic acid binding site显示文摘 | ELLEN D J PETER L C PTTER T L | 1987 | Vorlogy1987，156，： | 1 |
| 20 | Runoffproduction in a forested, shallow soil, Canadian Shield basin 显示文摘 | Peters D L | 1995 | Water Resour Res1995，31，5： | 1 |
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