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The outcomes and safety of patients undergoing endoscopic retrograde cholangiopancreatography combining a single-use cholangioscope and a single-use duodenoscope:A multicenter retrospective international study
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作者 Alessandro Fugazza Matteo Colombo +20 位作者 Michel Kahaleh V.Raman Muthusamy Bick Benjamin Wim Laleman Carmelo Barbera Carlo Fabbri Jose Nieto Abed Al-Lehibi Mohan Ramchandani Amy Tyberg Haroon Shahid Avik Sarkar Dean Ehrlich Stuart Shermand Cecilia Binda Marco Spadaccini Andrea Iannone Kareem Khalaf Nageshwar Reddy Andrea Anderloni Alessandro Repici 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS CSCD 2024年第1期71-76,共6页
Background: Duodenoscope-related multidrug-resistant organism(MDRO) infections raise concerns. Disposable duodenoscopes have been recently introduced in the market and approved by regulatory agencies with the aim to r... Background: Duodenoscope-related multidrug-resistant organism(MDRO) infections raise concerns. Disposable duodenoscopes have been recently introduced in the market and approved by regulatory agencies with the aim to reduce the risk of endoscopic retrograde cholangiopancreatography(ERCP) associated infections. The aim of this study was to evaluate the outcome of procedures performed with single-use duodenoscopes in patients with clinical indications to single-operator cholangiopancreatoscopy. Methods: This is a multicenter international, retrospective study combining all patients who underwent complex biliopancreatic interventions using the combination of a single-use duodenoscope and a single-use cholangioscope. The primary outcome was technical success defined as ERCP completion for the intended clinical indication. Secondary outcomes were procedural duration, rate of cross-over to reusable duodenoscope, operator-reported satisfaction score(1 to 10) on performance rating of the single-use duodenoscope, and adverse event(AE) rate. Results: A total of 66 patients(26, 39.4% female) were included in the study. ERCP was categorized according to ASGE ERCP grading system as 47(71.2%) grade 3 and 19(28.8%) grade 4. The technical success rate was 98.5%(65/66). Procedural duration was 64(interquartile range 15-189) min, cross-over rate to reusable duodenoscope was 1/66(1.5%). The satisfaction score of the single-use duodenoscope classified by the operators was 8.6 ± 1.3 points. Four patients(6.1%) experienced AEs not directly related to the single-use duodenoscope, namely 2 post-ERCP pancreatitis(PEP), 1 cholangitis and 1 bleeding.Conclusions: Single-use duodenoscope is effective, reliable and safe even in technically challenging procedures with a non-inferiority to reusable duodenoscope, making these devices a viable alternative to standard reusable equipment. 展开更多
关键词 Single-operator cholangioscopy Single-use duodenoscope Endoscopic retrograde CHOLANGIOPANCREATOGRAPHY Indeterminate biliary stricture Difficult biliary stones
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Periodontal treatment and microbiome-targeted therapy in management of periodontitis-related nonalcoholic fatty liver disease with oral and gut dysbiosis 被引量:1
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作者 Ryutaro Kuraji Takahiko Shiba +2 位作者 Tien S Dong Yukihiro Numabe Yvonne L Kapila 《World Journal of Gastroenterology》 SCIE CAS 2023年第6期967-996,共30页
A growing body of evidence from multiple areas proposes that periodontal disease,accompanied by oral inflammation and pathological changes in the microbiome,induces gut dysbiosis and is involved in the pathogenesis of... A growing body of evidence from multiple areas proposes that periodontal disease,accompanied by oral inflammation and pathological changes in the microbiome,induces gut dysbiosis and is involved in the pathogenesis of nonalcoholic fatty liver disease(NAFLD).A subgroup of NAFLD patients have a severely progressive form,namely nonalcoholic steatohepatitis(NASH),which is characterized by histological findings that include inflammatory cell infiltration and fibrosis.NASH has a high risk of further progression to cirrhosis and hepatocellular carcinoma.The oral microbiota may serve as an endogenous reservoir for gut microbiota,and transport of oral bacteria through the gastro-intestinal tract can set up a gut microbiome dysbiosis.Gut dysbiosis increases the production of potential hepatotoxins,including lipopolysaccharide,ethanol,and other volatile organic compounds such as acetone,phenol and cyclopentane.Moreover,gut dysbiosis increases intestinal permeability by disrupting tight junctions in the intestinal wall,leading to enhanced translocation of these hepatotoxins and enteric bacteria into the liver through the portal circulation.In particular,many animal studies support that oral administration of Porphyromonas gingivalis,a typical periodontopathic bacterium,induces disturbances in glycolipid metabolism and inflammation in the liver with gut dysbiosis.NAFLD,also known as the hepatic phenotype of metabolic syndrome,is strongly associated with metabolic complications,such as obesity and diabetes.Periodontal disease also has a bidirectional relationship with metabolic syndrome,and both diseases may induce oral and gut microbiome dysbiosis with insulin resistance and systemic chronic inflammation cooperatively.In this review,we will describe the link between periodontal disease and NAFLD with a focus on basic,epidemiological,and clinical studies,and discuss potential mechanisms linking the two diseases and possible therapeutic approaches focused on the microbiome.In conclusion,it is presumed that the pathogenesis of NAFLD involves a complex crosstalk between periodontal disease,gut microbiota,and metabolic syndrome.Thus,the conventional periodontal treatment and novel microbiome-targeted therapies that include probiotics,prebiotics and bacteriocins would hold great promise for preventing the onset and progression of NAFLD and subsequent complications in patients with periodontal disease. 展开更多
关键词 Periodontal disease Nonalcoholic fatty liver disease MICROBIOTA DYSBIOSIS Metabolic syndrome PROBIOTICS
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Noninvasive scores for the prediction of esophageal varices and risk stratification in patients with cirrhosis 被引量:3
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作者 Saroja Bangaru Jihane N Benhammou James H Tabibian 《World Journal of Hepatology》 2020年第11期908-918,共11页
The primary purpose of variceal screening in patients with cirrhosis is to detect gastroesophageal varices at high risk of hemorrhage and implement preventative intervention(s).It was previously recommended that all p... The primary purpose of variceal screening in patients with cirrhosis is to detect gastroesophageal varices at high risk of hemorrhage and implement preventative intervention(s).It was previously recommended that all patients with cirrhosis undergo initial and periodic longitudinal variceal screening via upper endoscopy.However,there has been growing interest and methods to identify patients with cirrhosis who may not have clinically significant portal hypertension and therefore be unlikely to have varices requiring intervention or benefit from upper endoscopy.Because the population of patients with compensated advanced chronic liver disease continues to grow,it is neither beneficial nor cost-effective to perform endoscopic variceal screening in all patients.Therefore,there is ongoing research into the development of methods to non-invasively risk stratify patients with cirrhosis for the presence of high-risk esophageal varices and effectively limit the population that undergoes endoscopic variceal screening.This is particularly important and timely in light of increasing healthcare reform and barriers to healthcare.In this review,we discuss and compare,with respect to test characteristics and clinical applicability,the available methods used to noninvasively predict the presence of esophageal varices. 展开更多
关键词 Gastroesophageal varices Variceal screening Advanced chronic liver disease CIRRHOSIS Non-invasive screening Upper endoscopy
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Ever-increasing diversity of drug-induced pancreatitis 被引量:8
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作者 Simcha Weissman Muhammad Aziz +3 位作者 Ryan B Perumpail Tej I Mehta Rutwik Patel James H Tabibian 《World Journal of Gastroenterology》 SCIE CAS 2020年第22期2902-2915,共14页
With over 100000 hospital admissions per annum,acute pancreatitis remains the leading gastrointestinal cause of hospitalization in the United States and has farreaching impact well beyond.It has become increasingly re... With over 100000 hospital admissions per annum,acute pancreatitis remains the leading gastrointestinal cause of hospitalization in the United States and has farreaching impact well beyond.It has become increasingly recognized that druginduced pancreatitis(DIP),despite accounting for less than 3%of all cases,represents an important and growing though often inconspicuous cause of acute pancreatitis.Nevertheless,knowledge of DIP is often curtailed by the limited availability of evidence needed to implicate given agents,especially for nonprescription medications.Indeed,the majority of available data is derived from case reports,case series,or case control studies.Furthermore,the mechanism of injury and causality for many of these drugs remain elusive as a definitive correlation is generally not established(<10%of cases).Several classification systems have been proposed,but no single system has been widely adopted,and periodic updates are required in light of ongoing pharmacologic expansion.Moreover,infrequently prescribed medications or those available over-thecounter(including herbal and other alternative remedies)are often overlooked as a potential culprit of acute pancreatitis.Herein,we review the ever-increasing diversity of DIP and the potential mechanisms of injury with the goal of raising awareness regarding the nature and magnitude of this entity.We believe this manuscript will aid in increasing both primary and secondary prevention of DIP,thus ultimately facilitating more expedient diagnosis and a decrease in DIPrelated morbidity. 展开更多
关键词 Drug-induced pancreatitis Acute pancreatitis PHARMACOLOGY Mechanism of action Inflammation ETIOLOGY
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Role of endoscopy in the management of primary sclerosing cholangitis 被引量:4
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作者 Neil Bharat Marya James H Tabibian 《World Journal of Gastrointestinal Endoscopy》 CAS 2019年第2期84-94,共11页
Primary sclerosing cholangitis(PSC) is a rare but prominent fibroinflammatory cholangiopathy which can affect individuals of essentially any age. It carries a median survival of 15-20 years, regardless of age at diagn... Primary sclerosing cholangitis(PSC) is a rare but prominent fibroinflammatory cholangiopathy which can affect individuals of essentially any age. It carries a median survival of 15-20 years, regardless of age at diagnosis, and is a foremost risk factor for cholangiocarcinoma. Given the chronic and progressive nature of PSC, its inherent risk for biliary tract and other complications, and the paucity of effective pharmacotherapies, endoscopy plays a major role in the care of many patients with this disorder. In this review, we discuss the endoscopic management of PSC, including established and evolving approaches to the diagnosis and treatment of its benign as well as malignant sequelae. Owing to the rarity of PSC and dearth of high-quality evidence, we propose pragmatic approaches based on both currently available data and expert opinion. 展开更多
关键词 BILE duct diseases CHOLANGIOCARCINOMA Inflammatory bowel disease Endoscopic RETROGRADE CHOLANGIOPANCREATOGRAPHY Biopsy Primary SCLEROSING CHOLANGITIS
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Metabolic syndrome does not affect sustained virologic response of direct-acting antivirals while hepatitis C clearance improves hemoglobin A1c 被引量:4
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作者 Tien S Dong Elizabeth S Aby +4 位作者 Jihane N Benhammou Jenna Kawamoto Steven-Huy Han Folasade P May Joseph R Pisegna 《World Journal of Hepatology》 CAS 2018年第9期612-621,共10页
AIM To determine whether successful treatment with direc-tacting antivirals(DAA) is associated with improvements in hemoglobin A1 c(HbA1 c) and if type 2 diabetes mellitus(T2 DM) or metabolic syndrome affects sustaine... AIM To determine whether successful treatment with direc-tacting antivirals(DAA) is associated with improvements in hemoglobin A1 c(HbA1 c) and if type 2 diabetes mellitus(T2 DM) or metabolic syndrome affects sustained virologic response(SVR).METHODS We performed a retrospective analysis of all hepatitis C virus(HCV) patients at the VA Greater Los Angeles Healthcare System treated with varying DAA therapy between 2014-2016. Separate multivariable logistic regression was performed to determine predictors of HbA1 c decrease ≥ 0.5 after DAA treatment and predictors of SVR 12-wk post treatment(SVR12).RESULTS A total of 1068 patients were treated with DAA therapy between 2014-2016. The presence of T2 DM or metabolic syndrome did not adversely affect SVR12. 106 patients had both HCV and T2 DM. Within that cohort,patients who achieved SVR12 had lower mean HbA1 c pre treatment(7.35 vs 8.60,P = 0.02),and lower mean HbA1 c post-treatment compared to non-responders(6.55 vs 8.61,P = 0.01). The mean reduction in HbA1 c after treatment was greater for those who achieved SVR12 than for non-responders(0.79 vs 0.01,P = 0.03). In adjusted models,patients that achieved SVR12 were more likely to have a HbA1 c decrease of ≥ 0.5 than those that did not achieve SVR12(adjusted OR = 7.24,95%CI: 1.22-42.94). CONCLUSION In HCV patients with T2 DM,successful treatment with DAA was associated with a significant reduction in HbA1 c suggesting that DAA may have a role in improving insulin sensitivity. Furthermore,the presence of T2 DM or metabolic syndrome does not adversely affect SVR12 rates in patients treated with DAA. 展开更多
关键词 Hepatitis C virus HEMOGLOBIN A1C Diabetes MELLITUS Direct-acting ANTIVIRALS Metabolic syndrome
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Peroral cholangioscopy:Update on the state-of-the-art 被引量:4
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作者 Amith Subhash James L Buxbaum James H Tabibian 《World Journal of Gastrointestinal Endoscopy》 2022年第2期63-76,共14页
Peroral cholangioscopy(POC)is an endoscopic procedure that allows direct intraductal visualization of the biliary tract.POC has emerged as a vital tool for indeterminate biliary stricture evaluation and treatment of d... Peroral cholangioscopy(POC)is an endoscopic procedure that allows direct intraductal visualization of the biliary tract.POC has emerged as a vital tool for indeterminate biliary stricture evaluation and treatment of difficult biliary stones.Over several generations of devices,POC has fulfilled additional clinical needs where other diagnostic or therapeutic modalities have been inadequate.With adverse event rates comparable to standard endoscopic retrograde cholangioscopy and unique technical attributes,the role of POC is likely to continue expand.In this frontiers article,we highlight the existing and growing clinical applications of POC as well as areas of ongoing research. 展开更多
关键词 Peroral cholangioscopy SpyGlass^(TM) Difficult bile duct stones Indeterminate biliary strictures Cholangioscope-guided biopsy Cholangioscope-guided lithotripsy
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Best practices for prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis 被引量:2
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作者 Simcha Weissman Mohamed Ahmed +2 位作者 Matthew R Baniqued Dean Ehrlich James H Tabibian 《World Journal of Gastrointestinal Endoscopy》 2021年第6期161-169,共9页
Acute pancreatitis is of one the most common gastroenterology-related indications for hospital admissions worldwide.With the widespread reliance on endoscopic retrograde cholangiopancreatography(ERCP)for the managemen... Acute pancreatitis is of one the most common gastroenterology-related indications for hospital admissions worldwide.With the widespread reliance on endoscopic retrograde cholangiopancreatography(ERCP)for the management of pancreaticobiliary conditions,post-ERCP pancreatitis(PEP)has come to represent an important etiology of acute pancreatitis.Despite many studies aiming to better understand the pathogenesis and prevention of this iatrogenic disorder,findings have been heterogeneous,and considerable variation in clinical practice exists.Herein,we review the literature regarding PEP with the goal to raise awareness of this entity,discuss recent data,and present evidence-based best practices.We believe this manuscript will be useful for gastrointestinal endoscopists as well as other specialists involved in the management of patients with PEP. 展开更多
关键词 Post-endoscopic retrograde cholangiopancreatography pancreatitis Endoscopic retrograde cholangiopancreatography PANCREATITIS Practice guidelines PHARMACOLOGY PREVENTION
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Gut microbiome and pancreatic cancer cachexia:An evolving relationship 被引量:1
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作者 Andrew Hendifar Rasaq Akinsola +8 位作者 Hayato Muranaka Arsen Osipov Shant Thomassian Natalie Moshayedi Julianne Yang Jonathan Jacobs Suzanne Devkota Neil Bhowmick Jun Gong 《World Journal of Gastrointestinal Oncology》 SCIE 2022年第7期1218-1226,共9页
Nearly 80% of patients with pancreatic ductal adenocarcinoma(PDAC)develop cachexia along their disease course.Cachexia is characterized by progressive weight loss,muscle wasting,and systemic inflammation and has been ... Nearly 80% of patients with pancreatic ductal adenocarcinoma(PDAC)develop cachexia along their disease course.Cachexia is characterized by progressive weight loss,muscle wasting,and systemic inflammation and has been linked to poorer outcomes and impairments in quality of life.Management of PDAC cachexia has historically involved a multidisciplinary effort comprised of nutritional support,pancreatic enzyme replacement therapy,and/or pharmacologic interventions.Despite current interventions to mitigate PDAC cachexia,a significant proportion of patients continue to die from complications associated with cachexia underscoring the need for novel insights and treatments for this syndrome.We highlight the feasibility and effectiveness of a recent enteral feeding prospective trial at our institution to improve cachexia outcomes in patients with advanced PDAC.Additionally,we were among the first to characterize the stool microbiome composition in patients with advanced PDAC receiving enteral feeding for the treatment of cachexia.Novel insights into the relationship between enteral nutritional support,cachexia,and the gut microbiome are presented.These promising results are discussed in the context of a potential ability to modulate the stool microbiome as a new interventional strategy to mitigate PDAC cachexia. 展开更多
关键词 Gut microbiome Pancreatic cancer STOOL CACHEXIA Inflammation Weight
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Large polyps:Pearls for the referring and receiving endoscopist 被引量:1
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作者 Eric Markarian Brian M Fung +1 位作者 Mohit Girotra James H Tabibian 《World Journal of Gastrointestinal Endoscopy》 2021年第12期638-648,共11页
Polyps are precursors to colorectal cancer,the third most common cancer in the United States.Large polyps,i.e.,,those with a size≥20 mm,are more likely to harbor cancer.Colonic polyps can be removed through various t... Polyps are precursors to colorectal cancer,the third most common cancer in the United States.Large polyps,i.e.,,those with a size≥20 mm,are more likely to harbor cancer.Colonic polyps can be removed through various techniques,with the goal to completely resect and prevent colorectal cancer;however,the management of large polyps can be relatively complex and challenging.Such polyps are generally more difficult to remove en bloc with conventional methods,and depending on level of expertise,may consequently be resected piecemeal,leading to an increased rate of incomplete removal and thus polyp recurrence.To effectively manage large polyps,endoscopists should be able to:(1)Evaluate the polyp for characteristics which predict high difficulty of resection or incomplete removal;(2)Determine the optimal resection technique(e.g.,snare polypectomy,endoscopic mucosal resection,endoscopic submucosal dissection,etc.);and(3)Recognize when to refer to colleagues with greater expertise.This review covers important considerations in this regard for referring and receiving endoscopists and methods to best manage large colonic polyps. 展开更多
关键词 ADENOMA Endoscopic mucosal resection Endoscopic tattoo Colorectal cancer POLYPECTOMY
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Colonoscopic management of diverticular disease 被引量:1
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作者 M Phillip Fejleh James H Tabibian 《World Journal of Gastrointestinal Endoscopy》 2020年第2期53-59,共7页
Diverticula are the most common incidental finding during routine colonoscopy,and their prevalence increases with patient age.The term“diverticular disease”encompasses the range of clinical manifestations and compli... Diverticula are the most common incidental finding during routine colonoscopy,and their prevalence increases with patient age.The term“diverticular disease”encompasses the range of clinical manifestations and complications that can occur with colonic diverticula,including diverticular bleeding,diverticulitisassociated strictures,and acute diverticulitis.Colonoscopy is a vital tool in the diagnosis and management of diverticular disease and can be useful in a variety of regards.In this editorial,we concisely delineate the current approach to and practices in colonoscopic management of diverticular disease.In particular,we discuss treatment options for diverticular bleeding,propose consideration of colonic stenting as a bridge to surgery in patients with diverticulitis-associated strictures,and the need for diagnostic colonoscopy following an episode of acute diverticulitis in order to rule out underlying conditions such as colonic malignancy or inflammatory bowel disease.In addition,we offer practical tips for performing safe and successful colonoscopy in patients with dense diverticulosis coli. 展开更多
关键词 Acute diverticulitis Diverticular bleeding Colon stricture
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Impact of sustained virologic response on chronic kidney disease progression in hepatitis C
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作者 Elizabeth S Aby Tien S Dong +2 位作者 Jenna Kawamoto Joseph R Pisegna Jihane N Benhammou 《World Journal of Hepatology》 CAS 2017年第36期1352-1360,共9页
AIM To determine how sustained virological response at 12 wk(SVR12) with direct acting antivirals(DAAs) for the treatment of hepatitis C virus(HCV) infection affects chronic kidney disease(CKD) progression. METHODS A ... AIM To determine how sustained virological response at 12 wk(SVR12) with direct acting antivirals(DAAs) for the treatment of hepatitis C virus(HCV) infection affects chronic kidney disease(CKD) progression. METHODS A retrospective analysis was performed in patients aged ≥ 18 years treated for HCV with DAAs at the VA Greater Los Angeles Healthcare System from 2014-2016. The treatment group was compared to patients with HCV from 2011-2013 who did not undergo HCV treatment, prior to the introduction of DAAs; the control group was matched to the study group in terms of age, gender, and ethnicity. Analysis of variance and co-variance was performed to compare means between SVR12 subgroups adjusting for co-variates.RESULTS Five hundred and twenty-three patients were evaluated. When comparing the rate of change in estimated glomerular filtration rate(e GFR) one-year after HCV treatment to one-year before treatment, patients who achieved SVR12 had a decline in GFR of 3.1 m L/min ± 0.75 m L/min per 1.73 m^2 compared to a decline in e GFR of 11.0 m L/min ± 2.81 m L/min per 1.73 m^2 in patients who did not achieve SVR12(P = 0.002). There were no significant clinical differences between patients who achieved SVR12 compared to those who did not in terms of cirrhosis, treatment course, treatment experience, CKD stage prior to treatment, diuretic use or other co-morbidities. The decline in e GFR in those with untreated HCV over 2 years was 2.8 m L/min ± 1.0 m L/min per 1.73 m^2, which was not significantly different from the e GFR decline noted in HCV-treated patients who achieved SVR12(P = 0.43).CONCLUSION Patients who achieve SVR12 have a lesser decline in renal function, but viral eradication in itself may not be associated improvement in renal disease progression. 展开更多
关键词 Hepatitis C Direct-acting antivirals Chronic kidney disease End stage renal disease Sustained virological response
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Timing of percutaneous endoscopic gastrostomy tube placement in post-stroke patients does not impact mortality, complications, or outcomes
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作者 Kavya M Reddy Preston Lee +4 位作者 Parul J Gor Antonio Cheesman Noor Al-Hammadi David John Westrich Jason Taylor 《World Journal of Gastrointestinal Pharmacology and Therapeutics》 2022年第5期77-87,共11页
BACKGROUND Percutaneous Endoscopic Gastrostomy(PEG)tubes are often placed for dysphagia following a stroke in order to maintain sufficient caloric intake.The 2011 ASGE guidelines recommend delaying PEG tube placement ... BACKGROUND Percutaneous Endoscopic Gastrostomy(PEG)tubes are often placed for dysphagia following a stroke in order to maintain sufficient caloric intake.The 2011 ASGE guidelines recommend delaying PEG tube placement for two weeks,as half of patients with dysphagia improve within 2 wk.There are few studies comparing outcomes based on timing of PEG tube placement,and there is increasing demand for early PEG tube placement to meet requirements for timely discharge to rehab and skilled nursing facilities.AIM To assess the safety of early(≤7 d post stroke)vs late(>7 d post stroke)PEG tube placement and evaluate whether pre-procedural risk factors could predict mortality or complications.METHODS We performed a retrospective study of patients undergoing PEG tube placement for dysphagia following a stroke at two hospitals in Saint Louis,MO between January 2011 and December 2017.Patients were identified by keyword search of endoscopy reports.Mortality,peri-procedural complication rates,and post-procedural complication rates were compared in both groups.Predictors of morbidity and mortality such as protein-calorie malnutrition,presence of an independent cardiovascular risk equivalent,and presence of Systemic inflammatory response syndrome(SIRS)criteria or documented infection were evaluated by multivariate logistic regression.RESULTS 154 patients had a PEG tube placed for dysphagia following a stroke,92 in the late group and 62 in the early group.There were 32 observed deaths,with 8 occurring within 30 d of the procedure.There was an increase in peri-procedural and post-procedural complications with delayed PEG placement which was not statistically significant.Hospital length of stay was significantly less in patients with early PEG tube placement(12.9 vs 22.34 d,P<0.001).Protein calorie malnutrition,presence of SIRS criteria and/or documented infection prior to procedure or having a cardiovascular disease risk equivalent did not significantly predict mortality or complications.CONCLUSION Early PEG tube placement following a stroke did not result in a higher rate of mortality or complications and significantly decreased hospital length of stay.Given similar safety outcomes in both groups,early PEG tube placement should be considered in the appropriate patient to potentially reduce length of hospital stay and incurred costs. 展开更多
关键词 Percutaneous endoscopic gastrostomy tube DYSPHAGIA Stroke Enteral nutrition Gastrostomy/adverse effect
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BZD9L1 benzimidazole analogue hampers colorectal tumor progression by impeding angiogenesis
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作者 Chern Ein Oon Ayappa V Subramaniam +6 位作者 Lik Yang Ooi Ashwaq Hamid Salem Yehya Yeuan Ting Lee Gurjeet Kaur Sreenivasan Sasidharan Beiying Qiu Xiaomeng Wang 《World Journal of Gastrointestinal Oncology》 SCIE 2023年第5期810-827,共18页
BACKGROUND The development of new vasculatures(angiogenesis)is indispensable in supplying oxygen and nutrients to fuel tumor growth.Epigenetic dysregulation in the tumor vasculature is critical to colorectal cancer(CR... BACKGROUND The development of new vasculatures(angiogenesis)is indispensable in supplying oxygen and nutrients to fuel tumor growth.Epigenetic dysregulation in the tumor vasculature is critical to colorectal cancer(CRC)progression.Sirtuin(SIRT)enzymes are highly expressed in blood vessels.BZD9L1 benzimidazole analogue is a SIRT 1 and 2 inhibitor with reported anticancer activities in CRC.However,its role has yet to be explored in CRC tumor angiogenesis.AIM To investigate the anti-angiogenic potential of BZD9L1 on endothelial cells(EC)in vitro,ex vivo and in HCT116 CRC xenograft in vivo models.METHODS EA.hy926 EC were treated with half inhibitory concentration(IC50)(2.5μM),IC50(5.0μM),and double IC50(10.0μM)of BZD9L1 and assessed for cell proliferation,adhesion and SIRT 1 and 2 protein expression.Next,2.5μM and 5.0μM of BZD9L1 were employed in downstream in vitro assays,including cell cycle,cell death and sprouting in EC.The effect of BZD9L1 on cell adhesion molecules and SIRT 1 and 2 were assessed via real-time quantitative polymerase chain reaction(qPCR).The growth factors secreted by EC post-treatment were evaluated using the Quantibody Human Angiogenesis Array.Indirect co-culture with HCT116 CRC cells was performed to investigate the impact of growth factors modulated by BZD9L1-treated EC on CRC.The effect of BZD9L1 on sprouting impediment and vessel regression was determined using mouse choroids.HCT116 cells were also injected subcutaneously into nude mice and analyzed for the outcome of BZD9L1 on tumor necrosis,Ki67 protein expression indicative of proliferation,cluster of differentiation 31(CD31)and CD34 EC markers,and SIRT 1 and 2 genes via hematoxylin and eosin,immunohistochemistry and qPCR,respectively.RESULTS BZD9L1 impeded EC proliferation,adhesion,and spheroid sprouting through the downregulation of intercellular adhesion molecule 1,vascular endothelial cadherin,integrin-alpha V,SIRT1 and SIRT2 genes.The compound also arrested the cells at G1 phase and induced apoptosis in the EC.In mouse choroids,BZD9L1 inhibited sprouting and regressed sprouting vessels compared to the negative control.Compared to the negative control,the compound also reduced the protein levels of angiogenin,basic fibroblast growth factor,platelet-derived growth factor and placental growth factor,which then inhibited HCT116 CRC spheroid invasion in co-culture.In addition,a significant reduction in CRC tumor growth was noted alongside the downregulation of human SIRT1(hSIRT1),hSIRT2,CD31,and CD34 EC markers and murine SIRT2 gene,while the murine SIRT1 gene remained unaffected,compared to vehicle control.Histology analyses revealed that BZD9L1 at low(50 mg/kg)and high(250 mg/kg)doses reduced Ki-67 protein expression,while BZD9L1 at the high dose diminished tumor necrosis compared to vehicle control.CONCLUSION These results highlighted the anti-angiogenic potential of BZD9L1 to reduce CRC tumor progression.Furthermore,together with previous anticancer findings,this study provides valuable insights into the potential of BZD9L1 to co-target CRC tumor vasculatures and cancer cells via SIRT1 and/or SIRT2 down-regulation to improve the therapeutic outcome. 展开更多
关键词 Colorectal cancer BZD9L1 SIRTUIN BENZIMIDAZOLE ANGIOGENESIS
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Hepatocellular carcinoma in nonalcoholic fatty liver disease:A growing challenge
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作者 Angelo Z Mattos Jose D Debes +5 位作者 Renu Dhanasekaran Jihane N Benhammou Marco Arrese Andre Luiz V Patricio Amanda C Zilio Angelo A Mattos 《World Journal of Hepatology》 2021年第9期1107-1121,共15页
Nonalcoholic fatty liver disease(NAFLD)is the most common cause of liver disease worldwide,and its prevalence increases continuously.As it predisposes to hepatocellular carcinoma both in the presence and in the absenc... Nonalcoholic fatty liver disease(NAFLD)is the most common cause of liver disease worldwide,and its prevalence increases continuously.As it predisposes to hepatocellular carcinoma both in the presence and in the absence of cirrhosis,it is not surprising that the incidence of NAFLD-related hepatocellular carcinoma would also rise.Some of the mechanisms involved in hepatocarcinogenesis are particular to individuals with fatty liver,and they help explain why liver cancer develops even in patients without cirrhosis.Genetic and immune-mediated mechanisms seem to play an important role in the development of hepatocellular carcinoma in this population.Currently,it is consensual that patients with NAFLD-related cirrhosis should be surveilled with ultrasonography every 6 mo(with or without alpha-fetoprotein),but it is known that they are less likely to follow this recommendation than individuals with other kinds of liver disease.Moreover,the performance of the methods of surveillance are lower in NAFLD than they are in other liver diseases.Furthermore,it is not clear which subgroups of patients without cirrhosis should undergo surveillance.Understanding the mechanisms of hepatocarcinogenesis in NAFLD could hopefully lead to the identification of biomarkers to be used in the surveillance for liver cancer in these individuals.By improving surveillance,tumors could be detected in earlier stages,amenable to curative treatments. 展开更多
关键词 Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis Hepatocellular carcinoma HEPATOCARCINOGENESIS SURVEILLANCE
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Increasing contribution of non-alcoholic fatty liver disease to hepatocellular carcinoma incidence and mortality in U.S. Medicare
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作者 Carrie R.Wong Joseph K.Lim 《Hepatobiliary Surgery and Nutrition》 SCIE 2019年第5期506-508,共3页
Hepatocellular carcinoma(HCC)has one of the fastestgrowing rates of cancer-related incidence and mortalityin the United States(U.S.)(1-3).From 2009 to 2013,theaverage annual percent change(AAPC)for liver cancerinciden... Hepatocellular carcinoma(HCC)has one of the fastestgrowing rates of cancer-related incidence and mortalityin the United States(U.S.)(1-3).From 2009 to 2013,theaverage annual percent change(AAPC)for liver cancerincidence became the highest among other reported cancersfor both males(+2.9%)and females(+3.8%)(1).In addition,cancer-related mortality rates for liver cancer are the highestamong solid malignancies from 2010 to 2014 for males(+2.6%)and females(+3.0%)(1). 展开更多
关键词 MORTALITY liver cancer
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Machine learning models compared to existing criteria for noninvasive prediction of endoscopic retrograde cholangiopancreatography-confirmed choledocholithiasis 被引量:3
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作者 Camellia Dalai John M Azizian +5 位作者 Harry Trieu Anand Rajan Formosa C Chen Tien Dong Simon W Beaven James H.Tabibian 《Liver Research》 CSCD 2021年第4期224-231,共8页
Background and aims:Noninvasive predictors of choledocholithiasis have generally exhibited marginal performance characteristics.We aimed to identify noninvasive independent predictors of endoscopic retrograde cholangi... Background and aims:Noninvasive predictors of choledocholithiasis have generally exhibited marginal performance characteristics.We aimed to identify noninvasive independent predictors of endoscopic retrograde cholangiopancreatography(ERCP)-confirmed choledocholithiasis and accordingly developed predictive machine learning models(MLMs).Methods:Clinical data of consecutive patients undergoing first-ever ERCP for suspected chol-edocholithiasis from 2015 to 2019 were abstracted from a prospectively-maintained database.Multiple logistic regression was used to identify predictors of ERCP-confirmed choledocholithiasis.MLMs were then trained to predict ERCP-confirmed choledocholithiasis using pre-ERCP ultrasound(US)imaging only as well as using all available noninvasive imaging(US,computed tomography,and/or magnetic reso-nance cholangiopancreatography).The diagnostic performance of American Society for Gastrointestinal Endoscopy(ASGE)“high-likelihood”criteria was compared to MLMs.Results:We identified 270 patients(mean age 46 years,62.2%female,73.7%Hispanic/Latino,59%with noninvasive imaging positive for choledocholithiasis)with native papilla who underwent ERCP for suspected choledocholithiasis,of whom 230(85.2%)were found to have ERCP-confirmed chol-edocholithiasis.Logistic regression identified choledocholithiasis on noninvasive imaging(odds ratio(OR)¼3.045,P¼0.004)and common bile duct(CBD)diameter on noninvasive imaging(OR¼1.157,P¼0.011)as predictors of ERCP-confirmed choledocholithiasis.Among the various MLMs trained,the random forest-based MLM performed best;sensitivity was 61.4%and 77.3%and specificity was 100%and 75.0%,using US-only and using all available imaging,respectively.ASGE high-likelihood criteria demonstrated sensitivity of 90.9%and specificity of 25.0%;using cut-points achieving this specificity,MLMs achieved sensitivity up to 97.7%.Conclusions:MLMs using age,sex,race/ethnicity,presence of diabetes,fever,body mass index(BMI),total bilirubin,maximum CBD diameter,and choledocholithiasis on pre-ERCP noninvasive imaging predict ERCP-confirmed choledocholithiasis with good sensitivity and specificity and outperform the ASGE criteria for patients with suspected choledocholithiasis. 展开更多
关键词 Machine learning models(MLMs) Endoscopic retrograde cholangiopancreatography(ERCP) Noninvasive imaging Bile duct disorders Common bile duct stones GALLSTONES
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Preventative care in cholestatic liver disease: Pearls for the specialist and subspecialist
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作者 Adnan Malik Ani A.Kardashian +2 位作者 Kais Zakharia Christopher L.Bowlus James H.Tabibian 《Liver Research》 2019年第2期118-127,共10页
Cholestatic liver diseases(CLDs)encompass a variety of disorders of abnormal bile formation and/or flow.CLDs often lead to progressive hepatic insult and injury and following the development of cirrhosis and associate... Cholestatic liver diseases(CLDs)encompass a variety of disorders of abnormal bile formation and/or flow.CLDs often lead to progressive hepatic insult and injury and following the development of cirrhosis and associated complications.Many such complications are clinically silent until they manifest with severe sequelae,including but not limited to life-altering symptoms,metabolic disturbances,cirrhosis,and hepatobiliary diseases as well as other malignancies.Primary sclerosing cholangitis(PSC)and primary biliary cholangitis(PBC)are the most common CLDs,and both relate to mutual as well as unique complications.This review provides an overview of PSC and PBC,with a focus on preventive measures aimed to reduce the incidence and severity of disease-related complications. 展开更多
关键词 Biliary tract diseases Primary sclerosing cholangitis(PSC) Primary biliary cholangitis(PBC) Cirrhosis Inflammatory bowel disease(IBD) Metabolic bone disease PRURITUS PROPHYLAXIS
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Emerging risk factors for nonalcoholic fatty liver disease associated hepatocellular carcinoma 被引量:4
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作者 Jihane NBenhammou Jonathan Lin +1 位作者 Shehnaz KHussain Mohamed El-Kabany 《Hepatoma Research》 2020年第6期92-106,共15页
Worldwide,nonalcoholic fatty liver disease(NAFLD)has reached epidemic proportions and in parallel,hepatocellular carcinoma(HCC)has become one of the fastest growing cancers.Epidemiological studies have not only shed l... Worldwide,nonalcoholic fatty liver disease(NAFLD)has reached epidemic proportions and in parallel,hepatocellular carcinoma(HCC)has become one of the fastest growing cancers.Epidemiological studies have not only shed light on the prevalence and incidence of the disease but have also unmasked important environmental risk factors,including the role of diabetes and dyslipidemia in disease pathogenesis.Genetic association studies have identified single nucleotide polymorphisms implicated in NAFLD-HCC,many of which are part of lipid metabolism pathways.Through these clinical studies and subsequently,translational and basic research,the role of statins as a chemoprotective agent has also emerged with ongoing clinical trials assessing their utility in HCC prevention and treatment.In this review,we summarize the recent epidemiological studies describing the burden of NAFLD-HCC in different patient populations and countries.We discuss the genetic and environmental risk factors for NAFLD-HCC and highlight the chemoprotective role of statins and aspirin.We also summarize what is known about NAFLD-HCC in the cirrhosis and non-cirrhosis populations and briefly address the role of surveillance in NAFLD-HCC patients. 展开更多
关键词 Nonalcoholic fatty liver disease nonalcoholic steatohepatitis hepatocellular carcinoma STATINS metabolic syndrome
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