Learn about the transformative and innovative research by our faculty.

Fibrosis-stage Specific Incidence of Hepatocellular Cancer after Hepatitis C Cure with Direct-Acting Antivirals: A Systematic Review & Meta-analysis

Kim NJ, Vutien P, Cleveland E, Cravero A, Ioannou GN

Background and Aims: Hepatitis C virus (HCV) eradication with direct-acting antivirals (DAA) reduces hepatocellular carcinoma (HCC) risk. Pooled HCC incidence rates by cirrhosis status and fibrosis stage have not been estimated using meta-analysis. Methods: We searched PubMed, Web of Science, Embase, and Cochrane Library from 1/1/2014-12/31/2020 to identify studies assessing HCC incidence or outcomes by cirrhosis status, in adults with HCV who achieved sustained virologic response (SVR) after DAAs. Pooled estimates were obtained using random-effects modeling. Subgroup, sensitivity, and meta-regression analyses were performed to evaluate heterogeneity.

Gawron AJ, Dominitz JA

Although community providers performed more timely colonoscopy than the Veterans Affairs medical center (mean 25 days earlier), colonoscopy quality was significantly lower for other important quality metrics, including adenoma detection, advanced adenoma detection, adenomas per colonoscopy, and appropriate surveillance recommendations. This study highlights the need for continued efforts to assure high-quality colonoscopy in all settings.

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Identifying Liver Transplant Candidates at Risk of Wait List Removal Due to Nonadherence Using a Quality-of-Life Survey: A Competing Risk Analysis

Nichols J, Vutien P, Perkins J, Biggins SW, Dick AAS, McCandlish S, Bambha K, Reyes J

Liver transplantation (LT) is a lifesaving treatment for patients with end-stage liver disease. However, there is a significant shortage of donor livers, and transplant programs have an ethical obligation to ensure that the limited supply of donor organs is allocated to those candidates who are most likely to benefit from LT. It is critical that transplant programs develop a rigorous candidate surveillance process for patients on wait lists to determine those who are nonadherent. Unfortunately, nonadherence in candidates on wait lists is not uncommon and has been shown to be as high as 16.7% in LT candidates. Nonadherence with prescribed therapies, lack of attendance to clinical appointments, not following medical recommendations, and active substance use are recognized as contraindications to remaining on wait lists by most transplant programs. In addition, it has been observed that patients in lower resourced socioeconomic areas have higher rates of nonadherence to medical care.

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Quality measures in HCC care by the Practice Metrics Committee of the American Association for the Study of Liver Diseases

Asrani SK, Ghabril MS, Kuo A, Merriman RB, Morgan T, Parikh ND, Ovchinsky N, Kanwal F, Volk ML, Ho C, Serper M, Mehta S, Agopian V, Cabrera R, Chernyak V, El-Serag HB, Heimbach J, Ioannou GN, Kaplan D, Marrero J, Mehta N, Singal A, Salem R, Taddei T, Walling AM, Tapper EB

The burden of HCC is substantial. To address gaps in HCC care, the American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) aimed to develop a standard set of process-based measures and patient-reported outcomes (PROs) along the HCC care continuum. We identified candidate process and outcomes measures for HCC care based on structured literature review. 

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Somatic whole genome dynamics of precancer in Barrett’s esophagus reveals features associated with disease progression

Paulson TG, Galipeau PC, Oman KM, Sanchez CA, Kuhner MK, Smith LP, Hadi K, Shah M, Arora K, Shelton J, Johnson M, Corvelo A, Maley CC, Yao X, Sanghvi R, Venturini E, Emde AK, Hubert B, Imielinski M, Robine N, Reid BJ, Li X

While the genomes of normal tissues undergo dynamic changes over time, little is understood about the temporal-spatial dynamics of genomes in premalignant tissues that progress to cancer compared to those that remain cancer-free. Here we use whole genome sequencing to contrast genomic alterations in 427 longitudinal samples from 40 patients with stable Barrett’s esophagus compared to 40 Barrett’s patients who progressed to esophageal adenocarcinoma (ESAD).

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A Phenome-Wide Association Study of genes associated with COVID-19 severity reveals shared genetics with complex diseases in the Million Veteran Program

Anurag Verma, Noah L Tsao, Lauren O Thomann, Yuk-Lam Ho, Sudha K Iyengar, Shiuh-Wen Luoh , Rotonya Carr, Dana C Crawford, Jimmy T Efird, Jennifer E Huffman, Adriana Hung, Kerry L Ivey, Michael G Levin, Julie Lynch, Pradeep Natarajan, Saiju Pyarajan, Alexander G Bick, Lauren Costa, Giulio Genoves, Richard Hauger, Ravi Madduri, Gita A Pathak, Renato Polimant, Benjamin Voight, Marijana Vujkovic, Seyedeh Maryam Zekavat, Hongyu Zhao, Marylyn D Ritchie, VA Million Veteran Program COVID-19 Science Initiative; Kyong-Mi Chang, Kelly Cho, Juan P Casas, Philip S Tsao, J Michael Gaziano, Christopher O'Donnell, Scott M Damrauer, Katherine P Liao

The study aims to determine the shared genetic architecture between COVID-19 severity with existing medical conditions using electronic health record (EHR) data. We conducted a Phenome-Wide Association Study (PheWAS) of genetic variants associated with critical illness (n = 35) or hospitalization (n = 42) due to severe COVID-19 using genome-wide association summary data from the Host Genetics Initiative. PheWAS analysis was performed using genotype-phenotype data from the Veterans Affairs Million Veteran Program (MVP). Phenotypes were defined by International Classification of Diseases (ICD) codes mapped to clinically relevant groups using published PheWAS methods. Among 658,582 Veterans, variants associated with severe COVID-19 were tested for association across 1,559 phenotypes.

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Diagnosis and Management of Cancer Risk in the Gastrointestinal Hamartomatous Polyposis Syndromes: Recommendations From the US Multi-Society Task Force on Colorectal Cancer

Boland, C. Richard, Idos, Gregory E., Durno, Carol, Giardiello, Francis M., Anderson, Joseph C., Burke, Carol A., Dominitz, Jason A., Gross, Seth, Gupta, Samir, Jacobson, Brian C.,  Patel, Swati G., Shaukat, Aasma, Syngal, Sapna, Robertson, Douglas J.

The gastrointestinal hamartomatous polyposis syndromes are rare, autosomal dominant disorders associated with an increased risk of benign and malignant intestinal and extraintestinal tumors. They include Peutz-Jeghers syndrome, juvenile polyposis syndrome, the PTEN hamartoma tumor syndrome (including Cowden’s syndrome and Bannayan-Riley-Ruvalcaba syndrome), and hereditary mixed polyposis syndrome. Diagnoses are based on clinical criteria and, in some cases, confirmed by demonstrating the presence of a germline pathogenic variant. 

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Methylation subtypes of primary prostate cancer predict poor prognosis

Wang X, Jordahl KM, Zhu C, Livingstone J, Rhie SK, Wright JL, Grady WM, Boutros PC, Stanford JL, Dai JY.

Background Prostate cancer patients experience heterogeneous outcomes after radical prostatectomy. Genomic studies including The Cancer Genome Atlas (TCGA) have reported molecular signatures of prostate cancer, but few studies have assessed the prognostic effects of DNA methylation profiles. Methods We conducted the largest methylome subtyping analysis for primary prostate tumors to date, using methylome data from three patient populations: TCGA, a prostate cancer cohort study conducted at the Fred Hutchinson Cancer Research Center (FH), and the Canadian International Cancer Genome Consortium (ICGC) cohort. Four subtypes were detected in the TCGA dataset, then independently assigned to FH and ICGC cohort data.

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Use and Safety of Per-Oral Endoscopic Myotomy for Achalasia in the US

Lois AW, Oelschlager BK, Wright AS, Templeton AW, Flum DR, Farjah F.

Importance: Several professional practice guidelines recommend per-oral endoscopic myotomy (POEM) as a potential first-line therapy for the management of achalasia, yet payers remain hesitant to reimburse for the procedure owing to unanswered questions regarding safety. Objective: To evaluate the use, safety, health care utilization, and costs associated with the use of POEM for treatment of achalasia relative to laparoscopic Heller myotomy (LHM) and pneumatic dilation (PD). Design, setting, and participants: This was a retrospective national cohort study of commercially insured patients, aged 18 to 63 years, who underwent index intervention for achalasia with either LHM, PD, or POEM in the US between July 1, 2010, and December 31, 2017.

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Pre-Endoscopy COVID-19 screening and SARS-CoV-2 nucleic acid amplification testing in the VA Healthcare System: Clinical practice patterns, outcomes, and relationship to procedure volume

Gawron AJ, Sultan S, Glorioso TJ, Califano S, Kralovic SM, Jones M, Kirsh S, Dominitz JA.

Background & aims: The COVID-19 pandemic has had profound impacts worldwide, including upon the performance of gastrointestinal endoscopy. We aimed to 1) describe the performance and outcomes of pre-endoscopy COVID-19 symptom and exposure screening and SARS-CoV-2 nucleic acid amplification (NAAT) across the national Veterans Affairs healthcare system and 2) describe the relationship of SARS-CoV-2 NAAT use and resumption of endoscopy services.

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Colonoscopy for colonic diverticular bleeding: more evidence for finding and treating stigmata of recent hemorrhage

Tomizawa Y, Strate LL

Acute overt lower GI bleeding (ALGIB) is one of the most common GI indications for hospitalization, and colonic diverticular bleeding (CDB) accounts for 30% to 65% of ALGIB. 1 There has been considerable controversy regarding the optimal management of CDB with respect to the timing of colonoscopy and endoscopic treatment of stigmata of recent hemorrhage (SRH).

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Endoscopic submucosal dissection for colorectal dysplasia in inflammatory bowel disease: a US multicenter study

Ngamruengphong S, Aihara H, Friedland S, Nishimura M, Faleck D, Benias P, Yang D, Draganov PV, Kumta NA, Borman ZA, Dixon RE, Marion JF, DʼSouza LS, Tomizawa Y, Jit S, Mohapatra S, Charabaty A, Parian A, Lazarev M, Figueroa EJ, Hanada Y, Wang AY, Wong Kee Song LM

In patients with inflammatory bowel disease (IBD), endoscopically visible lesions with distinct borders can be considered for endoscopic resection. The role of endoscopic submucosal dissection (ESD) for these lesions is not well defined because of a paucity of data. We aimed to evaluate the outcomes of colorectal ESD of dysplastic lesions in patients with IBD across centers in the United States.

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Evaluation of methylated DCR1 as a biomarker for response to adjuvant irinotecan-based therapy in stage III colon cancer: cancer and leukaemia Group B 89803 (Alliance)

Symonds L, Yu M, Zhang Y, Ou FS, Zemla TJ, Carter K, Bertagnolli M, Innocenti F, Bosch LJ, Meijer GA, Carvalho B, Grady WM, Cohen SA

Aberrantly methylated genes contribute to the landscape of epigenetic alterations in colorectal adenocarcinoma. The global CpG Island methylator phenotype (CIMP) and individually methylated genes are potential prognostic/predictive biomarkers. Research suggests an association between methylated DCR1 (mDCR1) and lack of benefit with irinotecan (IFL) treatment. We assessed the association between DCR1 methylation status and survival in patients receiving adjuvant fluorouracil/ leucovorin (5-FU/LV) or IFL. We analysed data from patients with stage III colon adenocarcinoma randomly assigned to adjuvant 5-FU/LV or IFL in CALGB 89803 (Alliance).

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Colorectal Cancer Is Associated with the Presence of Cancer Driver Mutations in Normal Colon

Matas J, Kohrn B, Fredrickson J, Carter K, Yu M, Wang T, Gui X, Soussi T, Moreno V, Grady WM, Peinado MA, Risques RA

Although somatic mutations in colorectal cancer are well characterized, little is known about the accumulation of cancer mutations in the normal colon before cancer. Here, we have developed and applied an ultrasensitive, single-molecule mutational test based on CRISPR-DS technology, which enables mutation detection at extremely low frequency (<0.001) in normal colon from patients with and without colorectal cancer.

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Higher vitamin B6 status is associated with improved survival among patients with stage I-III colorectal cancer

Holowatyj AN, Ose J, Gigic B, Lin T, Ulvik A, Geijsen AJMR, Brezina S, Kiblawi R, van Roekel EH, Baierl A, Böhm J, Bours MJL, Brenner H, Breukink SO, Chang-Claude J, de Wilt JHW, Grady WM, Grünberger T, Gumpenberger T, Herpel E, Hoffmeister M, Keulen ETP, Kok DE, Koole JL, Kosma K, Kouwenhoven EA, Kvalheim G, Li CI, Schirmacher P, Schrotz-King P, Singer MC, van Duijnhoven FJB, van Halteren HK, Vickers K, Vogelaar FJ, Warby CA, Wesselink E, Ueland PM, Ulrich AB, Schneider M, Habermann N, Kampman E, Weijenberg MP, Gsur A, Ulrich CM

Folate-mediated one-carbon metabolism requires several nutrients, including vitamin B6. Circulating levels of biomarkers indicating high vitamin B6 status are associated with a reduced risk of colorectal cancer (CRC). However, little is known about the effect of B6 status in relation to clinical outcomes in CRC patients.

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Annals On Call - Evidence-Based Care of Patients With Diverticulitis

Centor RM, Strate LL

In this episode of Annals On Call, Dr. Centor discusses the diagnosis and management of diverticulitis with Dr. Lisa Strate.

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Patient navigation for hereditary colorectal cancer: Design of a randomized controlled trial to determine the effectiveness of pathways to genetic counseling

Reed AK, Kohn MJ, Stayman S, Cole AM, Ko CW, Konnick EQ, Swanson PE, Zhang Y, Knerr S

Diagnosis of Lynch and other hereditary colorectal cancer (CRC) syndromes through germline genetic testing has important implications for treatment and risk-management, yet guideline-recommended genetic counseling referral and attendance is suboptimal. Our team developed an adapted patient navigation program—Pathways to Genetic Counseling—to address multilevel barriers to genetic counseling referral and receipt. This paper describes the methods of a randomized controlled trial (RCT) testing Pathways to Genetic Counseling's effectiveness at increasing genetic counseling attendance in the University of Washington Medicine health system.

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Identifying Liver Transplant Candidates at Risk of Wait List Removal Due to Nonadherence Using a Quality-of-Life Survey: A Competing Risk Analysis

Nichols J, Vutien P, Perkins J, Biggins SW, Dick AAS, McCandlish S, Bambha K, Reyes J

Objectives: We investigated whether the Liver Disease Health-Related Quality of Life Short Form or the Area Deprivation Index could be used to help identify liver transplant candidates at risk of delisting due to nonadherence. Materials and methods: We conducted a retrospective study of 358 adults (≥18 years old) listed for liver transplant at the University of Washington Medical Center from September 1, 2012, to August 30, 2017, who completed the Liver Disease Health-Related Quality of Life Short Form prior to listing.

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Renal Outcomes With Tenofovir Alafenamide in Liver Transplant Recipients

Liu JK, Vutien P, Huang DQ, Ishigami M, Landis CS, Nguyen MH; REAL-B Liver Transplant Study Group

The goals of this study were to examine changes in renal function in a large multicenter cohort of LT recipients with chronic hepatitis B who were treated with TAF, TDF, or ETV for the prevention of hepatitis B virus (HBV) reinfection or reactivation from receipt of a positive HBV core antibody graft.

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Tofacitinib Appears Well Tolerated and Effective for the Treatment of Patients with Refractory Crohn's Disease

Lee SD, Singla A, Harper J, Barahimi M, Jacobs J, Kamp KJ, Clark-Snustad KD

Background: Active Crohn's disease increases the risk of strictures, fistulas, and abscesses. Less than 30% of patients with Crohn's disease achieve endoscopic remission on any therapy. Tofacitinib may be a therapeutic option for patients with refractory Crohn's disease. Aims: We aimed to evaluate the safety and effectiveness of off-label tofacitinib for refractory Crohn's disease. Methods: We retrospectively assessed adverse events and clinical/endoscopic response after therapy.

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Provider Attitudes Toward Risk-Based Hepatocellular Carcinoma Surveillance in Patients With Cirrhosis in the United States

Kim NJ, Rozenberg-Ben-Dror K, Jacob DA, Rich NE, Singal AG, Aby ES, Yang JD, Nguyen V, Pillai A, Fuchs M, Moon AM, Shroff H, Agarwal PD, Perumalswami P, Chandna S, Zhou K, Patel YA, Latt NL, Wong R, Duarte-Rojo A, Lindenmeyer CC, Frenette C, Ge J, Mehta N, Yao F, Benhammou JN, Bloom PP, Leise M, Kim HS, Levy C, Barnard A, Khalili M, Ioannou GN

Hepatocellular carcinoma (HCC) surveillance rates are suboptimal in clinical practice. We aimed to elicit providers’ opinions on the following aspects of HCC surveillance: preferred strategies, barriers and facilitators, and the impact of a patient’s HCC risk on the choice of surveillance modality.

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Systematic Review With Meta-analysis: Safety and Effectiveness of Combining Biologics and Small Molecules in Inflammatory Bowel Disease 

Alayo QA, Fenster M, Altayar O, Glassner KL, Llano E, Clark-Snustad K, Patel A, Kwapisz L, Yarur AJ, Cohen BL, Ciorba MA, Thomas D, Lee SD, Loftus EV Jr, Fudman DI, Abraham BP, Colombel JF, Deepak P

Combining biologics and small molecules could potentially overcome the plateau of drug efficacy in inflammatory bowel disease (IBD). We conducted a systematic review and meta-analysis to assess the safety and effectiveness of dual biologic therapy (DBT), or small molecule combined with a biologic therapy (SBT) in IBD patients.

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Editorial: Higher Quality Colonoscopy -Worth the Wait?

Andrew J Gawron, Jason A Dominitz

Although community providers performed more timely colonoscopy than the VA medical center (mean 25 days earlier), colonoscopy quality was significantly lower for other important quality metrics, including adenoma detection, advanced adenoma detection, adenomas per colonoscopy and appropriate surveillance recommendations. This study highlights the need for continued efforts to assure high quality colonoscopy in all settings.

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Optimizing Risk Assessment In Simultaneous Liver and Kidney Transplant: Donor and Recipient Factors Associated With Improved Outcome

Hendele, J.B., Perkins, J.D., Leca, N., Biggins, S.W., Sibulesky, L.

Standardization in allocation of kidneys for transplant simultaneous with livers and the creation of a “safety net” for kidney transplant after liver transplant alone (LTA) was designed to encourage clinicians to list patients for LTA when the likelihood of renal recovery and the necessity of simultaneous liver and kidney (SLK) transplant were unclear. We analyzed the United Network for Organ Sharing database of SLK recipients starting January 1, 2015. Organs from one deceased donor were used in each individual case.

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Comparison of Moderna versus Pfizer-BioNTech COVID-19 vaccine outcomes: A target trial emulation study in the U.S. Veterans Affairs healthcare system

Ioannou GN, Locke ER, Green PK, Berry K

mRNA COVID-19 vaccines manufactured by Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273) have been shown to be efficacious but have not been compared in head-to-head clinical trials. We designed this observational study to emulate a target trial of COVID-19 vaccination by BNT162b2 versus mRNA-1273 among persons who underwent vaccination in the national U.S. Veterans Affairs (VA) healthcare system from 11/12/2020 to 25/03/2021 using combined VA and Medicare electronic health records. We identified the best matching mRNA-1273 recipient(s) for each BNT162b2 recipient...

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Management of gastrointestinal bleeding: Society of Abdominal Radiology (SAR) Institutional Survey

Fidler JL, Guglielmo FF, Brook OR, Strate LL, Bruining DH, Gupta A, Allen BC, Anderson MA, Wells ML, Ramalingam V, Gunn ML, Grand DJ, Gee MS, Huete A, Khandalwal A, Sokhandon F, Park SH, Yoo DC, Soto JA

Despite guidelines developed to standardize the diagnosis and management of gastrointestinal (GI) bleeding, significant variability remains in recommendations and practice. The purpose of this survey was to obtain information on practice patterns for the evaluation of overt lower GI bleeding (LGIB) and suspected small bowel bleeding. A 34-question electronic survey was sent to all Society of Abdominal Radiology (SAR) members. Responses were received from 52 unique institutions (40 from the United States).

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Can artificial intelligence be your angel to diagnose early gastric cancer in real clinical practice?

Abe S, Tomizawa Y, Saito Y

Early gastric cancer (EGC), which is defined as a gastric cancer confined to mucosa or submucosa regardless of lymph node metastasis, is known to be curable because of its excellent disease-specific survival: >95% after surgery. When a lesion is a...

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Trends Over Time in the Risk of Adverse Outcomes Among Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Ioannou GN, O'Hare AM, Berry K, Fan VS, Crothers K, Eastment MC, Locke E, Green P, Shah JA, Dominitz JA

Background: We aimed to describe trends in adverse outcomes among patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between February and September 2020 within a national healthcare system. Methods: We identified enrollees in the national United States Veterans Affairs healthcare system who tested positive for SARS-CoV-2 between 28 February 2020 and 30 September 2020 (n = 55 952), with follow-up extending to 19 November 2020. We determined trends over time in incidence of the following outcomes that occurred within 30 days of testing positive: hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and death.

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Towards health equity: the urgent need for upstream intervention studies in gastroenterology and hepatology

Joy J Liu, Nicole De Cuir, Leila Kia, Rachel B Issaka

Health inequity is a major challenge to achieving broader social equity and a just society. Interventions to reduce health inequity can be directed at downstream determinants of health, such as individual health-care needs, midstream determinants, such as neighbourhood conditions, or upstream determinants, such as structural racism and discrimination. For example, interventions to reduce inequities in colorectal cancer mortality in African-American people could include mailing reminders about faecal immunochemical tests (downstream intervention); providing patient navigation, transportation, or other direct aid to access health-care services (midstream intervention); or changing laws that redistribute power, wealth, and resources, including health insurance (upstream intervention).

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Impact of Fellow Participation During Colonoscopy on Adenoma Detection Rates

Araujo JL, Jaiswal P, Ragunathan K, Arroyo-Mercado FM, Chawla GS, Li C, Kazmi W, Le A, Gupta N, Chokshi T, Klinger CA, Salim S, Mirza RM, Grossman E, Vignesh S

Background: An endoscopist's adenoma detection rate (ADR) is inversely related to interval colorectal cancer risk and cancer mortality. Previous studies evaluating the impact of gastroenterology fellow participation in colonoscopy on ADR have generated conflicting results. Aims: We aimed to determine the impact of fellow participation, duration of fellowship training, and physician sex on ADR and advanced ADR (AADR).

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Core implementation strategies for improving cirrhosis care in the Veterans Health Administration

Yakovchenko V, Morgan TR, Miech EJ, Neely B, Lamorte C, Gibson S, Beste LA, McCurdy H, Scott D, Gonzalez R, Park A, Powell BJ, Bajaj JS, Dominitz JA, Chartier M, Ross D, Chinman MJ, Rogal SS

The Veterans Health Administration (VHA) provides care for more than 80,000 Veterans with cirrhosis. This longitudinal, multi-method evaluation of a novel cirrhosis care quality improvement program aimed to 1) identify implementation strategies associated with evidence-based, guideline-concordant cirrhosis care over time, and 2) use qualitative interviews to operationalize strategies for a manualized intervention.

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Acute liver failure secondary to acute antibody mediated rejection after compatible liver transplant: A case report

Todd J Robinson, James B Hendele, Idoia Gimferrer, Nicolae Leca, Scott W Biggins, Jorge D Reyes, Lena Sibulesky

The liver has traditionally been regarded as resistant to antibody-mediated rejection (AMR). AMR in liver transplants is a field in its infancy compared to kidney and lung transplants. In our case we present a patient with alpha-1-antitrypsin disease who underwent ABO compatible liver transplant complicated by acute liver failure (ALF) with evidence of antibody mediated rejection on allograft biopsy and elevated serum donor-specific antibodies (DSA). This case highlights the need for further investigations and heightened awareness for timely diagnosis.

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Prevalence of Gastrointestinal Symptoms and Irritable Bowel Syndrome Among Individuals With Symptomatic Posttraumatic Stress Disorder

Kearney DJ, Kamp KJ, Storms M, Simpson TL

Our aim was to describe the prevalence of irritable bowel syndrome (IBS) and other gastrointestinal symptoms in a sample of veterans with posttraumatic stress disorder (PTSD) and to examine the relationship between gastrointestinal symptoms, PTSD severity, depression severity, and number of prior traumatic events reported.

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AGA Clinical Practice Update on Management of Chronic Gastrointestinal Pain in Disorders of Gut-Brain Interaction: Expert Review

Keefer L, Ko CW, Ford AC

This expert review summarizes approaches to management of pain in disorders of gut–brain interaction. This review focuses specifically on approaches to pain that persist if first-line therapies aimed at addressing visceral causes of pain are unsuccessful. The roles of a therapeutic patient–provider relationship, nonpharmacologic and pharmacologic therapies, and avoidance of opioids are discussed.

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Clinical and Neurologic Outcomes in Acetaminophen-Induced Acute Liver Failure: A 21-Year Multicenter Cohort Study

MacDonald AJ, Speiser JL, Ganger DR, Nilles KM, Orandi BJ, Larson AM, Lee WM, Karvellas CJ; US Acute Liver Failure Study Group

Acetaminophen (APAP)-induced acute liver failure (ALF) is a rare disease associated with high mortality rates. This study aimed to evaluate changes in interventions, psychosocial profile, and clinical outcomes over a 21-year period using data from the ALF Study Group registry.

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Operationalizing a Rideshare Intervention for Colonoscopy Completion: Barriers, Facilitators, and Process Recommendations

Ari Bell-Brown, Lisa Chew, Bryan J. Weiner, Lisa Strate, Bryan Balmadrid, Cara C. Lewis, Peggy Hannon, John M. Inadomi, Scott D. Ramsey, Rachel B. Issaka

Transportation is a common barrier to colonoscopy completion for colorectal cancer (CRC) screening. The study aims to identify the barriers, facilitators, and process recommendations to implement a rideshare non-emergency medical transportation (NEMT) intervention following colonoscopy completion within a safety-net healthcare setting.

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Risk factors for adverse outcomes in emergency versus nonemergency open umbilical hernia repair and opportunities for elective repair in a national cohort of patients with cirrhosis

Johnson KM, Newman KL, Berry K, Itani K, Wu P, Kamath PS, Harris AHS, Cornia PB, Green PK, Beste LA, Ioannou GN

Whether to perform umbilical hernia repair in patients with cirrhosis is a common dilemma for surgeons. We aimed to determine the incidence, morbidity, and mortality associated with emergency and nonemergency umbilical hernia repair in patients with and without cirrhosis, and to explore opportunities for nonemergency repair.

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MELD 3.0: The Model for End-Stage Liver Disease Updated for the Modern Era

Kim WR, Mannalithara A, Heimbach JK, Kamath PS, Asrani SK, Biggins SW, Wood NL, Gentry SE, Kwong AJ

The Model for End-Stage Liver Disease (MELD) has been established as a reliable indicator of short-term survival in patients with end-stage liver disease. The current version (MELDNa), consisting of the international normalized ratio and serum bilirubin, creatinine, and sodium, has been used to determine organ allocation priorities for liver transplantation in the United States. The objective was to optimize MELD further by taking into account additional variables and updating coefficients with contemporary data.

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Building a Utility-based Liver Allocation Model in Preparation for Continuous Distribution

Kling CE, Perkins JD, Biggins SW, Wall AE, Reyes JD

The current model for end-stage liver disease-based liver allocation system in the United States prioritizes sickest patients first at the expense of long-term graft survival. In a continuous distribution model, a measure of posttransplant survival will also be included. We aimed to use mathematical optimization to match donors and recipients based on quality to examine the potential impact of an allocation system designed to maximize long-term graft survival.

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Timely Colonoscopy After Positive Fecal Immunochemical Tests in the Veterans Health Administration: A Qualitative Assessment of Current Practice and Perceived Barriers

Mog AC, Liang PS, Donovan LM, Sayre GG, Shaukat A, May FP, Glorioso TJ, Jorgenson MA, Wood GB, Mueller C, Dominitz JA

The Veterans Health Administration introduced a clinical reminder system in 2018 to help address process gaps in colorectal cancer screening, including the diagnostic evaluation of positive fecal immunochemical test (FIT) results. We conducted a qualitative study to explore the differences between facilities who performed in the top vs bottom decile for follow-up colonoscopy. Seventeen semi-structured interviews with gastroenterology (GI) providers and staff were conducted at 9 high-performing and 8 low-performing sites.

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Considerations of Bias and Reliability in Publicly Reported Physician Ratings

Marcotte LM, Issaka RB, Agrawal N

Many health systems have opted to publicly report physician ratings and patient comments alongside physician profiles on their websites. While this is meant to engage consumers to make informed decisions in choosing physicians, these ratings are subject to biases and poor statistical reliability that may disproportionately disadvantage certain groups of physicians.Health systems should be aware of and evaluate disparities arising from biases prior to publicly sharing these data.

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PTG-100, an Oral α4β7 Antagonist Peptide: Preclinical Development and Phase 1 and 2a Studies in Ulcerative Colitis

Sandborn WJ, Mattheakis LC, Modi NB, Pugatch D, Bressler B, Lee S, Bhandari R, Kanwar B, Shames R, D'Haens G, Schreiber S, Danese S, Feagan B, Pai RK, Liu DY, Gupta S.

Oral therapies targeting the integrin α4β7 may offer unique advantages for the treatment of inflammatory bowel disease. We characterized the oral α4β7 antagonist peptide PTG-100 in preclinical models and established safety, pharmacokinetic/pharmacodynamic relationships, and efficacy in a phase 2a trial in patients with ulcerative colitis (UC).

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The COVID-19 pandemic highlights opportunities to improve hepatocellular carcinoma screening and diagnosis in a national health system: COVID-19 and HCC screening and diagnosis

Kim NJ, Rozenberg-Ben-Dror K, Jacob DA, Berry K, Ioannou GN

We evaluated the COVID-19 pandemic’s impact on HCC screening and diagnosis among patients with cirrhosis in the Veterans Health Administration.

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Prognosis of hospitalized patients with cirrhosis and acute kidney disease

Wong F, Garcia-Tsao G, Reddy KR, O'Leary JG, Kamath PS, Tandon P, Lai JC, Vargas HE, Biggins SW, Fallon MB, Thuluvath PJ, Maliakkal BJ, Subramanian R, Thacker L, Bajaj JS.

The prognosis of acute kidney disease (AKD), defined as a glomerular filtration rate of <60ml/min/1.73m2 or a rise in serum creatinine (sCr) of <50% for <3 months, is not clearly known. Aim: To study the prevalence, predictive factors and clinical outcomes in hospitalized cirrhotic patients with AKD. Methods: The North American Consortium for the Study of End-Stage Liver Disease prospectively enrolled hospitalized decompensated cirrhotic patients.

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DNA methylation-based signature of CD8+ tumor-infiltrating lymphocytes enables evaluation of immune response and prognosis in colorectal cancer

Zou Q, Wang X, Ren D, Hu B, Tang G, Zhang Y, Huang M, Pai RK, Buchanan DD, Win AK, Newcomb PA, Grady WM, Yu H, Luo Y

Tumor-infiltrating lymphocytes (TILs), especially CD8+ TILs, can be used for predicting immunotherapy responsiveness and survival outcome. However, the evaluation of CD8+ TILs currently relies on histopathological methodology with high variability. We therefore aimed to develop a DNA methylation signature for CD8+ TILs (CD8+ MeTIL) that could evaluate immune response and prognosis in colorectal cancer (CRC).

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Relationship Between Endoscopic and Clinical Disease Activity With Fatigue in Inflammatory Bowel Disease

Kamp KJ, Clark-Snustad K, Barahimi M, Lee S

Fatigue is a prevalent symptom among individuals with inflammatory bowel disease. Yet, few studies have examined the relationship between fatigue and endoscopic disease activity. A retrospective chart review was conducted to determine the prevalence of fatigue based on endoscopic inflammation and clinical disease activity and describe the factors associated with fatigue among adults with inflammatory bowel disease. One hundred sixty patients were included. The majority had Crohn disease (72.5%), with an average age of 40.5 years. Sixty-one percent reported fatigue.

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Metformin Use Is Inversely Associated with Prevalent, but Not Incident Colorectal Adenomas

Krigel A, Nguyen STT, Talukder N, Huang CH, Buitrago C, Karkenny G, Lebwohl B, Abrams JA, Araujo JL

Background: Chemoprevention for colorectal neoplasia has attracted growing interest, with multiple medications investigated. Metformin may decrease the overall incidence of cancer in patients with diabetes and may decrease the incidence of colorectal cancer. Aims: We aimed to determine the impact of metformin use on the behavior of colorectal adenomas in a US veteran population.

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In Memoriam: Dawn Tranchino Provenzale, MD, MS

Dominitz JA, Fisher DA, Garman KS, Hunt CM, Lieberman D, Muir AJ, Onken JE, Robertson DJ, Sandler RS, Sultan S.

Many could write a loving tribute to Dr Dawn Tranchino Provenzale. Indeed, the joy of her work and the foundation of her legacy were her lasting relationships as mentor, colleague, and friend. Although it is impossible to include input from everyone who knew Dawn well, we wish to provide tribute by weaving together the story of her life through the experiences and voices of some of the people whose lives she touched. This tribute goes beyond her curriculum vitae that has been summarized so well in other similar pieces, including from the Duke School of Medicine.1 Rather, we reflect on lessons Dawn taught us and ways she impacted our lives.

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Biomarkers for Early Detection of Colorectal Cancer: The Early Detection Research Network, a Framework for Clinical Translation

Bresalier RS, Grady WM, Markowitz SD, Nielsen HJ, Batra SK, Lampe PD

Early detection by screening significantly reduces mortality from colorectal cancer, but 40% of guideline-eligible patients are not screened as recommended in the United States. Novel strategies to improve screening uptake overall and efforts to deploy best practices to underserved populations are a high priority for health care. This review focuses on existing biomarkers in practice and those in development...

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Barrett's Esophagus and Esophageal Adenocarcinoma Biomarkers

Grady WM, Yu M, Markowitz SD, Chak A

Esophageal adenocarcinoma is a major cause of cancer-related morbidity and mortality in Western countries. The incidences of esophageal adenocarcinoma and its precursor Barrett's esophagus have increased substantially in the last four decades. Current care guidelines recommend that endoscopy be used for the early detection and monitoring of patients with Barrett's esophagus; however, the efficacy of this approach is unclear. To prevent the increasing morbidity and mortality from esophageal adenocarcinoma, there is a tremendous need for early detection and surveillance biomarker assays that are accurate, low-cost, and clinically feasible to implement. 

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"Driver-passenger" bacteria and their metabolites in the pathogenesis of colorectal cancer

Avril M, DePaolo RW

Colorectal cancer (CRC) is a significant public health problem accounting for about 10% of all new cancer cases globally. Though genetic and epigenetic factors influence CRC, the gut microbiota acts as a significant component of the disease’s etiology. Further research is still needed to clarify the specific roles and identify more bacteria related to CRC development. This review aims to provide an overview of the “driver-passenger” model of CRC. The colonization and active invasion of the “driver(s)” bacteria cause damages allowing other commensals, known as “passengers,” or their by-products, i.e., metabolites, to pass through the epithelium .

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Prescriptive Analytics Determining Which Patients Undergoing Simultaneous Liver-Kidney Transplant May Benefit From High-Risk Organs

Dasari M, Perkins JD, Hendele JB, Leca N, Biggins SW, Sibulesky L

Objectives: Simultaneous liver-kidney transplant is a treatment option for patients with end-stage liver disease and concomitant irreversible kidney injury. We developed a decision tool to aid transplant programs to advise their candidates for simultaneous liver-kidney transplant on accepting high-risk grafts versus waiting for lower-risk grafts. Materials and Methods: To find the critical decision factors, we used the prescriptive analytic technique of microsimulation. All probabilities used in the simulation model were calculated from Organ Procurement and Transplantation Network data collected from February 27, 2002 to June 30, 2018. Results: The simulated patient population results revealed...

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Use of a Knowledge-Based Governance Approach to Plan a Post-COVID-19 Predoctoral Dental

Flake NM, Chan DCN, DiMarco AC, Silverstein BD

COVID-19 abruptly changed dental education, forcing educators out of their comfort zones and into using new technologies and teaching approaches. At the University of Washington School of Dentistry, a task force evaluated the curricular changes that resulted from COVID and made recommendations for the future predoctoral dental curriculum. This manuscript reports the process employed, the findings of the task force, and how these findings will impact the curriculum. A knowledge-based governance (KBG) approach was employed. KBG focuses on gathering all relevant information and identifying all choices. It separates dialogue from deliberation. Information was gathered via literature review, focus group interviews, electronic surveys, and other metrics. 

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COVID-19 Vaccination Effectiveness Against Infection or Death in a National U.S. Health Care System : A Target Trial Emulation Study

Ioannou GN, Locke ER, O'Hare AM, Bohnert ASB, Boyko EJ, Hynes DM, Berry K

Background: Little is known about real-world COVID-19 vaccine effectiveness (VE) in racially and ethnically diverse, elderly populations with high comorbidity burden.
Objective: To determine the effectiveness of messenger RNA COVID-19 vaccines.
Design: Target trial emulation study comparing newly vaccinated persons with matched unvaccinated controls.

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Adapted time-varying covariates Cox model for predicting future cirrhosis development performs well in a large hepatitis C cohort

Beste LA, Zhang X, Su GL, Van T, Ioannou GN, Oselio B, Tincopa M, Liu B, Singal AG, Zhu J, Waljee AK

Patients with hepatitis C virus (HCV) frequently remain at risk for cirrhosis after sustained virologic response (SVR). Existing cirrhosis predictive models for HCV do not account for dynamic antiviral treatment status and are limited by fixed laboratory covariates and short follow up time. Advanced fibrosis assessment modalities, such as transient elastography, remain inaccessible in many settings. Improved cirrhosis predictive models are needed.

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PolyG-DS: An ultrasensitive polyguanine tract-profiling method to detect clonal expansions and trace cell lineage

Zhang Y, Kohrn BF, Yang M, Nachmanson D, Soong TR, Lee IH, Tao Y, Clevers H, Swisher EM, Brentnall TA, Loeb LA, Kennedy SR, Salk JJ, Naxerova K, Risques RA

The ability to detect precancerous clones and reconstruct cancer evolution is important for early cancer detection and improving prevention and treatment strategies. We present PolyG-DS, a sequencing method that combines the unique properties of polyguanine tracts (PolyGs) for cell lineage tracing with ultrahighaccuracy duplex sequencing (DS). PolyG-DS enables accurate and reproducible PolyG genotyping, providing high sensitivity for the detection of low-frequency alleles in mixed populations.

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Ultrastructural Analysis of Volumetric Histotripsy Bio-effects in Large Human Hematomas

Ponomarchuk EM, Rosnitskiy PB, Khokhlova TD, Buravkov SV, Tsysar SA, Karzova MM, Tumanova KD, Kunturova AV, Wang YN, Sapozhnikov OA, Trakhtman PE, Starostin NN, Khokhlova VA

Large-volume soft tissue hematomas are a serious clinical problem, which, if untreated, can have severe consequences. Current treatments are associated with significant pain and discomfort. It has been reported that in an in vitro bovine hematoma model, pulsed high-intensity focused ultrasound (HIFU) ablation, termed histotripsy, can be used to rapidly and non-invasively liquefy the hematoma through localized bubble activity, enabling fine-needle aspiration. The goals of this study were to evaluate the efficiency and speed of volumetric histotripsy liquefaction using a large in vitro human hematoma model.

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Differential pre-malignant programs and microenvironment chart distinct paths to malignancy in human colorectal polyps

Bob Chen, Cherie' R Scurrah, Eliot T McKinley, et al, including William M. Grady

Colorectal cancers (CRCs) arise from precursor polyps whose cellular origins, molecular heterogeneity, and immunogenic potential may reveal diagnostic and therapeutic insights when analyzed at high resolution. We present a single-cell transcriptomic and imaging atlas of the two most common human colorectal polyps, conventional adenomas and serrated polyps, and their resulting CRC counterparts. Integrative analysis of 128 datasets from 62 participants reveals adenomas arise from WNT-driven expansion of stem cells, while serrated polyps derive from differentiated cells through gastric metaplasia. 

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A randomized double-blind placebo controlled pilot study of probiotics in adolescents with severe obesity

Verma A, Nelson MT, DePaolo WR, Hampe C, Roth CL

Purpose: The purpose of the study is to assess the effect of probiotic supplementation on gut microbiota and insulin resistance in adolescents with severe obesity. Methods: Through a randomized, double blind, placebo-controlled, 12-week pilot clinical trial, 15 adolescents with severe obesity received either an oral probiotic 'Visbiome®' (n = 8) or placebo (n = 7). Anthropometry, fasting glucose, insulin, hs-CRP and stool for microbiome and calprotectin were collected at baseline (week 0) and 12 weeks after intervention.

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Dietary fiber intake, the gut microbiome, and chronic systemic inflammation in a cohort of adult men

Ma W, Nguyen LH, Song M, Wang DD, Franzosa EA, Cao Y, Joshi A, Drew DA, Mehta R, Ivey KL, Strate LL, Giovannucci EL, Izard J, Garrett W, Rimm EB, Huttenhower C, Chan AT

Background: A higher intake of dietary fiber is associated with a decreased risk of chronic inflammatory diseases such as cardiovascular disease and inflammatory bowel disease. This may function in part due to abrogation of chronic systemic inflammation induced by factors such as dysbiotic gut communities. Data regarding the detailed influences of long-term and recent intake of differing dietary fiber sources on the human gut microbiome are lacking.

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Effects of Immunosuppressive Drugs on COVID-19 severity in Patients with Autoimmune Hepatitis

Cumali Efe, et al, including Rotonya M Carr

We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis (AIH). Data of AIH patients with laboratory confirmed COVID-19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID-19 were compared to patients who were not on AIH-medication. The clinical courses of COVID-19 was classified as (i)-no hospitalization, (ii)-hospitalization without oxygen supplementation, (iii)-hospitalization with oxygen supplementation by nasal cannula or mask, (iv)-intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v)-ICU admission with invasive mechanical ventilation or (vi)-death and analyzed using ordinal logistic regression.

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Factors associated with early receipt of COVID-19 vaccination and adherence to second dose in the Veterans Affairs healthcare system

Ioannou GN, Green P, Locke ER, Berry K

We aimed to determine factors independently associated with early COVID-19 vaccination and adherence to two-dose regimens. Among persons receiving care in the Veterans Affairs (VA) healthcare system (n = 5,766,638), we identified those who received at least one dose of COVID-19 vaccination through the VA, during the first ~3months following emergency use authorization, from December 11, 2020 to March 9, 2021 (n = 1,569,099, or 27.2%, including 880,200 (56.1%) Moderna, 676,279 (43.1%) Pfizer-BioNTech and 12,620 (0.8%) Janssen vaccines).

Guglielmo FF, Wells ML, Bruining DH, Strate LL, Huete Á, Gupta A, Soto JA, Allen BC, Anderson MA, Brook OR, Gee MS, Grand DJ, Gunn ML, Khandelwal A, Park SH, Ramalingam V, Sokhandon F, Yoo DC, Fidler JL

The purpose of this pictorial review by the Society of Abdominal Radiology GI Bleeding Disease-Focused Panel is to provide a practical resource for radiologists interpreting GI bleeding CT studies that reviews the proper GI bleeding terminology, the most common causes of GI bleeding, key patient history and risk factors, the optimal CT imaging technique, and guidelines for case interpretation and illustrates many common causes of GI bleeding. A CT reporting template is included to help generate radiology reports that can add value to patient care.

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Pcsk9 Deletion Promotes Murine Nonalcoholic Steatohepatitis and Hepatic Carcinogenesis: Role of Cholesterol

Ioannou GN, Lee SP, Linsley PS, Gersuk V, Yeh MM, Chen YY, Peng YJ, Dutta M, Mascarinas G, Molla B, Cui JY, Savard C

Proprotein convertase subtilisin/kexin type 9 (Pcsk9) binds to hepatic low-density lipoprotein receptor (LDLR) and induces its internalization and degradation. Pcsk9 inhibition increases LDLR expression by hepatocytes, which causes increased uptake of circulating LDL, thereby reducing plasma LDL-cholesterol. However, by increasing the uptake of LDL by the liver, Pcsk9 inhibition increases the exposure of the liver to cholesterol, which may result in higher risk of steatohepatitis and ever carcinogenesis.

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Statins and risk of diverticular disease: Nested case–control study

Skajaa N, Schønfeldt Troelsen F, Pedersen L, Ekholm O, Strate LL, Erichsen R, Sørensen HT

Aims: To examine the effect of statin on the subsequent risk of diverticular disease. Methods: We conducted a nested case-control study in Denmark among respondents (>18 years) of the 2010 or the 2013 Danish National Health Survey. Among these, we identified 8809 cases of hospital-diagnosed diverticular disease and risk-set sampled population controls without diverticular disease. Using complete prescription and hospital records, we used conditional logistic regression to compute odds ratios (ORs) associating statin use with diverticular disease. In adjusted analyses, we controlled for hospital-based diagnoses, medication use other than statins, and lifestyle and socioeconomic factors.

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Updates on Age to Start and Stop Colorectal Cancer Screening: Recommendations From the U.S. Multi-Society Task Force on Colorectal Cancer

Patel SG, May FP, Anderson JC, Burke CA, Dominitz JA, Gross SA, Jacobson BC, Shaukat A, Robertson DJ

This document is a focused update to the 2017 colorectal cancer (CRC) screening recommendations from the U.S. Multi-Society Task Force on Colorectal Cancer, which represents the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy. This update is restricted to addressing the age to start and stop CRC screening in average-risk individuals and the recommended screening modalities. Although there is no literature demonstrating that CRC screening in individuals under age 50 improves health outcomes such as CRC incidence or CRC-related mortality, sufficient data support the U.S. Multi-Society Task Force to suggest average-risk CRC screening begin at age 45. 

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Marker-based assays for studying gut transit in gnotobiotic and conventional mouse models

Koester ST, Li N, Lachance DM, Dey N

Gastrointestinal motility is regulated by a variety of environmental factors including gut microbes and metabolites. The ability to interrogate mouse models of gut motility has enabled elucidation of these relationships. Here we describe integration of the red carmine dye and fluorescence isothiocyanate-dextran marker-based assays for characterizing gut transit with spatial resolution, along with an optional intracolonic infusion protocol for studying the effects of metabolites on colonic transit. These protocols can be adapted for use in gnotobiotic and conventional mouse models. For complete details on the use and execution of this protocol, please refer to Li et al. (2021).

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Quality measures in HCC care by the Practice Metrics Committee of the American Association for the Study of Liver Diseases. 

Asrani SK, Ghabril MS, Kuo A, Merriman RB, Morgan T, Parikh ND, Ovchinsky N, Kanwal F, Volk ML, Ho C, Serper M, Mehta S, Agopian V, Cabrera R, Chernyak V, El-Serag HB, Heimbach J, Ioannou GN, Kaplan D, Marrero J, Mehta N, Singal A, Salem R, Taddei T, Walling A, Tapper EB.

The burden of hepatocellular carcinoma (HCC) is substantial. To address gaps in HCC care, the American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) aimed to develop a standard set of process-based measures and patient-reported outcomes along the HCC care continuum.

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Selection of patients for large mailed fecal immunochemical test colorectal cancer screening outreach programs: A systematic review

Wang A, Lee B, Patel S, Whitaker E, Issaka RB, Somsouk M

Digital health care offers an opportunity to scale and personalize cancer screening programs, such as mailed outreach for colorectal cancer (CRC) screening. However, studies that describe the patient selection strategy and process for CRC screening are limited. Our objective was to evaluate implementation strategies for selecting patients for CRC screening programs in large health care systems.

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Advancing diversity: the role of international medical graduates

David YN, Issaka RB

A physician workforce that reflects the population it serves has been highlighted as one solution for persistent race-based health disparities. Efforts to diversify the gastroenterology and hepatology workforce in the USA have, historically, focused on improving diversity among fellows and faculty and increasing the number of potential trainees at the medical school and residency levels. Non-US international medical graduates (IMGs) help to diversify the US gastroenterology and hepatology workforce, but several issues need to be addressed so that the effect of IMGs on diversity is sustained.

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A new perspective on NAFLD: focusing on lipid droplets

Eleonora Scorletti, Rotonya M. Carr

Though recent research has improved our understanding of the mechanisms linking LDs accumulation to NAFLD progression, numerous aspects of LD biology are either poorly understood or unknown. In this review, we provide a description of several key mechanisms that contribute to LDs accumulation in the hepatocytes, favouring NAFLD progression.

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Temporal Trends and Evolving Outcomes After Simultaneous Liver-Kidney Transplantation: Results from the US SLKT Consortium

Cullaro G, Sharma P, Jo J, Rassiwala J, VanWagner LB, Wong R, Lai JC, Magee J, Schluger A, Barman P, Patel YA, Walter K, Biggins SW, Verna EC

We aimed to understand the contemporary changes in the characteristics and the determinants of outcomes among simultaneous liver-kidney transplantation (SLKT) recipients at 6 liver transplantation centers in the United States. We retrospectively enrolled SLKT recipients between 2002 and 2017 in the US Multicenter SLKT Consortium. We analyzed time-related trends in recipient characteristics and outcomes with linear regression and nonparametric methods. 

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Risk Factors for Testing Positive for Severe Acute Respiratory Syndrome Coronavirus 2 in a National United States Healthcare System

Fan VS, Dominitz JA, Eastment MC, Locke ER, Green P, Berry K, O'Hare AM, Shah JA, Crothers K, Ioannou GN

Identifying risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection could help health systems improve testing and screening strategies. The aim of this study was to identify demographic factors, comorbid conditions, and symptoms independently associated with testing positive for SARS-CoV-2.

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Impact of exposure to patients with COVID-19 on residents and fellows: an international survey of 1420 trainees

Cravero AL, Kim NJ, Feld LD, Berry K, Rabiee A, Bazarbashi N, Bassin S, Lee TH, Moon AM, Qi X, Liang PS, Aby ES, Khan MQ, Young KJ, Patel A, Wijarnpreecha K, Kobeissy A, Hashim A, Houser A, Ioannou GN.

Objectives: To determine how self-reported level of exposure to patients with novel coronavirus 2019 (COVID-19) affected the perceived safety, training and well-being of residents and fellows. Methods: We administered an anonymous, voluntary, web-based survey to a convenience sample of trainees worldwide. The survey was distributed by email and social media posts from April 20th to May 11th, 2020. Respondents were asked to estimate the number of patients with COVID-19 they cared for in March and April 2020.

Imperiale TF, Daggy JK, Imler TD, Sherer EA, Kahi CJ, Larson J, Cardwell J, Johnson CS, Ahnen DJ, Antaki F, Ashley C, Baffy G, Dominitz JA, Hou J, Korsten MA, Nagar A, Promrat K, Robertson DJ, Saini S, Shergill A, Smalley WE.

We sought to quantify the independent effects of age, sex, and race/ethnicity on risk of colorectal cancer (CRC) and advanced neoplasia (AN) in Veterans. We conducted a retrospective, cross-sectional study of Veterans aged 40 to 80 years who had diagnostic or screening colonoscopy between 2002 and 2009 from 1 of 14 Veterans Affairs Medical Centers.

Barahimi M, Lee S, Clark-Snustad K.

We report the case of a 51-year-old male with Crohn's disease (CD) who developed a reproducible pustular rash after ustekinumab (UST) administration. The patient first presented with a pustular rash on his hands, body, extremities, and scalp starting 5 weeks after his initial weight-based UST induction.

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Changes in the associations of race and rurality with SARS-CoV-2 infection, mortality, and case fatality in the United States from February 2020 to March 2021: A population-based cohort study

George N. Ioannou, Jacqueline M. Ferguson, Ann M. O’Hare, Amy S. B. Bohnert, Lisa I. Backus, Edward J. Boyko, Thomas F. Osborne, Matthew L. Maciejewski, C. Barrett Bowling, Denise M. Hynes, Theodore J. Iwashyna, Melody Saysana, Pamela Green, Kristin Berry

We examined whether key sociodemographic and clinical risk factors for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and mortality changed over time in a population-based cohort study. Methods and findings: In a cohort of 9,127,673 persons enrolled in the United States Veterans Affairs (VA) healthcare system, we evaluated the independent associations of sociodemographic and clinical characteristics with SARS-CoV-2 infection (n = 216,046), SARS-CoV-2–related mortality (n = 10,230), and case fatality at monthly intervals between February 1, 2020 and March 31, 2021.

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Dual-Use Transducer for Ultrasound Imaging and Pulsed Focused Ultrasound Therapy

Maria M Karzova, Petr V Yuldashev, Vera A Khokhlova, Fedor A Nartov, Kyle P Morrison, Tatiana D Khokhlova

The use of nonlinear pFUS without contrast agents was recently shown to be beneficial for localized tissue disruption, but required higher ultrasound pressure levels than a conventional ultrasound imaging probe could produce. In this work, we present the design of a compact dual-use 1-MHz transducer for ultrasound-guided pFUS without contrast agents. Nonlinear pressure fields that could be generated by the probe, under realistic power input, were simulated using the Westervelt equation.

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Validation of genetic classifiers derived from mouse and human tumors to identify molecular subtypes of colorectal cancer

Snow SM, Matkowskyj KA, Maresh M, Clipson L, Vo TN, Johnson KA, Deming DA, Newton MA, Grady WM, Pickhardt PJ, Halberg RB.

In this study, we assessed whether an immunohistochemical approach could be used for molecular subtyping of colorectal cancers. We validated two previously published, independent sets of immunohistochemistry classifiers and modified the published methods to improve the accuracy of the scoring methods. In addition, we evaluated whether protein and genetic signatures identified originally in the mouse were linked to clinical outcomes of patients with CRC. 

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Incidence and Risk Factors of Postoperative Mortality and Morbidity After Elective Versus Emergent Abdominal Surgery in a National Sample of 8193 Patients With Cirrhosis

Johnson KM, Newman KL, Green PK, Berry K, Cornia PB, Wu P, Beste LA, Itani K, Harris AHS, Kamath PS, Ioannou GN

Objective: To describe the incidence and risk factors for mortality and morbidity in patients with cirrhosis undergoing elective or emergent abdominal surgeries.
Background: Postoperative morbidity and mortality are higher in patients with cirrhosis; variation by surgical procedure type and cirrhosis severity remain unclear.

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Partial Respiratory Motion Compensation for Abdominal Extracorporeal Boiling Histotripsy Treatments With a Robotic Arm

Gilles P L Thomas, Tatiana D Khokhlova, Vera A Khokhlova

Extracorporeal boiling histotripsy (BH), a noninvasive method for mechanical tissue disintegration, is getting closer to clinical applications. However, the motion of the targeted organs, mostly resulting from the respiratory motion, reduces the efficiency of the treatment. Here, a practical and affordable unidirectional respiratory motion compensation method for BH is proposed and evaluated in ex vivo tissues. 

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AGA Clinical Practice Guideline on the Management of Coagulation Disorders in Patients With Cirrhosis

Robert S. O’Shea, Perica Davitkov, Cynthia W. Ko, Anita Rajasekhar, Grace L. Su, Shahnaz Sultan, Alina M. Allen, Yngve Falck-Ytter

Cirrhosis is a disease state that is accompanied by significant alterations in laboratory parameters, such as platelet count (PLT) and prothrombin time/international normalized ratio (PT/INR), routinely used to estimate clotting. Based on this measured thrombocytopenia and coagulopathy, it has traditionally been assumed that these results convey a high risk of bleeding and, therefore, significantly increased risk for patients undergoing invasive procedures. However, it has become clear that this understanding underestimates the balanced nature of alterations in hemostasis associated with end-stage liver disease, and that neither thrombocytopenia nor elevated PT/INR necessarily predicts bleeding outcomes in most of these patients.

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Survey Finds Gender Disparities Impact Both Women Mentors and Mentees in Gastroenterology

Rabinowitz, Loren Galler; Grinspan, Lauren Tal; Zylberberg, Haley; Dixon, Rebekah; David, Yakira.; Aroniadis, Olga.; Chiang, Austin; Christie, Jennifer; Fayad, Nabil; Ha, Christina; Harris, Lucinda; Ko, Cynthia; Kolb, Jennifer; Kwah, Joann; Lee, Linda; Lieberman, David; Raffals, Laura; Rex, Douglas; Shah, Shailja; Siddiqui, Uzma; Smith, Michael; Wallace, Michael; Williams, Renee; Woods, Karen; Crowe, Sheila; Kumta, Nikhil; Kim, Michelle Kang; Greenwald, David

Gastroenterologists at all levels of practice benefit from formal mentoring. Much of the current literature on mentoring in gastroenterology is based on expert opinion rather than data. In this study, we aimed to identify gender-related barriers to successful mentoring relationships from the mentor and mentee perspectives.

A voluntary, web-based survey was distributed to physicians at 20 academic institutions across the United States. Overall, 796 gastroenterology fellows and faculty received the survey link, with 334 physicians responding to the survey (42% response rate), of whom 299 (90%; 129 women and 170 men) completed mentorship questions and were included in analysis.

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Genomic and functional characterization of a mucosal symbiont involved in early-stage colorectal cancer

Melissa C. Kordahi, Ian B. Stanaway, Marion Avril, Denise Chac, Marie-Pierre Blanc, Benjamin Ross, Christian Diener, Sumita Jain, Paul McCleary, Ana Parker, Vincent Friedman, Jennifer Huang, Wynn Burke, Sean M. Gibbons, Amy D. Willis, Richard P. Darveau, William M. Grady, Cynthia W. Ko, R. William DePaolo

Colorectal cancer is a major health concern worldwide. Growing evidence for the role of the gut microbiota in the initiation of CRC has sparked interest in approaches that target these microorganisms. However, little is known about the composition and role of the microbiota associated with precancerous polyps. Here, we found distinct microbial signatures between patients with and without polyps and between polyp subtypes using sequencing and culturing techniques. We found a correlation between Bacteroides fragilis recovered and the level of inflammatory cytokines in the mucosa adjacent to the polyp.

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Gastrointestinal Bleeding at CT Angiography and CT Enterography: Imaging Atlas and Glossary of Terms

Guglielmo FF, Wells ML, Bruining DH, Strate LL, Huete Á, Gupta A, Soto JA, Allen BC, Anderson MA, Brook OR, Gee MS, Grand DJ, Gunn ML, Khandelwal A, Park SH, Ramalingam V, Sokhandon F, Yoo DC, Fidler JL.

For radiologists, interpreting CT scans in patients with GI bleeding can be challenging owing to the large number of images and the diverse potential causes of bleeding. The purpose of this pictorial review by the Society of Abdominal Radiology GI Bleeding Disease-Focused Panel is to provide a practical resource for radiologists interpreting GI bleeding CT studies that reviews the proper GI bleeding terminology, the most common causes of GI bleeding, key patient history and risk factors, the optimal CT imaging technique, and guidelines for case interpretation and illustrates many common causes of GI bleeding. A CT reporting template is included to help generate radiology reports that can add value to patient care.

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A Tailored FIT for Improved Colorectal Cancer Screening 

Dominitz JA

Colorectal cancer (CRC) is a quintessential example of a condition meriting screening on the basis of the burden of disease and availability of acceptable screening tests that are not only effective at reducing CRC incidence and death but are also cost-effective (1). The wide array of recommended tests reflects the fact that none are clearly established as the “best”. Each test has its own strengths and limitations, including burden on the screenee, harms, costs, and efficacy (2). Options range from noninvasive stool-based tests (for example, fecal immunochemical test [FIT] and stool DNA tests combined with FIT) to invasive direct visualization tests (for example, colonoscopy, flexible sigmoidoscopy, and computed tomography colonography).

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Associations Between Alcohol Use and Liver-Related Outcomes in a Large National Cohort of Patients With Cirrhosis.

Pearson MM, Kim NJ, Berry K, Moon AM, Su F, Vutien P, Green PK, Williams EC, Ioannou GN.

Alcohol use can cause hepatic necroinflammation and worsening portal hypertension in patients with cirrhosis. We aimed to evaluate the associations between degree of alcohol use and clinical liver-related outcomes according to etiology of cirrhosis. In this retrospective cohort analysis, 44,349 U.S. veterans with cirrhosis from alcohol-associated liver disease (ALD), chronic hepatitis C virus (HCV) infection, or nonalcoholic fatty liver disease were identified who completed the Alcohol Use Disorders Identification Test Consumption questionnaire in 2012. Based on this score, level of alcohol use was categorized as none, low level, or unhealthy. 

Esophageal granular cell tumor and eosinophils: a multicenter experience

Reddi D, Chandler C, Cardona D, Schild M, Westerhoff M, McMullen E, Tomizawa Y, Clinton L, Swanson PE

Esophageal granular cell tumor (eGCT) is rare, and the recent literature suggests a link between eosinophilic esophagitis (EoE) and eGCT. The aim of our study was to determine if EoE or other disorders associated with eosinophilia are consistently associated with eGCT.

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Financial Incentives to Improve Colorectal Cancer Screening—Time to Cut Our Losses

Issaka RB, Dominitz JA

Colorectal cancer (CRC) screening reduces mortality from this second leading cause of cancer deaths in the United States. However, only 69% of eligible adults in the United States are up to date with CRC screening, with lower rates of screening among racial/ethnic minority groups and individuals with lower socioeconomic status. Therefore, evidence-based interventions to improve CRC screening adherence are needed, especially interventions that address screening disparities.

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