Transformative and innovative research from UW GI 

See up-to-date research papers on PubMed:

University of Washington Gastroenterology Research on Pubmed


A selection of recent publications:

Pre- and Post-Portosystemic Shunt Placement Metabolomics Reveal Molecular Signatures for the Development of Hepatic Encephalopathy

Dantas Machado AC, Ramos SF, Gauglitz JM, Carpenter AM, Petras D, Aksenov AA, Kim UB, Lazarowicz M, Giustini AB, Aryafar H, Vodkin I, Warren C, Dorrestein PC, Zarrinpar A, Zarrinpar A.

Hepatic encephalopathy (HE) is a common complication of advanced liver disease causing brain dysfunction. This is likely due to the accumulation of unfiltered toxins within the bloodstream. A known risk factor for developing or worsening HE is the placement of a transjugular intrahepatic portosystemic shunt (TIPS), which connects the pre-hepatic and post-hepatic circulation allowing some blood to bypass the dysfunctional liver and decreases portal hypertension. To better understand the pathophysiology of post-TIPS HE, we conducted a multi-center prospective cohort study.

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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

Tenofovir disoproxil fumarate (TDF) is associated with a higher risk of nephrotoxicity compared with entecavir (ETV) or tenofovir alafenamide (TAF).1,2 One-fifth of transplant recipients develop chronic kidney disease (CKD) within 5 years after transplantation, contributed by the use of nephrotoxic immunosuppressive medications.3 Prior studies conducted in the nontransplant setting reported superior renal safety in TAF compared with TDF but data in liver transplant (LT) recipients have so far been limited to small case series.1,4-6 Therefore, 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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Multi-pilot implementation experiences of patient-centered pathology reports: lessons learned for the advancement of patient-centered tools for cancer decision-making

Austin EJ, Kilgore MR, Ko CW, Parker EU, Alvarez R, Koch LK, Donlan AW, Lee JM, Flanagan MR, DeStefano LM, Javid SH, Gore JL

Purpose: New federal legislation in the United States grants patients expanded access to their medical records, making it critical that medical records information is understandable to patients. Provision of informational summaries significantly increase patient perceptions of patient-centered care and reduce feelings of uncertainty, yet their use for cancer pathology is limited. Methods: Our team developed and piloted patient-centered versions of pathology reports (PCPRs) for four cancer organ sites: prostate, bladder, breast, and colorectal polyp. The objective of this analysis was to identify common barriers and facilitators to support dissemination of PCPRs in care delivery settings.

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Birth weight, childhood body mass index, and risk of diverticular disease in adulthood

Laursen ASD, Jensen BW, Strate LL, Sørensen TIA, Baker JL, Sørensen HT

Objective: Adult overweight is associated with increased risk of diverticular disease (DD). We investigated associations between birthweight and childhood body mass index (BMI) and DD. Methods: Cohort study of 346,586 persons born during 1930–1996 with records in the Copenhagen School Health Records Register. Data included birthweight, and height and weight from ages 7 through 13. We used Cox proportional hazard regression to examine associations between birthweight and BMI z-scores and DD registered in the Danish National Patient Registry. Due to non-proportionality, we followed participants from age 18–49 and from age 50.

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The Conundrum of Patients With Compensated Cirrhosis Requiring Kidney Transplantation; Kidney Alone or Simultaneous Liver Kidney Transplantation

Dodge JL, Lee BT, Kassem ACZ, Biggins SW, Rana PA, Nadim MK, Asrani SK, Fong TL

Patients with compensated cirrhosis and chronic kidney disease are increasing along with demand for simultaneous liver kidney transplant (SLKT) and shortages of organs for transplantation. Although these well-compensated patients may not need a liver organ, the alternative of kidney transplant alone (KTA) poses the risk of liver decompensation. Therefore, we aim to characterize outcomes among patients with compensated cirrhosis and chronic kidney disease listed for SLKT or receiving KTA to inform clinical decisions.

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The road to pandemic recovery: Tracking COVID-19’s impact on cirrhosis care and outcomes among 111,558 veterans

Adejumo AC, Yakovchenko V, Morgan TR, Spoutz P, Chia L, Bajaj JS, Chang MF, Dominitz JA, Rogal SS

This study aimed to evaluate quarterly trends in process and health outcomes among Veterans with cirrhosis and assess the factors associated with cirrhosis outcomes prior to and during the COVID-19 pandemic.

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Cancer risk in patients with diverticular disease: A nationwide cohort study

Ma W, Walker MM, Thuresson M, Roelstraete B, Sköldberg F, Olén O, Strate LL, Chan AT, Ludvigsson JF

Background: There are little data on diverticular disease and cancer development other than colorectal cancer. Methods: We conducted a population-based, matched cohort study with linkage of nationwide registers to the Epidemiology Strengthened by histoPathology Reports in Sweden histopathology cohort. We included 75 704 patients with a diagnosis of diverticular disease and colorectal histopathology and 313 480 reference individuals from the general population matched on age, sex, calendar year, and county.

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Genetic deletion or pharmacologic inhibition of the Nlrp3 Inflammasome did not ameliorate experimental NASH

Ioannou GN, Horn CL, Kothari V, Yeh MM, Shyu I, Lee SP, Savard C

It has been postulated that inflammasomes, in particular the NLRP3 inflammasome, mediate the necroinflammation and fibrosis that characterize nonalcoholic steatohepatitis (NASH) by engaging innate immune responses. We aimed to investigate the impact of genetic deletion or pharmacologic inhibition of the NLRP3 inflammasome on experimental steatohepatitis. 

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Dedifferentiated Liposarcoma Presenting as Dysphagia and Weight Loss: Common Symptoms but an Uncommon Diagnosis

Pham L, Swanson PE, Tomizawa Y.

Liposarcoma is a malignant soft-tissue tumor that frequently occurs in extremities and the retroperitoneum, but only uncommonly affects the gastrointestinal tract. We report a rare case of dedifferentiated liposarcoma affecting the esophagus with manifestation of dysphagia and early satiety. The diagnosis was suggested by histologic evaluation and confirmed by fluorescent in situ hybridization for MDM2 amplification.

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Recurrent lower abdominal pain, altered bowel habits and malaise: Conservative or surgical approach to a common disorder

Arden M. Morris, Jeff L. Fider, Brian Mau, Lisa L. Strate

Case History: A 60-year-old woman presented with recurrent abdominal pain, loose stools, malaise, anorexia and low-grade fevers. She described her pain as severe cramping located in the left lower quadrant with lower abdominal bloating. Her first episode of pain and symptoms occurred four years earlier while she was on vacation. An urgent care provider made a presumptive diagnosis of diverticulitis. Treatment with ciprofloxacin and metronidazole resulted in severe nausea and diarrhea prompting an emergency department visit where computerized tomography (CT) of the abdomen and pelvis demonstrated subtle inflammation and wall thickening of the sigmoid colon suggestive of uncomplicated diverticulitis. A subsequent colonoscopy found sigmoid diverticulosis and two small sessile serrated adenomas.

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Nondestructive 3D Pathology Image Atlas of Barrett Esophagus With Open-Top Light-Sheet Microscopy

Reddi DM, Barner LA, Burke W, Gao G, Grady WM, Liu JTC

Anatomic pathologists render diagnosis on tissue samples sectioned onto glass slides and viewed under a bright-field microscope. This approach is destructive to the sample, which can limit its use for ancillary assays that can inform patient management. Objective: To evaluate 3D pathology data sets of thick formalin-fixed Barrett esophagus specimens imaged nondestructively with open-top light-sheet (OTLS) microscopy.

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A Microbiome-targeting Fiber-enriched Nutritional Formula is Well Tolerated and Improves Quality of Life and Hemoglobin A1c in Type 2 Diabetes: A Double-Blind, Randomized, Placebo-Controlled Trial

Frias JP, Lee ML, Carter MM, Ebel ER, Lai RH, Rikse L, Washington ME, Sonneburg JL, Damman CJ

Aims: To investigate a prebiotic fiber-enriched nutritional formula on health-related quality of life and metabolic control in type 2 diabetes. This was a 12-week, double-blind, placebo-controlled study with an unblinded dietary advice only comparator arm.

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Long-term clinical outcomes of patients with COVID-19 and chronic liver disease: US multicenter COLD study

Aby, Elizabeth S.; Moafa, Ghady; Latt, Nyan; Sultan, Mohammad T.; Cacioppo, Paula A.; Kumar, Sonal; Chung, Raymond T.; Bloom, Patricia P.; Gustafson, Jenna; Daidone, Michael; Reinus, Zoe; Debes, Jose D.; Sandhu, Sunny; Sohal, Aalam; Khalid, Sameeha; Roytman, Marina; Catana, Andreea Maria; Wegermann, Kara; Carr, Rotonya M.; Saiman, Yedidya; Kassab, Ihab; Chen, Vincent L.; Rabiee, Atoosa; Rosenberg, Carly; Nguyen, Veronica; Gainey, Christina; Zhou, Kali; Chavin, Kenneth; Lizaola-Mayo, Blanca C.; Chascsa, David M.; Varelas, Lee; Moghe, Akshata; Dhanasekaran, Renumathy

Background: COVID-19 is associated with higher morbidity and mortality in patients with chronic liver diseases (CLDs). However, our understanding of the long-term outcomes of COVID-19 in patients with CLD is limited. Methods: We conducted a multicenter, observational cohort study of adult patients with CLD who were diagnosed with COVID-19 before May 30, 2020, to determine long-term clinical outcomes. We used a control group of patients with CLD confirmed negative for COVID-19.

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Tools to Measure the Impact of Structural Racism and Discrimination on Gastrointestinal and Hepatology Disease Outcomes: A Scoping Review

Joy J Liu, Nicole DeCuir, Leila Kia, Jonna Peterson, Corinne Miller, Rachel Issaka

Background and aims: Structural racism and discrimination (SRD) are important upstream determinants of health perpetuated by discriminatory laws and policies. Therefore, measuring SRD and its impact on health is critical to developing interventions that address resultant health disparities. We aimed to identify gastrointestinal (GI) or liver studies that report measures of SRD or interventions to achieve health equity in these domains by addressing upstream determinants of health.

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What's in a Number? Assessing the Burden of Diverticular Disease

Hantouli MN, Khor S, Strate LL, Lavallee DC, Mower WR, Porter AJ, Flum DR, Davidson GH

In this prospective observational cohort of patients with a history of diverticulitis, we assessed the correlation between the diverticulitis quality of life survey (DVQOL) and other patient-reported expressions of disease measures including work and activity impairment, and contentment with gastrointestinal-related health. Then, we assessed whether the DVQOL is better correlated with these measures than diverticulitis episode count. 

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Emerging Tests for Non-Invasive Colorectal Cancer Screening

Hanna M, Dey N, Grady WM

Current CRC screening methods are effective for preventing CRC and have been shown to reduce CRC-related mortality. However, none of the currently available tests is ideal, and many people are not compliant with CRC screening. Novel CRC screening tests based on advances in CRC molecular biology, genetics, and epigenetics combined with developments in sequencing technologies and computational analytic methods, have been developed to address the shortcomings of current CRC screening tests. These emerging tests include blood-based assays that use plasma-derived circulating tumor DNA and serum proteins to detect early CRC and advanced adenomas, assays that use stool DNA or mRNA, and methods for profiling the gut microbiome. Here we review current screening modalities, and we discuss the principles behind the most promising emerging CRC screening tests and the data supporting their potential to be used in clinical practice.

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Effectiveness of COVID-19 treatment with nirmatrelvir-ritonavir or molnupiravir among U.S. Veterans: target trial emulation studies with one-month and six-month outcomes

Bajema KL, Berry K, Streja E, Rajeevan N, Li Y, Yan L, Cunningham F, Hynes DM, Rowneki M, Bohnert A, Boyko EJ, Iwashyna TJ, Maciejewski ML, Osborne TF, Viglianti EM, Aslan M, Huang GD, Ioannou GN

Information about the effectiveness of oral antivirals in preventing short- and long-term COVID-19-related outcomes during the Omicron surge is limited. We sought to determine the effectiveness of nirmatrelvir-ritonavir and molnupiravir for the outpatient treatment of COVID-19.

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Interhospital transfers resulting in liver transplantation: Clinical, regulatory, and economic issues

Hussain SF, Kim NJ, Biggins SW, Naugler S, Ahn J, Volk ML

Interhospital transfers resulting in liver transplantation are defined as hospital admissions resulting in liver transplantation in which the patient's admission originated at another hospital. This includes patients already on the transplant list and those who get evaluated, listed, and transplanted during that hospitalization. In addition, there undoubtedly exist many more transfers for the purpose of transplant evaluation, in which the transplant occurs during a later hospitalization or never occurs at all.

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IgG and IgM Immunohistochemistry in Primary Biliary Cholangitis (PBC) and Autoimmune Hepatitis (AIH) Liver Explants

Hsu M, Ju JY, Pearson MM, Yu L, Swanson PE, Yeh MM

Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) can be difficult to distinguish in end-stage liver disease. Previous studies have shown that immunoglobulin G (IgG) and immunoglobulin M (IgM) immunostaining can differentiate AIH from PBC in needle core biopsy specimens, and we seek to extend these data to cirrhotic liver explants, in which the histology of AIH or PBC may be indiscernible.

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Combining FIB-4 and Liver Stiffness Into the FIB-5, a Single Model that Accurately Predicts Complications of Portal Hypertension

Vutien P, Berry K, Feng Z, VoPham T, He Q, Green PK, Ioannou GN

We aimed to combine the fibrosis (FIB)-4 score and fibroscan-derived liver stiffness (LS) into a single score (FIB-5) that predicts incident complications of portal hypertension (PH) in persons with compensated liver disease.

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Initial Assessment of Boiling Histotripsy for Mechanical Ablation of Ex Vivo Human Prostate Tissue

Khokhlova VA, Rosnitskiy PB, Tsysar SA, Buravkov SV, Ponomarchuk EM, Sapozhnikov OA, Karzova MM, Khokhlova TD, Maxwell AD, Wang YN, Kadrev AV, Chernyaev AL, Chernikov VP, Okhobotov DA, Kamalov AA, Schade GR

Boiling histotripsy (BH) is a focused ultrasound technology that uses millisecond-long pulses with shock fronts to induce mechanical tissue ablation. The pulsing scheme and mechanisms of BH differ from those of cavitation cloud histotripsy, which was previously developed for benign prostatic hyperplasia. The goal of the work described here was to evaluate the feasibility of using BH to ablate fresh ex vivo human prostate tissue as a proof of principle for developing BH for prostate applications.

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Burnout Among US Gastroenterologists and Fellows in Training Identifying Contributing Factors and Offering Solutions

Anderson, Joseph C.; Bilal, Mohammad; Burke, Carol A. ; Gaidos, Jill K.; Lopez, Rocio; Oxentenko, Amy S.; Surawicz, Christina M.

Consequences of physician burnout include medical errors, higher rate of staff turnover, and decreased patient satisfaction. We examined the prevalence of burnout and identified the contributing factors in gastroenterologists and fellows in training.

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Quantitative Assessment of Boiling Histotripsy Progression Based on Color Doppler Measurements

Song M, Thomas GPL, Khokhlova VA, Sapozhnikov OA, Bailey MR, Maxwell AD, Yuldashev PV, Khokhlova TD

Boiling histotripsy (BH) is a mechanical tissue liquefaction method that uses sequences of millisecond-long high intensity focused ultrasound (HIFU) pulses with shock fronts. The BH treatment generates bubbles that move within the sonicated volume due to acoustic radiation force. Since the velocity of the bubbles and tissue debris is expected to depend on the lesion size and liquefaction completeness, it could provide a quantitative metric of the treatment progression. In this study, the motion of bubble remnants and tissue debris immediately following BH pulses was investigated using high-pulse repetition frequency (PRF) plane-wave color Doppler ultrasound in ex vivo myocardium tissue. 

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Tips for the Medical Management of Diverticulitis

Strate LL, Peery AF

Chronic divertiuclitus is common and is increasing in incidence, particularly in younger adults. In the United States, there are more than a million outpatient and emergency department visits and 300,000 hospital admissions for diverticulitis each year.

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Factors Associated With Advanced Histological Diagnosis and Upstaging After Endoscopic Submucosal Dissection of Superficial Gastric Neoplasia

Franciska J. Gudenkauf, Yutaka Tomizawa, Saowanee Ngamruengphong, et al.

Endoscopic submucosal dissection (ESD) is an important treatment for gastric neoplasia. Some gastric adenomas with low-grade dysplasia (LGD) and high-grade dysplasia (HGD) on endoscopic forceps biopsy (EFB) are diagnosed as gastric adenocarcinoma (GAC) after ESD. We aimed to identify factors associated with histological diagnosis of gastric lesions and predictors for pathological upstaging following ESD.

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Predictors of Length of Stay and Mortality During Simultaneous Liver-Kidney Transplant Index Admission: Results From the US-Multicenter SLKT Consortium

Barman PM, Patel YA, Xie J, Zhang M, Jo J, Sinha J, Answine A, Schluger A, Walter K, Biggins SW, Cullaro G, Wong R, Lai JC, VanWagner LB, Magee J, Verna EC, Sharma P

Length of stay (LOS) during index solid organ transplant impacts morbidity and healthcare costs. To date, there are no studies evaluating characteristics and outcomes of simultaneous liver-kidney transplant (SLKT) index hospitalization. We examined factors associated with LOS and mortality during index SLKT admission.

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Consensus elements for observational research on COVID-19-related long-term outcomes

Admon AJ, Wander PL, Iwashyna TJ, Ioannou GN, Boyko EJ, Hynes DM, Bowling CB, Bohnert ASB, O'Hare AM, Smith VA, Pura J, Hebert PL, Wong ES, Niederhausen M, Maciejewski ML

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its long-term outcomes may be jointly caused by a wide range of clinical, social, and economic characteristics. Studies aiming to identify mechanisms for SARS-CoV-2 morbidity and mortality must measure and account for these characteristics to arrive at unbiased, accurate conclusions. We sought to inform the design, measurement, and analysis of longitudinal studies of long-term outcomes among people infected with SARS-CoV-2.

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Implementation of a mailed faecal immunochemical test programme for colorectal cancer screening among Veterans

Deeds SA, Moore CB, Gunnink EJ, Wheat CL, Robinson AE, Bomsztyk MD, Geyer JR, Chen A, Godbout RM, Nelson KM, Dominitz JA, Reddy A

Background: Screening for colorectal cancer (CRC) with faecal immunochemical test (FIT) is effective at reducing CRC mortality. Unfortunately, the COVID-19 pandemic has been associated with deferred care, especially screening for CRC. Aim: We sought to develop a mailed FIT programme (MFP) to increase CRC screening and make recommendations for adoption across the Veterans Health Administration (VHA) and for other large healthcare systems.

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Early Adoption of Anti-SARS-CoV-2 Pharmacotherapies Among US Veterans With Mild to Moderate COVID-19, January and February 2022

Bajema KL, Wang XQ, Hynes DM, Rowneki M, Hickok A, Cunningham F, Bohnert A, Boyko EJ, Iwashyna TJ, Maciejewski ML, Viglianti EM, Streja E, Yan L, Aslan M, Huang GD, Ioannou GN

Importance: Older adults and individuals with medical comorbidities are at increased risk for severe COVID-19. Several pharmacotherapies demonstrated to reduce the risk of COVID-19-related hospitalization and death have been authorized for use. Objective: To describe factors associated with receipt of outpatient COVID-19 pharmacotherapies in the Veterans Affairs (VA) health care system.

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Picking up microbial clues in early-onset colorectal cancer

Neelendu Dey

The recognition that early-onset colorectal cancer (EO-CRC) rates are rising has sent shockwaves through the field of gastroenterology in recent years. Cases of celebrities affected by EO-CRC have similarly shocked the broader public and have drawn attention to the importance of screening. After television anchor Katie Couric’s husband died of EO-CRC at age 42, she underwent an on-air colonoscopy in 2000, which led to a significant increase in screening colonoscopy rates that was dubbed ‘the Katie Couric effect’.

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Role Of Oral Health, Frailty and Minimal Hepatic Encephalopathy In The Risk Of Hospitalization: A Prospective Multi-Center Cohort Of Outpatients with Cirrhosis

Bajaj JS, Lai JC, Tandon P, O'Leary JG, Wong F, Garcia-Tsao G, Vargas HE, Kamath PS, Biggins SW, Limon-Moro A, Shaw J, Mbachi C, Chew M, Deeb JG, Thacker LR, Reddy KR

Hospitalizations are a sentinel event in cirrhosis; however, the changing cirrhosis demographics in require updated hospitalization prediction models. Periodontitis is a risk factor for liver disease and potentially progression. Aim: Determine factors, including poor oral health, associated with 3-month hospitalizations in a multi-center cohort of cirrhosis outpatients.

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A digital health intervention to improve nutrition and physical activity in breast cancer survivors: Rationale and design of the Cook and Move for Your Life pilot and feasibility randomized controlled trial

Ueland K, Sanchez SC, Rillamas-Sun E, Shen H, Schattenkerk L, Garcia G, VanDoren M, Myers SA, Santiago-Torres M, Di C, Dey N, Guthrie KA, Yung R, Davidson NE, Greenlee H.

Background: The design of a randomized pilot trial evaluating the feasibility of two doses of a digital health intervention promoting changes in nutrition and physical activity in breast cancer (BC) survivors is described.

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Complexity of diagnosing and managing long COVID

Ann M. O’Hare, Elizabeth K. Vig, Theodore J. Iwashyna, Alexandra Fox, Janelle S. Taylor, Elizabeth M. Viglianti, Catherine R. Butler, Kelly C. Vranas, Mark Helfand, Anaïs Tuepker, Shannon M. Nugent, Kara A. Winchell, Ryan J. Laundry, C. Barrett Bowling, Denise M. Hynes, Matthew L. Maciejewski, Amy S. B. Bohnert, Emily R. Locke, Edward J. Boyko, George N. Ioannou, for the VA COVID Observational Research Collaboratory (CORC).

Question: What themes pertaining to long COVID can be identified in qualitative analysis of health records from the Department of Veterans Affairs health system? Findings: This qualitative study including health records from 200 randomly sampled veterans identified 2 dominant themes: (1) clinical uncertainty: it was often unclear whether particular symptoms were due to long COVID, given the medical complexity and functional limitations of many patients and absence of specific markers for this condition, which led to ongoing monitoring, diagnostic testing, and referral; and (2) care fragmentation: post–COVID-19 care processes were often siloed from other care and could be burdensome to patients.

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Mitochondrial dysfunction reactivates α-fetoprotein expression that drives copper-dependent immunosuppression in mitochondrial disease models

Jett KA, Baker ZN, Hossain A, Boulet A, Cobine PA, Ghosh S, Ng P, Yilmaz O, Barreto K, DeCoteau J, Mochoruk K, Ioannou GN, Savard C, Yuan S, Abdalla OH, Lowden C, Kim BE, Cheng HM, Battersby BJ, Gohil VM, Leary SC

Signaling circuits crucial to systemic physiology are widespread, yet uncovering their molecular underpinnings remains a barrier to understanding the etiology of many metabolic disorders. Here, we identify a copper-linked signaling circuit activated by disruption of mitochondrial function in the murine liver or heart that results in atrophy of the spleen and thymus and causes a peripheral white blood cell deficiency. We demonstrate that the leukopenia is caused by α-fetoprotein, which requires copper and the cell surface receptor CCR5 to promote white blood cell death.

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Rapid detection of hepatitis C virus using recombinase polymerase amplification

Catherine T. Chia, Andrew T. Bender, Lorraine Lillis, Benjamin P. Sullivan, Coleman D. Martin, Wynn Burke, Charles Landis, David S. Boyle, Jonathan D. Posner

Over 71 million people are infected with hepatitis C virus (HCV) worldwide, and approximately 400,000 global deaths result from complications of untreated chronic HCV. Pan-genomic direct-acting antivirals (DAAs) have recently become widely available and feature high cure rates in less than 12 weeks of treatment. The rollout of DAAs is reliant on diagnostic tests for HCV RNA to identify eligible patients with viremic HCV infections.

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Burden of early hospitalization after simultaneous liver-kidney transplantation: Results from the US Multicenter SLKT Consortium

Sharma P, Xie J, Wang L, Zhang M, Magee J, Answine A, Barman P, Jo J, Sinha J, Schluger A, Perreault GJ, Walters KE, Cullaro G, Wong R, Filipek N, Biggins SW, Lai JC, VanWagner LB, Verna EC, Patel YA

The burden of early hospitalization (within 6 months) following simultaneous liver–kidney transplant (SLKT) is not known. We examined risk factors associated with early hospitalization after SLKT and their impact on patient mortality conditional on 6-month survival. We used data from the US Multicenter SLKT Consortium cohort study of all adult SLKT recipients between 2002 and 2017 who were discharged alive following SLKT. We used Poisson regression to model rates of early hospitalizations after SLKT.

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Effect of risankizumab on health-related quality of life in patients with Crohn's disease: results from phase 3 MOTIVATE, ADVANCE and FORTIFY clinical trials

Peyrin-Biroulet L, Ghosh S, Lee SD, Lee WJ, Griffith J, Wallace K, Berg S, Liao X, Panes J, Loftus EV Jr, Louis E

Crohn's disease has a substantial negative impact on health-related quality of life (HRQoL). Aim: To examine the effects of risankizumab on HRQoL in Crohn's disease. Methods: We analysed data from patients with Crohn's disease from 12-week induction trials ADVANCE (N = 850) and MOTIVATE (N = 569) with risankizumab 600 mg or 1200 mg intravenous (IV) versus placebo IV and a 52-week maintenance trial FORTIFY (N = 462) with risankizumab 180 or 360 mg subcutaneous (SC) versus placebo SC. 

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Metabolic targeting of NRF2 potentiates the efficacy of the TRAP1 inhibitor G-TPP through reduction of ROS detoxification in colorectal cancer

Hong-YuanTsai, Mary P. Bronner, Jordon K. March, John F. Valentine, Noah F. Shroyer, Lisa A. Lai, Teresa A. Brentnall, Sheng Pan, Ru Chen

Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial homolog of HSP90 chaperones. It plays an important role in protection against oxidative stress and apoptosis by regulating reactive oxidative species (ROS). To further elucidate the mechanistic role of TRAP1 in regulating tumor cell survival, we used gamitrinib-triphenylphosphonium (G-TPP) to inhibit TRAP1 signaling pathways in colon cancer.

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Deep Remission in Severe Refractory Crohn’s Disease With Mycophenolate Mofetil

Jeffrey Jacobs, Kindra Clark-Snustad, Scott Lee

Studies using mycophenolate mofetil (MMF) in Crohn’s disease (CD) are limited. We present a case of robust response to MMF in a patient with CD.

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Understanding the Results of a Randomized Trial of Screening Colonoscopy

Jason A. Dominitz, Douglas J. Robertson

For more than two decades, colonoscopy has been recommended as one of several available options for colorectal cancer screening, and it has been the predominant form of screening for colorectal cancer used in the United States. However, the best evidence to support its use has been limited to data from cohort studies, which have estimated that this type of screening has been associated with a 40 to 69% decrease in the incidence of colorectal cancer and a 29 to 88% decrease in the risk of death from this disease.

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Cancer risk in patients with diverticular disease: a nationwide cohort study

Ma W, Walker MM, Thuresson M, Roelstraete B, Sköldberg F, Olén O, Strate LL, Chan AT, Ludvigsson JF

There are little data on diverticular disease and cancer development, other than colorectal cancer. We conducted a population-based, matched cohort study with linkage of nationwide registers to the ESPRESSO histopathology cohort. We included 75,704 patients with a diagnosis of diverticular disease and colorectal histopathology and 313,480 reference individuals from the general population matched on age, sex, calendar year, and county. 

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The Conundrum of Patients With Compensated Cirrhosis Requiring Kidney Transplantation; Kidney Alone or Simultaneous Liver Kidney Transplantation

Dodge JL, Lee BT, Kassem ACZ, Biggins SW, Rana PA, Nadim MK, Asrani SK, Fong TL

Patients with compensated cirrhosis and chronic kidney disease are increasing along with demand for simultaneous liver kidney transplant (SLKT) and shortages of organs for transplantation. Although these well-compensated patients may not need a liver organ, the alternative of kidney transplant alone (KTA) poses the risk of liver decompensation. Therefore, we aim to characterize outcomes among patients with compensated cirrhosis and chronic kidney disease listed for SLKT or receiving KTA to inform clinical decisions.

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Effectiveness of mRNA COVID-19 Vaccine Boosters Against Infection, Hospitalization, and Death: A Target Trial Emulation in the Omicron (B.1.1.529) Variant Era

Ioannou GN, Bohnert ASB, O'Hare AM, Boyko EJ, Maciejewski ML, Smith VA, Bowling CB, Viglianti E, Iwashyna TJ, Hynes DM, Berry K; COVID-19 Observational Research Collaboratory (CORC)*.

The effectiveness of a third mRNA COVID-19 vaccine dose (booster dose) against the Omicron (B.1.1.529) variant is uncertain, especially in older, high-risk populations. Objective: To determine mRNA booster vaccine effectiveness (VE) against SARS-CoV-2 infection, hospitalization, and death in the Omicron era by booster type, primary vaccine type, time since primary vaccination, age, and comorbidity burden.

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Development and validation of a new ICD-10-based screening colonoscopy overuse measure in a large integrated healthcare system: a retrospective observational study

Adams MA, Kerr EA, Dominitz JA, Gao Y, Yankey N, May FP, Mafi J, Saini SD

Low-value use of screening colonoscopy is wasteful and potentially harmful to patients. Decreasing low-value colonoscopy prevents procedural complications, saves patient time and reduces patient discomfort, and can improve access by reducing procedural demand. The objective of this study was to develop and validate an electronic measure of screening colonoscopy overuse using International Classification of Diseases, Tenth Edition codes and then apply this measure to estimate facility-level overuse to target quality improvement initiatives to reduce overuse in a large integrated healthcare system.

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Mechanical damage thresholds for hematomas near gas-containing bodies in pulsed HIFU fields

Ponomarchuk EM, Hunter C, Song M, Khokhlova VA, Sapozhnikov OA, Yuldashev PV, Khokhlova TD

Boiling histotripsy (BH) is a novel high intensity focused ultrasound (HIFU) application currently being developed for non-invasive mechanical fractionation of soft tissues and large hematomas. In the context of development of BH treatment planning approaches for ablating targets adjacent to gas-containing organs, this study aimed at investigation of the ultrasound pressure thresholds of atomization-induced damage to the tissue-air interface and correlation of the danger zone dimensions with spatial structure of nonlinear HIFU field parameters. 

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DNA Methylation Profile in CpG-depleted Regions Uncovers a High-Risk Subtype of Early-stage Colorectal Cancer

Yu H, Wang X, Bai L, Tang G, Carter KT, Cui J, Huang P, Liang L, Ding Y, Cai M, Huang M, Liu H, Cao G, Gallinger S, Pai RK, Buchanan DD, Win AK, Newcomb PA, Wang J, Grady WM, Luo Y

The current risk stratification system defined by clinicopathological features does not identify the risk of recurrence in early-stage (stage I-II) colorectal cancer (CRC) with sufficient accuracy. We aimed to investigate whether DNA methylation could serve as novel biomarkers for predicting prognosis in early-stage CRC patients.

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COVID-19 Pandemic Had Minimal Impact on Colonoscopy Completion After Colorectal Cancer Red Flag Sign or Symptoms in US Veterans. 

Demb J, Liu L, Bustamante R, Dominitz JA, Earles A, Shah SC, Gawron AJ, Martinez ME, Gupta S

Background: Delays in colonoscopy work-up for red flag signs or symptoms of colorectal cancer (CRC) during the COVID-19 pandemic are not well characterized. Aims: To examine colonoscopy uptake and time to colonoscopy after red flag diagnosis, before and during the COVID-19 pandemic.

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Hepatocellular Carcinoma Risk Declines but Remains High Enough for Screening in the First 7 Years After Hepatitis C Virus Cure With Direct-Acting Antivirals in Patients With Cirrhosis or High Fibrosis-4 Score

Nicole J. Kim, Philip Vutien, Kristin Berry, George N. Ioannou

In a previous study, annual HCC risk declined during the first 4 years of follow-up, but the follow-up time was not long enough to determine whether HCC risk continues to decline to levels low enough that HCC screening may no longer be warranted. In this study, we extended the follow-up of this DAA-cured cohort up to 7 years to determine whether annual HCC risk, stratified by cirrhosis and FIB-4 categories, declines to levels low enough to preclude the requirement for HCC screening.

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AGA Clinical Practice Update on Management of Refractory Celiac Disease: Expert Review

Green PHR, Paski S, Ko CW, Rubio-Tapia A

The purpose of this expert review is to summarize the diagnosis and management of refractory celiac disease. It will review evaluation of patients with celiac disease who have persistent or recurrent symptoms, differential diagnosis, nutritional support, potential therapeutic options, and surveillance for complications of this condition.

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Metabolic targeting of NRF2 potentiates the efficacy of the TRAP1 inhibitor G-TPP through reduction of ROS detoxification in colorectal cancer

Tsai HY, Bronner MP, March JK, Valentine JF, Freeman Shroyer N, Lai LA, Brentnall TA, Pan S, Chen R

Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial homolog of HSP90 chaperones. It plays an important role in protection against oxidative stress and apoptosis by regulating reactive oxidative species (ROS). To further elucidate the mechanistic role of TRAP1 in regulating tumor cell survival, we used gamitrinib-triphenylphosphonium (G-TPP) to inhibit TRAP1 signaling pathways in colon cancer.

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Complete Genome Sequences of Two Bacteroides uniformis Bacteriophages

Bean EM, Morella NM, Dey N

Here, we describe the isolation and genomic annotation of two novel siphovirus species of bacteriophages that infect Bacteroides uniformis: Bacteroides phage EMB1 and Bacteroides phage EMB2. EMB1 has a 34,204-bp genome with 48 coding sequences, and EMB2 has a 34,008-bp genome with 47 coding sequences.

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Indications for surgical treatment of diverticulitis: factors that influence surgical decision-making for patients and surgeons

Hantouli MN, Droullard DJ, Khor S, Strate LL, Lavallee DC, Flum DR, Davidson GH

Nearly 3 million Americans are diagnosed with acute uncomplicated diverticulitis annually, and up to 25 per cent have a recurrent episode. The American Society of Colon and Rectal Surgeons guidelines recommend individualizing the decision to operate based on the impact of diverticulitis on health-related quality of life.

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Associations of individual and combined physical activity and body mass index groups with pro-inflammatory biomarkers among colorectal cancer patients

Himbert C, Warby CA, Gigic B, Ose J, Lin T, Viskochil R, Peoples AR, Ashworth A, Schrotz-King P, Scaife CL, Cohan JN, Jedrzkiewicz J, Schirmacher P, Grady WM, Cohen SA, Krane M, Figueiredo JC, Toriola AT, Siegel EM, Shibata D, Round JL, Huang LC, Li CI, Schneider M, Ulrich A, Hardikar S, Ulrich CM

Physical activity and obesity are well-established factors of colorectal cancer (CRC) risk and prognosis. Here, we investigate associations of individual and combined physical activity and BMI groups with pro-inflammatory biomarkers in CRC patients.

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Diversity, Equity, and Inclusion in Gastroenterology and Hepatology: A Survey of Where We Stand

Rahal HK, Tabibian JH, Issaka RB, Quezada S, Gray DM, Balzora S, Yang L, Badiee J, May FP

In the setting of increasing attention to representation in medicine, we aimed to assess current perspectives of racial and ethnic workforce diversity and health care disparities among gastroenterology (GI) and hepatology professionals in the United States. Methods: We developed and administered a 33-item electronic cross-sectional survey to members of 5 national GI and hepatology societies. Survey items were organized into thematic modules and solicited perspectives on racial and ethnic workforce diversity, health care disparities in GI and hepatology, and potential interventions to enhance workforce diversity and improve health equity.

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IgG and IgM Immunohistochemistry in Primary Biliary Cholangitis (PBC) and Autoimmune Hepatitis (AIH) Liver Explants

Hsu M, Ju JY, Pearson MM, Yu L, Swanson PE, Yeh MM

Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) can be difficult to distinguish in end-stage liver disease. Previous studies have shown that immunoglobulin G (IgG) and immunoglobulin M (IgM) immunostaining can differentiate AIH from PBC in needle core biopsy specimens, and we seek to extend these data to cirrhotic liver explants, in which the histology of AIH or PBC may be indiscernible.

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Moving Away from a One-Size-Fits-All Approach to Hepatocellular Carcinoma Surveillance

Andrew M Moon, George N Ioannou

Liver cancer, primarily from hepatocelular carcinoma (HCC), is the third leading cause of cancer-related deaths worldwide. 

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In Vivo Aberration Correction for Transcutaneous HIFU Therapy using a Multi-element Array

Thomas GPL, Khokhlova TD, Sapozhnikov OA, Wang YN, Totten S, Khokhlova VA

One of the challenges of transcutaneous high intensity focused ultrasound (HIFU) therapies, especially ones relying heavily on shock formation such as boiling histotripsy (BH), is the loss of focusing from aberration induced by the heterogeneities of the body wall. Here, a methodology to execute aberration correction in vivo is proposed. A custom BH system consisting of a 1.5 MHz phased array of 256 elements connected to a Verasonics V1 system is used in pulse/echo mode on a porcine model under general anaesthesia. Estimation of the time shifts needed to correct for aberration in the liver and kidney is done by maximizing the value of the coherence factor on the acquired backscattered signals. 

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The association between non-steroidal anti-inflammatory drug use and inflammatory bowel disease exacerbations: a true association or residual bias?

Cohen-Mekelburg, Shirley; Van, Tony; Wallace, Beth; Berinstein, Jeff; Yu, Xianshi; Lewis, James; Hou, Jason; Dominitz, Jason A.; Waljee, Akbar K. 

Studies suggest that non-steroidal anti-inflammatory drugs (NSAID) may contribute to inflammatory bowel disease (IBD) exacerbations. We examined whether variation in the likelihood of IBD exacerbations is attributable to NSAIDs.

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Pre-endoscopy coronavirus disease 2019 screening and severe acute respiratory syndrome coronavirus-2 nucleic acid amplification testing in the Veterans Affairs 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

The coronavirus disease 2019 (COVID-19) pandemic has had profound impacts worldwide, including on the performance of GI endoscopy. We aimed to describe the performance and outcomes of pre-endoscopy COVID-19 symptom and exposure screening and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) nucleic acid amplification testing (NAAT) across the national Veterans Affairs healthcare system and describe the relationship of SARS-CoV-2 NAAT use and resumption of endoscopy services.

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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

Background and study aims: 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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A Comparison of Logistic Regression Against Machine Learning Algorithms for Gastric Cancer Risk Prediction Within Real-World Clinical Data Streams

Huang RJ, Kwon NS, Tomizawa Y, Choi AY, Hernandez-Boussard T, Hwang JH

Noncardia gastric cancer (NCGC) is a leading cause of global cancer mortality, and is often diagnosed at advanced stages. Development of NCGC risk models within electronic health records (EHR) may allow for improved cancer prevention. There has been much recent interest in use of machine learning (ML) for cancer prediction, but few studies comparing ML with classical statistical models for NCGC risk prediction.

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Rates and Factors Associated With Documentation of Diagnostic Codes for Long COVID in the National Veterans Affairs Health Care System

Ioannou GN, Baraff A, Fox A, Shahoumian T, Hickok A, O'Hare AM, Bohnert ASB, Boyko EJ, Maciejewski ML, Bowling CB, Viglianti E, Iwashyna TJ, Hynes DM

Question  What are the rates, clinical settings, and factors associated with documentation of care related to COVID-19 at 3 or more months after acute infection? Findings  In this cohort study of 198 601 persons with a positive SARS-CoV-2 test, COVID-19 care was documented in 13.5% of individuals 3 or more months after infection during a mean follow-up of 13.5 months and was documented more commonly in older persons, those with higher comorbidity burden, those with more severe acute COVID-19 presentation, and those who were unvaccinated at the time of infection.

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GWAS meta-analysis of 16 790 patients with Barrett's oesophagus and oesophageal adenocarcinoma identifies 16 novel genetic risk loci and provides insights into disease aetiology beyond the single marker level

Schröder J, Chegwidden L, Maj C, Gehlen J, Speller J, Böhmer AC, Borisov O, Hess T, Kreuser N, Venerito M, Alakus H, May A, Gerges C, Schmidt T, Thieme R, Heider D, Hillmer AM, Reingruber J, Lyros O, Dietrich A, Hoffmeister A, Mehdorn M, Lordick F, Stocker G, Hohaus M, Reim D, Kandler J, Müller M, Ebigbo A, Fuchs C, Bruns CJ, Hölscher AH, Lang H, Grimminger PP, Dakkak D, Vashist Y, May S, Görg S, Franke A, Ellinghaus D, Galavotti S, Veits L, Weismüller J, Dommermuth J, Benner U, Rösch T, Messmann H, Schumacher B, Neuhaus H, Schmidt C, Wissinowski TT, Nöthen MM; Wellcome Trust Case Control Consortium 2 (WTCCC2); Esophageal Adenocarcinoma Genetics Consortium (EAGLE); Barrett's and Esophageal Adenocarcinoma Consortium (BEACON), Dong J, Ong JS, Buas MF, Thrift AP, Vaughan TL, Tomlinson I, Whiteman DC, Fitzgerald RC, Jankowski J, Vieth M, Mayr A, Gharahkhani P, MacGregor S, Gockel I, Palles C, Schumacher J.

Objective: Oesophageal cancer (EC) is the sixth leading cause of cancer-related deaths. Oesophageal adenocarcinoma (EA), with Barrett's oesophagus (BE) as a precursor lesion, is the most prevalent EC subtype in the Western world. This study aims to contribute to better understand the genetic causes of BE/EA by leveraging genome wide association studies (GWAS), genetic correlation analyses and polygenic risk modelling.

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North American Practice-Based Recommendations for Transjugular Intrahepatic Portosystemic Shunts in Portal Hypertension

Boike JR, Thornburg BG, Asrani SK, Fallon MB, Fortune BE, Izzy MJ, Verna EC, Abraldes JG, Allegretti AS, Bajaj JS, Biggins SW, Darcy MD, Farr MA, Farsad K, Garcia-Tsao G, Hall SA, Jadlowiec CC, Krowka MJ, Laberge J, Lee EW, Mulligan DC, Nadim MK, Northup PG, Salem R, Shatzel JJ, Shaw CJ, Simonetto DA, Susman J, Kolli KP, VanWagner LB; Advancing Liver Therapeutic Approaches (ALTA) Consortium

Complications of portal hypertension, including ascites, gastrointestinal bleeding, hepatic hydrothorax, and hepatic encephalopathy, are associated with significant morbidity and mortality. Despite few high-quality randomized controlled trials to guide therapeutic decisions, transjugular intrahepatic portosystemic shunt (TIPS) creation has emerged as a crucial therapeutic option to treat complications of portal hypertension. In North America, the decision to perform TIPS involves gastroenterologists, hepatologists, and interventional radiologists, but TIPS creation is performed by interventional radiologists. This is in contrast to other parts of the world...

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Peer evaluation and feedback for invasive medical procedures: a systematic review

Thai T, Louden DKN, Adamson R, Dominitz JA, Doll JA

There is significant variability in the performance and outcomes of invasive medical procedures such as percutaneous coronary intervention, endoscopy, and bronchoscopy. Peer evaluation is a common mechanism for assessment of clinician performance and care quality, and may be ideally suited for the evaluation of medical procedures. We therefore sought to perform a systematic review to identify and characterize peer evaluation tools for practicing clinicians, assess evidence supporting the validity of peer evaluation, and describe best practices of peer evaluation programs across multiple invasive medical procedures.

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Epigenetic silencing and tumor suppressor gene of HAND2 by targeting ERK signaling in colorectal cancer

Yuan Z, Yu X, Chen W, Chen D, Cai J, Jiang Y, Liu X, Wu Z, Wang L, Grady WM, Wang H

The screening biomarkers for early detection of colorectal cancer (CRC) is lacking. The aim is to identify epigenetic silenced genes and clarify its roles and underlying mechanism in CRC. We conducted integrative analyses of epigenome-wide Human Methylation 450 K arrays and transcriptome to screen out candidate epigenetic driver genes with transcription silencing. Methylated silencing HAND2 were identified and verified in large CRC cohort.

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Interventions to improve adenoma detection rates for colonoscopy

Shaukat A, Tuskey A, Rao VL, Dominitz JA, Murad MH, Keswani RN, Bazerbachi F, Day LW; (ASGE Quality Assurance in Endoscopy Committee Chair)

The purpose of this document is to augment the previously developed endoscopy quality indicator publications first drafted in 2006 by the joint task force on quality in endoscopy of the ASGE/American College of Gastroenterology and that integrated new data in 2014. The ASGE Quality Assurance in Endoscopy Committee outlined the proposal, and the methodology was reviewed with an expert evidence-based medicine methodologist (M.H.M.). Clinically relevant questions18 were selected to guide the systematic literature review.19 All clinically relevant questions were written and approved by the Quality Assurance in Endoscopy Committee members and designed to conjure ameliorating interventions to the previously prioritized quality indicators.

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Combining FIB-4 and liver stiffness into the FIB-5, a single model that accurately predicts complications of portal hypertension

Vutien P, Berry K, Feng Z, VoPham T, He Q, Green PK, Ioannou GN

We aimed to combine the fibrosis-4 (FIB-4) score and fibroscan-derived liver stiffness (LS) into a single score (FIB-5) that predicts incident complications of portal hypertension (PH) in persons with compensated liver disease.

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

David J Kearney, Kendra J Kamp, Meghan Storms, Tracy L Simpson

Goals: 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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How safety-net health systems can advance equity in gastroenterology and hepatology

Nicole J Kim, Rachel B Issaka

Despite serving a substantial proportion of the population in the USA, safety-net health systems are often excluded from gastroenterology and hepatology research. The importance of addressing this research gap cannot be overstated. For example, 34% of people in the USA are uninsured or receive Medicaid3 and 25% of all hospitals in the USA are safety-net hospitals.6 However, less than 5% of research studies and less than 1% of gastroenterology and hepatology studies funded by the US National Institutes of Health include “safety-net” in the project terms. As research often leads to innovation in clinical care and improved health outcomes, increasing the representation of safety-net health systems in research is crucial to improving the quality of gastroenterology and hepatology care provided to all patients.

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On the Importance of Safe Access to Reproductive Options for Adolescents and Women with Liver Disease

Alexandra Shingina, Monika Sarkar, Lauren Feld

This paper is only available as a PDF.

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Novel DNA Methylation Biomarker Panel for Detection of Esophageal Adenocarcinoma and High-grade Dysplasia

Ming Yu, Helen R. Moinova, Amber Willbanks, Victoria K. Cannon, Ting Wang, Kelly Carter, Andrew Kaz, Deepti Reddi, John Inadomi, Georg Luebeck, Prasad G. Iyer, Marcia I. Canto, Jean S. Wang, Nicholas J. Shaheen, Prashanthi N. Thota, Joseph E. Willis, Thomas LaFramboise, Amitabh Chak, Sanford D. Markowitz, William M. Grady 

Current endoscopy-based screening and surveillance programs have not been proven effective at decreasing esophageal adenocarcinoma (EAC) mortality, creating an unmet need for effective molecular tests for early detection of this highly lethal cancer. We conducted a genome-wide methylation screen to identify novel methylation markers that distinguish EAC and high grade dysplasia (HGD) from normal squamous epithelium (SQ) or non-dysplastic BE (NDBE).

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Hepatocellular carcinoma risk declines but remains high enough for screening in the first 7 years after HCV cure with DAAs in patients with cirrhosis or high FIB-4

Nicole J Kim, Philip Vutien, Kristin Berry, George N Ioannou

This paper is only available as a PDF.

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GA White Paper: Challenges and Gaps in Innovation for the Performance of Colonoscopy for Screening and Surveillance of Colorectal Cancer

Komanduri S, Dominitz JA, Rabeneck L, Kahi C, Ladabaum U, Imperiale TF, Byrne MF, Lee JK, Lieberman D, Wang AY, Sultan S, Shaukat A, Pohl H, Muthusamy VR

In 2018 the American Gastroenterological Association’s (AGA) Center for GI Innovation and Technology (CGIT) convened a consensus conference, entitled, “Colorectal Cancer Screening and Surveillance: Role of Emerging Technology and Innovation to Improve Outcomes.” The conference participants, which included more than 60 experts in colorectal cancer (CRC), considered recent improvements in CRC screening rates and polyp detection, persistent barriers to colonoscopy uptake, and opportunities for performance improvement and innovation.

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PM 2.5 air pollution exposure and nonalcoholic fatty liver disease in the Nationwide Inpatient Sample

VoPham T, Kim NJ, Berry K, Mendoza JA, Kaufman JD, Ioannou GN

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Particulate matter air pollution <2.5 μm in diameter (PM2.5) is a ubiquitous exposure primarily produced from fossil fuel combustion. Previous epidemiologic studies have been mixed. The objective of this study was to examine the association between ambient PM2.5 exposure and NAFLD among hospitalized patients in the Nationwide Inpatient Sample (NIS).

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Development of Tough Hydrogel Phantoms to Mimic Fibrous Tissue for Focused Ultrasound Therapies

Nanda Kumar Y, Singh Z, Wang YN, Schade GR, Kreider W, Bruce M, Vlaisavljevich E, Khokhlova TD, Maxwell AD

Tissue-mimicking gels provide a cost-effective medium to optimize histotripsy treatment parameters with immediate feedback. Agarose and polyacrylamide gels are often used to evaluate treatment outcomes as they mimic the acoustic properties and stiffness of a variety of soft tissues, but they do not exhibit high toughness, a characteristic of fibrous connective tissue. To mimic pathologic fibrous tissue found in benign prostate hyperplasia (BPH) and other diseases that are potentially treatable with histotripsy, an optically transparent hydrogel with high toughness was developed that is a hybrid of polyacrylamide and alginate.

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Lower Gastrointestinal Tract Disorders

Ray J, LaBundy J

Lower gastrointestinal (GI) diseases and associated symptoms account for a large number of health care visits each year. Many women visit their obstetrician–gynecologists more often than their primary care physicians or use them as primary health care providers. Many gynecologic and lower GI disorders share symptoms, such as lower abdominal or pelvic pain and bloating. Some diseases are more common in women compared with men, such as irritable bowel syndrome (IBS), or warrant special consideration in women.

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Robust and durable aberrative and absorptive phantom for therapeutic ultrasound applications

Peek AT, Thomas GPL, Leotta DF, Yuldashev PV, Khokhlova VA, Khokhlova TD

Phase aberration induced by soft tissue inhomogeneities often complicates high-intensity focused ultrasound (HIFU) therapies by distorting the field and, previously, we designed and fabricated a bilayer gel phantom to reproducibly mimic that effect. A surface pattern containing size scales relevant to inhomogeneities of a porcine body wall was introduced between gel materials with fat- and muscle-like acoustic properties—ballistic and polyvinyl alcohol gels. Here, the phantom design was refined to achieve relevant values of ultrasound absorption and scattering and make it more robust, facilitating frequent handling and use in various experimental arrangements. 

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Burden of Early Hospitalization after Simultaneous Liver-Kidney Transplantation: Results from the US Multicenter SLKT Consortium

Sharma P, Xie J, Wang L, Zhang M, Magee J, Answine A, Barman P, Jo J, Sinha J, Schluger A, Perreault GJ, Walters K, Cullaro G, Wong R, Filipek N, Biggins SW, Lai JC, VanWagner LB, Verna EC, Patel YA

The burden of early hospitalization (within 6 months) following simultaneous liver-kidney transplant (SLKT) is not known. We examined risk factors associated with early hospitalization after SLKT and their impact on patient mortality conditional of six-month survival.

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Barriers associated with inadequate follow-up of abnormal fecal immunochemical test results in a safety-net system: A mixed-methods analysis

Issaka RB, Bell-Brown A, Kao J, Snyder C, Atkins DL, Chew LD, Weiner BJ, Strate L, Inadomi JM, Ramsey SD

In safety-net healthcare systems, colonoscopy completion within 1-year of an abnormal fecal immunochemical test (FIT) result rarely exceeds 50%. Understanding how electronic health records (EHR) documented reasons for missed colonoscopy match or differ from patient-reported reasons, is critical to optimize effective interventions to address this challenge. We conducted a convergent mixed-methods study which included a retrospective analysis of EHR data and semi-structured interviews of adults 50–75 years old, with abnormal FIT results between 2014 and 2020 in a large safety-net healthcare system. 

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Age-stratified prevalence and predictors of neoplasia among US adults undergoing screening colonoscopy in a national endoscopy registry

Peter S. Liang, J. Lucas Williams, Jason A. Dominitz, Douglas A. Corley, Ann G. Zauber

Several US organizations now recommend starting average-risk colorectal cancer (CRC) screening at age 45 years, but the prevalence of colonic neoplasia in individuals younger than 50 years has not been well characterized. We used a national endoscopic registry to calculate age-stratified prevalence and predictors of colorectal neoplasia.

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A multiancestry genome-wide association study of unexplained chronic ALT elevation as a proxy for nonalcoholic fatty liver disease with histological and radiological validation

Rotonya M Carr, et al. See publication for full author list

Nonalcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver disease. Using a proxy NAFLD definition of chronic elevation of alanine aminotransferase (cALT) levels without other liver diseases, we performed a multiancestry genome-wide association study (GWAS) in the Million Veteran Program (MVP) including 90,408 cALT cases and 128,187 controls. Seventy-seven loci exceeded genome-wide significance, including 25 without prior NAFLD or alanine aminotransferase associations, with one additional locus identified in European American-only and two in African American-only analyses (P < 5 × 10−8).

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A TEAM Approach to Diversity, Equity, and Inclusion in Gastroenterology and Hepatology

Williams R, White PM, Balzora S; Association of Black Gastroenterologists and Hepatologists Board of Directors (with Rotonya M Carr, Rachel B Issaka, et al)

In this commentary, we aim to define DEI in the physician workforce with a focus on race and ethnicity in GI. Next, we outline distinct structural barriers and facilitators to DEI efforts. Finally, we provide a framework for institutions seeking to improve DEI efforts through a roadmap for physician workforce diversity in GI. The target, establish, acquire, and measure (TEAM) approach describes a set of proactive behaviors necessary to advance DEI in the GI community.

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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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