Publications by authors named "Nadim Mahmud"

107 Publications

Hypoglycemia is an early, independent predictor of bacteremia and in-hospital death in patients with cirrhosis.

Eur J Gastroenterol Hepatol 2021 May 31. Epub 2021 May 31.

Division of Gastroenterology, Perelman School of Medicine Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Background And Aims: Bacteremia is a common cause of death in patients with cirrhosis and early antimicrobial therapy can be life-saving. Severe liver disease impairs glucose metabolism such that hypoglycemia may be a presenting sign of infection in patients with cirrhosis. We explored this association using granular retrospective data.

Methods: We conducted a case-control analysis from 1 January 2008 to 31 December 17 in the University of Pennsylvania Health System. We identified the first blood culture results from all cirrhosis hospitalizations and obtained detailed vital sign and laboratory data in the 24-72 h prior to culture results. We used multivariable logistic regression to develop models predicting blood culture positivity and in-hospital mortality. We repeated these analyses restricted to normothermic individuals. Restricted cubic splines were used to model nonlinearity in the glucose variable.

Results: We identified 1274 cirrhosis admissions with blood culture results (52.7% positive). In adjusted models, minimum glucose 24-72 h prior to blood culture result date was a significant predictor of blood culture positivity. In particular, glucose levels below 100 mg/dL significantly increased the probability of subsequent positive blood culture (e.g. odds ratio 1.89 for 50 mg/dL vs. 100 mg/dL, P = 0.004). This relationship persisted when restricting the cohort to normothermic individuals. Glucose levels <100 mg/dL in patients with bacteremia were also positively associated with in-hospital mortality.

Conclusions: Early hypoglycemia is predictive of subsequently documented bacteremia and in-hospital mortality in patients with cirrhosis, even among normothermic individuals. In patients without other overt signs of infection, low glucose values may serve as an additional data point to justify early antibiosis.
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http://dx.doi.org/10.1097/MEG.0000000000002218DOI Listing
May 2021

Endoscopy Is Not Associated with Infectious Adverse Events After Hematopoietic Cell Transplantation: A Retrospective Cohort Study.

Dig Dis Sci 2021 May 29. Epub 2021 May 29.

Division of Gastroenterology and Hepatology and Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Perelman Center 7th Floor, Philadelphia, PA, 19104, USA.

Background: Patients with recent hematopoietic cell transplantation (HCT) are considered high risk for gastrointestinal endoscopy due to the potential for procedural bacterial translocation. Prior studies investigating these risks do not account for the higher baseline rate of infectious complications among those who are immunocompromised. We performed a retrospective cohort study of patients with recent HCT who underwent endoscopy and their matched controls who did not undergo endoscopy.

Methods: We identified patients who underwent HCT followed by upper and/or lower endoscopy at the University of Pennsylvania from 2000 to 2018. Individuals were matched 1:1 by age, sex, and type of HCT to controls who underwent HCT without subsequent endoscopy. Infectious adverse events were assessed by Sepsis-3 and Sepsis-2 criteria. Factors associated with infectious adverse events after endoscopy/index date were assessed using multivariable conditional logistic regression.

Results: We identified 149 patients who underwent HCT and endoscopy and 149 matched controls who underwent HCT without endoscopy. Sepsis-3 infectious adverse events occurred in 3.4% of patients in each group. Sepsis-2 infectious adverse events occurred in 20.1% of patients who underwent endoscopy compared to 19.5% of controls. There was no association between endoscopy and Sepsis-2 infectious adverse events in the multivariable regression analysis (adjusted odds ratio 1.65, 95% CI 0.51-5.26).

Conclusions: When compared to controls with similar immune statuses, patients who underwent endoscopy after HCT did not have a higher risk of infectious adverse events. These results may inform clinical decision making regarding the risks and benefits of endoscopic management after HCT.
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http://dx.doi.org/10.1007/s10620-021-07062-7DOI Listing
May 2021

Effectiveness of SARS-CoV-2 vaccination in a Veterans Affairs Cohort of Inflammatory Bowel Disease Patients with Diverse Exposure to Immunosuppressive Medications.

Gastroenterology 2021 May 25. Epub 2021 May 25.

Division of Gastroenterology, Corporal Michael J Crescenz VA Medical Center, Philadelphia, PA; Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA; Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA; Leonard Davis Institute of Health Economics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. Electronic address:

Background And Aims: Vaccination against SARS-CoV-2 has rapidly expanded, however clinical trials excluded patients taking immunosuppressive medications such as those with inflammatory bowel disease (IBD). Therefore, we explored real-world effectiveness of COVID-19 vaccination on subsequent infection in IBD patients with diverse exposure to immunosuppressive medications.

Methods: This was a retrospective cohort study of patients in the Veterans Health Administration with IBD diagnosed prior to 12/18/20, the start date of the VHA patient vaccination program. IBD medication exposures included 5-aminosalicylic acid, thiopurines, anti-tumor necrosis factor biologic agents, vedolizumab, ustekinumab, tofacitinib, methotrexate, and corticosteroid use. We used inverse probability weighting and Cox regression with vaccination status as a time-updating exposure, and computed vaccine effectiveness from incidence rates.

Results: The cohort comprised 14,697 patients, 7,321 of whom received at least one vaccine dose (45.2% Pfizer, 54.8% Moderna). The cohort had median age 68 years, was 92.2% male, 80.4% white, and 61.8% with ulcerative colitis. In follow-up data through April 20, 2021, unvaccinated individuals had the highest raw proportion of SARS-CoV-2 infection (197 [1.34%] versus 7 [0.11%] fully vaccinated). Full vaccination status, but not partial vaccination status, was associated with a 69% reduced hazard of infection relative to an unvaccinated status (hazard ratio [HR] 0.31, 95% confidence interval [CI] 0.17-0.56, p<0.001), corresponding to an 80.4% effectiveness.

Conclusion: Full vaccination (>7 days after the 2 dose) against SARS-CoV-2 infection has an approximately 80.4% effectiveness in a broad IBD cohort with diverse exposure to immunosuppressive medications. These results may serve to increase patient and provider willingness to pursue vaccination in these settings.
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http://dx.doi.org/10.1053/j.gastro.2021.05.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146263PMC
May 2021

Race/ethnicity and underlying disease influences hematopoietic stem/progenitor cell mobilization response: A single center experience.

J Clin Apher 2021 May 28. Epub 2021 May 28.

Division of Hematology/Oncology, Department of Medicine, University of Illinois College of Medicine, Chicago, Illinois, USA.

Background: Whether race/ethnicity plays a role in hematopoietic stem/progenitor cells (HSPC) mobilization in autologous donors has not been studied. We hypothesize that donor characteristic including race/ethnicity, age, sex, body mass index, and diagnostic groups influences HSPC mobilization. Diagnostic groups include healthy allogeneic donors, autologous multiple myeloma (MM) and non-MM donors.

Study Design And Methods: Here, we conducted a single-center retrospective study in 64 autologous patients and 48 allogeneic donors. Autologous donors were patients diagnosed with MM or non-MM. All donors were grouped as African American (AA), White (W), or "Other"(O).

Results: Multivariate analysis demonstrated diagnostic group differences for CD34+ cell yields between race/ethnicity. Specifically, non-MM patients had the lowest CD34+ cell yields in AA and O, but not in W. For pre-apheresis peripheral blood (PB) CD34+ cell numbers, race/ethnicity had a significant effect both in bivariate and multivariate analyses. Non-MM patients had the lowest, and AA patients had the highest PB CD34+ cells. The results support the view that past therapies used in MM are likely more conducive of recovery of HSPC.

Conclusions: Our study shows that race/ethnicity and diagnostic group differences influenced CD34+ cell mobilization response across donor types. Interestingly, autologous MM donors with the aid of plerixafor displayed comparable CD34 yields to allogeneic donors. Even though both MM and non-MM donors received plerixafor, non-MM donors had significantly lower CD34 yields among AA and O donors but not in W donors. Larger studies would be required to validate the role of diagnostic groups and race/ethnicity interactions.
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http://dx.doi.org/10.1002/jca.21914DOI Listing
May 2021

Validating a novel algorithm to identify patients with autoimmune hepatitis in an administrative database.

Pharmacoepidemiol Drug Saf 2021 May 12. Epub 2021 May 12.

Department of Medicine, Division of Digestive Health and Liver Disease, University of Miami, Miller School of Medicine, Miami, Florida, USA.

Purpose: Population-level studies on the treatment practices and comparative effectiveness of therapies in autoimmune hepatitis (AIH) are lacking due to the absence of validated methods to identify patients with AIH in large databases, such as administrative claims or electronic health records. This study ascertained the performance of International Classification of Diseases (ICD) codes for AIH, and developed and validated a novel algorithm that reliably identifies patients with AIH in health administrative data and claims.

Methods: This was a cross-sectional study of patients with ≥1 inpatient or ≥2 outpatient ICD codes for AIH between 2008 and 2019 at a single health system. In a random sample of 250 patients, definite or probable AIH was determined using the Simplified AIH score, Revised AIH score or expert adjudication. The positive predictive value (PPV) was obtained. Variations of this base algorithm were evaluated using additional criteria to increase its performance.

Results: Of the 250 patients, 143 (57.2%) patients had sufficient records available for review. The PPV of the base algorithm was 77.6% (95% CI: 69.9-84.2%). Exclusion of patients with ≥1 ICD code for primary biliary cholangitis or primary sclerosing cholangitis yielded a PPV of 89.7% (95% CI: 82.8-94.6%). Further exclusion of patients with recent immune checkpoint inhibitor therapy increased the PPV to 92.9% (95% CI: 86.5-96.9%).

Conclusions: The use of ICD codes for AIH alone are insufficient to reliably identify patients with AIH in health administrative data and claims. Our proposed algorithm that includes additional diagnostic and medication-related coding criteria demonstrates excellent performance.
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http://dx.doi.org/10.1002/pds.5291DOI Listing
May 2021

COVID-19 related pancreatic cancer surveillance disruptions amongst high-risk individuals.

Pancreatology 2021 Apr 20. Epub 2021 Apr 20.

The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA. Electronic address:

Background: COVID-19 pandemic-related disruptions to EUS-based pancreatic cancer surveillance in high-risk individuals remain uncertain.

Methods: Analysis of enrolled participants in the CAPS5 Study, a prospective multicenter study of pancreatic cancer surveillance in high-risk individuals.

Results: Amongst 693 enrolled high-risk individuals under active surveillance, 108 (16%) had an EUS scheduled during the COVID-19 pandemic-related shutdown (median length of 78 days) in the spring of 2020, with 97% of these procedures being canceled. Of these canceled surveillance EUSs, 83% were rescheduled in a median of 4.1 months, however 17% were not rescheduled after 6 months follow-up. Prior history of cancer was associated with increased likelihood of rescheduling. To date no pancreatic cancer has been diagnosed among those whose surveillance was delayed.

Conclusions: COVID-19 delayed pancreatic cancer surveillance with no adverse outcomes in efficiently rescheduled individuals. However, 1 in 6 high-risk individuals had not rescheduled surveillance, indicating the need for vigilance to ensure timely surveillance rescheduling.
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http://dx.doi.org/10.1016/j.pan.2021.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055495PMC
April 2021

External Validation of the VOCAL-Penn Cirrhosis Surgical Risk Score in Two Large, Independent Health Systems.

Liver Transpl 2021 Mar 31. Epub 2021 Mar 31.

Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

Background & Aims: Cirrhosis poses an increased risk of post-operative mortality, however it remains challenging to accurately risk stratify patients in clinical practice. The VOCAL-Penn cirrhosis surgical risk score was recently developed and internally validated in the national Veterans Affairs health system, however to date this score has not been evaluated in independent cohorts. The goal of this study was to compare the predictive performance of VOCAL-Penn to the Mayo risk, model for end-stage liver disease (MELD), and MELD-sodium (MELD-Na) scores in two large health systems.

Approach & Results: We performed a retrospective cohort study of patients with cirrhosis undergoing surgical procedures of interest at the Beth Israel Deaconess Medical Center or University of Pennsylvania Health System from 1/1/2008-10/1/2015. The outcomes of interest were 30- and 90-day post-operative mortality. C-statistics, calibration curves, Brier scores, and the index of prediction accuracy (IPA) were compared for each predictive model.

Results: A total 855 surgical procedures were identified. The VOCAL-Penn score had the numerically highest C-statistic through 90 days post-operative mortality, (e.g., 0.82 vs. 0.79 Mayo vs. 0.78 MELD-Na vs. 0.79 MELD), though differences were not statistically significant. Calibration was excellent for VOCAL-Penn, MELD, and MELD-Na, however the Mayo score consistently overestimated risk. VOCAL-Penn had the lowest Brier score and highest IPA at both timepoints, suggesting superior overall predictive model performance. In subgroup analyses of higher-MELD patients, VOCAL-Penn had significantly higher C-statistics as compared to MELD and MELD-Na.

Conclusions: The VOCAL-Penn score (www.vocalpennscore.com) has excellent discrimination and calibration for post-operative mortality among diverse patients with cirrhosis. Overall performance is superior to Mayo, MELD, and MELD-Na scores. In contrast to MELD/MELD-Na, VOCAL-Penn retains excellent discrimination among higher MELD patients.
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http://dx.doi.org/10.1002/lt.26060DOI Listing
March 2021

Race Adjustment in eGFR Equations Does Not Improve Estimation of Acute Kidney Injury Events in Patients with Cirrhosis.

Dig Dis Sci 2021 Mar 24. Epub 2021 Mar 24.

Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, 3400 Civic Center Boulevard, 4th Floor, South Pavilion, Philadelphia, PA, 19104, USA.

Background: Accuracy of glomerular filtration rate estimating (eGFR) equations has significant implications in cirrhosis, potentially guiding simultaneous liver kidney allocation and drug dosing. Most equations adjust for Black race, partially accounted for by reported differences in muscle mass by race. Patients with cirrhosis, however, are prone to sarcopenia which may mitigate such differences. We evaluated the association between baseline eGFR and incident acute kidney injury (AKI) in patients with cirrhosis with and without race adjustment.

Methods: We conducted a retrospective national cohort study of veterans with cirrhosis. Baseline eGFR was calculated using multiple eGFR equations including Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), both with and without race adjustment. Poisson regression was used to investigate the association between baseline eGFR and incident AKI events per International Club of Ascites criteria.

Results: We identified 72,267 patients with cirrhosis, who were 97.3% male, 57.8% white, and 19.7% Black. Over median follow-up 2.78 years (interquartile range 1.22-5.16), lower baseline eGFR by CKD-EPI was significantly associated with higher rates of AKI in adjusted models. For all equations this association was minimally impacted when race adjustment was removed. For example, removal of race adjustment from CKD-EPI resulted in a 0.1% increase in the association between lower eGFR and higher rate of AKI events per 15 mL/min/1.73 m change (p < 0.001).

Conclusions: Race adjustment in eGFR equations did not enhance AKI risk estimation in patients with cirrhosis. Further study is warranted to assess the impacts of removing race from eGFR equations on clinical outcomes and policy.
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http://dx.doi.org/10.1007/s10620-021-06943-1DOI Listing
March 2021

Risk factors for SARS-CoV-2 infection and course of COVID-19 disease in patients with IBD in the Veterans Affair Healthcare System.

Gut 2021 Mar 22. Epub 2021 Mar 22.

Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

Objective: Our aim was to explore the risk of infection with all classes of inflammatory bowel disease (IBD) medications and the impact of these medications on the disease course in a nationwide cohort of patients with IBD.

Design: This was a retrospective national cohort study of patients with IBD in the Veterans Affairs Healthcare System. We categorised IBD medication use immediately prior to the COVID-19 pandemic and used survival analysis methods to study associations with SARS-CoV-2 infection, as well as a combined secondary outcome of COVID-19 hospitalisation or COVID-19-related mortality.

Results: The analytical cohort of 30 911 patients was primarily male (90.9%), white (78.6%) and with ulcerative colitis (58.8%). Over a median follow-up of 10.7 months, 649 patients (2.1%) were diagnosed with SARS-CoV-2 infection and 149 (0.5%) met the combined secondary outcome. In adjusted models, vedolizumab (VDZ) use was significantly associated with infection relative to mesalazine alone (HR 1.70, 95% CI 1.16 to 2.48, p=0.006). Patients on no IBD medications had increased risk of the combined secondary outcome relative to mesalazine alone (sub-HR 1.64, 95% CI 1.12 to 2.42, p=0.01), however, no other IBD medication categories were significantly associated with this outcome, relative to mesalazine alone (each p>0.05). Corticosteroid use was independently associated with both SARS-CoV-2 infection (HR 1.60, 95% CI 1.23 to 2.09, p=0.001) and the combined secondary outcome (sub-HR 1.90, 95% CI 1.14 to 3.17, p=0.01).

Conclusion: VDZ and corticosteroid were associated with an increased risk of SARS-CoV-2 infection. Except for corticosteroids no medications including mesalazine were associated with an increased risk of severe COVID-19.
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http://dx.doi.org/10.1136/gutjnl-2021-324356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985980PMC
March 2021

Disentangling the obesity paradox in upper gastrointestinal cancers: Weight loss matters more than body mass index.

Cancer Epidemiol 2021 06 26;72:101912. Epub 2021 Feb 26.

Division of Gastroenterology and Hepatology, Perelman School of Medicine at the University of Pennsylvania, United States; Gastroenterology Section, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, United States. Electronic address:

Objectives: The obesity paradox, whereby obesity appears to confer protection against cancer-related mortality, remains controversial. This has not yet been evaluated in upper gastrointestinal cancers.

Designs: We identified esophageal, cardia, and non-cardia gastric adenocarcinomas in the Veterans Health Administration between 2006-2016. Multivariable Cox proportional hazard models evaluate the impact of BMI at- and prior to- cancer diagnosis on mortality, adjusting for demographics, clinical characteristics, weight loss, and clinical stage (early: T1B/2N0; locally advanced: ≥T2N+).

Results: We identify 1308 patients: 99 % male, median 66 years. In early disease, relative to BMI 30, BMI 18 and 20 at diagnosis had increased risk of death (HR 1.83, 95 %CI: 1.38-2.44 and HR 1.50, 95 %CI: 1.20-1.87, respectively, p < 0.0001). Patients with BMI > 30 did not. In locally advanced disease, at diagnosis BMI 18 (HR 1.58, 95 %CI: 1.0001-1.48, p = 0.05), BMI 20 (HR 1.46, 95 %CI: 1.01-2.09, p = 0.04), and BMI 25 (HR 1.20, 95 %CI: 1.04-1.38, p = 0.01) had increased risk of death, but BMI > 30 did not. In models assessing premorbid BMI and weight loss, increasing amounts of weight loss were associated with mortality independent of BMI in early cancers. For locally advanced cancers, without weight loss, there was no association with death, regardless of BMI.

Conclusion: The predominant driver of mortality across clinical stages is weight loss. The obesity paradox appears to exist in early stage disease only. Future studies should investigate mechanisms for the obesity paradox, accompanying physiologic changes with weight loss preceding diagnosis, and if patients with low BMI and weight loss benefit from early nutritional support.
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http://dx.doi.org/10.1016/j.canep.2021.101912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141012PMC
June 2021

COVID-19 Disruptions to Endoscopic Surveillance in Lynch Syndrome.

Cancer Prev Res (Phila) 2021 05 24;14(5):521-526. Epub 2021 Feb 24.

Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

Disruptions in cancer screening due to the COVID-19 pandemic may disproportionally affect patients with inherited cancer predisposition syndromes, including Lynch syndrome. Herein, we study the effect of the COVID-19 pandemic on endoscopic surveillance in Lynch syndrome through a prospective study of patients with Lynch syndrome at a tertiary referral center who were scheduled for endoscopic surveillance during the COVID-19 pandemic shutdown between March 16, 2020 and June 4, 2020. Of our cohort of 302 individuals with Lynch syndrome, 34 (11%) had endoscopic procedures scheduled during the COVID-19 pandemic shutdown. Of the 27 patients whose endoscopic surveillance was canceled during this period, 85% rescheduled procedures within 6 months with a median delay of 72 days [interquartile range (IQR), 55-84 days], with identification of an advanced adenoma or gastrointestinal cancer in 13%. Individuals who did not have a rescheduled endoscopic procedure were significantly younger than those with a rescheduled procedure [age 35 (IQR, 26-43) vs. age 55 (IQR, 43-63), = 0.018]. Male sex was also suggestive of increasing likelihood of not having a rescheduled procedure. Taken together, our study demonstrates that the COVID-19 pandemic shutdown led to delayed endoscopic surveillance in Lynch syndrome, with potentially impactful delays among young patients. These data also emphasize the importance of timely surveillance in Lynch syndrome during this current, as well as potential future, global pandemics. PREVENTION RELEVANCE: The COVID-19 pandemic has led to unprecedented disruptions in cancer screening, which may have disproportionate effects on individuals at increased cancer risk, including those with Lynch syndrome. Herein, we show that the COVID-19 pandemic led to significant disruptions in Lynch syndrome surveillance with potentially impactful delays, thus highlighting the importance of ensuring timely surveillance among this high-risk cohort.
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http://dx.doi.org/10.1158/1940-6207.CAPR-20-0565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102358PMC
May 2021

Gender Differences in Publication Authorship During COVID-19: A Bibliometric Analysis of High-Impact Cardiology Journals.

J Am Heart Assoc 2021 02 23;10(5):e019005. Epub 2021 Feb 23.

Division of Cardiovascular Medicine Department of Medicine Perelman School of Medicine at the University of Pennsylvania Philadelphia PA.

Background The purpose of this study was to examine gender differences in authorship of manuscripts in select high-impact cardiology journals during the early coronavirus disease 2019 (COVID-19) pandemic. Methods and Results All manuscripts published between March 1, 2019 to June 1, 2019 and March 1, 2020 to June 1, 2020 in 4 high-impact cardiology journals (, , , and ) were identified using bibliometric data. Authors' genders were determined by matching first name with predicted gender using a validated multinational database (Genderize.io) and manual adjudication. Proportions of women and men first, co-first, senior, and co-senior authors, manuscript types, and whether the manuscript was COVID-19 related were recorded. In 2019, women were first authors of 176 (22.3%) manuscripts and senior authors of 99 (15.0%) manuscripts. In 2020, women first authored 230 (27.4%) manuscripts and senior authored 138 (19.3%) manuscripts. Proportions of woman first and senior authors were significantly higher in 2020 compared with 2019. Women were more likely to be first authors if the manuscript's senior author was a woman (33.8% for woman first/woman senior versus 23.4% for woman first/man senior; <0.001). Women were less likely to be first authors of COVID-19-related original research manuscripts (=0.04). Conclusions Representation of women as key authors of manuscripts published in major cardiovascular journals increased during the early COVID-19 pandemic compared with similar months in 2019. However, women were significantly less likely to be first authors of COVID-19-related original research manuscripts. Future investigation into the gender-disparate impacts of COVID-19 on academic careers is critical.
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http://dx.doi.org/10.1161/JAHA.120.019005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174290PMC
February 2021

Effect of Text Messaging on Bowel Preparation and Appointment Attendance for Outpatient Colonoscopy: A Randomized Clinical Trial.

JAMA Netw Open 2021 01 4;4(1):e2034553. Epub 2021 Jan 4.

Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

Importance: Outpatient colonoscopy is important for colorectal cancer screening. However, nonadherence and poor bowel preparation are common.

Objective: To determine if an automated text messaging intervention with a focus on informational and reminder functions could improve attendance rates and bowel preparation quality for outpatient colonoscopy.

Design, Setting, And Participants: This randomized clinical trial was conducted in an endoscopy center at an urban academic medical center. Adult patients scheduled for outpatient colonoscopy between January and September 2019 were enrolled by telephone call (early phase) or by automated text message (late phase). Data were analyzed from October 2019 to January 2020.

Interventions: After enrollment, patients were randomized in a 1:1 ratio to usual care (ie, written instructions and nurse telephone call) or to the intervention (ie, usual care plus an automated series of 9 educational or reminder text messages in the week prior to scheduled colonoscopy).

Main Outcomes And Measures: The primary outcome was appointment attendance rate with good or excellent bowel preparation. Secondary outcomes included appointment attendance rate, bowel preparation quality (poor or inadequate, fair or adequate, and good or excellent), and cancellation lead time (in days).

Results: Among 753 patients included and randomized in the trial (median [interquartile range] age, 56 [49-64] years; 364 [48.3%] men; 429 [57.2%] Black), 367 patients were randomized to the intervention group and 386 patients were randomized to the control group. There was no significant difference in the primary outcome between groups (patients attending appointments with good or excellent bowel preparation: intervention, 195 patients [53.1%]; control, 210 patients [54.4%]; P = .73), including when stratified by early or late phase enrollment groups. Similarly, there were no significant differences in secondary outcomes.

Conclusions And Relevance: This randomized clinical trial found no significant difference in appointment attendance or bowel preparation quality with an automated text messaging intervention compared with the usual care control. Future work could optimize the content and delivery of text message interventions or identify patient subgroups that may benefit from this approach.

Trial Registration: ClinicalTrials.gov Identifier: NCT03710213.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.34553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835713PMC
January 2021

Changes in Hepatocellular Carcinoma Surveillance and Risk Factors for Noncompletion in the Veterans Health Administration Cohort During the Coronavirus Disease 2019 Pandemic.

Gastroenterology 2021 05 9;160(6):2162-2164.e3. Epub 2021 Jan 9.

Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Gastroenterology Section, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania; Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania.

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http://dx.doi.org/10.1053/j.gastro.2021.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142896PMC
May 2021

Trends in surgical volume and in-hospital mortality among United States cirrhosis hospitalizations.

Ann Gastroenterol 2021 20;34(1):85-92. Epub 2020 Nov 20.

Division of Gastroenterology, Perelman School of Medicine (Nadim Mahmud).

Background: In the aging population of patients with cirrhosis in the United States, there is a potentially increased need for surgical procedures. However, individuals with cirrhosis have increased perioperative risk relative to patients without cirrhosis. We sought to quantify temporal trends in cirrhosis surgical procedures and in-hospital mortality in relation to surgical procedure type, elective admission status and compensated vs. decompensated status.

Methods: We performed a retrospective cohort study of cirrhosis hospitalizations between 2005 and 2014 using the National Inpatient Sample. Surgical procedures of interest included cholecystectomy, hernia repair, and major abdominal, orthopedic and cardiovascular surgery. We plotted trends in volume and in-hospital mortality by procedure type, and used linear regression to test the significance of trends.

Results: While the number of cirrhosis hospitalizations increased over time, the number of surgeries per 1000 admissions decreased (b=-1.454, P<0.001). When stratified by elective admission status, elective major orthopedic surgeries significantly increased over time (b=177.9; P<0.001). In-hospital mortality rates for most surgeries were significantly higher in the non-elective vs. elective setting (each P<0.001). In patients with compensated cirrhosis, there was a significant increase in the number of orthopedic (b=272.4; P<0.001) and hernia repair surgeries over time (b=191.1; P<0.001). Overall, there was significantly greater in-hospital mortality among patients with decompensated cirrhosis (each P<0.05). Q. Please mention the exact P-value unless <0.001.

Conclusions: Despite an increasing number of cirrhosis hospitalizations, the decreasing relative number of cirrhosis surgeries may indicate progressive surgical risk aversion. Future cirrhosis surgical risk scores should consider surgical procedure type, elective/non-elective status, and decompensation status.
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http://dx.doi.org/10.20524/aog.2020.0554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774658PMC
November 2020

Frailty Is a Risk Factor for Postoperative Mortality in Patients With Cirrhosis Undergoing Diverse Major Surgeries.

Liver Transpl 2021 05 15;27(5):699-710. Epub 2021 Feb 15.

Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, FL.

With a rising burden of cirrhosis surgeries, understanding risk factors for postoperative mortality is more salient than ever. The role of baseline frailty has not been assessed in this context. We evaluated the association between patient frailty and postoperative risk among diverse patients with cirrhosis and determined if frailty improves prognostication of cirrhosis surgical risk scores. This was a retrospective cohort study of U.S. veterans with cirrhosis identified between 2008 and 2016 who underwent nontransplant major surgery. Frailty was ascertained using the Hospital Frailty Risk Score (HFRS). Cox regression analysis was used to investigate the impact of patient frailty on postoperative mortality. Logistic regression was used to identify incremental changes in discrimination for postoperative mortality when frailty was added to the risk prediction models, including the Model for End-Stage Liver Disease (MELD), MELD-sodium (MELD-Na), Child-Turcotte-Pugh (CTP), Mayo Risk Score (MRS), and Veterans Outcomes and Costs Associated With Liver Disease (VOCAL)-Penn. A total of 804 cirrhosis surgeries were identified. The majority of patients (48.5%) had high-risk frailty at baseline (HFRS >15). In adjusted Cox regression models, categories of increasing frailty scores were associated with poorer postoperative survival. For example, intermediate-risk frailty (HFRS 5-15) conferred a 1.77-fold increased hazard relative to low-risk frailty (HFRS, <5; 95% confidence interval [CI], 1.06-2.95; P = 0.03). High-risk frailty demonstrated a similarly increased hazard (hazard ratio, 1.74; 95% CI, 1.05-2.88; P = 0.03), suggesting a threshold effect of frailty on postoperative mortality. The incorporation of frailty improved discrimination of MELD, MELD-Na, and CTP for postoperative mortality, but did not do so for the MRS or VOCAL-Penn score. Patient frailty was an additional important predictor of cirrhosis surgical risk. The incorporation of preoperative frailty assessments may help to risk stratify patients, especially in settings where the MELD-Na and CTP are commonly applied.
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http://dx.doi.org/10.1002/lt.25953DOI Listing
May 2021

Type II achalasia is associated with a comparably favorable outcome following per oral endoscopic myotomy.

Dis Esophagus 2021 Jun;34(6)

Division of Gastroenterology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.

Per oral endoscopic myotomy (POEM) is a safe and effective treatment for esophageal motility disorder in treatment-naïve patients as well as salvage therapy. Though type II achalasia, compared to other subtypes, is reported to have a more favorable outcome with pneumatic dilation (PD) or Heller myotomy (HM), it is unclear whether achalasia subtype predicts symptom response to POEM. We aimed to evaluate whether type II achalasia is associated with a comparably favorable outcome following POEM. We performed a retrospective review of patients with esophageal motility disorder who were referred for POEM from April 2014 to June 2017. The main outcome was clinical success based on Eckardt score ≤3 and its association with subtype and safety. A total of 63 patients (mean age 51 years [SD 15]; 63% male) underwent a total of 68 POEMs with median of 263 days follow-up. Of these, 45 (71.3%) patients were type II achalasia. In all, 29 (46%) patients were treatment-naïve and 34 (54%) patients had previous endoscopic or surgical therapy including botulinum toxin injection in 16 (25%), PD in 10 (16%), both botulinum toxin injection and PD in 8 (13%) and HM in 3 (5%). Technical success was 100% and clinical success was achieved in 51 (81%) patients. The rate of clinical success was higher in patients with type II achalasia compared to the other subtypes (88.9% vs. 61.1% [P = 0.028]) and type II achalasia patients required fewer redo POEM (2.2% vs. 22.2% [P = 0.021]). Multivariate logistic regression analysis demonstrated the positive prediction of clinical success for type II achalasia following POEM (P = 0.046). As observed with PD and HM, type II achalasia was associated with a favorable clinical outcome following POEM.
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http://dx.doi.org/10.1093/dote/doaa107DOI Listing
June 2021

Training a computer-aided polyp detection system to detect sessile serrated adenomas using public domain colonoscopy videos.

Endosc Int Open 2020 Oct 7;8(10):E1448-E1454. Epub 2020 Oct 7.

Center for Advanced Endoscopy, Division of Gastroenterology, Beth Israel Deaconess, Medical Center and Harvard Medical School, Boston, Massachusetts 02130.

Colorectal cancer (CRC) is a major public health burden worldwide, and colonoscopy is the most commonly used CRC screening tool. Still, there is variability in adenoma detection rate (ADR) among endoscopists. Recent studies have reported improved ADR using deep learning models trained on videos curated largely from private in-house datasets. Few have focused on the detection of sessile serrated adenomas (SSAs), which are the most challenging target clinically. We identified 23 colonoscopy videos available in the public domain and for which pathology data were provided, totaling 390 minutes of footage. Expert endoscopists annotated segments of video with adenomatous polyps, from which we captured 509 polyp-positive and 6,875 polyp-free frames. Via data augmentation, we generated 15,270 adenomatous polyp-positive images, of which 2,310 were SSAs, and 20,625 polyp-negative images. We used the CNN AlexNet and fine-tuned its parameters using 90 % of the images, before testing its performance on the remaining 10 % of images unseen by the model. We trained the model on 32,305 images and tested performance on 3,590 images with the same proportion of SSA, non-SSA polyp-positive, and polyp-negative images. The overall accuracy of the model was 0.86, with a sensitivity of 0.73 and a specificity of 0.96. Positive predictive value was 0.93 and negative predictive value was 0.96. The area under the curve was 0.94. SSAs were detected in 93 % of SSA-positive images. Using a relatively small set of publicly-available colonoscopy data, we obtained sizable training and validation sets of endoscopic images using data augmentation, and achieved an excellent performance in adenomatous polyp detection.
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http://dx.doi.org/10.1055/a-1229-3927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541193PMC
October 2020

The Predictive Role of Model for End-Stage Liver Disease-Lactate and Lactate Clearance for In-Hospital Mortality Among a National Cirrhosis Cohort.

Liver Transpl 2021 02 9;27(2):177-189. Epub 2020 Dec 9.

Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.

The burden of cirrhosis hospitalizations is increasing. The admission Model for End-Stage Liver Disease-lactate (MELD-lactate) was recently demonstrated to be a superior predictor of in-hospital mortality compared with MELD in limited cohorts. We identified specific classes of hospitalizations where MELD-lactate may be especially useful and evaluated the predictive role of lactate clearance. This was a retrospective cohort study of 1036 cirrhosis hospitalizations for gastrointestinal bleeding, infection, or other portal hypertension-related indications in the Veterans Health Administration where MELD-lactate was measured on admission. Performance characteristics for in-hospital mortality were compared between MELD-lactate and MELD/MELD-sodium (MELD-Na), with stratified analyses of MELD categories (≤15, >15 to <25, ≥25) and reason for admission. We also incorporated day 3 lactate levels into modeling and tested for an interaction between day 1 MELD-lactate and day 3 lactate clearance. MELD-lactate had superior discrimination for in-hospital mortality compared with MELD or MELD-Na (area under the curve [AUC] 0.789 versus 0.776 versus 0.760, respectively; P < 0.001) and superior calibration. MELD-lactate had higher discrimination among hospitalizations with MELD ≤15 (AUC 0.763 versus 0.608 for MELD, global P = 0.01) and hospitalizations for infection (AUC 0.791 versus 0.674 for MELD, global P < 0.001). We found a significant interaction between day 1 MELD-lactate and day 3 lactate clearance; heat maps were created as clinical tools to risk-stratify patients based on these clinical data. MELD-lactate had significantly superior performance in predicting in-hospital mortality among patients hospitalized for infection and/or with MELD ≤15 when compared with MELD or MELD-Na. Incorporating day 3 lactate clearance may further improve prognostication.
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http://dx.doi.org/10.1002/lt.25913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880877PMC
February 2021

Rethinking Transplant Quality: New Performance Measures and Wait-List Prioritization.

Liver Transpl 2020 12 27;26(12):1564-1565. Epub 2020 Oct 27.

Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.

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http://dx.doi.org/10.1002/lt.25914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897466PMC
December 2020

Acute on Chronic Liver Failure From Nonalcoholic Fatty Liver Disease: A Growing and Aging Cohort With Rising Mortality.

Hepatology 2021 May 25;73(5):1932-1944. Epub 2021 Mar 25.

Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA.

Background And Aims: We assessed the burden of nonalcoholic fatty liver disease (NAFLD)-related acute on chronic liver failure (ACLF) among transplant candidates in the United States, along with waitlist outcomes for this population.

Approach And Results: We analyzed the United Network for Organ Sharing registry from 2005 to 2017. Patients with ACLF were identified using the European Association for the Study of the Liver/Chronic Liver Failure criteria and categorized into NAFLD, alcohol-associated liver disease (ALD), and hepatitis C virus (HCV) infection. We used linear regression and Chow's test to determine significance in trends and evaluated waitlist outcomes using Fine and Gray's competing risks regression and Cox proportional hazards regression. Between 2005 and 2017, waitlist registrants for NAFLD-ACLF rose by 331.6% from 134 to 574 candidates (P < 0.001), representing the largest percentage increase in the study population. ALD-ACLF also increased by 206.3% (348-1,066 registrants; P < 0.001), whereas HCV-ACLF declined by 45.2% (P < 0.001). As of 2017, the NAFLD-ACLF population consisted primarily of persons aged ≥60 years (54.1%), and linear regression demonstrated a significant rise in the proportion of patients aged ≥65 in this group (β = 0.90; P = 0.011). Since 2014, NAFLD-ACLF grade 1 was associated with a greater risk of waitlist mortality relative to ALD-ACLF (subhazard ratio [SHR] = 1.24; 95% confidence interval [CI], 1.05-1.44) and HCV-ACLF (SHR = 1.35; 95% CI, 1.08-1.71), among patients aged ≥60 years. Mortality was similar among the three groups for patients with ACLF grade 2 or 3.

Conclusions: NAFLD is the fastest rising etiology of cirrhosis associated with ACLF among patients listed in the United States. As the NAFLD population continues to grow and age, patients with NAFLD-ACLF will likely have the highest risk of waitlist mortality.
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http://dx.doi.org/10.1002/hep.31566DOI Listing
May 2021

Patient Frailty Is Independently Associated With the Risk of Hospitalization for Acute-on-Chronic Liver Failure.

Liver Transpl 2021 01 28;27(1):16-26. Epub 2020 Oct 28.

Department of Medicine, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA.

There is significant interest in identifying risk factors associated with acute-on-chronic liver failure (ACLF). In transplant candidates, frailty predicts wait-list mortality and posttransplant outcomes. However, the impact of frailty on ACLF development and mortality is unknown. This was a retrospective study of US veterans with cirrhosis identified between 2008 and 2016. First hospitalizations were characterized as ACLF or non-ACLF admissions. Prehospitalization patient frailty was ascertained using a validated score based on administrative coding data. We used logistic regression to investigate the impact of an increasing frailty score on the odds of ACLF hospitalization and short-term ACLF mortality. Cox regression was used to analyze the association between frailty and longterm survival from hospitalization. We identified 16,561 cirrhosis hospitalizations over a median follow-up of 4.19 years (interquartile range, 2.47-6.34 years). In adjusted models, increasing frailty score was associated with significantly increased odds of ACLF hospitalization versus non-ACLF hospitalization (odds ratio, 1.03 per point; 95% CI 1.02-1.03; P < 0.001). By contrast, frailty score was not associated with ACLF 28- or 90-day mortality (P = 0.13 and P = 0.33, respectively). In an adjusted Cox analysis of all hospitalizations, increasing frailty scores were associated with poorer longterm survival from the time of hospitalization (hazard ratio, 1.02 per 5 points; 95% confidence interval, 1.01-1.03; P = 0.004). Frailty increases the likelihood of ACLF hospitalization among patients with cirrhosis, but it does not impact short-term ACLF mortality. These findings have implications for clinicians caring for frail outpatients with cirrhosis, including tailored follow-up, risk mitigation strategies, and possible expedited transplant evaluation.
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http://dx.doi.org/10.1002/lt.25896DOI Listing
January 2021

Risk Prediction Models for Post-Operative Mortality in Patients With Cirrhosis.

Hepatology 2021 01 10;73(1):204-218. Epub 2020 Dec 10.

Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

Background And Aims: Patients with cirrhosis are at increased risk of postoperative mortality. Currently available tools to predict postoperative risk are suboptimally calibrated and do not account for surgery type. Our objective was to use population-level data to derive and internally validate cirrhosis surgical risk models.

Approach And Results: We conducted a retrospective cohort study using data from the Veterans Outcomes and Costs Associated with Liver Disease (VOCAL) cohort, which contains granular data on patients with cirrhosis from 128 U.S. medical centers, merged with the Veterans Affairs Surgical Quality Improvement Program (VASQIP) to identify surgical procedures. We categorized surgeries as abdominal wall, vascular, abdominal, cardiac, chest, or orthopedic and used multivariable logistic regression to model 30-, 90-, and 180-day postoperative mortality (VOCAL-Penn models). We compared model discrimination and calibration of VOCAL-Penn to the Mayo Risk Score (MRS), Model for End-Stage Liver Disease (MELD), Model for End-Stage Liver Disease-Sodium MELD-Na, and Child-Turcotte-Pugh (CTP) scores. We identified 4,712 surgical procedures in 3,785 patients with cirrhosis. The VOCAL-Penn models were derived and internally validated with excellent discrimination (30-day postoperative mortality C-statistic = 0.859; 95% confidence interval [CI], 0.809-0.909). Predictors included age, preoperative albumin, platelet count, bilirubin, surgery category, emergency indication, fatty liver disease, American Society of Anesthesiologists classification, and obesity. Model performance was superior to MELD, MELD-Na, CTP, and MRS at all time points (e.g., 30-day postoperative mortality C-statistic for MRS = 0.766; 95% CI, 0.676-0.855) in terms of discrimination and calibration.

Conclusions: The VOCAL-Penn models substantially improve postoperative mortality predictions in patients with cirrhosis. These models may be applied in practice to improve preoperative risk stratification and optimize patient selection for surgical procedures (www.vocalpennscore.com).
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http://dx.doi.org/10.1002/hep.31558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902392PMC
January 2021

Selection for Liver Transplantation: Indications and Evaluation.

Authors:
Nadim Mahmud

Curr Hepatol Rep 2020 Jun 19:1-10. Epub 2020 Jun 19.

Division of Gastroenterology, Hospital of the University of Pennsylvania, Philadelphia, PA USA.

Purpose Of Review: Liver transplantation is an important therapeutic option for patients with life-limiting liver disease, which may present in the form of acute liver failure, end-stage chronic liver disease, primary hepatic cancers, or inborn metabolic disorders. While significant strides have been made with respect to liver transplantation outcomes, the practice is constrained by an organ supply/demand mismatch. The purpose of this review, therefore, is to review the general indications and contraindication to liver transplantation, and to provide an overview of the transplant evaluation process. These considerations ultimately shape the specific criteria for patient selection, which will continue to evolve as means are developed to expand the donor pool, improve surgical techniques, broaden indications for safe transplant, and extend the lifetime of a graft.

Recent Findings: Selected patients with unresectable hilar cholangiocarcinoma may be candidates for liver transplantation. Patients over 65 years may be transplant candidates if they possess a favorable comorbidity profile. Patients at body mass index extremes (≥ 40 or < 18.5) have increased post-transplant mortality and require nutritional evaluation.

Summary: Liver transplantation may be life saving for patients with acute liver failure or end-stage liver disease. It is therefore critical for healthcare providers caring for patients with liver disease to be familiar with the general indications for transplantation and to know when it is appropriate or inappropriate to refer for transplant evaluation.
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http://dx.doi.org/10.1007/s11901-020-00527-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302921PMC
June 2020

Representation of Women Authors in International Heart Failure Guidelines and Contemporary Clinical Trials.

Circ Heart Fail 2020 08 6;13(8):e006605. Epub 2020 Aug 6.

American Heart Association, Dallas, TX (M.J.).

Background: Gender disparities in authorship of heart failure (HF) guideline citations and clinical trials have not been examined.

Methods: We identified authors of publications referenced in Class I Recommendations in United States (n=173) and European (n=100) HF guidelines and of publications of all HF trials with >400 participants (n=118) published between 2001 and 2016. Authors' genders were determined, and changes in authorship patterns over time were evaluated with linear regression and nonparametric testing.

Results: The median proportion of women authors per publication was 20% (interquartile range [IQR], 8%-33%) in United States guidelines, 14% (IQR, 2%-20%) in European guidelines, and 11% (IQR, 4%-20%) in HF trials. The proportion of women authors increased modestly over time in United States and European guidelines' references (β=0.005 and 0.003, respectively, from 1986 to 2016; <0.001) but not in HF trials (12.5% [IQR, 0%-20%] in 2001-2004 to 8.9% [IQR, 0%-20%] in 2013-2016; >0.50). Overall proportions of women as first or last authors in HF trials (16%) did not change significantly over time (=0.60). North American HF trials had the highest likelihood of having a woman as first or senior author (24%). HF trials with a woman first or senior author were associated with a higher proportion of enrolled female participants (39% versus 26%, =0.01).

Conclusions: In HF practice guidelines and trials, few women are authors of pivotal publications. Higher number of women authors is associated with higher enrollment of women in HF trials. Barriers to authorship and representation of women in HF guidelines and HF trial leadership need to be addressed.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.119.006605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719050PMC
August 2020

Patients with severe acute-on-chronic liver failure are disadvantaged by model for end-stage liver disease-based organ allocation policy.

Aliment Pharmacol Ther 2020 10 29;52(7):1204-1213. Epub 2020 Jul 29.

Liver Failure Group, Institute for Liver and Digestive Health, UCL Medical School, London, UK.

Background: Mortality for patients with acute-on-chronic liver failure (ACLF) may be underestimated by the model for end-stage liver disease-sodium (MELD-Na) score.

Aim: To assess waitlist outcomes across varying grades of ACLF among a cohort of patients listed with a MELD-Na score ≥35, and therefore having similar priority for liver transplantation.

Methods: We analysed the United Network for Organ Sharing (UNOS) database, years 2010-2017. Waitlist outcomes were evaluated using Fine and Gray's competing risks regression.

Results: We identified 6342 candidates at listing with a MELD-Na score ≥35, of whom 3122 had ACLF-3. Extra-hepatic organ failures were present primarily in patients with four to six organ failures. Competing risks regression revealed that candidates listed with ACLF-3 had a significantly higher risk for 90-day waitlist mortality (Sub-hazard ratio (SHR) = 1.41; 95% confidence interval [CI] 1.12-1.78) relative to patients with lower ACLF grades. Subgroup analysis of ACLF-3 revealed that both the presence of three organ failures (SHR = 1.40, 95% CI 1.20-1.63) or four to six organ failures at listing (SHR = 3.01; 95% CI 2.54-3.58) was associated with increased waitlist mortality. Candidates with four to six organ failures also had the lowest likelihood of receiving liver transplantation (SHR = 0.61, 95% CI 0.54-0.68). The Share 35 rule was associated with reduced 90-day waitlist mortality among the full cohort of patients listed with ACLF-3 and MELD-Na score ≥35 (SHR = 0.59; 95% CI 0.49-0.70). However, Share 35 rule implementation was not associated with reduced waitlist mortality among patients with four to six organ failures (SHR = 0.76; 95% CI 0.58-1.02).

Conclusions: The MELD-Na score disadvantages patients with ACLF-3, both with and without extra-hepatic organ failures. Incorporation of organ failures into allocation policy warrants further exploration.
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http://dx.doi.org/10.1111/apt.15988DOI Listing
October 2020

Longterm Outcomes of Patients Undergoing Liver Transplantation for Acute-on-Chronic Liver Failure.

Liver Transpl 2020 12 25;26(12):1594-1602. Epub 2020 Aug 25.

Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free Hospital, London, United Kingdom.

Recent data have demonstrated >80% 1-year survival probability after liver transplantation (LT) for patients with severe acute-on-chronic liver failure (ACLF). However, longterm outcomes and complications are still unknown for this population. Our aim was to compare longterm patient and graft survival among patients transplanted across all grades of ACLF. We analyzed the United Network for Organ Sharing database for the years 2004-2017. Patients with ACLF were identified using the European Association for the Study of the Liver-Chronic Liver Failure criteria. Kaplan-Meier and Cox regression methods were used to determine patient and graft survival and associated predictors of mortality in adjusted models. A total of 56,801 patients underwent transplantation of which 31,024 (54.6%) had no ACLF, 8757 (15.4%) had ACLF grade 1, 9039 (15.9%) had ACLF grade 2, and 7891 (14.1%) had ACLF grade 3. The 5-year patient survival after LT was lower in the ACLF grade 3 patients compared with the other groups (67.7%; P < 0.001), although after year 1, the percentage decrease in survival was similar among all groups. Infection was the primary cause of death among all patient groups in the first year. Infection was the primary cause of death among all patient groups in the first year. After the first year, infection was the main cause of death in patients transplanted with ACLF grade 1 (32.1%), ACLF grade 2 (33.9%), and ACLF grade 3 (37.6%), whereas malignancy was the predominant cause of death in those transplanted with no ACLF (28.5%). In conclusion, patients transplanted with ACLF grade 3 had lower 5-year survival as compared with patients with ACLF grades 0-2, but mortality rates were not significantly different after the first year following LT. Graft survival was excellent across all ACLF groups.
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http://dx.doi.org/10.1002/lt.25831DOI Listing
December 2020

Models for acute on chronic liver failure development and mortality in a veterans affairs cohort.

Hepatol Int 2020 Jul 9;14(4):587-596. Epub 2020 Jun 9.

Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Boulevard, PCAM 7S GI, 4th Floor, South Pavilion, Philadelphia, PA, 19104, USA.

Background And Purpose: The diagnosis of acute on chronic liver failure (ACLF) carries a high short-term mortality, making early identification of at-risk patients crucial. To date, there are no models that predict which patients with compensated cirrhosis will develop ACLF, and limited models exist to predict ACLF mortality. We sought to create novel risk prediction models using a large North American cohort.

Methods: We performed a retrospective study of 75,922 patients with compensated cirrhosis from the Veterans Outcomes and Costs Associated with Liver Disease (VOCAL) dataset. Using 70% derivation/30% validation sets, we identified ACLF patients using the Asian Pacific Association of Liver (APASL) definition. Multivariable logistic regression was used to derive prediction models (called VOCAL-Penn) for developing ACLF at 3, 6, and 12 months. We then created prediction models for ACLF mortality at 28 and 90 days.

Results: The VOCAL-Penn models for ACLF development had very good discrimination [concordance (C) statistics of 0.93, 0.92, and 0.89 at 3, 6, and 12 months, respectively] and calibration. The mortality models also had good discrimination at 28 and 90 days (C statistics 0.89 and 0.88, respectively), outperforming the Model for End-stage Liver Disease (MELD), MELD-sodium, and the APASL ACLF Research Consortium ACLF scores.

Conclusion: We have developed novel tools for predicting development of ACLF in compensated cirrhosis patients, as well as for ACLF mortality. These tools may be used to proactively guide patient follow-up, prognostication, escalation of care, and transplant evaluation. Receiver operating characteristic (ROC) curves for predicting development of APASL ACLF at 3 months (a), 6 months (b), and 1 year (c).
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http://dx.doi.org/10.1007/s12072-020-10060-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656856PMC
July 2020

The imperative for an updated cirrhosis surgical risk score.

Ann Hepatol 2020 Jul - Aug;19(4):341-343. Epub 2020 May 15.

Division of Gastroenterology, Hospital of the University of Pennsylvania, Philadelphia, PA, United States; Leonard David Institute of Health Economics, University of Pennsylvania, Philadelphia, PA, United States. Electronic address:

The burden of cirrhosis is increasing, as is the need for surgeries in patients with cirrhosis. These patients have increased surgical risk relative to non-cirrhotic patients. Unfortunately, currently available cirrhosis surgical risk prediction tools are non-specific, poorly calibrated, limited in scope, and/or outdated. The Mayo score is the only dedicated tool to provide discrete post-operative mortality predictions for patients with cirrhosis, however it has several limitations. First, its single-center nature does not reflect institution-specific practices that may impact surgical risk. Second, it pre-dates major surgical changes that have changed the landscape of patient selection and surgical risk. Third, it has been shown to overestimate risk in external validation. Finally, and perhaps most importantly, the score does not account for differences in risk based on surgery type. The clinical consequences of inaccurate prediction and risk overestimation are significant, as patients with otherwise acceptable risk may be denied elective surgical procedures, thereby increasing their future need for higher-risk emergent procedures. Confident evaluation of the risks and benefits of surgery in this growing population requires an updated, generalizable, and accurate cirrhosis surgical risk calculator that incorporates the type of surgery under consideration.
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http://dx.doi.org/10.1016/j.aohep.2020.04.005DOI Listing
June 2021

Colonoscopy Bowel Preparation-Is There an App for That?

Clin Gastroenterol Hepatol 2021 02 22;19(2):235-237. Epub 2020 May 22.

Division of Gastroenterology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Center for Health Care Innovation, University of Pennsylvania, Philadelphia, Pennsylvania.

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http://dx.doi.org/10.1016/j.cgh.2020.05.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897467PMC
February 2021