Safety of Endoscopy in Cirrhosis.

BACKGROUND: Endoscopic procedures are among the most commonly performed medical procedures and the serious adverse event rate is reported to be 1-3 adverse events per 1000 procedures. AIMS: Here, we have examined the safety of endoscopy specifically in cirrhotic populations. METHODS: We conducted a retrospective case (cirrhosis)-control (non-cirrhosis) study of the outcomes of patients undergoing endoscopy in a large academic medical center. The primary outcome was a procedural or post-procedural complication. Complete clinical data were collected for all patients undergoing endoscopic procedures-including esophagogastroduodenoscopy, colonoscopy, EUS, ERCP, flexible sigmoidoscopy, and others. Cirrhosis was carefully defined based on clinico-pathological grounds. RESULTS: We identified 16,779 patients who underwent endoscopy, including 2618 with cirrhosis and 14,161 without cirrhosis. There were 167 complications (0.99%), which included 15/2618 cirrhotics (0.6%) and 152/14,161 (1.1%) non-cirrhotics. The most common complications were cardiopulmonary (including hypotension and hypoxemia) found in 67% of patients; procedurally related complications occurred in 19% of patients. The complication rate was the same or lower in cirrhotics than controls undergoing esophagogastroduodenoscopy (0.6% vs 0.9%, p = 0.03), colonoscopy (0.6% vs. 0.6%, p = NS), or ERCP (0.7% vs. 1.4%, p = NS) Logistic regression analysis identified the following features to be associated with an increased risk of having a complication: inpatient status, history of myocardial infarction, and an EUS procedure. CONCLUSIONS: Endoscopy in cirrhotic patients was as safe or safer than non-cirrhotic patients undergoing similar procedures.

The Role of Imaging for Gastrointestinal Bleeding: Consensus Recommendations From the American College of Gastroenterology and Society of Abdominal Radiology.

Gastrointestinal (GI) bleeding is the most common GI diagnosis leading to hospitalization within the United States. Prompt diagnosis and treatment of GI bleeding is critical to improving patient outcomes and reducing high healthcare utilization and costs. Radiologic techniques including computed tomography angiography, catheter angiography, computed tomography enterography, magnetic resonance enterography, nuclear medicine red blood cell scan, and technetium-99m pertechnetate scintigraphy (Meckel scan) are frequently used to evaluate patients with GI bleeding and are complementary to GI endoscopy. However, multiple management guidelines exist which differ in the recommended utilization of these radiologic examinations. This variability can lead to confusion as to how these tests should be used in the evaluation of GI bleeding. In this document, a panel of experts from the American College of Gastroenterology and Society of Abdominal Radiology provide a review of the radiologic examinations used to evaluate for GI bleeding including nomenclature, technique, performance, advantages, and limitations. A comparison of advantages and limitations relative to endoscopic examinations is also included. Finally, consensus statements and recommendations on technical parameters and utilization of radiologic techniques for GI bleeding are provided.

AGA Clinical Practice Update on Management of Iron Deficiency Anemia: Expert Review.

DESCRIPTION: In this Clinical Practice Update (CPU), we will Best Practice Advice (BPA) guidance on the appropriate management of iron deficiency anemia. METHODS: This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPUC and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. These Best Practice Advice (BPA) statements were drawn from a review of the published literature and from expert opinion. Since systematic reviews were not performed, these BPA statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. BEST PRACTICE ADVICE 1: No single formulation of oral iron has any advantages over any other. Ferrous sulfate is preferred as the least expensive iron formulation. BEST PRACTICE ADVICE 2: Give oral iron once a day at most. Every-other-day iron dosing may be better tolerated for some patients with similar or equal rates of iron absorption as daily dosing. BEST PRACTICE ADVICE 3: Add vitamin C to oral iron supplementation to improve absorption. BEST PRACTICE ADVICE 4: Intravenous iron should be used if the patient does not tolerate oral iron, ferritin levels do not improve with a trial of oral iron, or the patient has a condition in which oral iron is not likely to be absorbed. BEST PRACTICE ADVICE 5: Intravenous iron formulations that can replace iron deficits with 1 or 2 infusions are preferred over those that require more than 2 infusions. BEST PRACTICE ADVICE 6: All intravenous iron formulations have similar risks; true anaphylaxis is very rare. The vast majority of reactions to intravenous iron are complement activation-related pseudo-allergy (infusion reactions) and should be treated as such. BEST PRACTICE ADVICE 7: Intravenous iron therapy should be used in individuals who have undergone bariatric procedures, particularly those that are likely to disrupt normal duodenal iron absorption, and have iron-deficiency anemia with no identifiable source of chronic gastrointestinal blood loss. BEST PRACTICE ADVICE 8: In individuals with inflammatory bowel disease and iron-deficiency anemia, clinicians first should determine whether iron-deficiency anemia is owing to inadequate intake or absorption, or loss of iron, typically from gastrointestinal bleeding. Active inflammation should be treated effectively to enhance iron absorption or reduce iron depletion. BEST PRACTICE ADVICE 9: Intravenous iron therapy should be given in individuals with inflammatory bowel disease, iron-deficiency anemia, and active inflammation with compromised absorption. BEST PRACTICE ADVICE 10: In individuals with portal hypertensive gastropathy and iron-deficiency anemia, oral iron supplements initially should be used to replenish iron stores. Intravenous iron therapy should be used in patients with ongoing bleeding who do not respond to oral iron therapy. BEST PRACTICE ADVICE 11: In individuals with portal hypertensive gastropathy and iron-deficiency anemia without another identified source of chronic blood loss, treatment of portal hypertension with nonselective ß-blockers can be considered. BEST PRACTICE ADVICE 12: In individuals with iron-deficiency anemia secondary to gastric antral vascular ectasia who have an inadequate response to iron replacement, consider endoscopic therapy with endoscopic band ligation or thermal methods such as argon plasma coagulation. BEST PRACTICE ADVICE 13: In patients with iron-deficiency anemia and celiac disease, ensure adherence to a gluten-free diet to improve iron absorption. Consider oral iron supplementation based on the severity of iron deficiency and patient tolerance, followed by intravenous iron therapy if iron stores do not improve. BEST PRACTICE ADVICE 14: Deep enteroscopy performed in patients with iron-deficiency anemia suspected to have small-bowel bleeding angioectasias should be performed with a distal attachment to improve detection and facilitate treatment. Small-bowel angioectasias may be treated with ablative thermal therapies such as argon plasma coagulation or with mechanical methods such as hemostatic clips. BEST PRACTICE ADVICE 15: Endoscopic treatment of angioectasias should be accompanied with iron replacement. Medical therapy for small-bowel angioectasias should be reserved for compassionate treatment in refractory cases when iron replacement and endoscopic therapy are ineffective.

Impact of blood transfusion on mortality and rebleeding in gastrointestinal bleeding: an 8-year cohort from a tertiary care center.

Background: The aim of this study was to investigate the impact of blood transfusion (BT) on mortality and rebleeding in patients with gastrointestinal bleeding (GIB) and whether BT at a threshold of ≤7 g/dL may improve these outcomes. Methods: A prospective study was conducted in patients admitted with GIB between 2013 and 2021. Antithrombotic (AT) use and clinical outcomes were compared between transfused and non-transfused patients, and between those transfused at a threshold of ≤7 vs. >7 g/dL. Multivariate analysis was performed to identify predictors of mortality and rebleeding. Results: A total of 667 patients, including 383 transfused, were followed up for a median of 56 months. Predictors of end-of-follow-up mortality included: age-adjusted Charlson Comorbidity Index, stigmata of recent hemorrhage (SRH), and being on anticoagulants only upon presentation (P=0.026). SRH was a predictor of end-of-follow-up rebleeding, while having been on only antiplatelet therapy (AP) upon presentation was protective (P<0.001). BT was not associated with mortality or rebleeding at 1 month or end of follow up. Among transfused patients, being discharged only on AP protected against mortality (P=0.044). BT at >7 g/dL did not affect the risk of short or long-term rebleeding or mortality compared to BT at ≤7 g/dL. Conclusions: Short- and long-term mortality and rebleeding in GIB were not affected by BT, nor by a transfusion threshold of ≤7 vs. >7 g/dL, but were affected by the use of AT. Further studies that account for AT use are needed to determine the best transfusion strategy in GIB.

H2FPEF Scores Are Increased in Patients with NASH Cirrhosis and Are Associated with Post-liver Transplant Heart Failure.

INTRODUCTION: Patients with cirrhosis are at risk for cardiac complications such as heart failure, particularly heart failure with preserved ejection fraction (HFpEF) due to left ventricular diastolic dysfunction (LVDD). The H2FPEF score is a predictive model used to identify patients with HFpEF. Our primary aim was to assess the H2FPEF score in patients with cirrhosis and determine its potential to identify patients at risk for heart failure after liver transplant. METHODS: This was a cohort study of patients undergoing liver transplant for cirrhosis from January 2010 and October 2018 who had a pre-transplant transthoracic echocardiogram. RESULTS: 166 cirrhosis subjects were included in the study. The majority were men (65%) and Caucasian (85%); NASH was the most common cause of cirrhosis (41%) followed by alcohol (34%). The median H2FPEF score was 2.0 (1.0-4.0). Patients with NASH cirrhosis had higher H2FPEF scores (3.22, 2.79-3.64) than those with alcohol induced cirrhosis (1.89, 1.5-2.29, p < 0.001) and other causes of cirrhosis (1.73, 1.28-2.18, p < 0.001). All subjects with a H2FPEF score > 6 had NASH cirrhosis. There was no association between the H2FPEF scores and measures of severity of liver disease (bilirubin, INR, or MELD score). Patients with heart failure after liver transplant had higher H2FPEF scores than those without heart failure (4.0, 3.1-4.9 vs. 2.3, 2.1-2.6, respectively; p = 0.015), but the score did not predict post-transplant mortality. CONCLUSION: H2FPEF scores are higher in cirrhosis patients with NASH and appear to be associated with post-transplant heart failure, but not death.

Genome resources for three modern cotton lines guide future breeding efforts.

Cotton (Gossypium hirsutum L.) is the key renewable fibre crop worldwide, yet its yield and fibre quality show high variability due to genotype-specific traits and complex interactions among cultivars, management practices and environmental factors. Modern breeding practices may limit future yield gains due to a narrow founding gene pool. Precision breeding and biotechnological approaches offer potential solutions, contingent on accurate cultivar-specific data. Here we address this need by generating high-quality reference genomes for three modern cotton cultivars ('UGA230', 'UA48' and 'CSX8308') and updating the 'TM-1' cotton genetic standard reference. Despite hypothesized genetic uniformity, considerable sequence and structural variation was observed among the four genomes, which overlap with ancient and ongoing genomic introgressions from 'Pima' cotton, gene regulatory mechanisms and phenotypic trait divergence. Differentially expressed genes across fibre development correlate with fibre production, potentially contributing to the distinctive fibre quality traits observed in modern cotton cultivars. These genomes and comparative analyses provide a valuable foundation for future genetic endeavours to enhance global cotton yield and sustainability.

Is it time to reduce the length of postgraduate training for physician-scientists in internal medicine?

Physician-scientists play a crucial role in advancing medical knowledge and patient care, yet the long periods of time required to complete training may impede expansion of this workforce. We examined the relationship between postgraduate training and time to receipt of NIH or Veterans Affairs career development awards (CDAs) for physician-scientists in internal medicine. Data from NIH RePORTER were analyzed for internal medicine residency graduates who received specific CDAs (K08, K23, K99, or IK2) in 2022. Additionally, information on degrees and training duration was collected. Internal medicine residency graduates constituted 19% of K awardees and 28% of IK2 awardees. Of MD-PhD internal medicine-trained graduates who received a K award, 92% received a K08 award; of MD-only graduates who received a K award, a majority received a K23 award. The median time from medical school graduation to CDA was 9.6 years for K awardees and 10.2 years for IK2 awardees. The time from medical school graduation to K or IK2 award was shorter for US MD-PhD graduates than US MD-only graduates. We propose that the time from medical school graduation to receipt of CDAs must be shortened to accelerate training and retention of physician-scientists.

Imaging-based non-invasive liver disease assessment for staging liver fibrosis in chronic liver disease: A systematic review supporting the AASLD Practice Guideline.

BACKGROUND AND AIMS: Transient elastography (TE), shear-wave elastography (SWE), and/or magnetic resonance elastography (MRE), each providing liver stiffness measurement (LSM), are the most studied imaging-based noninvasive liver disease assessment (NILDA) techniques. To support the American Association for the Study of Liver Diseases guidelines on NILDA, we summarized the evidence on the accuracy of these LSM methods to stage liver fibrosis (F). APPROACH AND RESULTS: A comprehensive search for studies assessing LSM by TE, SWE, or MRE for the identification of significant fibrosis (F2-4), advanced fibrosis (F3-4), or cirrhosis (F4), utilizing histopathology as standard of reference by liver disease etiology in adults or children from inception to April 2022 was performed. We excluded studies with <50 patients with a single disease entity and mixed liver disease etiologies (with the exception of HCV/HIV co-infection). Out of 9447 studies, 240 with 61,193 patients were included in this systematic review. In adults, sensitivities for the identification of F2-4 ranged from 51% to 95%, for F3-4 from 70% to 100%, and for F4 from 60% to 100% across all techniques/diseases, whereas specificities ranged from 36% to 100%, 74% to 100%, and 67% to 99%, respectively. The largest body of evidence available was for TE; MRE appeared to be the most accurate method. Imaging-based NILDA outperformed blood-based NILDA in most comparisons, particularly for the identification of F3-4/F4. In the pediatric population, imaging-based NILDA is likely as accurate as in adults. CONCLUSION: LSM from TE, SWE, and MRE show acceptable to outstanding accuracy for the detection of liver fibrosis across various liver disease etiologies. Accuracy increased from F2-4 to F3-4 and was the highest for F4. Further research is needed to better standardize the use of imaging-based NILDA, particularly in pediatric liver diseases.

Accuracy of blood-based biomarkers for staging liver fibrosis in chronic liver disease: A systematic review supporting the AASLD Practice Guideline.

BACKGROUND AND AIMS: Blood-based biomarkers have been proposed as an alternative to liver biopsy for non-invasive liver disease assessment (NILDA) in chronic liver disease (CLD). Our aims for this systematic review were to evaluate the diagnostic utility of selected blood-based tests either alone, or in combination, for identifying significant fibrosis (F2-4), advanced fibrosis (F3-4) and cirrhosis (F4), as compared to biopsy in CLD. APPROACH AND RESULTS: We included a comprehensive search of databases including Ovid MEDLINE(R), EMBASE, Cochrane Database, and Scopus through to April 2022. Two independent reviewers selected 286 studies with 103,162 patients. The most frequently identified studies included the simple aminotransferase-to-platelet ratio index (APRI) and fibrosis (FIB)-4 markers (with low-to-moderate risk of bias) in hepatitis B virus (HBV) and C virus (HCV), HIV-HCV/HBV co-infection, and nonalcoholic fatty liver disease (NAFLD). Positive (LR+) and negative (LR) likelihood ratios across direct and indirect biomarker tests for HCV and HBV for F2-4, F3-4, or F4 were 1.66-6.25 and 0.23-0.80, 1.89-5.24 and 0.12-0.64, and 1.32-7.15 and 0.15-0.86 respectively; LR+ and LR for NAFLD F2-4, F3-4 and F4 were 2-65-3.37 and 0.37-0.39, 2.25-6.76 and 0.07-0.87, and 3.90 and 0.15 respectively. Overall, proportional odds ratio indicated FIB-4 <1.45 was better than APRI <0.5 for F2-4. FIB-4 >3.25 was also better than APRI >1.5 for F3-4 and F4. There was limited data for combined tests. CONCLUSIONS: Blood-based biomarkers are associated with small-to-moderate change in pre-test probability for diagnosing F2-4, F3-4, and F4 in viral hepatitis, HIV-HCV co-infection, and NAFLD, with limited comparative or combination studies for other CLD.

First Report of Neofabraea actinidiae causing a Cranberry Fruit Rot in Oregon.

Cranberry (Vaccinium macrocarpon, L.) is a commercial small fruit that is native to North America. Oregon ranks fourth in cranberry production in the U.S.A. with 1052 Ha of cranberry beds and annual production of 23,590 metric tonnes (USDA NASS 2021). Cranberry fruit rot diseases are caused by a complex of 15 fungal pathogens belonging to 10 genera (Polashock et al. 2017). In fruit rot surveys of 'Stevens' cranberry beds in Coos and Curry Counties, Oregon, berries were collected before harvest and sorted by symptoms (e.g. softening, shriveling, or discoloration). Cranberries with field rot symptoms were surface-disinfested and lesion margin tissue placed on V8 agar. Cultures were incubated at room temperature and outgrowing fungi were transferred twice onto fresh V8 agar to obtain single isolates. Storage rots that developed on asymptomatic cranberries held at 4°C for 8 weeks were processed similarly. Since 2017, we periodically isolated Neofabraea actinidiae, which is not a member of the cranberry fruit rot complex, from rotted cranberries (Polashock et al. 2017). In 2022, N. actinidiae was isolated from 22% of 45 cranberries collected from an organically managed farm and developed storage rot and from 6% of 50 storage-rot cranberries from three conventionally managed farms. Symptoms associated with N. actinidiae on 'Stevens' cranberries often include softening and brown tissue surrounded by a yellow-colored ring. On V8 agar, N. actinidiae grew as compact white circular colonies with dense aerial hyphae near the center and accompanied by a red pigment in the agar. Pink-colored mucoidal irregular conidiomata often developed on the colony after 3 weeks. Conidia were hyaline, aseptate, and ellipsoidal to fusiform ranging from 7.5 to 12.6 µm long X 3.5 to 5.6 µm wide (n=100). Genomic DNA was extracted from N. actinidiae isolates from cranberries in 2017 and 2022. ß-tubulin and the ITS 5/4 region were amplified and sequenced with primers Bt-T2m-Up/Bt-LEV-Lo1 and ITS5/ITS4 using conditions of de Jong et al. (2001) and White et al. (1990), respectively. Sequences were deposited in NCBI Genbank (Accessions: OR606303, OR606305, OR606306, & OR606309 for ITS; OR610314, OR610316, OR610317, & OR610320 for ß-tubulin). BlastN analysis of ß-tubulin (695 bp) and ITS (489-490 bp) had a 99.6 to 99.8% and 99.8 to 100% identity, respectively, to Neofabraea actinidiae (CBS 121403) (Accession numbers: KR859285 ß-tubulin and KR859079 ITS). Phylogenetic analysis of concatenated sequences using Tamura-Nei neighbor-joining (Tamura et al. 2004) confirmed identity of cranberry isolates as N. actinidiae. Koch's Postulates were confirmed with four N. actinidiae isolates from cranberry. Agar or hyphal plugs were placed in a 3 mm wound on the side of six surface-disinfested, asymptomatic berries and incubated in a moist chamber at 20°C for 15 days or 4°C for 55 days. Similar symptoms developed on each berry inoculated with N. actinidiae, but not agar alone. The fungus was recovered from symptomatic tissues and identity confirmed by colony morphology. N. actinidiae causes a ripe rot and storage rot in kiwifruit and is one of the species causing Bull's Eye Rot of pome fruits (Tyson et al. 2019). Cryptosporiopsis actinidiae (anamorph) was isolated from cranberries roots in British Columbia, CA, but considered unlikely to be the causal agent of dieback disease of cranberry vines (Sabaratnam et al. 2009). We have demonstrated that N. actinidiae causes a cranberry fruit rot in beds and in storage. Its prevalence, associated fruit rot symptoms, and disease incidence will continue to be monitored.

Non-invasive liver disease assessment to identify portal hypertension: A systematic review supporting the AASLD Practice Guideline.

INTRODUCTION: Portal hypertension is a serious complication of cirrhosis, which leads to life-threatening complications. Hepatic venous pressure gradient (HVPG), a surrogate of portal pressure, is the reference standard test to assess the severity of portal hypertension. However, since HVPG is limited by its invasiveness and by its availability, non-invasive liver disease assessments (NILDAs) to assess portal pressure, especially clinically significant portal hypertension (CSPH), are needed. METHODS: We conducted a systematic review of Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, and Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus from each database's inception to April 22 nd , 2022. We included only studies in English that examined ≥50 patients in single liver disease etiologies which compared non-invasive tests (blood, and/or imaging) to HVPG for predicting clinically significant portal hypertension (CSPH; defined as HVPG ≥10 mm Hg) in patients with chronic liver disease (this therefore limited the number of studies that could be included). Outcomes reported included measures of diagnostic test accuracy. Additionally, a narrative review of studies not eligible for the systematic review is also provided. RESULTS: Nine studies with 2,492 patients met the inclusion criteria. There was substantial heterogeneity with regard to liver disease studied and cutoff values used to detect CSPH. Blood based tests, including aspartate to platelet ratio index (APRI) (56% sensitivity and 68% specificity) and fibrosis-4 (FIB-4) (54% sensitivity and 73% specificity) had low accuracy measures. Imaging based tests (transient elastography (TE) and shear wave elastography detection of liver stiffness (LSM)) had better accuracy, but also had substantial variation; at 15 kPa, TE sensitivity was 90%-96% and specificity was 48%-50% while at 25 kPa, its sensitivity and specificity were 57%-85% and 82%-93%, respectively. The narrative review suggested that imaging based tests are the best available NILDA to detect CSPH, CSPH is highly unlikely to be present at an LSM ≤15 kPa and likely to be present at an LSM ≥25 kPa. CONCLUSION: While imaging-based NILDA appeared to have higher accuracy than blood-based tests to detect CSPH, only 9 studies fit the a priori established inclusion criteria for the SR. In addition, there was substantial study heterogeneity and variation in cutoffs for LSM to detect CSPH, limiting the ability to establish definitive cutoffs to detect CSPH.

The Role of Imaging for GI Bleeding: ACG and SAR Consensus Recommendations.

Gastrointestinal (GI) bleeding is the most common GI diagnosis leading to hospitalization within the United States. Prompt diagnosis and treatment of GI bleeding is critical to improving patient outcomes and reducing high health care utilization and costs. Radiologic techniques including CT angiography, catheter angiography, CT enterography, MR enterography, nuclear medicine red blood cell scan, and technetium-99m pertechnetate scintigraphy (Meckel scan) are frequently used to evaluate patients with GI bleeding and are complementary to GI endoscopy. However, multiple management guidelines exist, which differ in the recommended utilization of these radiologic examinations. This variability can lead to confusion as to how these tests should be used in the evaluation of GI bleeding. In this document, a panel of experts from the American College of Gastroenterology and Society of Abdominal Radiology provide a review of the radiologic examinations used to evaluate for GI bleeding including nomenclature, technique, performance, advantages, and limitations. A comparison of advantages and limitations relative to endoscopic examinations is also included. Finally, consensus statements and recommendations on technical parameters and utilization of radiologic techniques for GI bleeding are provided. © Radiological Society of North America and the American College of Gastroenterology, 2024. Supplemental material is available for this article. This article is being published concurrently in American Journal of Gastroenterology and Radiology. The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. Citations from either journal can be used when citing this article. See also the editorial by Lockhart in this issue.