Publications by authors named "Somashekar G Krishna"

126 Publications

Serum Lipase Elevations in COVID-19 Patients Reflect Critical Illness and not Acute Pancreatitis.

Clin Gastroenterol Hepatol 2021 Apr 18. Epub 2021 Apr 18.

Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center. Electronic address:

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http://dx.doi.org/10.1016/j.cgh.2021.04.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053356PMC
April 2021

More Than Skin Deep: Beneath the Surface of a Routine Ampullary Adenoma.

Gastroenterology 2021 Mar 4. Epub 2021 Mar 4.

Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio. Electronic address:

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http://dx.doi.org/10.1053/j.gastro.2021.02.067DOI Listing
March 2021

Impact of Recreational Cannabis Legalization on Hospitalizations for Hyperemesis.

Am J Gastroenterol 2021 03;116(3):609-612

Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.

Introduction: Chronic cannabis use had been associated with hyperemesis. We sought to determine whether cannabis liberalization contributed to increased hospitalizations for hyperemesis.

Methods: Cannabis use and admissions for hyperemesis in legalized states were compared with those of nonlegalized states, before and after cannabis legalization, using state inpatient databases.

Results: From 2011 to 2015, cannabis use increased 2.2 times in legalized states and 1.8 times in nonlegalized states. The odds of presentation with hyperemesis were higher in 2015 compared with those of 2011 in all states.

Discussion: Recreational legalization may be contributing to rising cannabis use. Hospitalizations for hyperemesis have also increased but did not seem to be solely due to cannabis legalization.
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http://dx.doi.org/10.14309/ajg.0000000000001182DOI Listing
March 2021

Hospital outcomes and early readmission for the most common gastrointestinal and liver diseases in the United States: Implications for healthcare delivery.

World J Gastrointest Surg 2021 Feb;13(2):141-152

Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States.

Background: Gastrointestinal (GI) and liver diseases contribute to substantial inpatient morbidity, mortality, and healthcare resource utilization. Finding ways to reduce the economic burden of healthcare costs and the impact of these diseases is of crucial importance. Thirty-day readmission rates and related hospital outcomes can serve as objective measures to assess the impact of and provide further insights into the most common GI ailments.

Aim: To identify the thirty-day readmission rates with related predictors and outcomes of hospitalization of the most common GI and liver diseases in the United States.

Methods: A cross-sectional analysis of the 2012 National Inpatient Sample was performed to identify the 13 most common GI diseases. The 2013 Nationwide Readmission Database was then queried with specific International Classification of Diseases, Ninth Revision, Clinical Modification codes. Primary outcomes were mortality (index admission, calendar-year), hospitalization costs, and thirty-day readmission and secondary outcomes were predictors of thirty-day readmission.

Results: For the year 2013, the thirteen most common GI diseases contributed to 2.4 million index hospitalizations accounting for about $25 billion. The thirty-day readmission rates were highest for chronic liver disease (25.4%), () infection (23.6%), functional/motility disorders (18.5%), inflammatory bowel disease (16.3%), and GI bleeding (15.5%). The highest index and subsequent calendar-year hospitalization mortality rates were chronic liver disease (6.1% and 12.6%), infection (2.3% and 6.1%), and GI bleeding (2.2% and 5.0%), respectively. Thirty-day readmission correlated with any subsequent admission mortality ( = 0.798, = 0.001). Medicare/Medicaid insurances, ≥ 3 Elixhauser comorbidities, and length of stay > 3 d were significantly associated with thirty-day readmission for all the thirteen GI diseases.

Conclusion: Preventable and non-chronic GI disease contributed to a significant economic and health burden comparable to chronic GI conditions, providing a window of opportunity for improving healthcare delivery in reducing its burden.
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http://dx.doi.org/10.4240/wjgs.v13.i2.141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898184PMC
February 2021

High performance in risk stratification of intraductal papillary mucinous neoplasms by confocal laser endomicroscopy image analysis with convolutional neural networks (with video).

Gastrointest Endosc 2021 Jan 16. Epub 2021 Jan 16.

Division of Gastroenterology, Hepatology, and Nutrition, Division of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.

Background And Aims: EUS-guided needle-based confocal laser endomicroscopy (EUS-nCLE) can differentiate high-grade dysplasia/adenocarcinoma (HGD-Ca) in intraductal papillary mucinous neoplasms (IPMNs) but requires manual interpretation. We sought to derive predictive computer-aided diagnosis (CAD) and artificial intelligence (AI) algorithms to facilitate accurate diagnosis and risk stratification of IPMNs.

Methods: A post hoc analysis of a single-center prospective study evaluating EUS-nCLE (2015-2019; INDEX study) was conducted using 15,027 video frames from 35 consecutive patients with histopathologically proven IPMNs (18 with HGD-Ca). We designed 2 CAD-convolutional neural network (CNN) algorithms: (1) a guided segmentation-based model (SBM), where the CNN-AI system was trained to detect and measure papillary epithelial thickness and darkness (indicative of cellular and nuclear stratification), and (2) a reasonably agnostic holistic-based model (HBM) where the CNN-AI system automatically extracted nCLE features for risk stratification. For the detection of HGD-Ca in IPMNs, the diagnostic performance of the CNN-CAD algorithms was compared with that of the American Gastroenterological Association (AGA) and revised Fukuoka guidelines.

Results: Compared with the guidelines, both n-CLE-guided CNN-CAD algorithms yielded higher sensitivity (HBM, 83.3%; SBM, 83.3%; AGA, 55.6%; Fukuoka, 55.6%) and accuracy (SBM, 82.9%; HBM, 85.7%; AGA, 68.6%; Fukuoka, 74.3%) for diagnosing HGD-Ca, with comparable specificity (SBM, 82.4%; HBM, 88.2%; AGA, 82.4%; Fukuoka, 94.1%). Both CNN-CAD algorithms, the guided (SBM) and agnostic (HBM) models, were comparable in risk stratifying IPMNs.

Conclusion: EUS-nCLE-based CNN-CAD algorithms can accurately risk stratify IPMNs. Future multicenter validation studies and AI model improvements could enhance the accuracy and fully automatize the process for real-time interpretation.
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http://dx.doi.org/10.1016/j.gie.2020.12.054DOI Listing
January 2021

Predictors of hospital transfer and associated risks of mortality in acute pancreatitis.

Pancreatology 2021 Jan 14;21(1):25-30. Epub 2020 Dec 14.

Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, USA. Electronic address:

Background: There is limited research in prognosticators of hospital transfer in acute pancreatitis (AP). Hence, we sought to determine the predictors of hospital transfer from small/medium-sized hospitals and outcomes following transfer to large acute-care hospitals.

Methods: Using the 2010-2013 Nationwide Inpatient Sample (NIS), patients ≥18 years of age with a primary diagnosis of AP were identified. Hospital size was classified using standard NIS Definitions. Multivariable analyses were performed for predictors of "transfer-out" from small/medium-sized hospitals and mortality in large acute-care hospitals.

Results: Among 381,818 patients admitted with AP to small/medium-sized hospitals, 13,947 (4%) were transferred out to another acute-care hospital. Multivariable analysis revealed that older patients (OR = 1.04; 95%CI 1.03-1.06), men (OR = 1.15; 95%CI 1.06-1.24), lower income quartiles (OR = 1.54; 95%CI 1.35-1.76), admission to a non-teaching hospital (OR = 3.38; 95%CI 3.00-3.80), gallstone pancreatitis (OR = 3.32; 95%CI 2.90-3.79), pancreatic surgery (OR = 3.14; 95%CI 1.76-5.58), and severe AP (OR = 3.07; 95%CI 2.78-3.38) were predictors of "transfer-out". ERCP (OR = 0.53; 95%CI 0.43-0.66) and cholecystectomy (OR = 0.14; 95%CI 0.12-0.18) were associated with decreased odds of "transfer-out". Among 507,619 patients admitted with AP to large hospitals, 31,058 (6.1%) were "transferred-in" from other hospitals. The mortality rate for patients "transferred-in" was higher than those directly admitted (2.54% vs. 0.91%, p < 0.001). Multivariable analysis revealed that being "transferred-in" from other hospitals was an independent predictor of mortality (OR = 1.47; 95% CI 1.22-1.77).

Conclusions: Patients with AP transferred into large acute-care hospitals had a higher mortality than those directly admitted likely secondary to more severe disease. Early implementation of published clinical guidelines, triage, and prompt transfer of high-risk patients may potentially offset these negative outcomes.
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http://dx.doi.org/10.1016/j.pan.2020.12.001DOI Listing
January 2021

Clinical impact of endoscopic ultrasound-guided through-the-needle microbiopsy in patients with pancreatic cysts.

Endoscopy 2021 01 17;53(1):103. Epub 2020 Dec 17.

Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States.

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http://dx.doi.org/10.1055/a-1259-1409DOI Listing
January 2021

Psychological Health Among Gastroenterologists During the COVID-19 Pandemic: A National Survey.

Clin Gastroenterol Hepatol 2021 04 3;19(4):836-838.e3. Epub 2020 Dec 3.

Division of Gastroenterology, Hepatology & Nutrition, The Ohio State Wexner Medical Center, Columbus, Ohio. Electronic address:

The COVID-19 pandemic poses unprecedented and unique challenges to gastroenterologists eager to maintain clinical practice, patients' health, and their own physical/mental well-being. We aimed to estimate the prevalence and critical determinants of psychological distress in gastroenterologists during the COVID-19 pandemic.
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http://dx.doi.org/10.1016/j.cgh.2020.11.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955767PMC
April 2021

Confocal endomicroscopy for evaluation of pancreatic cystic lesions: a systematic review and international Delphi consensus report.

Endosc Int Open 2020 Nov 22;8(11):E1566-E1581. Epub 2020 Oct 22.

Division of Gastroenterology Mount Auburn Hospital Cambridge, Massachusetts, United States.

The aim of thi systematic review and consensus report is to standardize the practice of endoscopic ultrasound (EUS-guided needle-based confocal laser endomicroscopy (nCLE) for pancreatic cystic lesion (PCL) evaluation. We performed an international, systematic, evidence-based review of the applications, outcomes, procedural processes, indications, training, and credentialing of EUS-nCLE in management of PCLs. Based on available clinical evidence, preliminary nCLE consensus statements (nCLE-CS) were developed by an international panel of 15 experts in pancreatic diseases. These statements were then voted and edited by using a modified Delphi approach. An a priori threshold of 80 % agreement was used to establish consensus for each statement. Sixteen nCLE-CS were discussed. Thirteen (81 %) nCLE-CS reached consensus addressing indications (non-communication PCL meeting criteria for EUS-FNA or with prior non-diagnostic EUS-FNA), diagnostic outcomes (improved accuracy for mucinous PCLs and serous cystadenomas with substantial interobserver agreement of image patterns), low incidence of adverse events (fluorescein-associated and pancreatitis), procedural processes (nCLE duration, manipulation of needle with probe), and training (physician knowledge and competence). Based on a high level of agreement pertaining to expert consensus statements, this report standardizes the practice of EUS-nCLE. EUS-nCLE should be systematically considered when EUS-FNA is indicated for PCL evaluation.
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http://dx.doi.org/10.1055/a-1229-4156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581463PMC
November 2020

Morphologic and Microscopic Characterization of an Unusual Pancreatic Cystic Lesion.

Gastroenterology 2021 May 8;160(6):e14-e16. Epub 2020 Oct 8.

Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio. Electronic address:

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http://dx.doi.org/10.1053/j.gastro.2020.09.046DOI Listing
May 2021

International multicenter comprehensive analysis of adverse events associated with lumen-apposing metal stent placement for pancreatic fluid collection drainage.

Gastrointest Endosc 2020 10;92(4):980

Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.

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http://dx.doi.org/10.1016/j.gie.2020.05.008DOI Listing
October 2020

Through-the-needle forceps biopsy for pancreatic cystic lesions: multiple meta-analyses but limited prospective data.

Endosc Int Open 2020 Sep 31;8(9):E1134-E1136. Epub 2020 Aug 31.

Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States.

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http://dx.doi.org/10.1055/a-1198-4785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458749PMC
September 2020

Class III obesity rather than metabolic syndrome impacts clinical outcomes of acute pancreatitis: A propensity score weighted analysis.

Pancreatology 2020 Oct 23;20(7):1287-1295. Epub 2020 Aug 23.

Division of Gastroenterology, Hepatology, and Nutrition, Division of Internal Medicine, The Ohio State University, Wexner Medical Center, Columbus, OH, 43210, USA; The Comprehensive Cancer Center, Arthur G. James Cancer Hospital, Richard J. Solove Research Institute, The Ohio State University, Columbus, OH, 43210, USA. Electronic address:

Objectives: The incidence rates of acute pancreatitis (AP) and the prevalence of class III obesity, and metabolic syndrome (MetS) are increasing in the US. Since class III obesity was associated with adverse clinical outcomes of AP, we sought to understand if the presence of metabolic comorbidities collectively recognized, as MetS were associated with worse clinical outcomes and increased health-care utilization.

Methods: The Nationwide Readmissions Database (NRD) (2010-2014) was reviewed to identify all adult subjects with a principal discharge diagnosis of AP. Inpatient mortality, severe AP (SAP), and 30-day readmissions were the primary outcomes analyzed. Propensity score weighted analyses were used to compare AP subjects with and without MetS and were further stratified by class III obesity status.

Results: MetS was associated with 12.91% (139,165/1,078,183) of all admissions with AP. Propensity score weighted analyses showed that MetS was associated with an increased proportion of SAP (OR 1.21, 95% CI 1.17, 1.25), but decreased mortality (OR 0.62, 95% CI 0.54, 0.70) and 30-day readmissions (OR 0.86, 95% CI 0.83, 0.89). Propensity score weighted analyses also revealed that class III obesity was independently associated with increased mortality in AP subjects with (OR 1.92, 95% CI 1.41, 2.61) and without MetS (OR 1.55, 95% CI 1.26, 1.92), and increased SAP in subjects with and without MetS.

Conclusions: Class III obesity appears to be the primary factor associated with adverse clinical outcomes in subjects with MetS admitted with AP. This has significant implications for patient management and future research targeting AP.
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http://dx.doi.org/10.1016/j.pan.2020.08.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780090PMC
October 2020

Activation of the RAS pathway through uncommon BRAF mutations in mucinous pancreatic cysts without KRAS mutation.

Mod Pathol 2021 02 13;34(2):438-444. Epub 2020 Aug 13.

James Molecular Laboratory at Polaris, The Ohio State University James Cancer Center, Columbus, OH, USA.

Diagnostic testing of pancreatic cyst fluid obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has traditionally utilized elevated carcinoembryonic antigen (CEA) (≥192 ng/ml) and cytomorphologic examination to differentiate premalignant mucinous from benign pancreatic cystic lesions (PCLs). Molecular testing for KRAS/GNAS mutations has been shown to improve accuracy of detecting mucinous PCLs. Using a targeted next-generation sequencing (NGS) panel, we assess the status of PCL-associated mutations to improve understanding of the key diagnostic variables. Molecular analysis of cyst fluid was performed on 108 PCLs that had concurrent CEA and/or cytological analysis. A 48-gene NGS assay was utilized, which included genes commonly mutated in mucinous PCLs such as GNAS, KRAS, CDKN2A, and TP53. KRAS and/or GNAS mutations were seen in 59 of 68 (86.8%) cases with multimodality diagnosis of a mucinous PCL. Among 31 patients where surgical histopathology was available, the sensitivity, specificity, and diagnostic accuracy of NGS for the diagnosis of mucinous PCL was 88.5%, 100%, and 90.3%, respectively. Cytology with mucinous/atypical findings were found in only 29 of 62 cases (46.8%), with fluid CEA elevated in 33 of 58 cases (56.9%). Multiple KRAS mutations at different variant allele frequencies were seen in seven cases favoring multiclonal patterns, with six of them showing at least two separate PCLs by imaging. Among the 6 of 10 cases with GNAS + /KRAS- results, uncommon, non-V600E exon 11/15 hotspot BRAF mutations were identified. The expected high degree of accuracy of NGS detection of KRAS and/or GNAS mutations for mucinous-PCLs, as compared with CEA and cytological examination, was demonstrated. Multiple KRAS mutations correlated with multifocal cysts demonstrated by radiology. In IPMNs that lacked KRAS mutations, the concurring BRAF mutations with GNAS mutations supports an alternate mechanism of activation in the Ras pathway.
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http://dx.doi.org/10.1038/s41379-020-00647-zDOI Listing
February 2021

Radiomics for the Diagnosis and Differentiation of Pancreatic Cystic Lesions.

Diagnostics (Basel) 2020 Jul 21;10(7). Epub 2020 Jul 21.

Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.

Radiomics, also known as quantitative imaging or texture analysis, involves extracting a large number of features traditionally unmeasured in conventional radiological cross-sectional images and converting them into mathematical models. This review describes this approach and its use in the evaluation of pancreatic cystic lesions (PCLs). This discipline has the potential of more accurately assessing, classifying, risk stratifying, and guiding the management of PCLs. Existing studies have provided important insight into the role of radiomics in managing PCLs. Although these studies are limited by the use of retrospective design, single center data, and small sample sizes, radiomic features in combination with clinical data appear to be superior to the current standard of care in differentiating cyst type and in identifying mucinous PCLs with high-grade dysplasia. Combining radiomic features with other novel endoscopic diagnostics, including cyst fluid molecular analysis and confocal endomicroscopy, can potentially optimize the predictive accuracy of these models. There is a need for multicenter prospective studies to elucidate the role of radiomics in the management of PCLs.
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http://dx.doi.org/10.3390/diagnostics10070505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399814PMC
July 2020

Endosonographic diagnosis of advanced neoplasia in intraductal papillary mucinous neoplasms.

World J Gastroenterol 2020 Jun;26(23):3201-3212

Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States.

Pancreatic cancer has a high mortality rate with minimal proven interventions. Intraductal Papillary Mucinous Neoplasms (IPMNs) are known precursor lesions for pancreatic cancer. Identification of pancreatic cysts has improved from advances in abdominal imaging. Despite multiple revisions of the international consensus recommendations and various guidelines by other major societies, successful risk stratification of the malignant potential of mucinous pancreatic cysts remains challenging. Specifically, detection and accurate classification of advanced neoplasia (high-grade dysplasia and/or adenocarcinoma) in IPMNs is suboptimal with current diagnostic strategies. Development of interventional techniques utilizing endoscopic ultrasound include - through-the-needle microforceps biopsy, next-generation or whole genome molecular analysis of cyst fluid, and needle-based confocal laser endomicroscopy. These techniques suffer from a series of limitations in technical success, diagnostic yield, and clinical feasibility, but a combination approach may offer a solution that optimizes their cyst evaluation and risk stratification. Assessment and comparison of these techniques is restricted by lack of adequate surgical specimens for testing of diagnostic accuracy, resulting in a possible sample bias. Additional large-scale multicenter studies are needed to accumulate evidence for the utility and feasibility of their translation into clinical practice. Great strides have been made in pancreatic cyst evaluation, but further research is required to improve diagnostic accuracy and clinical management of IPMNs.
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http://dx.doi.org/10.3748/wjg.v26.i23.3201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336327PMC
June 2020

Reduction of inflammation in chronic pancreatitis using a soy bread intervention: A feasibility study.

Pancreatology 2020 Jul 6;20(5):852-859. Epub 2020 Jun 6.

Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, USA. Electronic address:

Introduction: Chronic pancreatitis is a chronic inflammatory disease, which progresses to fibrosis. Currently there are no interventions to delay or stop the progression to irreversible organ damage. In this study, we assessed the tolerability and feasibility of administering soy bread to reduce circulating inflammatory mediators.

Methods: Subjects with chronic pancreatitis diagnosed using the American Pancreatic Association diagnostic guidelines were enrolled. During the dose escalation (DE) phase, subjects received one week of soy bread based using a 3 + 3 dose-escalation design, which was then followed by a maximally tolerated dose (MTD) phase with four weeks of intervention. Dose-limiting toxicities (DLTs) were monitored. Plasma cytokine levels were measured using a Meso Scale Discovery multiplex assay kit. Isoflavonoid excretion in 24-h urine collection was used to measure soy bread compliance.

Results: Nine subjects completed the DE phase, and one subject completed the MTD phase without any DLTs at a maximum dosage of three slices (99 mg of isoflavones) per day. Reported compliance to soy bread intervention was 98%, and this was confirmed with urinary isoflavones and their metabolites detected in all subjects. There was a significant decline in the TNF-α level during the DE phase (2.667 vs 2.382 pg/mL, p = 0.039); other levels were similar.

Conclusions: In this feasibility study, there was excellent compliance with a short-term intervention using soy bread in chronic pancreatitis. Reduction was seen in at least one pro-inflammatory cytokine with short-term intervention. Larger cohorts and longer interventions with soy are warranted to assess the efficacy of reducing pro-inflammatory mediators of disease.
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http://dx.doi.org/10.1016/j.pan.2020.04.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780088PMC
July 2020

Treatment of gastrointestinal bleeding in left ventricular assist devices: A comprehensive review.

World J Gastroenterol 2020 May;26(20):2550-2558

Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center; Columbus, OH 43210, United States.

Left ventricular assist devices (LVAD) are increasingly become common as life prolonging therapy in patients with advanced heart failure. Current devices are now used as definitive treatment in some patients given the improved durability of continuous flow pumps. Unfortunately, continuous flow LVADs are fraught with complications such as gastrointestinal (GI) bleeding that are primarily attributed to the formation of arteriovenous malformations. With frequent GI bleeding, antiplatelet and anticoagulation therapies are usually discontinued increasing the risk of life-threatening events. Small bowel bleeds account for 15% as the source and patients often undergo multiple endoscopic procedures. Treatment strategies include resuscitative measures and endoscopic therapies. Medical treatment is with octreotide. Novel treatment options include thalidomide, angiotensin converting enzyme inhibitors/angiotensin II receptor blockers, estrogen-based hormonal therapies, doxycycline, desmopressin and bevacizumab. Current research has explored the mechanism of frequent GI bleeds in this population, including destruction of von Willebrand factor, upregulation of tissue factor, vascular endothelial growth factor, tumor necrosis factor-α, tumor growth factor-β, and angiopoetin-2, and downregulation of angiopoetin-1. In addition, healthcare resource utilization is only increasing in this patient population with higher admissions, readmissions, blood product utilization, and endoscopy. While some of the novel endoscopic and medical therapies for LVAD bleeds are still in their development stages, these tools will yet be crucial as the number of LVAD placements will likely only increase in the coming years.
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http://dx.doi.org/10.3748/wjg.v26.i20.2550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265145PMC
May 2020

The increasing prevalence and adverse impact of morbid obesity in paediatric acute pancreatitis.

Pediatr Obes 2020 08 14;15(8):e12643. Epub 2020 May 14.

Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.

Objective: Morbid obesity is proinflammatory has been associated with adverse clinical outcomes in acute pancreatitis (AP) among adults. Obesity is increasingly prevalent in children and hence, we sought to evaluate the impact of morbid obesity on the clinical outcomes of AP using a large paediatric population-based cohort.

Methods: We analysed the US Kids' Inpatient Database between years 2003 and 2016 to include all patients (age ≤ 21 years) with a primary diagnosis of AP using specific ICD-9-CM and ICD-10-CM codes. We compared clinical outcomes between children without obesity (controls) and those with morbid obesity (cases). The primary outcome was severe AP (2012 revised Atlanta classification) and secondary outcomes included healthcare resource utilization (length of stay and hospital costs).

Results: Among 36 698 paediatric AP hospitalizations, 1275 (3.5%) were found to have morbid obesity. From 2003 to 2016, the proportion of children with morbid obesity among AP patients increased from 1.3% to 5.5% (P < .001). More than half (54%) of the children with morbid obesity were presented with cholelithiasis as contributive aetiology. The prevalence of severe AP was significantly higher in morbid obesity (7.3% vs 3.8%, P < .001). Multivariate analysis revealed that morbid obesity was increasingly associated with severe AP (OR 1.79, 95% CI 1.4, 2.26), prolonged hospitalization (by 0.41 days, P = .03), and higher hospital costs (by $1596, P < .001).

Conclusion: Unlike adult population, there is a lack of other confounding comorbidities in children and this national-level analysis shows that morbid obesity independently prognosticates adverse clinical outcomes in paediatric AP.
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http://dx.doi.org/10.1111/ijpo.12643DOI Listing
August 2020

Phase I Trial of Trametinib with Neoadjuvant Chemoradiation in Patients with Locally Advanced Rectal Cancer.

Clin Cancer Res 2020 07 6;26(13):3117-3125. Epub 2020 Apr 6.

Moffitt Cancer Center, Tampa, Florida.

Purpose: The RAS/RAF/MEK/ERK signaling pathway is critical to the development of colorectal cancers, and , , and mutations foster resistance to radiation. We performed a phase I trial to determine the safety of trametinib, a potent MEK1/2 inhibitor, with 5-fluorouracil (5-FU) chemoradiation therapy (CRT) in patients with locally advanced rectal cancer (LARC).

Patients And Methods: Patients with stage II/III rectal cancer were enrolled on a phase I study with 3+3 study design, with an expansion cohort of 9 patients at the MTD. Following a 5-day trametinib lead-in, with pre- and posttreatment tumor biopsies, patients received trametinib and CRT, surgery, and adjuvant chemotherapy. Trametinib was given orally daily at 3 dose levels: 0.5 mg, 1 mg, and 2 mg. CRT consisted of infusional 5-FU 225 mg/m/day and radiation dose of 28 daily fractions of 1.8 Gy (total 50.4 Gy). The primary endpoint was to identify the MTD and recommended phase II dose. IHC staining for phosphorylated ERK (pERK) and genomic profiling was performed on the tumor samples.

Results: Patients were enrolled to all dose levels, and 18 patients were evaluable for toxicities and responses. Treatment was well tolerated, and there was one dose-limiting toxicity of diarrhea, which was attributed to CRT rather than trametinib. At the 2 mg dose level, 25% had pathologic complete response. IHC staining confirmed dose-dependent decrease in pERK with increasing trametinib doses.

Conclusions: The combination of trametinib with 5-FU CRT is safe and well tolerated, and may warrant additional study in a phase II trial, perhaps in a -mutant selected population.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-4193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334091PMC
July 2020

Endoscopic ultrasound-guided confocal endomicroscopy requires high-quality imaging and interpretation for diagnostic evaluation of pancreatic cystic lesions.

Endosc Int Open 2020 Mar 21;8(3):E310-E311. Epub 2020 Feb 21.

Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, USA.

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http://dx.doi.org/10.1055/a-1067-4595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035129PMC
March 2020

Changing epidemiology of esophageal stent placement for dysphagia: a decade of trends and the impact of benign indications.

Gastrointest Endosc 2020 07 24;92(1):56-64.e7. Epub 2020 Feb 24.

Division of Gastroenterology, Hepatology, and Nutrition, Wexner Medical Center, The Ohio State University, Columbus, Ohio, USA.

Background And Aims: In addition to managing malignant obstruction, esophageal stents (ESs) have evolved to address various benign etiologies of dysphagia. We sought to evaluate national trends and changes in practice of ES placement for both benign and malignant etiologies in hospitalized patients with dysphagia.

Methods: The National Inpatient Sample (2003-2013) was used to include all adult inpatients (≥18 years of age) with endoscopy-guided ES placement for a symptom of dysphagia. Multivariable analyses for indications that impact temporal trends (3 time periods: 2003-2005, 2006-2009, and 2010-2013) and for hospital outcomes were performed.

Results: A total of 7198 ESs were deployed endoscopically in hospitalized patients with dysphagia. Compared with malignant etiologies, there was a significant increase in ES placement for benign conditions (2013 vs 2003: 32.7% vs 14.5%, respectively; P < .001). Multivariable analysis using 2003 to 2005 as a reference showed that patients with benign etiologies for dysphagia predominantly contributed to the increase of ES placement during the most recent time period (2010-2013: odds ratio, 2.09; 95% confidence interval, 1.40-3.13). Multivariable analysis of hospital outcomes revealed no differences in inpatient mortality, duration of hospital stay, and hospital costs between malignant and benign indications.

Conclusions: In the preceding decade, ES placement for hospitalized patients with dysphagia has increased, driven largely by an over 8-fold rise in stent placement for benign indications. These findings warrant continued efforts to improve stent technology to decrease the risk of migration and review practice guidelines involving ES placement for benign etiologies.
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http://dx.doi.org/10.1016/j.gie.2020.02.018DOI Listing
July 2020

Lipocalin-2 expression and function in pancreatic diseases.

Pancreatology 2020 Apr 7;20(3):419-424. Epub 2020 Jan 7.

Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, USA; The James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA. Electronic address:

Lipocalin-2 (LCN2) is a secreted molecule, expressed in various cell types, that is involved in the progression of numerous diseases and disorders. The biological functions and expression levels of LCN2 in diseases including pancreatic cancer, pancreatitis (acute and chronic), and diabetes mellitus, suggest the potential role of LCN2 as a biomarker and/or therapeutic target. However, findings on the role of LCN2 in pancreatic diseases have been contradictory. In pancreatic cancer and pancreatitis, LCN2 has been identified as a potential biomarker; increased expression levels in various biological specimens correlate with the presence of the disease and may be able to differentiate cancer and chronic pancreatitis from healthy subjects. LCN2 is also known to be an adipokine; it is upregulated in obesity and is a common co-factor in the development of pancreatic diseases. Emerging research suggests LCN2 is elevated in type 2 diabetes mellitus, but the exact role of LCN2 in this disease is not clear. In this review, we summarize research on LCN2 as it relates to pancreatic diseases, highlighting the discrepancies in the literature. By explaining and clarifying the role of LCN2 in these disorders, we aim to promote research in developing novel diagnostic and treatment strategies to reduce the burden of pancreatic diseases.
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http://dx.doi.org/10.1016/j.pan.2020.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160010PMC
April 2020

Diverticulitis in Morbidly Obese Adults: A Rise in Hospitalizations with Worse Outcomes According to National US Data.

Dig Dis Sci 2020 09 3;65(9):2644-2653. Epub 2020 Jan 3.

Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, OH, USA.

Background And Aims: Obesity is a known risk factor for diverticulitis. Our objective was to examine the less investigated impact of morbid obesity (MO) on admissions and clinical course of diverticulitis in a US representative database.

Methods: We retrospectively queried the 2010-2014 Nationwide Readmission Database to compare diverticulitis hospitalizations in 48,651 MO and 841,381 non-obese patients. Outcomes of mortality, clinical course, surgical events, and readmissions were compared using multivariable and propensity-score-matched analyses.

Results: The number of MO patients admitted with diverticulitis increased annually from 7570 in 2010 to 11,935 in 2014, while the total number of patients admitted with diverticulitis decreased (p = 0.003). Multivariable analysis demonstrates that MO was associated with increased mortality (adjusted odds ratio [aOR] 1.54; 95% confidence internal [CI]: 1.16, 2.05), intensive care admissions (aOR = 1.92; 95% CI: 1.61, 2.31), emergent surgery (aOR = 1.20; 95% CI: 1.11, 1.30), colectomy (aOR = 1.13; 95% CI: 1.08, 1.18), open laparotomy (aOR = 1.28; 95% CI: 1.21, 1.34), and colostomy (aOR = 1.34; 95% CI: 1.25, 1.43). Additionally, MO was associated with higher risk for multiple readmissions for diverticulitis within 30 days (aOR = 1.45; 95% CI: 1.08, 1.96) and 6 months (aOR = 1.21; 95% CI: 1.03, 1.42). A one-to-one matched propensity-score analysis confirmed our multivariable analysis findings.

Conclusions: Analysis of national data demonstrates an increasing trend of MO patients' admissions for diverticulitis, with a presentation at a younger age. Furthermore, MO is associated with an increased risk of adverse outcomes and readmissions of diverticulitis. Future strategies are needed to ameliorate these outcomes.
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http://dx.doi.org/10.1007/s10620-019-06002-wDOI Listing
September 2020

Unavailability of Endoscopic Retrograde Cholangiography Adversely Impacts Hospital Outcomes of Acute Biliary Pancreatitis: A National Survey and Propensity-Matched Analysis.

Pancreas 2020 01;49(1):39-45

From the Division of Gastroenterology, Hepatology, and Nutrition.

Objectives: There is a paucity of literature assessing the impact of endoscopic retrograde cholangiopancreatography (ERCP) availability at hospitals and the management of acute biliary pancreatitis (ABP). Thus, we sought to evaluate the impact of ERCP availability on the clinical outcomes of ABP.

Methods: The Nationwide Inpatient Sample (2004-2013) was reviewed to identify adult inpatients (≥18 years) with ABP. Clinical outcomes (mortality, severe acute pancreatitis, and health care resource utilization) between hospitals that perform ERCP versus hospitals that do not perform ERCP were compared using multivariate and propensity score-matched analyses.

Results: A majority of the non-ERCP hospitals were rural (73%) in location. Multivariate analysis demonstrated that the lack of ERCP availability was independently associated with increased mortality from ABP (odds ratio, 1.83; 95% confidence interval, 1.16-2.88). A propensity score-matched cohort analysis confirmed a significant increase in mortality from ABP in non-ERCP hospitals (1.1% vs 0.53%; odds ratio, 2.08; 95% confidence interval, 1.05-4.15, P = 0.037) compared with ERCP hospitals.

Conclusions: This national survey reveals increased mortality for patients with ABP admitted to hospitals lacking ERCP services. While there is a need to increase ERCP availability in rural areas, optimizing strategies for early transfer of patients with ABP to hospitals with ERCP availability can potentially offset these limitations.
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http://dx.doi.org/10.1097/MPA.0000000000001435DOI Listing
January 2020

Pancreatic Cysts in the Elderly.

Curr Treat Options Gastroenterol 2019 Dec;17(4):457-469

Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, 395 W 12th Avenue, Room 226, Columbus, OH, 43210, USA.

Purpose Of Review: Incidental pancreatic cysts are common, and management strategies continue to evolve. This review summarizes diagnostic and management recommendations in older patients with these lesions based on guidelines and best clinical evidence.

Recent Findings: Diagnosis of cyst type has been enhanced with improved imaging and cyst fluid analysis and visualization. Recent outcome studies indicate that certain cyst types should be followed independent of patient age as long as certain criteria which are reviewed are met. Differentiation of pancreatic cyst type is important as this dictates the need for long-term follow-up. Because most cyst-related neoplasia occurs in older patients, surveillance should continue within certain guidelines.
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http://dx.doi.org/10.1007/s11938-019-00260-3DOI Listing
December 2019

Cathepsin E expression and activity: Role in the detection and treatment of pancreatic cancer.

Pancreatology 2019 Oct 20;19(7):951-956. Epub 2019 Sep 20.

Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, USA; The James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA. Electronic address:

Cathepsin E (CTSE) is an intracellular, hydrolytic aspartic protease found to be expressed in cells of the immune and gastrointestinal systems, lymphoid tissues, erythrocytes, and cancer cells. The precise functions are not fully understood; however, various studies have investigated its numerous cell-type specific roles. CTSE expression has been shown to be a potential early biomarker for pancreatic ductal adenocarcinoma (PDAC). PDAC patients have low survival rates mostly due to the lack of early detection methods. CTSE-specific activity probes have been developed and tested to assist in tumor imaging and functional studies investigating the role of CTSE expression in PDAC tumors. Furthermore, a CTSE protease-specific, photodynamic therapy pro-drug was developed to explore its potential use to treat tumors that express CTSE. Since CTSE is expressed in pancreatic diseases that are risk factors for PDAC, such as pancreatic cysts and chronic pancreatitis, learning about its function in these disease types could assist in early PDAC detection and in understanding the biology of PDAC progression. Overall, CTSE expression and activity shows potential to detect PDAC and other pancreatic diseases. Further research is needed to fully understand its functions and potential translational applicability.
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http://dx.doi.org/10.1016/j.pan.2019.09.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829043PMC
October 2019

EUS-guided confocal laser endomicroscopy: prediction of dysplasia in intraductal papillary mucinous neoplasms (with video).

Gastrointest Endosc 2020 03 19;91(3):551-563.e5. Epub 2019 Sep 19.

Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.

Background And Aims: Previous studies have validated EUS-guided needle-based confocal laser endomicroscopy (nCLE) diagnosis of intraductal papillary mucinous neoplasms (IPMNs). We sought to derive EUS-guided nCLE criteria for differentiating IPMNs with high-grade dysplasia/adenocarcinoma (HGD-Ca) from those with low/intermediate-grade dysplasia (LGD).

Methods: We performed a post hoc analysis of consecutive IPMNs with a definitive diagnosis from a prospective study evaluating EUS-guided nCLE in the diagnosis of pancreatic cysts. Three internal endosonographers reviewed all nCLE videos for the patients and identified potential discriminatory EUS-guided nCLE variables to differentiate HGD-Ca from LGD IPMNs (phase 1). Next, an interobserver agreement (IOA) analysis of variables from phase 1 was performed among 6 blinded external nCLE experts (phase 2). Last, 7 blinded nCLE-naïve observers underwent training and quantified variables with the highest IOA from phase 2 using dedicated software (phase 3).

Results: Among 26 IPMNs (HGD-Ca in 16), the reference standard was surgical histopathology in 24 and cytology confirmation of metastatic liver lesions in 2 patients. EUS-guided nCLE characteristics of increased papillary epithelial "width" and "darkness" were the most sensitive variables (90%; 95% confidence interval [CI], 84%-94% and 91%; 95% CI, 85%-95%, respectively) and accurate (85%; 95% CI, 78%-90% and 84%; 95% CI, 77%-89%, respectively) with substantial (κ = 0.61; 95% CI, 0.51-0.71) and moderate (κ = 0.55; 95% CI, 0.45-0.65) IOAs for detecting HGD-Ca, respectively (phase 2). Logistic regression models were fit for the outcome of HGD-Ca as predictor variables (phase 3). For papillary width (cut-off ≥50 μm), the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) for detection of HGD-Ca were 87.5% (95% CI, 62%-99%), 100% (95% CI, 69%-100%), and 0.95, respectively. For papillary darkness (cut-off ≤90 pixel intensity), the sensitivity, specificity, and AUC for detection of HGD-Ca were 87.5% (95% CI, 62%-99%), 100% (95% CI, 69%-100%), and 0.90, respectively.

Conclusions: In this derivation study, quantification of papillary epithelial width and darkness identified HGD-Ca in IPMNs with high accuracy. These quantifiable variables can be used in multicenter studies for risk stratification of IPMNs. (Clinical trial registration number: NCT02516488.).
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http://dx.doi.org/10.1016/j.gie.2019.09.014DOI Listing
March 2020

Application of Artificial Intelligence in the Detection and Differentiation of Colon Polyps: A Technical Review for Physicians.

Diagnostics (Basel) 2019 Aug 20;9(3). Epub 2019 Aug 20.

Division of Gastroenterology, Hepatology and Nutrition, the Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.

Research in computer-aided diagnosis (CAD) and the application of artificial intelligence (AI) in the endoscopic evaluation of the gastrointestinal tract is novel. Since colonoscopy and detection of polyps can decrease the risk of colon cancer, it is recommended by multiple national and international societies. However, the procedure of colonoscopy is performed by humans where there are significant interoperator and interpatient variations, and hence, the risk of missing detection of adenomatous polyps. Early studies involving CAD and AI for the detection and differentiation of polyps show great promise. In this appraisal, we review existing scientific aspects of AI in CAD of colon polyps and discuss the pitfalls and future directions for advancing the science. This review addresses the technical intricacies in a manner that physicians can comprehend to promote a better understanding of this novel application.
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http://dx.doi.org/10.3390/diagnostics9030099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787748PMC
August 2019