Publications by authors named "Vikesh K Singh"

236 Publications

Rectal INdomethacin, oral TacROlimus, or their combination for the prevention of post-ERCP pancreatitis (INTRO Trial): Protocol for a randomized, controlled, double-blinded trial.

Pancreatology 2022 Jul 19. Epub 2022 Jul 19.

Department of Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India.

Background: Acute pancreatitis remains the most common and morbid complication of endoscopic retrograde cholangiopancreatography (ERCP). The use of rectal indomethacin and pancreatic duct stenting has been shown to reduce the incidence and severity of post-ERCP pancreatitis (PEP), but these interventions have limitations. Recent clinical and translational evidence suggests a role for calcineurin inhibitors in the prevention of pancreatitis, with multiple retrospective case series showing a reduction in PEP rates in tacrolimus users.

Methods: The INTRO trial is a multicenter, international, randomized, double-blinded, controlled trial. A total of 4,874 patients undergoing ERCP will be randomized to receive either oral tacrolimus (5 mg) or oral placebo 1-2 h before ERCP, and followed for 30 days post-procedure. Blood and pancreatic aspirate samples will also be collected in a subset of patients to quantify tacrolimus levels. The primary outcome of the study is the incidence of PEP. Secondary endpoints include the severity of PEP, ERCP-related complications, adverse drug events, length of hospital stay, cost-effectiveness, and the pharmacokinetics, pharmacodynamics, and pharmacogenomics of tacrolimus immune modulation in the pancreas.

Conclusions: The INTRO trial will assess the role of calcineurin inhibitors in PEP prophylaxis and develop a foundation for the clinical optimization of this therapeutic strategy from a pharmacologic and economic standpoint. With this clinical trial, we hope to demonstrate a novel approach to PEP prophylaxis using a widely available and well-characterized class of drugs.

Trial Registration: NCT05252754, registered on February 14, 2022.
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http://dx.doi.org/10.1016/j.pan.2022.07.008DOI Listing
July 2022

Predicting persistent organ failure on admission in patients with acute pancreatitis: development and validation of a mobile nomogram.

HPB (Oxford) 2022 Jun 6. Epub 2022 Jun 6.

Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Center and West China-Liverpool Biomedical Research Center, West China Hospital, Sichuan University, Chengdu, China. Electronic address:

Background: Early prediction of persistent organ failure (POF) is important for triage and timely treatment of patients with acute pancreatitis (AP).

Methods: All AP patients were consecutively admitted within 48 h of symptom onset. A nomogram was developed to predict POF on admission using data from a retrospective training cohort, validated by two prospective cohorts. The clinical utility of the nomogram was defined by concordance index (C-index), decision curve analysis (DCA), and clinical impact curve (CIC), while the performance by post-test probability.

Results: There were 816, 398, and 880 patients in the training, internal and external validation cohorts, respectively. Six independent predictors determined by logistic regression analysis were age, respiratory rate, albumin, lactate dehydrogenase, oxygen support, and pleural effusion and were included in the nomogram (web-based calculator: https://shina.shinyapps.io/DynNomapp/). This nomogram had reasonable predictive ability (C-indexes 0.88/0.91/0.81 for each cohort) and promising clinical utility (DCA and CIC). The nomogram had a positive likelihood ratio and post-test probability of developing POF in the training, internal and external validation cohorts of 4.26/31.7%, 7.89/39.1%, and 2.75/41%, respectively, superior or equal to other prognostic scores.

Conclusions: This nomogram can predict POF of AP patients and should be considered for clinical practice and trial allocation.
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http://dx.doi.org/10.1016/j.hpb.2022.05.1347DOI Listing
June 2022

Prevention and Management of Complications of Biliary Endoscopy.

Gastrointest Endosc Clin N Am 2022 Jul;32(3):397-409

Division of Gastroenterology, Johns Hopkins Medical Institutions, Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 428, Baltimore, MD 21205, USA. Electronic address:

Endoscopic retrograde cholangiopancreatography (ERCP) is an essential procedure for the management of pancreaticobiliary disorders. ERCP is, however, associated with the risk of complications including pancreatitis, bleeding, perforation, infection, and instrument failure, which can often be fatal. It is, therefore, necessary to recognize the risk of ERCP-associated complications and understand the methods to prevent and treat such complications.
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http://dx.doi.org/10.1016/j.giec.2022.03.001DOI Listing
July 2022

Rectal Nonsteroidal Anti-inflammatory Drugs for Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis Prophylaxis: A Case Study in a Price-Escalation Era.

Gastroenterology 2022 May 19. Epub 2022 May 19.

Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India.

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http://dx.doi.org/10.1053/j.gastro.2022.05.026DOI Listing
May 2022

Corrigendum to "Prevalence of primary painless chronic pancreatitis: A systematic review and meta-analysis" [Pancreatology 22 (1) (January 2022) 20-29].

Pancreatology 2022 Apr 11;22(3):448. Epub 2022 Mar 11.

Division of Gastroenterology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Pancreatitis Center, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA.

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http://dx.doi.org/10.1016/j.pan.2022.03.003DOI Listing
April 2022

The present and future of gastroenterology and hepatology: an international SWOT analysis (the GASTROSWOT project).

Lancet Gastroenterol Hepatol 2022 05 2;7(5):485-494. Epub 2022 Mar 2.

Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, Netherlands. Electronic address:

GASTROSWOT is a strategic analysis of the current and projected states of the different subspecialties in gastroenterology that aims to provide guidance for research, clinical, and financial planning in gastroenterology. We executed a consensus-based international strengths, weaknesses, opportunities, and threats (SWOT) analysis. Four general coordinators, six field coordinators, and 12 experts participated in the study. SWOTs were provided for the following fields: neurogastroenterology, functional gastrointestinal disorders, and upper gastrointestinal diseases; inflammatory bowel disease; pancreatology and biliary diseases; endoscopy; gastrointestinal oncology; and hepatology. The GASTROSWOT analysis highlights the following in the current state of the field of gastroenterology: the incidence and complexity of several gastrointestinal diseases, including malignancies, are increasing; the COVID-19 pandemic has affected patient care on several levels; and with the advent of technical innovations in gastroenterology, a well trained workforce and strategic planning are required to optimise health-care utilisation. The analysis calls attention to the following in the future of gastroenterology: artificial intelligence and the use of big data will speed up discovery and smarter health-care provision in the field; the growth and diversification of gastroenterological specialties will improve specialised care for patients, but could promote fragmentation of care and health system inefficiencies; and furthermore, thoughtful planning is needed to reach an effective balance between the need for subspecialists and the value of general gastroenterology services.
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http://dx.doi.org/10.1016/S2468-1253(21)00442-8DOI Listing
May 2022

Pain Management in Acute Pancreatitis: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Front Med (Lausanne) 2021 17;8:782151. Epub 2021 Dec 17.

Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, China.

Pain management is an important priority in the treatment of acute pancreatitis (AP). Current evidence and guideline recommendations are inconsistent on the most effective analgesic protocol. This systematic review and meta-analysis of randomised controlled trials (RCTs) aimed to compare the safety and efficacy of analgesics for pain relief in AP. A literature search was performed to identify all RCTs assessing analgesics in patients with AP. The primary outcome was the number of participants who needed rescue analgesia. Study quality was assessed using Jadad score. Pooled odds ratios (ORs) or weighted mean differences (WMDs) with 95% confidence intervals (CI) were analysed using a random-effects model. Twelve studies comprising 699 patients with AP (83% mild AP) were analysed. The tested analgesics significantly decreased the need for rescue analgesia (3 studies, OR.36, 95% CI 0.21 to 0.60) vs. placebo or conventional treatment. The analgesics also improved the pain score [Visual Analogue Scale (Δ-VAS)] at 24 h (WMD 18.46, 0.84 to 36.07) and by the 3rd to 7th days (WMD 11.57, 0.87 to 22.28). Opioids vs. non-opioids were associated with a decrease in the need for rescue analgesia (6 studies, OR 0.25, 95% CI 0.07 to 0.86, = 0.03) but without significance in pain score. In subgroup analyses, opioids were similar to non-steroidal anti-inflammatory drugs (NSAIDs) regarding the primary outcome (4 studies, OR 0.56, 95% CI 0.24 to 1.32, = 0.18). There were no significant differences in other clinical outcomes and rate of adverse events. Other studies, comparing epidural anaesthesia vs. patient-controlled analgesia and opioid (buprenorphine) vs. opioid (pethidine) did not show significant difference in primary outcome. Study quality issues significantly contributed to overall study heterogeneity. NSAIDs and opioids are equally effective in decreasing the need for rescue analgesia in patients with mild AP. The relative paucity of trials and high-quality data in this setting is notable and the optimal analgesic strategy for patients with moderately severe and severe AP still requires to be determined.
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http://dx.doi.org/10.3389/fmed.2021.782151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718672PMC
December 2021

Rationale for and Development of the Pancreatic Quantitative Sensory Testing Consortium to Study Pain in Chronic Pancreatitis.

Pancreas 2021 10;50(9):1298-1304

From the Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.

Objectives: Abdominal pain is the primary symptom of chronic pancreatitis (CP), but pain is difficult to assess, and objective methods for pain assessment are lacking. The characterization of the sensory component of pain as a surrogate for nociception can be achieved by sensory testing using standardized stimuli. Herein, we describe the rationale for and development of an international consortium to better understand and characterize CP pain.

Methods: A collaboration was initially formed between the University of Aalborg, Johns Hopkins University, and the University of Pittsburgh. This group refined the protocol for pancreatic quantitative sensory testing (P-QST) and then expanded the collaboration with plans for incorporating P-QST into prospective studies.

Results: The collaboration has successfully developed a P-QST nomogram. Chronic pancreatitis patients identified with P-QST as having widespread hyperalgesia had higher pain intensity scores, higher prevalence of constant pain, and decreased quality of life. Psychiatric comorbidities were independent of pain phenotypes. Multiple studies are underway to validate these findings and evaluate their utility in clinical trials.

Conclusions: Development of the P-QST Consortium will facilitate collaborative efforts to use P-QST as a means for evaluation and characterization of pain in CP patients, and optimize methods to guide individualized pain management approaches.
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http://dx.doi.org/10.1097/MPA.0000000000001912DOI Listing
October 2021

Prevalence of primary painless chronic pancreatitis: A systematic review and meta-analysis.

Pancreatology 2022 Jan 18;22(1):20-29. Epub 2021 Nov 18.

Division of Gastroenterology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Pancreatitis Center, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA. Electronic address:

Background/objectives: While pain is the predominant symptom of chronic pancreatitis (CP), a subset of patients may experience a painless course. This systematic review aimed to determine the prevalence of primary painless CP.

Methods: MEDLINE (PubMed), EMBASE and Web of Science Core Collection databases were searched for published studies through September 15, 2020 that included at least 10 consecutive patients with CP and which reported the number with painless CP. The presence of a history of recurrent acute pancreatitis (RAP), exocrine pancreatic insufficiency (EPI), diabetes mellitus (DM) and pancreatic adenocarcinoma (PA) in the painless CP patients was also recorded. A random effects model was used to determine pooled prevalence estimates with 95% confidence intervals (95% CI).

Results: Among the 5057 studies identified and screened, 42 full-text articles were included in the final analysis. There were a total of 14,277 patients with CP among whom 1569 had painless CP. The pooled prevalence of painless CP was 12% (95% CI 10-15%). Among a subset of studies that reported on calcifications (n = 11), DM (n = 12), EPI (n = 8) and history of RAP (n = 14), the pooled prevalence estimates were 96% (95% CI 73-100%), 51% (95% CI 32-70%), and 47% (95% CI 15-81%), respectively. Alcohol, idiopathic/genetic and other etiologies were attributed to be the cause of painless CP in 32.4%, 56.9% and 8.9% patients, respectively.

Conclusion: Approximately one in ten patients with CP have primary painless disease with the majority being attributable to an idiopathic/genetic etiology. Further research is needed to determine the optimal management of these patients.
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http://dx.doi.org/10.1016/j.pan.2021.11.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8785146PMC
January 2022

Early infection is an independent risk factor for increased mortality in patients with culture-confirmed infected pancreatic necrosis.

Pancreatology 2022 Jan 9;22(1):67-73. Epub 2021 Nov 9.

Institute for Translational Medicine, Medical School, University of Pecs, Pecs, Hungary.

Background: Mortality in infected pancreatic necrosis (IPN) is dynamic over the course of the disease, with type and timing of interventions as well as persistent organ failure being key determinants. The timing of infection onset and how it pertains to mortality is not well defined.

Objectives: To determine the association between mortality and the development of early IPN.

Methods: International multicenter retrospective cohort study of patients with IPN, confirmed by a positive microbial culture from (peri) pancreatic collections. The association between timing of infection onset, timing of interventions and mortality were assessed using Cox regression analyses.

Results: A total of 743 patients from 19 centers across 3 continents with culture-confirmed IPN from 2000 to 2016 were evaluated, mortality rate was 20.9% (155/734). Early infection was associated with a higher mortality, when early infection occurred within the first 4 weeks from presentation with acute pancreatitis. After adjusting for comorbidity, advanced age, organ failure, enteral nutrition and parenteral nutrition, early infection (≤4 weeks) and early open surgery (≤4 weeks) were associated with increased mortality [HR: 2.45 (95% CI: 1.63-3.67), p < 0.001 and HR: 4.88 (95% CI: 1.70-13.98), p = 0.003, respectively]. There was no association between late open surgery, early or late minimally invasive surgery, early or late percutaneous drainage with mortality (p > 0.05).

Conclusion: Early infection was associated with increased mortality, independent of interventions. Early surgery remains a strong predictor of excess mortality.
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http://dx.doi.org/10.1016/j.pan.2021.11.003DOI Listing
January 2022

Overlap and cumulative effects of pancreatic duct obstruction, abnormal pain processing and psychological distress on patient-reported outcomes in chronic pancreatitis.

Gut 2021 Oct 21. Epub 2021 Oct 21.

Centre for Pancreatic Diseases, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.

Objective: Several factors have been suggested to mediate pain in patients with chronic pancreatitis. However, it is unknown whether these factors are overlapping and if they have cumulative effects on patient-reported outcomes (PROs).

Design: We performed a multicentre cross-sectional study of 201 prospectively enrolled subjects with definitive chronic pancreatitis. All subjects underwent evaluation for pancreatic duct obstruction, abnormalities in pain processing using quantitative sensory testing, and screening for psychological distress (anxiety, depression and pain catastrophising) based on validated questionnaires. Abnormality was defined by normal reference values. PROs included pain symptom severity (Brief Pain Inventory short form) and quality of life (EORTC-QLQ-C30 questionnaire). Associations between pain-related factors and PROs were investigated by linear trend analyses, multiple regression models and mediation analyses.

Results: Clinical evaluation suggestive of pancreatic duct obstruction was observed in 29%, abnormal pain processing in 23%, anxiety in 47%, depression in 39% and pain catastrophising in 28%; each of these factors was associated with severity of at least one PRO. Two or more factors were present in 51% of subjects. With an increasing number of factors, there was an increase in pain severity scores (p<0.001) and pain interference scores (p<0.001), and a reduction in quality of life (p<0.001). All factors had independent and direct effects on PROs, with the strongest effect size observed for psychological distress.

Conclusion: Pain-related factors in chronic pancreatitis are often present in an overlapping manner and have a cumulative detrimental effect on PROs. These findings support a multidisciplinary strategy for pain management.

Trial Registration Number: The study was registered with ClinicalTrials.gov (NCT03434392).
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http://dx.doi.org/10.1136/gutjnl-2021-325855DOI Listing
October 2021

Impact of genetic testing and smoking on the distribution of risk factors in patients with recurrent acute and chronic pancreatitis.

Scand J Gastroenterol 2022 Jan 18;57(1):91-98. Epub 2021 Oct 18.

Pancreatitis Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA.

Objective: The aim of the present study is to assess the impact of smoking dose and duration on the distribution of risk factor(s) in patients with RAP and CP, and the impact of genetic testing on the distribution of risk factor(s) in patients with idiopathic RAP and CP.

Methods: All adult patients with RAP and CP referred to a multidisciplinary pancreatitis clinic between 2010 and 2017 were evaluated. Risk factors included alcohol and smoking, hypertriglyceridemia, biliary, and other etiologies. Genetic testing was only pursued in patients with idiopathic RAP or CP.

Results: Among the 1770 patients evaluated, 167 had RAP and 303 had CP. After genetic testing and smoking, the most common risk factors for RAP and CP were pathogenic variant(s) (23%) and the combination of alcohol and smoking (23%), respectively. Genetic testing and smoking assessment decreased the proportion of patients with alcoholic RAP from 17% to 5%, alcoholic CP from 33% to 10%, idiopathic RAP from 49% to 12%, and idiopathic CP from 54% to 14%. Pathogenic CFTR variants were the most common variant in patients with RAP (51%) and CP (43%). Among the 68 patients with pancreas divisum, other risk factor(s) were identified in 72%.

Conclusion: Genetic testing and a detailed assessment of smoking dose and duration reduce the proportion of patients with alcoholic and idiopathic pancreatitis. Other risk factor(s) for pancreatitis are found in the majority of patients with pancreas divisum further questioning its role as an independent risk factor.1. What is the current knowledge?Approximately 30% of patients with pancreatitis have no clear risk factor(s) and are categorized as having an idiopathic etiology.Pathogenic variant(s) as well as smoking dose and duration are well-established risk factors for recurrent acute and chronic pancreatitis but are not widely recognized or incorporated into clinical practice.2. What is new here?Genetic testing and a detailed assessment of smoking dose and duration reduced the proportion of patients with alcoholic and idiopathic acute recurrent and chronic pancreatitis.Approximately three-fourths of patients with pancreas divisum have a risk factor for pancreatitis.
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http://dx.doi.org/10.1080/00365521.2021.1984573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9278560PMC
January 2022

The relationship between pre-existing diabetes mellitus and the severity of acute pancreatitis: Report from a large international registry.

Pancreatology 2022 Jan 10;22(1):85-91. Epub 2021 Oct 10.

Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Background/objectives: The relationship between pre-existing diabetes mellitus (DM) and acute pancreatitis (AP) severity has not been established. We assessed the impact of pre-existing DM on AP severity in an international, prospectively ascertained registry.

Methods: APPRENTICE registry prospectively enrolled 1543 AP patients from 22 centers across 4 continents (8 US, 6 Europe, 5 Latin America, 3 India) between 2015 and 2018, and collected detailed clinical information. Pre-existing DM was defined a diagnosis of DM prior to AP admission. The primary outcome was AP severity defined by the Revised Atlanta Classification (RAC). Secondary outcomes were development of systemic inflammatory response syndrome (SIRS) or intensive care unit (ICU) admission.

Results: Pre-existing DM was present in 270 (17.5%) AP patients, of whom 252 (93.3%) had type 2 DM. Patients with pre-existing DM were significantly (p < 0.05) older (55.8 ± 16 vs. 48.3 ± 18.7 years), more likely to be overweight (BMI 29.5 ± 7 vs. 27.2 ± 6.2), have hypertriglyceridemia as the etiology (15% vs. 2%) and prior AP (33 vs. 24%). Mild, moderate, and severe AP were noted in 66%, 23%, and 11% of patients, respectively. On multivariable analysis, pre-existing DM did not significantly impact AP severity assessed by the RAC (moderate-severe vs. mild AP, OR = 0.86, 95% CI 0.63-1.18; severe vs. mild-moderate AP, OR = 1.05, 95% CI, 0.67-1.63), development of SIRS, or the need for ICU admission. No interaction was noted between DM status and continent.

Conclusion: About one in 5 patients with AP have pre-existing DM. Once confounding risk factors are considered, pre-existing DM per se is not a risk factor for severe AP.
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http://dx.doi.org/10.1016/j.pan.2021.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8894899PMC
January 2022

Pancreatic Pain-Knowledge Gaps and Research Opportunities in Children and Adults: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop.

Pancreas 2021 08;50(7):906-915

Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine.

Abstract: A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to focus on research gaps and opportunities in pancreatic pain. The event was held on July 21, 2021, and structured into 4 sessions: (1) pathophysiology; (2) biomarkers, mediators, and pharmacology of pain; (3) pain assessment; and (4) pain treatment challenges and opportunities. The current state of knowledge was reviewed; many knowledge gaps and research needs were identified that require further investigation. Common themes included the need to better understand the underlying mechanisms of pain in pancreatic diseases, the relationship of visceral neural pathways and central pain centers, the role of behavioral factors and disorders on the perception of pain, and differences in pain perception and processes in children when compared with adults. In addition, the role of genetic risk factors for pain and the mechanisms and role of placebos in pain treatment were discussed. Methods of pain assessment including quantitative sensory testing were examined, as well as the process of central sensitization of pain. Finally, newer approaches to pain management including cognitive behavioral therapy, nerve stimulation, experimental (nonopioid) drugs, and cannabinoid compounds were covered.
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http://dx.doi.org/10.1097/MPA.0000000000001899DOI Listing
August 2021

Surgical approach and short-term outcomes in adults and children undergoing total pancreatectomy with islet autotransplantation: A report from the Prospective Observational Study of TPIAT.

Pancreatology 2022 Jan 29;22(1):1-8. Epub 2021 Sep 29.

Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA; Department of Surgery, University of Minnesota Medical School, Minneapolis, MN, USA.

Background: Total pancreatectomy with islet autotransplantation (TPIAT) is a viable option for treating debilitating recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) in adults and children. No data is currently available regarding variation in approach to operation.

Methods: We evaluated surgical techniques, islet isolation and infusion approaches, and outcomes and complications, comparing children (n = 84) with adults (n = 195) enrolled between January 2017 and April 2020 by 11 centers in the United States in the Prospective Observational Study of TPIAT (POST), which was launched in 2017 to collect standard history and outcomes data from patients undergoing TPIAT for RAP or CP.

Results: Children more commonly underwent splenectomy (100% versus 91%, p = 0.002), pylorus preservation (93% versus 67%; p < 0.0001), Roux-en-Y duodenojejunostomy reconstruction (92% versus 35%; p < 0.0001), and enteral feeding tube placement (93% versus 63%; p < 0.0001). Median islet equivalents/kg transplanted was higher in children (4577; IQR 2816-6517) than adults (2909; IQR 1555-4479; p < 0.0001), with COBE purification less common in children (4% versus 15%; p = 0.0068). Median length of hospital stay was higher in children (15 days; IQR 14-22 versus 11 days; IQR 8-14; p < 0.0001), but 30-day readmissions were lower in children (13% versus 26%, p = 0.018). Rate of portal vein thrombosis was significantly lower in children than in adults (2% versus 10%, p = 0.028). There were no mortalities in the first 90 days post-TPIAT.

Conclusions: Pancreatectomy techniques differ between children and adults, with islet yields higher in children. The rates of portal vein thrombosis and early readmission are lower in children.
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http://dx.doi.org/10.1016/j.pan.2021.09.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8748311PMC
January 2022

The Modified Pancreatitis Activity Scoring System Shows Distinct Trajectories in Acute Pancreatitis: An International Study.

Clin Gastroenterol Hepatol 2022 06 17;20(6):1334-1342.e4. Epub 2021 Sep 17.

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

Background & Aims: The aims of this study were to: (1) assess the performance of the Pancreatitis Activity Scoring System (PASS) in a large intercontinental cohort of patients with acute pancreatitis (AP); and (2) investigate whether a modified PASS (mPASS) yields a similar predictive accuracy and produces distinct early trajectories between severity subgroups.

Methods: Data was prospectively collected through the Acute Pancreatitis Patient Registry to Examine Novel Therapies In Clinical Experience (APPRENTICE) consortium (2015-2018) involving 22 centers from 4 continents. AP severity was categorized per the revised Atlanta classification. PASS trajectories were compared between the three severity groups using the generalized estimating equations model. Four mPASS models were generated by modifying the morphine equivalent dose (MED), and their trajectories were compared.

Results: A total of 1393 subjects were enrolled (median age, 49 years; 51% males). The study cohort included 950 mild (68.2%), 315 (22.6%) moderately severe, and 128 (9.2%) severe AP. Mild cases had the lowest PASS at each study time point (all P < .001). A subset of patients with outlier admission PASS values was identified. In the outlier group, 70% of the PASS variation was attributed to the MED, and 66% of these patients were from the United States centers. Among the 4 modified models, the mPASS-1 (excluding MED from PASS) demonstrated high performance in predicting severe AP with an area under the receiver operating characteristic curve of 0.88 (vs area under the receiver operating characteristic of 0.83 in conventional PASS) and produced distinct trajectories with distinct slopes between severity subgroups (all P < .001).

Conclusion: We propose a modified model by removing the MED component, which is easier to calculate, predicts accurately severe AP, and maintains significantly distinct early trajectories.
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http://dx.doi.org/10.1016/j.cgh.2021.09.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9060638PMC
June 2022

Psychiatric Disease Susceptibility and Pain in Chronic Pancreatitis: Association or Causation?

Am J Gastroenterol 2021 10;116(10):2026-2028

Pancreatitis Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.

Abstract: Pain perception in chronic pancreatitis (CP) is governed by the transmission of nociceptive inputs into the pain processing centers of the brain. These regions of the brain overlap with those that regulate and process emotions and cognition. Disorders in these regions also result in psychiatric conditions such as depression, anxiety, and posttraumatic stress disorder. The present study by Dunbar et al. evaluated 24 single nucleotide polymorphisms associated with anxiety and/or posttraumatic stress disorder and found correlations with constant and severe pain phenotypes in CP patients from a large cross-sectional cohort study. Although causation cannot be proven, the findings suggest that there may be a role for neuromodulator drugs for the treatment of pain in CP based on individual genetic susceptibility.
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http://dx.doi.org/10.14309/ajg.0000000000001491DOI Listing
October 2021

The Association of Smoking and Alcohol Abuse on Anxiety and Depression in Patients With Recurrent Acute or Chronic Pancreatitis Undergoing Total Pancreatectomy and Islet Autotransplantation: A Report From the Prospective Observational Study of TPIAT Cohort.

Pancreas 2021 07;50(6):852-858

Division of Pediatric Endocrinology, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN.

Objectives: Smoking and alcohol use are risk factors for acute and chronic pancreatitis, and their role on anxiety, depression, and opioid use in patients who undergo total pancreatectomy and islet autotransplantation (TPIAT) is unknown.

Methods: We included adults enrolled in the Prospective Observational Study of TPIAT (POST). Measured variables included smoking (never, former, current) and alcohol abuse or dependency history (yes vs no). Using univariable and multivariable analyses, we investigated the association of smoking and alcohol dependency history with anxiety and depression, opioid use, and postsurgical outcomes.

Results: Of 195 adults studied, 25 were current smokers and 77 former smokers, whereas 18 had a history of alcohol dependency (of whom 10 were current smokers). A diagnosis of anxiety was associated with current smoking (P = 0.005), and depression was associated with history of alcohol abuse/dependency (P = 0.0001). However, active symptoms of anxiety and depression at the time of TPIAT were not associated with smoking or alcohol status. Opioid use in the past 14 days was associated with being a former smoker (P = 0.005).

Conclusions: Active smoking and alcohol abuse history were associated with a diagnosis of anxiety and depression, respectively; however, at the time of TPIAT, symptom scores suggested that they were being addressed.
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http://dx.doi.org/10.1097/MPA.0000000000001850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373657PMC
July 2021

Non-steroidal anti-inflammatory drugs, intravenous fluids, pancreatic stents, or their combinations for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a systematic review and network meta-analysis.

Lancet Gastroenterol Hepatol 2021 09 30;6(9):733-742. Epub 2021 Jun 30.

Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs), intravenous fluid, pancreatic stents, or combinations of these have been evaluated in randomised controlled trials (RCTs) for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, but the comparative efficacy of these treatments remains unclear. Our aim was to do an exploratory network meta-analysis of previous RCTs to systematically compare the direct and indirect evidence and rank NSAIDs, intravenous fluids, pancreatic stents, or combinations of these to determine the most efficacious method of prophylaxis for post-ERCP pancreatitis.

Methods: We searched PubMed, Embase, and the Cochrane Central Register from inception to Nov 15, 2020, for full-text RCTs that evaluated the efficacy of NSAIDs, pancreatic stents, intravenous fluids, or combinations of these for post-ERCP pancreatitis prevention in adult (aged ≥18 years) patients undergoing ERCP. Summary data from intention-to-treat analyses were extracted from published reports. We analysed incidence of post-ERCP pancreatitis across studies using network meta-analysis under the frequentist framework, obtaining pairwise odds ratios (ORs) and 95% CIs. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system for the confidence rating. This study is registered with PROSPERO, CRD42020172606.

Findings: We identified 1503 studies, of which 55 RCTs evaluating 20 interventions in 17 062 patients were included in the network meta-analysis. The mean incidence of post-ERCP pancreatitis in the placebo or active control group was 12·2% (95% CI 11·4-13·0). Normal saline plus rectal indometacin (OR 0·02, 95% CI 0·00-0·40), intramuscular diclofenac 75 mg (0·24, 0·09-0·69), intravenous high-volume Ringer's lactate plus rectal diclofenac 100 mg (0·30, 0·16-0·55), intravenous high-volume Ringer's lactate (0·31, 0·12-0·78), 5-7 Fr pancreatic stents (0·35, 0·26-0·48), rectal diclofenac 100 mg (0·36, 0·25-0·52), 3 Fr pancreatic stents (0·47, 0·26-0·87), and rectal indometacin 100 mg (0·60, 0·50-0·73) were all more efficacious than placebo for preventing post-ERCP pancreatitis in pairwise comparisons. 5-7 Fr pancreatic stents (0·59, 0·41-0·84), intravenous high-volume Ringer's lactate plus rectal diclofenac 100 mg (0·49, 0·26-0·94), intravenous standard-volume normal saline plus rectal indometacin 100 mg (0·04, 0·00-0·66), and rectal diclofenac 100 mg (0·59, 0·40-0·89) were more efficacious than rectal indometacin 100 mg. The GRADE confidence rating was low to moderate for 98·3% of the pairwise comparisons.

Interpretation: This systematic review and network meta-analysis summarises the available literature on NSAIDs, pancreatic stents, intravenous fluids, or combinations of these for prophylaxis of post-ERCP pancreatitis. Rectal diclofenac 100 mg is the best performing rectal NSAID in this network meta-analysis. Combinations of prophylaxis might be more effective, but there is little evidence. These findings help to establish prophylaxis of post-ERCP pancreatitis for future research and practice, and could reduce costs and increase adoption of prophylaxis.

Funding: None.
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http://dx.doi.org/10.1016/S2468-1253(21)00170-9DOI Listing
September 2021

Lifetime smoking history and cohort-based smoking prevalence in chronic pancreatitis.

Pancreatology 2021 May 29. Epub 2021 May 29.

Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Background/objective: Smoking prevalence in patients with chronic pancreatitis [CP] is high. We aimed to understand lifetime history of smoking and cohort trends in CP patients to inform effective strategies for smoking cessation.

Method: Data on 317 CP patients from the North American Pancreatitis Study 2 [NAPS2] Continuation and Validation Study and the NAPS2 Ancillary Study were analyzed. Smoking history was assessed for each phase of life from the onset of smoking to study enrollment. Data on second-hand smoke and drinking history were also collected. We compared demographic factors, drinking history, pain level and pancreas morphology by smoking status at age 25 (non-smoking, <1 pack per day [PPD], ≥1 PPD). We compared smoking prevalence by birth cohorts: 1930-1949, 1950-1969, 1970-1989.

Result: Fifty-one percent of CP patients reported smoking at the time of enrollment. Those who smoked ≥1 PPD at age 25 smoked a cumulative total of 30.3 pack-years of cigarettes over a lifetime. Smoking at age 25 was associated with greater lifetime drinking and greater exposure to second-hand smoke at home and at workplace. Pancreatic atrophy and pseudocysts were more common among smokers. Pancreatic pain was more severe among smokers, and 12-13% of smokers reported smoking to alleviate pain. Male CP patients born in 1950-1969 reported the highest peak prevalence of smoking, and female CP patients born in 1970-1989 reported highest peak prevalence of smoking.

Conclusion: CP patients exhibit intense and sustained smoking behavior once established in the 20s. Regardless, cohort analyses demonstrate that the behaviors could potentially be altered by policy changes.
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http://dx.doi.org/10.1016/j.pan.2021.05.302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8628024PMC
May 2021

Pancreatic QST Differentiates Chronic Pancreatitis Patients into Distinct Pain Phenotypes Independent of Psychiatric Comorbidities.

Clin Gastroenterol Hepatol 2022 01 22;20(1):153-161.e2. Epub 2020 Oct 22.

Centre for Pancreatic Diseases and Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.

Background & Aims: Quantitative sensory testing (QST) has been previously used to study pain in chronic pancreatitis (CP) but included methods that are not suitable for clinical purposes. The aims of this study were to determine if pancreatic QST (P-QST) can differentiate patients into distinct pain phenotypes and to determine the association of these with their clinical pain and psychiatric comorbidities.

Methods: A multicenter cross-sectional study was conducted where patients completed validated questionnaires assessing quality of life (QoL), depression and anxiety scores as well as clinical pain symptoms followed by P-QST which included a cold pressor test, repetitive pinprick stimuli and pressure stimulation of the upper abdominal (T10) and control dermatomes. P-QST categorized patients into pain phenotypes based on a previously established nomogram. QoL, clinical pain and psychiatric assessment scores were compared across these groups.

Results: A total of 179 patients were enrolled with a mean age of 54.1±13.6 years among whom 59% were males and 42% had an alcoholic etiology. P-QST showed no hyperalgesia in 91 (51%), segmental hyperalgesia in 50 (28%) and widespread hyperalgesia in 38 (21%) patients. Patients with widespread hyperalgesia had significantly higher pain intensity scores (P = .03) and rates of constant pain (P = .002) as well as decreased QoL (P < .001) and physical functioning (P =.03) in comparison with the other two pain phenotypes. In contrast, psychiatric comorbidities were similar across all groups.

Conclusions: P-QST may serve as a novel unbiased pain assessment tool in CP as it categorizes patients into distinct pain phenotypes independent of their psychiatric comorbidities.
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http://dx.doi.org/10.1016/j.cgh.2020.10.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8629107PMC
January 2022

Development of the Comprehensive Pain Assessment Tool Short Form for Chronic Pancreatitis: Validity and Reliability Testing.

Clin Gastroenterol Hepatol 2022 04 2;20(4):e770-e783. Epub 2021 Jun 2.

Centre for Pancreatic Diseases & Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. Electronic address:

Background & Aims: Pain is the foremost complication to chronic pancreatitis (CP), but no validated questionnaires for assessment exist. The COMPAT questionnaire includes all relevant pain dimensions in CP, but a short form is needed to make it usable in clinical practice.

Methods: The full COMPAT questionnaire was completed by 91 patients and systematically reduced to 6 questions. Pain severity and analgesic use were merged, leaving 5 pain dimensions. The pain dimension ratings were normalized to a 0-100 scale, and the weighted total score was calculated, where 3 dimensions were weighted double. Reliability of the short form was tested in a test-retest study in 76 patients, and concurrent validity tested against the Brief Pain Inventory and Izbicki pain questionnaire. Convergent validity was verified using confirmatory factor analysis, and criterion validity tested against quality-of-life and hospitalization rates.

Results: The COMPAT-SF questionnaire consisted of the following pain dimensions: a) pain severity, b) pain pattern, c) factors provoking pain, d) widespread pain, and e) a qualitative pain-describing dimension. Quality of life correlated with the total score and all pain dimensions (P <.05). The total score, pain severity, pain pattern, and factors provoking pain were correlated with hospitalization rates (P <.05). The total score correlated with the Izbicki and Brief Pain Inventory scores (P <.0001). The reliability of the questionnaire in patients in a stable phase was good with an interclass correlation coefficient of 0.89.

Conclusion: The COMPAT-SF questionnaire includes the most relevant aspects of pain in CP and is a feasible, reliable, and valid pain assessment instrument recommended to be used in future trials.
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http://dx.doi.org/10.1016/j.cgh.2021.05.055DOI Listing
April 2022

Autoimmune Pancreatitis: A Critical Analysis of the Surgical Experience in an Era of Modern Diagnostics.

Pancreas 2021 04;50(4):556-563

From the Department of Surgery.

Objective: The aim of this study was to critically analyze the surgical experience of managing autoimmune pancreatitis (AIP) in an era of modern diagnostics and compare these patients with those who were managed conservatively.

Methods: Two prospectively maintained databases were used to retrospectively identify patients with AIP who were either managed conservatively or underwent pancreatectomy.

Results: Eighty-eight patients were included in the study, of which 56 (63.6%) underwent resection and 32 (36.4%) were managed conservatively. Patients who underwent resection were more likely to present with jaundice (64.3% vs 18.1%, P < 0.001) and weight loss (53.6% vs 15.6%, P = 0.005). The cohort who underwent resection had a significantly higher median carbohydrate antigen 19-9 (40.0 vs 18.6 U/mL, P = 0.034) and was less likely to have elevated immunoglobulin G4 (26.1% vs 50.0%, P < 0.001). The most frequent initial diagnosis in the cohort who underwent resection was ductal adenocarcinoma (82.1%). Nine patients (28.1%) in the conservatively managed cohort experienced AIP relapse compared with 6 patients (10.7%) in the cohort who underwent resection.

Conclusions: The most frequent reason for surgical resection of AIP is concern for malignancy. Carbohydrate antigen 19-9 elevations were more common than immunoglobulin G4 in our cohort, suggesting that this laboratory profile is suboptimal for this population.
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http://dx.doi.org/10.1097/MPA.0000000000001812DOI Listing
April 2021

Stress Hyperglycemia Is Independently Associated with Persistent Organ Failure in Acute Pancreatitis.

Dig Dis Sci 2022 05 3;67(5):1879-1889. Epub 2021 May 3.

Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, No. 37 Wannan Guoxue Alley, Chengdu, 610041, Sichuan Province, China.

Background/aims: Stress hyperglycemia is common in critical illness but it has not been clearly studied in patients with acute pancreatitis (AP). This study aimed to investigate the specific blood glucose (BG) level that defines stress hyperglycemia and to determine the impact of stress hyperglycemia on clinical outcomes in AP patients.

Methods: AP patients admitted ≤ 48 h after abdominal pain onset were retrospectively analyzed. Patients were stratified by pre-existing diabetes and stress hyperglycemia was defined using stratified BG levels for non-diabetes and diabetes with clinical outcomes compared.

Results: There were 967 non-diabetic and 114 diabetic (10.5%) patients met the inclusion criteria and the clinical outcomes between these two groups were not significantly different. In non-diabetes, the cut-off BG level of ≥ 180 mg/dl was selected to define stress hyperglycemia with an 8.8-fold higher odds ratio for persistent organ failure (POF) (95% CI 5.4-14.3; P < 0.001). For diabetes, ≥ 300 mg/dl was selected with a 7.5-fold higher odds ratio for POF (95% CI 1.7-34.3; P = 0.009). In multivariable logistic regression, stress hyperglycemia was independently associated with POF, acute necrotic collection, major infection and mortality. The combination of BG and systemic inflammatory response syndrome (SIRS) score in predicting POF was better than SIRS or Glasgow score alone.

Conclusions: This study identifies a cut-off BG level of ≥ 180 mg/dl and ≥ 300 mg/dl was optimal to define stress hyperglycemia for non-diabetic and diabetic AP patients, respectively. There was a significant relationship between stress hyperglycemia and adverse clinical outcomes.
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http://dx.doi.org/10.1007/s10620-021-06982-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9142444PMC
May 2022

Circulating miRNA in Patients Undergoing Total Pancreatectomy and Islet Autotransplantation.

Cell Transplant 2021 Jan-Dec;30:963689721999330

University of Minnesota Medical School, Minneapolis, MN, USA.

Circulating microRNAs (miRNAs) can be biomarkers for diagnosis and progression of several pathophysiological conditions. In a cohort undergoing total pancreatectomy with islet autotransplantation (TPIAT) from the multicenter Prospective Observational Study of TPIAT (POST), we investigated associations between a panel of circulating miRNAs (hsa-miR-375, hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-216a-5p, hsa-miR-320d, hsa-miR-200c, hsa-miR-125b, hsa-miR-7-5p, hsa-miR-221-3p, hsa-miR-122-5p) and patient, disease and islet-isolation characteristics. Plasma samples ( = 139) were collected before TPIAT and miRNA levels were measured by RTPCR. Disease duration, prior surgery, and pre-surgical diabetes were not associated with circulating miRNAs. Levels of hsa-miR-29b-3p ( = 0.03), hsa-miR-148a-3p ( = 0.04) and hsa-miR-221-3p ( = 0.01) were lower in those with genetic risk factors. Levels of hsa-miR-148a-3p ( = 0.04) and hsa-miR-7-5p ( = 0.04) were elevated in toxic/metabolic disease. Participants with exocrine insufficiency had lower hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-320d, hsa-miR-221-3p ( < 0.01) and hsa-miR-375, hsa-miR-200c-3p, and hsa-miR-125b-5p ( < 0.05). Four miRNAs were associated with fasting C-peptide before TPIAT (hsa-miR-29b-3p, = 0.18; hsa-miR-148a-3p, = 0.21; hsa-miR-320d, = 0.19; and hsa-miR-221-3p, = 0.21; all < 0.05), while hsa-miR-29b-3p was inversely associated with post-isolation islet equivalents/kg and islet number/kg ( = -0.20, = 0.02). Also, hsa-miR-200c ( = 0.18, = 0.03) and hsa-miR-221-3p ( = 0.19, = 0.03) were associated with islet graft tissue volume. Further investigation is needed to determine the predictive potential of these miRNAs for assessing islet autotransplant outcomes.
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http://dx.doi.org/10.1177/0963689721999330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718159PMC
December 2021

Mortality in acute pancreatitis with persistent organ failure is determined by the number, type, and sequence of organ systems affected.

United European Gastroenterol J 2021 03;9(2):139-149

Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Background: Persistent organ failure (POF) is the strongest determinant of mortality in acute pancreatitis (AP). There is a paucity of data regarding the impact of different POF attributes on mortality and the role of different characteristics of systemic inflammatory response syndrome (SIRS) in the risk of developing POF.

Objective: We aimed to assess the association of POF dynamic features with mortality and SIRS characteristics with POF.

Methods: We studied 1544 AP subjects prospectively enrolled at 22 international centers (APPRENTICE consortium). First, we estimated the association of onset, duration, and maximal score of SIRS with POF. Then, we evaluated the risk of mortality based on POF onset, duration, number, type, and sequence of organs affected. Analyses were adjusted for potential confounders.

Results: 58% had SIRS, 11% developed POF, and 2.5% died. Early SIRS, persistent SIRS, and maximal SIRS score ≥ 3 were independently associated with higher risk of POF (p < 0.05). Mortality risk in POF was higher with two (33%, odds ratio [OR] = 10.8, 3.3-34.9) and three (48%, OR = 20.2, 5.9-68.6) organs failing, in comparison to single POF (4%). In subjects with multiple POF, mortality was higher when the cardiovascular and respiratory systems failed first or concurrently as compared to when the renal system failed first or concurrently with other organ (p < 0.05). In multivariate regression model, the number and sequence of organs affected in POF were associated with mortality (p < 0.05). Onset and duration of POF had no impact mortality.

Conclusion: In AP patients with POF, the risk of mortality is influenced by the number, type, and sequence of organs affected. These results are useful for future revisions of AP severity classification systems.
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http://dx.doi.org/10.1002/ueg2.12057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259236PMC
March 2021

Morphologic Severity of Acute Pancreatitis on Imaging Is Independently Associated with Opioid Dose Requirements in Hospitalized Patients.

Dig Dis Sci 2022 04 9;67(4):1362-1370. Epub 2021 Apr 9.

Division of Gastroenterology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA.

Background: Prior studies have evaluated clinical characteristics associated with opioid dose requirements in hospitalized patients with acute pancreatitis (AP) but did not incorporate morphologic findings on CT imaging.

Aims: We sought to determine whether morphologic severity on imaging is independently associated with opioid dose requirements in AP.

Methods: Adult inpatients with a diagnosis of AP from 2006 to 2017 were reviewed. The highest modified CT severity index (MCTSI) score and the daily oral morphine equivalent (OME) for each patient over the first 7 days of hospitalization were used to grade the morphologic severity of AP and calculate mean OME per day(s) of treatment (MOME), respectively. Multiple regression analysis was used to evaluate the association of MOME with MCSTI.

Results: There were 249 patients with AP, of whom 196 underwent contrast-enhanced CT. The mean age was 46 ± 13.6 years, 57.9% were male, and 60% were black. The mean MOME for the patient cohort was 60 ± 52.8 mg/day. MCTSI (β = 3.5 [95% CI 0.3, 6.7], p = 0.03), early hemoconcentration (β = 21 [95% CI 4.6, 39], p = 0.01) and first episode of AP (β =  - 17 [95% CI - 32, - 2.7], p = 0.027) were independently associated with MOME. Among the 19 patients undergoing ≥ 2 CT scans, no significant differences in MOME were seen between those whose MCTSI score increased (n = 12) versus decreased/remained the same (n = 7).

Conclusion: The morphologic severity of AP positively correlated with opioid dose requirements. No difference in opioid dose requirements were seen between those who did versus those who did not experience changes in their morphologic severity.
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http://dx.doi.org/10.1007/s10620-021-06944-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225947PMC
April 2022

Simvastatin in the Prevention of Recurrent Pancreatitis: Design and Rationale of a Multicenter Triple-Blind Randomized Controlled Trial, the SIMBA Trial.

Front Med (Lausanne) 2020 10;7:494. Epub 2021 Feb 10.

Pancreatic Unit, Department of Gastroenterology, Alicante University General Hospital, Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain.

One in every four patients with a first episode of non-gallstone-related acute pancreatitis (AP) develops recurrent disease. Recurrent episodes of AP or acute flares of chronic pancreatitis (CP) are associated with decreased quality of life and progression of the disease. Besides removing the etiology of pancreatitis (which sometimes is not possible), there are no effective measures to prevent recurrence. Meta-analyses of randomized controlled trials, as well as epidemiological and cohort studies, suggest that statins may be protective against the development of index AP. The SIMBA study is a triple-blind randomized placebo-controlled, parallel-group multicenter trial. Patients with recurrent AP or with acute flares of CP (at least two episodes in the last 12 months) will be randomized to receive simvastatin 40 mg daily or placebo. During a 3-year study period, 144 patients (72 per arm of treatment) from 26 centers will be enrolled. The patients will receive the study treatment for 1 year. The primary aim is to compare the recurrence of AP or acute flares in CP. Secondary endpoints include the incidence of new-onset diabetes mellitus, new-onset exocrine pancreatic insufficiency (EPI), new-onset imaging signs of CP, frequency of all-cause hospital admissions, severity of AP, adherence to treatment, and frequency of adverse events. The SIMBA trial will ascertain whether simvastatin, a safe, widely used and inexpensive drug, can change the natural course of recurrent pancreatitis. : ClinicalTrials.gov Identifier: NCT04021498.
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http://dx.doi.org/10.3389/fmed.2020.00494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902790PMC
February 2021

Dynamic changes in the pancreatitis activity scoring system during hospital course in a multicenter, prospective cohort.

J Gastroenterol Hepatol 2021 Sep 18;36(9):2416-2423. Epub 2021 Feb 18.

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

Background And Aim: The primary aim was to validate the Pancreatitis Activity Scoring System (PASS) in a multicenter prospectively ascertained acute pancreatitis (AP) cohort. Second, we investigated the association of early PASS trajectories with disease severity and length of hospital stay (LOS).

Methods: Data were prospectively collected through the APPRENTICE consortium (2015-2018). AP severity was categorized based on revised Atlanta classification. Delta PASS (ΔPASS) was calculated by subtracting activity score from baseline value. PASS trajectories were compared between severity subsets. Subsequently, the cohort was subdivided into three LOS subgroups as short (S-LOS): 2-3 days; intermediate (I-LOS): 3-7 days; and long (L-LOS): ≥7 days. The generalized estimating equations model was implemented to compare PASS trajectories.

Results: There were 434 subjects analyzed including 322 (74%) mild, 86 (20%) moderately severe, and 26 (6%) severe AP. Severe AP subjects had the highest activity levels and the slowest rate of decline in activity (P = 0.039). Focusing on mild AP, L-LOS subjects (34%) had 28 points per day slower decline; whereas, S-LOS group (13%) showed 34 points per day sharper decrease compared with I-LOS (53%; P < 0.001). We noticed an outlier subset with a median admission-PASS of 466 compared with 140 in the rest. Morphine equivalent dose constituted 80% of the total PASS in the outliers (median morphine equivalent dose score = 392), compared with only 25% in normal-range subjects (score = 33, P value < 0.001).

Conclusions: This study highlighted that PASS can quantify AP activity. Significant differences in PASS trajectories were found both in revised Atlanta classification severity and LOS groups, which can be harnessed in AP monitoring/management (ClincialTrials.gov number, NCT03075618).
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http://dx.doi.org/10.1111/jgh.15430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9058811PMC
September 2021

Post-Acute Pancreatitis Pancreatic Exocrine Insufficiency: Rationale and Methodology of a Prospective, Observational, Multicenter Cohort Study.

Pancreas 2021 02;50(2):147-152

Division of Gastroenterology, Hepatology, & Nutrition, Department of Internal Medicine, Ohio State University, Wexner Medical Center, Columbus, OH.

Objectives: We describe the methodology of Post-Acute Pancreatitis Pancreatic Exocrine Insufficiency (PAPPEI), a prospective, observational, multicenter cohort study. The objectives of PAPPEI are to estimate the incidence rate of post-acute pancreatitis (AP) pancreatic exocrine insufficiency (PEI), define factors that determine the development of post-AP PEI, and evaluate the impact of post-AP PEI on nutritional status and quality of life.

Methods: Enrollment started in June 2017 in 3 expert academic centers in the United States. Data were collected during hospitalization (baseline) at 3 and 12 months after enrollment. Fecal elastase-1 was used to assess PEI. Study questionnaires are completed by patient interview and review of electronic medical records. Blood is obtained to evaluate vitamin deficiencies and nutritional markers.

Results: As of August 2020, 77 subjects have completed the baseline evaluation. The median age was 58 years (interquartile range, 39-67 years), 38% were male, and 90% were white. The etiology of AP was biliary in 39 subjects (51%), and 51 subjects (66%) had mild AP. Three- and 12-month follow-up data have been collected in 29 and 13 subjects, respectively.

Conclusion: The PAPPEI study aims to expand our understanding of post-AP PEI incidence, including its impact on nutritional status and quality of life.
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http://dx.doi.org/10.1097/MPA.0000000000001743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9194920PMC
February 2021
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