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Current treatments for chronic pancreatitis focus on symptom management and therapeutics targeting disease reversal are lacking. Given the role of the cyclooxygenase-2 (COX-2) enzyme in producing prostaglandin EThis pilot two-center randomized controlled trial seeks to examine 32 subjects with chronic pancreatitis who have no contraindications to indomethacin. Subjects will be randomized to either oral indomethacin 50 mg twice a day or placebo twice a day for a total of 28 days. Baseline (pre-treatment) assessment of pain and quality of life will be performed using the Brief Pain Inventory and the PROMIS-10 questionnaires, respectively. Biological specimens including blood, urine, and saliva will be collected at pre-treatment and post-treatment(day 28). Endoscopic pancreatic function testing with concomitant pancreatic fluid collection will also be performed pre- and post-treatment to assess the change in pancreatic fluid PGEThis study will elucidate the effect of oral indomethacin on PGE

OBJECTIVE Diabetes that arises from chronic pancreatitis (CP) is associated with increased morbidity and mortality. Methods to predict which patients with CP are at greatest risk for diabetes are urgently needed. We aimed to examine independent risk factors for diabetes in a large cohort of patients with CP. RESEARCH DESIGN AND METHODS This cross-sectional study comprised 645 individuals with CP enrolled in the PROCEED study, of whom 276 had diabetes. We conducted univariable and multivariable regression analyses of potential risk factors for diabetes. Model performance was assessed by area under the receiver operating characteristic curve (AUROC) analysis, and accuracy was evaluated by cross validation. Exploratory analyses were stratified according to the timing of development of diabetes relative to the diagnosis of pancreatitis. RESULTS Independent correlates of diabetes in CP included risk factors for type 2 diabetes (older age, overweight/obese status, male sex, non-White race, tobacco use) as well as pancreatic disease–related factors (history of acute pancreatitis complications, nonalcoholic etiology of CP, exocrine pancreatic dysfunction, pancreatic calcification, pancreatic atrophy) (AUROC 0.745). Type 2 diabetes risk factors were predominant for diabetes occurring before pancreatitis, and pancreatic disease–related factors were predominant for diabetes occurring after pancreatitis. CONCLUSIONS Multiple factors are associated with diabetes in CP, including canonical risk factors for type 2 diabetes and features associated with pancreatitis severity. This study lays the groundwork for the future development of models integrating clinical and nonclinical data to identify patients with CP at risk for diabetes and identifies modifiable risk factors (obesity, smoking) on which to focus for diabetes prevention.

Background & Aims Chronic pancreatitis (CP) is associated with osteopathy (osteoporosis or osteopenia). However, existing literature is mostly limited to retrospective or administrative studies that have not clearly defined the prevalence and risk factors. Our aim was to identify patient- and disease-related associations with osteopathy in a prospective cohort study of CP. Methods We studied 282 subjects with definitive CP enrolled in the PROCEED study who had a baseline dual-energy X-ray absorptiometry (DXA) scan. Osteopenia and osteoporosis were defined using the lowest T-scores. Clinical data were collected using standardized case report forms. Comparisons were performed with a multivariate logistic regression model with forward selection to identify risk factors for osteopathy. Results The majority of subjects had osteopathy on DXA scan (56.0%; 17.0% osteoporosis; 39.0% osteopenia). Subjects with osteopathy had a higher prevalence of traumatic (40.0% vs 26.4%; P = .02) and spontaneous fractures (3.9% vs 0; P = .04). On multivariate analysis, older age (odds ratio [OR], 1.29 per 5 years; 95% confidence interval [CI], 1.15–1.45), female sex (OR, 3.08; 95% CI, 1.75–5.43), white race (OR, 2.68; 95% CI, 1.20–6.01), and underweight body mass index category (OR, 7.40; 95% CI, 1.56–34.99) were associated with higher probability of osteopathy. There were no significant associations between osteopathy and other patient and disease-related features of CP. Conclusion In the largest study of patients with CP who underwent DXA screening, the majority had osteopathy. There are overlapping risk factors with osteopathy in the general population, but the high prevalence in men and younger women supports the need for future investigations into the mechanisms of bone loss in CP. ClinicalTrials.gov number, NCT03099850.

In industrialized countries, nutritional dermatoses are likely underdiagnosed and result in increased disease morbidity and utilization of hospital resources. These findings underscore the need for physicians to be able to correctly identify these deficiencies. Nutritional dermatoses may be split into micronutrient deficiencies and macronutrient deficiencies. This article is intended to serve as a supplement to a 2-part review of micronutrient deficiency dermatoses and highlights cutaneous findings in patients with protein-energy malnutrition and essential fatty acid deficiency. This article reviews the evaluation, cutaneous manifestations, and management of macronutrient deficiencies.

Recurrent acute pancreatitis and chronic pancreatitis represent high morbidity diseases, which are frequently associated with chronic abdominal pain, pancreatic insufficiencies, and reduced quality of life. Currently, there are no therapies to reverse or delay disease progression, and clinical trials are needed to investigate potential interventions that would address this important gap. This conference report provides details regarding information shared during a National Institute of Diabetes and Digestive and Kidney Diseases-sponsored workshop on Clinical Trials in Pancreatitis that sought to clearly delineate the current gaps and opportunities related to the design and conduct of patient-focused trials in recurrent acute pancreatitis and chronic pancreatitis. Key stakeholders including representatives from patient advocacy organizations, physician investigators (including clinical trialists), the US Food and Drug Administration, and the National Institutes of Health convened to discuss challenges and opportunities with particular emphasis on lessons learned from trials in participants with other painful conditions, as well as the value of incorporating the patient perspective throughout all stages of trials.

Recruitment and retention of patients with acute pancreatitis (AP) in clinical studies can be challenging. While some obstacles are similar to other clinical conditions, some are unique to AP. Identifying potential barriers early and developing targeted solutions can help optimize recruitment and retention in AP studies. Such preemptive and detailed planning can help prospective, longitudinal studies focusing on exocrine and endocrine complications of AP in accurately measuring outcomes. This manuscript highlights the challenges in recruitment and retention strategies in AP studies and reviews available resources to create opportunities to address them. We describe the multifaceted approach used by the Recruitment and Retention Committee of the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC), which builds upon earlier experiences to develop a recruitment and retention plan for the DREAM (Diabetes RElated to Acute pancreatitis and its Mechanisms) study.

OBJECTIVES: The metabolic abnormalities that lead to diabetes mellitus (DM) following an episode of acute pancreatitis (AP) have not been extensively studied. This manuscript describes the objectives, hypotheses, and methods of mechanistic studies of glucose metabolism that comprise secondary outcomes of the Diabetes RElated to Acute pancreatitis and its Mechanisms (DREAM) Study. METHODS: Three months after an index episode of AP, participants without pre-existing DM will undergo baseline testing with an oral glucose tolerance test. Participants will be followed longitudinally in three sub-cohorts with distinct metabolic tests. In the first and largest subcohort, oral glucose tolerance tests will be repeated 12 months after AP and annually to assess changes in β-cell function, insulin secretion, and insulin sensitivity. In the second, mixed meal tolerance tests will be performed at 3 and 12 months, then annually, and following incident DM to assess incretin and pancreatic polypeptide responses. In the third, frequently-sampled intravenous glucose tolerance tests will be performed at 3 months and 12 months to assess the first-phase insulin response and more precisely measure β-cell function and insulin sensitivity. CONCLUSIONS: The DREAM study will comprehensively assess the metabolic and endocrine changes that precede and lead to the development of DM after AP.

Acute pancreatitis (AP) is a disease characterized by an acute inflammatory phase followed by a convalescent phase. Diabetes mellitus (DM) was historically felt to be a transient phenomenon related to acute inflammation; however, it is increasingly recognized as an important late and chronic complication. There are several challenges that have prevented precisely determining the incidence rate of DM following AP and understanding the underlying mechanisms. The Diabetes RElated to Acute Pancreatitis and its Mechanisms (DREAM) Study is a prospective cohort study designed to address these and other knowledge gaps to provide the evidence needed to screen for, prevent, and treat DM following AP. In the following article, we summarize literature regarding the epidemiology of DM following AP, and provide the rationale and an overview of the DREAM study.

Pain is common in chronic pancreatitis (CP) and profoundly reduces quality of life (QoL). Multiple underlying mechanisms contribute to a heterogenous pain experience and reduce efficacy of pain management. This study was designed to characterize the distribution of mechanism-based pain phenotypes in painful CP. The data analyzed were collected as part of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, an NCI/NIDDK-funded longitudinal study of the natural history of CP. The PROspective Evaluation of Chronic pancreatitis for EpidEmiologic and translational stuDies includes patient-reported outcome (PRO) measures of pain, medication use, global health, and QoL. Of subjects (N = 681) with CP, 80% experienced abdominal pain within the year before enrollment. Subjects who experienced pain in the week before enrollment (N = 391) completed PROMIS Neuropathic and Nociceptive Pain Quality instruments which were then used to classify them by pain type: 40% had nociceptive, 5% had neuropathic-like, and 32% had both types of pain. The prevalence of having both types of pain was higher among women and subjects with diabetes mellitus, whereas nociceptive-only pain was more prevalent among men and those with pancreatic duct stricture. Other factors, including pain medication use and healthcare utilization, did not differ between groups based on pain type. Subjects in the Both group had significantly worse health and QoL scores relative to those with nociceptive-only pain, suggesting that using psychosocial pain surveys may be useful for understanding pain subtypes in patients with CP. Additional research is needed to identify biochemical and biophysical signatures that may associate with and predict responses to mechanism-specific interventions.

There is a paucity of literature evaluating new-onset diabetes mellitus (NODM) after resection of pancreatic cystic lesions (PCLs). We sought to characterize the incidence and risk factors associated with NODM after partial pancreatectomy for PCLs.We utilized the IBM MarketScan Database (2012-2018) to identify all nondiabetic adults who underwent partial pancreatectomy for PCLs. Patients with any other pancreatic disease were excluded. We performed Kaplan-Meier analysis and multivariable Cox proportional hazards regression to define the incidence and risk factors of postoperative NODM.Among 311 patients, the overall risk (95% confidence interval) of NODM was 9.1% (6.3-12.9%), 15.1% (11.3-20.2%), and 20.2% (15.3-26.4%) at 6, 12 and 24 months, respectively. Multivariable analysis (adjusted hazard ratio; 95% confidence interval) revealed that older age (1.97; 1.04-3.72; 55-64 vs 18-54 years), obesity (2.63; 1.35-5.12), hypertension (1.79; 1.01-3.17), and cardiovascular disease (2.54; 1.02-6.28) were independent predictors of NODM. Rates of NODM were similar after distal pancreatectomy versus pancreaticoduodenectomy.Within 2 years, 1 in 5 patients without any other pancreatic disease will develop NODM after partial pancreatectomy for PCLs. Those with advanced age, metabolic syndrome features, and/or cardiovascular disease may benefit from preoperative counseling and intensive postoperative monitoring, education, and treatment for diabetes mellitus.

Nutritional dermatoses are traditionally taught in the context of developing countries, famine, population displacement, and limited access to healthcare. In the United States, nutritional dermatoses may be underdiagnosed and lead to increased morbidity and utilization of hospital resources. These findings underscore the need for providers in developed nations to be able to identify these deficiencies. Dermatologists play a critical role in the diagnosis and management of nutritional deficiencies as they often present with cutaneous findings. Part two of this review series will focus on the epidemiology, impact, manifestations, and diagnosis of B-complex vitamins that can present with cutaneous findings, including thiamine, riboflavin, niacin, pyridoxine, and biotin.

Background and Aims : EUS-guided needle-based confocal laser endomicroscopy (nCLE) improves the diagnostic accuracy of pancreatic cystic lesions (PCLs) but concerns regarding its expense have limited widespread adoption of this technology. We conducted a cost-benefit analysis to assess the healthcare resource implications of adding EUS-nCLE to the standard of care (SOC) management of PCLs. Methods : A post-hoc analysis of a prospective study (2015-2018) evaluating EUS-nCLE for the diagnosis of PCLs was performed. The SOC diagnosis was based on clinical history, PCL morphology, and cyst fluid analysis. A minimum of 5-years of surveillance was included, the cost of EUS and MRI/MRCP was derived from institutional billing data (US$), and the total hospital costs (adjusted for inflation) for pancreatic operations were derived from the National (US) Readmission Database. Results : A reference diagnosis was available in 93 subjects (mean cyst size=36.4±15.7 mm; surgical histopathology, n=67 and diagnostic molecular markers in cyst fluid, n=26). SOC and nCLE were discordant in 13 (14%) subjects. The addition of nCLE led to 11 subjects being clinically downstaged from mucinous to non-mucinous not warranting surgery (total cost savings= $1,080,418), 1 subject upstaged from non-mucinous to mucinous, warranting surgical resection (cost savings of 5-years surveillance: $46,200), and 1 subject incorrectly classified as non-mucinous (cost excess of 5-years surveillance: $46,200). Overall, the addition of nCLE led to a net savings of $ 442,438 (mean: $ 4,757.40 /patient) for this cohort. Conclusions : EUS-nCLE is potentially cost-beneficial in the management of PCLs (≥ 3 cm) by preventing at least one unnecessary pancreatic surgery for every ten subjects undergoing evaluation by current practices. ClinicalTrials.gov number: NCT02516488.

ObjectivesChronic pancreatitis (CP) is an inflammatory disease that affects the absorption of nutrients like fats. Molecular signaling in pancreatic cells can be influenced by fatty acids (FAs) and changes in FA abundance could impact CP-associated complications. Here, we investigated FA abundance in CP compared to controls and explored how CP-associated complications and risk factors affect FA abundance.MethodsBlood and clinical parameters were collected from subjects with (n=47) and without CP (n=22). Plasma was analyzed for relative FA abundance using gas chromatography and compared between controls and CP. Changes in FA abundance due to clinical parameters were also assessed in both groups.ResultsDecreased relative abundance of polyunsaturated fatty acids (PUFAs) and increased monounsaturated fatty acids (MUFAs) were observed in subjects with CP in a sex-dependent manner. The relative abundance of linoleic acid increased, and oleic acid decreased in CP subjects with exocrine pancreatic dysfunction and a history of substance abuse.ConclusionsPlasma FAs like linoleic acid are dysregulated in CP in a sex-dependent manner. Additionally, risk factors and metabolic dysfunction further dysregulate FA abundance in CP. These results enhance our understanding of CP and highlight potential novel targets and metabolism-related pathways for treating CP.

ObjectiveSeveral 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).DesignWe 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.ResultsClinical 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 (pConclusionPain-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 numberThe study was registered with ClinicalTrials.gov (NCT03434392).

Introduction Acute pancreatitis (AP) occurs among patients with pancreas-sufficient cystic fibrosis (PS-CF) but is reportedly less common among patients with pancreas-insufficient cystic fibrosis (PI-CF). The incidence of AP may be influenced by cystic fibrosis transmembrane conductance regulator (CFTR) modulator use. We hypothesized that CFTR modulators would reduce AP hospitalizations, with the greatest benefit in PS-CF. Methods MarketScan (2012-2018) was queried for AP hospitalizations and CFTR modulator use among patients with CF. Multivariable Poisson models that enabled crossover between CFTR modulator treatment groups were used to analyze the rate of AP hospitalizations on and off therapy. Pancreas insufficiency was defined by the use of pancreas enzyme replacement therapy. Results A total of 10,417 patients with CF were identified, including 1,795 who received a CFTR modulator. AP was more common in PS-CF than PI-CF (2.9% vs 0.9%, P = 0.007). Overall, the observed rate ratio of AP during CFTR modulator use was 0.33 (95% confidence interval [CI] 0.10, 1.11, P = 0.07) for PS-CF and 0.38 (95% CI 0.16, 0.89, P = 0.03) for PI-CF, indicating a 67% and 62% relative reduction in AP hospitalizations, respectively. In a subset analysis of 1,795 patients who all had some CFTR modulator use, the rate ratio of AP during CFTR modulator use was 0.36 (95% CI 0.13, 1.01, P = 0.05) for PS-CF and 0.53 (95% CI 0.18, 1.58, P = 0.26) for PI-CF. Discussion CFTR modulator use is associated with a reduction in AP hospitalizations among patients with CF. These observational data support the prospective study of CFTR modulators to reduce AP hospitalizations among patients with CF.

Purpose Pancreatogenic diabetes refers to diabetes mellitus (DM) that develops in the setting of a disease of the exocrine pancreas, including pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). We sought to evaluate whether a blunted nutrient response of pancreatic polypeptide (PP) can differentiate these DM subtypes from type 2 DM (T2DM). Methods Subjects with new-onset DM ( Results The fasting PP concentration was lower in both the PDAC-DM and CP-DM groups than in the T2DM group (P = 0.03 and Conclusions Fasting PP concentrations and the response to meal stimulation are reduced in new-onset DM associated with PDAC or CP compared with T2DM. These findings support further investigations into the use of PP concentrations to characterize pancreatogenic DM and to understand the pathophysiological role in exocrine pancreatic diseases (NCT03460769).

Pain is a cardinal symptom of chronic pancreatitis (CP). Using Patient-Reported Outcomes Measurement Information System (PROMIS) measures, we characterized physical and mental health and symptom profiles of a well-defined cohort of individuals with CP and compared them with control subjects. Among patients with CP, we also examined associations between pain (intensity, temporal nature) and PROMIS symptom profiles and the prevalence of clinically significant psychological comorbidities.We analyzed baseline data in 488 CP patients and 254 control subjects enrolled in PROCEED (Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies), an ongoing longitudinal cohort study. Participants completed the PROMIS-Global Health, which captures global physical and mental health, and the PROMIS-29 profile, which captures 7 symptom domains. Self-reported pain was categorized by severity (none, mild-moderate, severe) and temporal nature (none, intermittent, constant). Demographic and clinical data were obtained from the PROCEED database.Pain was significantly associated with impairments in physical and mental health. Compared with participants with no pain, CP participants with severe pain (but not mild-moderate pain) had more decrements in each PROMIS domain in multivariable models (effect sizes, 2.54-7.03) and had a higher prevalence of clinically significant depression, anxiety, sleep disturbance, and physical disability (odds ratios, 2.11-4.74). Similar results were noted for constant pain (but not intermittent pain) for PROMIS domains (effect sizes, 4.08-10.37) and clinically significant depression, anxiety, sleep disturbance and physical disability (odds ratios, 2.80-5.38).Severe and constant pain are major drivers for poor psychological and physical health in CP. Systematic evaluation and management of psychiatric comorbidities and sleep disturbance should be incorporated into routine management of patients with CP. (ClinicalTrials.gov, Number: NCT03099850).

PURPOSE OF REVIEW: To discuss the spectrum of diabetes related to acute and chronic pancreatitis (which are types of pancreatogenic diabetes) and its overlapping features with type 1 and type 2 diabetes.RECENT FINDINGS: Patients with diabetes related to acute and chronic pancreatitis present clinically within a spectrum of overlapping features with other forms of diabetes. In this spectrum, glucose metabolism alterations range from increased insulin resistance following acute pancreatitis (resembling type 2 diabetes) towards a permanent loss of beta-cell function and impaired insulin secretion in end-stage chronic pancreatitis. Overlapping features with type 1 diabetes (beta cell autoantibodies) and type 2 diabetes (obesity, dyslipidemia, and hereditary/genetic factors) contribute to the heterogeneity of this spectrum.SUMMARY: Pancreatogenic diabetes secondary to acute or chronic pancreatitis is a heterogeneous entity with a variable clinical presentation, including many cases that are misdiagnosed and treated as type 2 diabetes. This is problematic as pancreatogenic diabetes is associated with a poor prognosis and entails special considerations for management. Recent discoveries showing overlapping features with type 1 and type 2 diabetes along with an improved understanding of its pathophysiology are expected to improve the diagnosis and treatment of these and other forms of pancreatogenic diabetes.

PURPOSE OF REVIEW: Diabetes secondary to pancreatic diseases (i.e., acute pancreatitis, chronic pancreatitis, and pancreatic cancer) is increasingly studied, but remains challenging to distinguish from type 2 diabetes (T2DM). We review the clinical significance and potential biomarkers that may help differentiate these types of diabetes. RECENT FINDINGS: Recent studies have identified several complications (including non-vascular) that occur more frequently in patients with diabetes secondary to acute and chronic pancreatitis than T2DM, and biomarkers to differentiate the two types of diabetes. There have been advances that may enable the enrichment of a population of adults with new onset diabetes to potentially screen for occult pancreatic cancer, but efforts are needed to identify and validate promising diagnostic biomarkers. SUMMARY: High-quality studies are needed to more precisely understand the risk factors and natural course of diabetes secondary to pancreatic diseases. Mechanistic and interventional studies are awaited to provide insights that will distinguish diabetes secondary to pancreatic diseases and refine the management of hyperglycemia in this patient population.

Same-admission cholecystectomy (CCY) is recommended for mild acute biliary pancreatitis (biliary-AP). However, there is a paucity of research investigating reasons for early (30-day) unplanned readmissions in patients who undergo CCY for biliary-AP. Hence, we sought to investigate this gap using a large population database. Using the Nationwide Readmission Database (2010–2014), we identified all adults (age ≥ 18 years) with a principal diagnosis of biliary-AP who had undergone CCY during the index hospitalization. Multivariable logistic regression models were obtained to assess independent predictors for 30-day readmission. Principal diagnosis for all readmissions was collected to ascertain the indications for early readmission. During the study period, 118,224 patients underwent same-admission CCY for biliary-AP. Three-fourths of all patients underwent invasive cholangiography during the hospitalization (intraoperative cholangiogram (IOC) = 57,038, ERCP = 31,500). The rate of early (30-day) readmission was 7.25% (n = 8574). Exacerbation of prior medical conditions (42.2%), sequelae of biliary-AP (resolving and recurrent pancreatitis, pseudocysts) (27.6%), surgical site and other postoperative complications (16%), choledocholithiasis and/or bile leak (9.6%), and preventable hospital-acquired conditions (4.6%) accounted for early readmissions. On multivariable analysis, predictors for readmission included male sex (odds ratio [OR] 1.18, 95% confidence interval [CI] 1.08–1.28), insurance type (Medicare insurance [OR 1.26, 95% CI 1.13–1.40]; Medicaid [OR 1.22, 95% CI 1.09–1.38]), outside-facility discharge (OR 1.35, 95% CI 1.16–1.57), severe AP (OR 1.35, 95% CI 1.21–1.50), and ≥ 3 Elixhauser comorbidities (OR 1.55, 95% CI 1.41–1.69). Performance of IOC (OR 0.90, 95% CI 0.82–0.97) and ERCP (OR 0.81, 95% CI 0.73–0.89) were associated with decreased risk of early readmission. In this study, using a national population database evaluating patients who underwent same-admission CCY after biliary-AP, we identified potentially modifiable risk factors and causes for early readmission as well as opportunities to improve clinical care.

PURPOSE OF REVIEW: The purpose of this review is to delineate risk factors for the development of diabetes in patients with chronic pancreatitis. The natural history including progression to diabetes and complications that develop once diabetes occurs in chronic pancreatitis is also reviewed. RECENT FINDINGS: Studies have found that predictors of diabetes in chronic pancreatitis include both risk factors for type 2 diabetes (e.g., obesity, genetic variants) as well as pancreas-specific factors (e.g., pancreatic calcification, exocrine insufficiency). Rates of diabetes in chronic pancreatitis are strongly related to the duration of chronic pancreatitis, reflecting progressive dysfunction and damage to the insulin-secreting beta-cells. Patients with diabetes and chronic pancreatitis experience an excess burden of complications, including higher all-cause and cancer-related mortality. SUMMARY: The high incidence and significant impact of diabetes on the morbidity and mortality of patients with chronic pancreatitis highlights the urgent need for clinically applicable models to predict diabetes in those with chronic pancreatitis, allowing efforts for targeted interventions to prevent diabetes. Research being carried out in the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) holds promise to fulfill these goals.

Biliary strictures caused by inflammation or fibrosis lead to jaundice and cholangitis which often make it difficult to distinguish malignant strictures. In cases when malignancy cannot be excluded, surgery is often performed. The concept of immunoglobulin G4 (IgG4)-related sclerosing cholangitis (SC) as a benign biliary stricture was recently proposed. The high prevalence of the disease in Asian countries has resulted in multiple diagnostic and treatment guidelines; however, there is need to formulate a standardized diagnostic strategy among various countries considering the utility, invasiveness, and cost-effectiveness. We evaluated accuracies of various diagnostic modalities for biliary strictures comparing pathology in the Delphi meetings which were held in Rochester, MN. The diagnostic utility for each modality was graded according to the experts, including gastroenterologists, endoscopists, radiologists, and pathologists from the United States and Japan. Diagnostic utility of 10 modalities, including serum IgG4 level, noninvasive imaging, endoscopic ultrasound, endoscopic retrograde cholangiopancreatography-related diagnostic procedures were advocated and the reasons were specified. Serum IgG4 level, noninvasive imaging, diagnostic endoscopic ultrasound and intraductal ultrasonography under endoscopic retrograde cholangiopancreatography were recognized as useful modalities for the diagnosis. The information in this article will aid in the diagnosis of biliary strictures particularly for distinguishing IgG4-SC from cholangiocarcinoma and/or primary SC.

The coronavirus disease 2019 pandemic led to changes in individuals' behaviors and healthcare delivery. We examined the impact of these changes on the rates and clinical course of acute pancreatitis (AP).Hospitalizations for AP from March 1 through August 31 in 2019 (baseline group) and the same period in 2020 (pandemic group) were retrospectively reviewed. Univariate and multivariate analyses were used for demographics and outcomes.Two hundred eighty subjects (315 admissions) were identified in 2019 and 237 subjects (264 admissions) in 2020. Subjects in the pandemic group were more likely to have systemic inflammatory response syndrome (40% vs 25%, P0.01), pancreatic necrosis (14% vs 10%, P = 0.03), and persistent organ failure (17% vs 9%, P = 0.01) compared with prepandemic. There was no difference in etiology of AP. A multivariable model indicates that increased comorbidities, prior pancreatitis, pancreatic necrosis, and prescription of opiates at discharge were associated with 30-day readmissions during the pandemic.Fewer patients were admitted for AP during the pandemic, suggesting that patients with milder symptoms avoided hospital interaction. Practices followed during the pandemic, especially avoidance of hospitalization and improved efficiency of hospital management, may reduce the burden of pancreatitis care in the future.

To determine if quantitative MRI techniques can be helpful to evaluate chronic pancreatitis (CP) in a setting of multi-institutional study.This study included a subgroup of participants (n = 101) enrolled in the Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) study (NCT03099850) from February 2019 to May 2021. MRI was performed on 1.5 T using Siemens and GE scanners at seven clinical centers across the USA. Quantitative MRI parameters of the pancreas included T1 relaxation time, extracellular volume (ECV) fraction, apparent diffusion coefficient (ADC), and fat signal fraction. We report the diagnostic performance and mean values within the control (n = 50) and CP (n = 51) groups. The T1, ECV and fat signal fraction were combined to generate the quantitative MRI score (Q-MRI).There was significantly higher T1 relaxation time; mean 669 ms (± 171) vs. 593 ms (± 82) (p = 0.006), ECV fraction; 40.2% (± 14.7) vs. 30.3% (± 11.9) (p 0.001), and pancreatic fat signal fraction; 12.2% (± 5.5) vs. 8.2% (± 4.4) (p 0.001) in the CP group compared to controls. The ADC was similar between groups (p = 0.45). The AUCs for the T1, ECV, and pancreatic fat signal fraction were 0.62, 0.72, and 0.73, respectively. The composite Q-MRI score improved the diagnostic performance (cross-validated AUC: 0.76).Quantitative MR parameters evaluating the pancreatic parenchyma (T1, ECV fraction, and fat signal fraction) are helpful in the diagnosis of CP. A Q-MRI score that combines these three MR parameters improves diagnostic performance. Further studies are warranted with larger study populations including patients with acute and recurrent acute pancreatitis and longitudinal follow-ups.

OBJECTIVE The empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) scores assess the insulinemic and inflammatory potentials of habitual dietary patterns, irrespective of the macronutrient content, and are based on plasma insulin response or inflammatory biomarkers, respectively. The glycemic index (GI) and glycemic load (GL) assess postprandial glycemic potential based on dietary carbohydrate content. We tested the hypothesis that dietary patterns promoting hyperinsulinemia, chronic inflammation, or hyperglycemia may influence type 2 diabetes risk. RESEARCH DESIGN AND METHODS We calculated dietary scores from baseline (1993–1998) food frequency questionnaires among 73,495 postmenopausal women in the Women’s Health Initiative, followed through March 2019. We used multivariable-adjusted Cox regression to estimate hazard ratios (HRs) and 95% CIs for type 2 diabetes risk. We also estimated multivariable-adjusted absolute risk of type 2 diabetes. RESULTS During a median 13.3 years of follow-up, 11,009 incident cases of type 2 diabetes were diagnosed. Participants consuming the most hyperinsulinemic or proinflammatory dietary patterns experienced greater risk of type 2 diabetes; HRs (95% CI) comparing highest to lowest dietary index quintiles were EDIH 1.49 (1.32–1.68; Ptrend < 0.0001) and EDIP 1.45 (1.29–1.63; Ptrend < 0.0001). The absolute excess incidence for the same comparison was 220 (EDIH) and 271 (EDIP) cases per 100,000 person-years. GI and GL were not associated with type 2 diabetes risk: GI 0.99 (0.88–1.12; Ptrend = 0.46) and GL 1.01 (0.89–1.16; Ptrend = 0.30). CONCLUSIONS Our findings in this diverse cohort of postmenopausal women suggest that lowering the insulinemic and inflammatory potentials of the diet may be more effective in preventing type 2 diabetes than focusing on glycemic foods.

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.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.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).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.

Background and study aims There is limited evidence on the diagnostic performance of endoscopic ultrasound (EUS)-guided tissue acquisition in autoimmune pancreatitis (AIP). The aim of this meta-analysis was to provide a pooled estimate of the diagnostic performance of EUS-guided fine-needle aspiration (FNA) and fine-needle biopsy (FNB) in patients with AIP. Patients and methods Computerized bibliographic search was performed through January 2020. Pooled effects were calculated using a random-effects model by means of DerSimonian and Laird test. Primary endpoint was diagnostic accuracy compared to clinical diagnostic criteria. Additional outcomes were definitive histopathology, pooled rates of adequate material for histological diagnosis, sample adequacy, mean number of needle passes. Diagnostic sensitivity and safety data were also analyzed. Results Fifteen studies with 631 patients were included, of which four were prospective series and one randomized trial. Overall diagnostic accuracy of EUS tissue acquisition was 54.7 % (95 % confidence interval, 40.9 %–68.4 %), with a clear superiority of FNB over FNA (63 %, 52.7 % to 73.4 % versus 45.7 %, 26.5 %–65 %; p Conclusion The results of this meta-analysis demonstrate that the diagnostic performance of EUS-guided tissue acquisition is modest in patients with AIP, with an improved performance of FNB compared to FNA.

OBJECTIVES: Endoscopic pancreatic function tests are used to diagnose pancreatic diseases and are a viable source for the discovery of biomarkers to better characterize pancreatic disorders. However, pancreatic fluid (PF) contains active enzymes that degrade biomolecules. Therefore, we tested how preservation methods and time to storage influences the integrity and quality of proteins and nucleic acids. METHODS: We obtained PF from 9 subjects who underwent an endoscopic pancreatic function test. Samples were snap frozen at the time of collection, after 1, 2, 4 hours on ice, or after storage overnight at 4°C with or without RNase or protease inhibitors. Electrophoresis and mass spectrometry analysis determined protein abundance and quality while nucleic acid integrity values determined DNA and RNA degradation. RESULTS: Protein degradation increased after 4 hours on ice and DNA degradation after 2 hours on ice. Adding protease inhibitors delayed degradation. RNA was significantly degraded under all conditions compared to the snap frozen samples. Isolated RNA from PF-derived exosomes exhibited similar poor quality as RNA isolated from matched PF samples. CONCLUSIONS: Adding protease inhibitors immediately after collecting PF and processing the fluid within 4 hours of collection maintains the protein and nucleic acid integrity for use in downstream molecular analyses.